The potential of extracellular microvesicles of mesenchymal stromal cells in obstetrics.

Abstract:
BACKGROUND
The rate of cesarean deliveries is steadily growing worldwide as a result of increasing maternal age at first delivery. Ensuring optimal recovery after surgery, specifically the development of a functionally competent uterine scar to facilitate vaginal birth after a cesarean delivery (VBAC), is one of the challenges in modern obstetrics. Extracellular microvesicles (EMVs) are secreted by multiple cell types and act as mediators of intercellular interaction during tissue reparation. The immunomodulatory and regenerative effects of EMVs of mesenchymal stromal cells (MSCs) have been studied shown in pre-clinical studies.

AIM OF THE STUDY
To evaluate the safety profile of EMVs of mesenchymal stromal placental cells (MSPCs) injected during the cesarean delivery and the impact of this pilot approach on post-surgery recovery.

MATERIALS AND METHODS
This pilot study included 53 women undergoing cesarean delivery with (n = 23) or without (n = 30) an injection of 500 µl of MSC EMVs after closing the uterine incision with a single continuous Vicryl suture.

RESULTS
All study participants had uncomplicated post-surgery period. The mean inpatient stay duration in women receiving the EMV injection was 4.26 ± 0.09 days vs. 5.33 ± 0.38 in the control group (p<.05). There were no postpartum inflammatory complications in the study group compared with two cases (6.7%) by postpartum endometritis/myometrial infection and one case (3.3%) of lochiometra in the control group.

SUMMARY
Intra-surgery injection of MSC EMVs was well-tolerated and associated with a lower rate of infectious post-partum complications in women undergoing cesarean delivery.

Extracellular microvesicles
cesarean delivery
uterine scar
endometritis
postpartum hospital stay


Evaluation of the Psychometric Properties of the Five Facet of Mindfulness Questionnaire.

Abstract:
Objective
The Five Facet of Mindfulness Questionnaire (FFMQ) is widely used to assess mindfulness. The present study provides a psychometric evaluation of the FFMQ that includes item response theory (IRT) analyses and evaluation of item characteristic curves.

Method
We administered the FFMQ, the Beck Depression Inventory-II, the Ruminative Response Scale, and the Emotion Regulation Questionnaire to a heterogenous sample of 240 community-based adults. We estimated internal consistency reliability, item-scale correlations, categorical confirmatory factor analysis, and IRT graded response models for the FFMQ. We also estimated correlations among the FFMQ scales and correlations with the other measures included in the study.

Results
Internal consistency reliabilities for the five FFMQ scales were 0.82 or higher. A five-factor categorical model fit the data well. IRT-estimated item characteristic curves indicated that the five response options were monotonically ordered for most of the items. Product-moment correlations between simple-summated scoring and IRT scoring of the scales were 0.97 or higher.

Conclusions
The FFMQ accurately identifies varying levels of trait mindfulness. IRT-derived estimates will inform future adaptations to the FFMQ (e.g., briefer versions) and the development of future mindfulness instruments.

Shallcross|Amanda|A|
Lu|Nathaniel Y|NY|
Hays|Ron D|RD|

Mindfulness
Item Response Theory
Item Characteristic Curves


2-Arylidene-1-indandiones as Pleiotropic Agents with Antioxidant and Inhibitory Enzymes Activities.

Abstract: Indandiones are a relatively new group of compounds presenting a wide range of biological activities. The synthesis of these compounds was performed via a Knoevenagel reaction between an aldehyde and 1,3-indandione and were obtained with a yield up to 54%. IR, 1H-Nucleic Magnetic Resonance (NMR), 13C-NMR, LC/MS ESI+ and elemental analysis were used for the confirmation of the structures of the novel derivatives. Lipophilicity values of compounds were calculated theoretically and experimentally by reversed chromatography method as values RM. The novel derivatives were studied through in vitro and in vivo experiments for their activity as anti-inflammatory and antioxidant agents and as inhibitors of lipoxygenase, trypsin, and thrombin. The inhibition of the carrageenin-induced paw edema (CPE) was also determined for representative structures. In the above series of experiments, we find that all the compounds showed moderate to satisfying interaction with the stable DPPH free radical in relation to the concentration and the time 2-arylidene-1-indandione (10) was the strongest. We observed moderate or very low antioxidant activities for selected compounds in the decolorization assay with ABTS+•. Most of the compounds showed high anti-lipid peroxidation of linoleic acid induced by AAPH.2-arylidene-1-indandione (7) showed a strongly inhibited soybean LOX. Only 2-arylidene-1-indandione (3) showed moderate scavenging activity of superoxide anion, whereas 2-arylidene-1-indandione (8) and 2-arylidene-1-indandione (9) showed very strong inhibition on proteolysis. 2-arylidene-1-indandione (8) highly inhibited serine protease thrombin. 2-arylidene-1-indandiones (7, 8 and 9) can be used as lead multifunctional molecules. The compounds were active for the inhibition of the CPE (30-57%) with 2-arylidene-1-indandione (1) being the most potent (57%). According to the predicted results a great number of the derivatives can cross the Blood-Brain Barrier (BBB), act in CNS and easily transported, diffused, and absorbed. Efforts are conducted a) to correlate quantitatively the in vitro/in vivo results with the most important physicochemical properties of the structural components of the molecules and b) to clarify the correlation of actions among them to propose a possible mechanism of action. Hydration energy as EHYDR and highest occupied molecular orbital (HOMO) better describe their antioxidant profile whereas the lipophilicity as RM values governs the in vivo anti-inflammatory activity. Docking studies are performed and showed that soybean LOX oxidation was prevented by blocking into the hydrophobic domain the substrates to the active site.

antioxidants
2-arylidene-1,3-indandiones
Lipinski “Rule of five”
lipoxygenase inhibitors


In vitro baselining of new pyrrolopyrimidine EGFR-TK inhibitors with Erlotinib.

Abstract: Epidermal growth factor receptor tyrosine kinase inhibitors are useful in treatment of non-small cell lung cancer, and show promise in combination therapy settings. Two novel chiral pyrrolopyrimidines have been baselined towards Erlotinib, Lapatinib and Dasatinib using in vitro cellular studies and ADME profiling. One of these, (S)-2-((6-(4-(hydroxymethyl)-2-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-2-phenylethan-1-ol, was more active than Erlotinib in lung and breast cancer cell models. The compound also had promising activity towards ovarian cancer cell lines, while low activity was seen towards cells of haematological origin. ADME profiling revealed good solubility, higher metabolic stability than Erlotinib and no inhibitory effect towards the hERG voltage-gated ion channel. Investigation of inhibitory potency towards 6 CYP isoforms generally revealed low inhibitory potency, but in the case of CYP3A4, a substrate dependent inhibition was noted using testosterone as substrate (IC50: 12.5μM). No cellular or gene toxicity was noted for the compounds or products of phase I metabolism. However, permeability studies using Caco-2 cells revealed a high efflux ratio. Further experiments using ABC transporter inhibitors revealed that the pyrrolopyrimidines are actively transported by the breast cancer resistant protein and P-glycoprotein transporters, which might prevent their further development into drugs.

Sundby|Eirik|E|
Han|Jin|J|
Kaspersen|Svein Jacob|SJ|
Hoff|Bård Helge|BH|

D065607:Cytochrome P-450 Enzyme Inhibitors

2-[[6-[4-(Hydroxymethyl)-2-methoxyphenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-2-phenylethanol (PubChem CID: 90466098)


From food to hospital: we need to talk about Acinetobacter spp.

Abstract: Some species of the genus Acinetobacter are admittedly important hospital pathogens. Additionally, various animal and plant foods have been linked to the presence of Acinetobacter, including resistant strains. However, due to isolation difficulties and the lack of official standard methods, there is a dearth of work and epidemiological data on foodborne diseases caused by this microorganism. Considering that Acinetobacter spp. may represent a serious public health problem, especially because of their resistance to carbapenems and colistin, and because of the fact that these pathogens may transfer resistance genes to other bacteria, studies are needed to evaluate the pathogenicity of both food and clinical isolates and to search for them using control strategies, such as the adoption of more efficient disinfection measures and use of antimicrobial substances (AMS). In contrast, AMS production by strains of the genus Acinetobacter has already been described, and its potential for application against other Gram-negative food or clinical pathogens, reveals a new field to be explored.

Ramos|Gustavo Luis de Paiva Anciens|GLPA|

Acinetobacter spp
antimicrobial substances
antibiotic resistance
food contamination
infections


Visual recovery after retinal detachment with macula-off: is surgery within the first 72 h better than after?

Abstract:
AIMS
To investigate the influence of lag time between the onset of central visual acuity loss and surgical intervention of macula-off retinal detachment.

METHODS
This retrospective case series examined all consecutively treated eyes with primary macula-off retinal detachment at the University Hospital Hamburg (Germany) from February 2010 to February 2015. Records of 1727 patients operated by six surgeons were reviewed. Eighty-nine eyes (5.2%) from 89 patients met the inclusion and exclusion criteria. The main outcome measure studied was final visual acuity as a function of symptom duration of macula-off detachment. Secondary outcome measures studied were influence of age and surgical technique. Symptom duration was defined as the time from the onset of loss of central vision to surgical intervention.

RESULTS
After 10 days no clinically relevant difference was seen in final visual acuity. Eyes with symptom duration of 3 days or less achieved best final visual acuity (p<0.001). Age and preoperative visual acuity had no influence while vitrectomised eyes had better outcome compared with those with scleral buckling.

CONCLUSIONS
Our study suggests that 1. After 10 days of central visual acuity loss, the final visual outcome is clinically comparable and independent of further delay of surgery up to 30 days. 2. Eyes treated up to 3 days after onset of loss of central vision have better final visual acuity than eyes with longer lag time. However, we did not find statistically significant differences within the first 3 days. 3. Surgery for macula-off retinal detachment may therefore most likely not be postponed without compromising the patient's visual prognosis.

Frings|Andreas|A| Markau|Nastassija|N| Katz|Toam|T| Stemplewitz|Birthe|B| Skevas|Christos|C| Druchkiv|Vasyl|V| Wagenfeld|Lars|L|

Vision
Rehabilitation
Retina
Treatment Surgery


Persistent deep water anoxia in the eastern South Atlantic during the last ice age.

Abstract: During the last glacial interval, marine sediments recorded reduced current ventilation within the ocean interior below water depths of approximately >1,500 m [B. A. Hoogakker et al., Nat. Geosci. 8, 40-43 (2015)]. The degree of the associated oxygen depletion in the different ocean basins, however, is still poorly constrained. Here, we present sedimentary records of redox-sensitive metals from the southwest African margin. These records show evidence of continuous bottom water anoxia in the eastern South Atlantic during the last glaciation that led to enhanced carbon burial over a prolonged period of time. Our geochemical data indicate that upwelling-related productivity and the associated oxygen minimum zone in the eastern South Atlantic shifted far seaward during the last glacial period and only slowly retreated during deglaciation times. While increased productivity during the last ice age may have contributed to oxygen depletion in bottom waters, especially on the upper slope, slow-down of the Late Quaternary deep water circulation pattern [Rutberg et al., Nature 405, 935-938 (2000)] appears to be the ultimate driver of anoxic conditions in deep waters.

South Atlantic
last glacial
carbon cycle
deep water redox
trace metal accumulation


Quantification of Glomerular Structural Lesions: Associations With Clinical Outcomes and Transcriptomic Profiles in Nephrotic Syndrome.

Abstract:
RATIONALE & OBJECTIVE
The current classification system for focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) does not fully capture the complex structural changes in kidney biopsies, nor the clinical and molecular heterogeneity of these diseases.

STUDY DESIGN
Prospective observational cohort study.

SETTING & PARTICIPANTS
N=221 MCD and FSGS patients enrolled in the Nephrotic Syndrome Study Network (NEPTUNE).

EXPOSURES
The NEPTUNE Digital Pathology Scoring System (NDPSS) was applied to generate scores for 37 glomerular descriptors.

OUTCOMES
Time from biopsy to complete proteinuria remission, time from biopsy to kidney disease progression (40% eGFR decline or kidney failure), and eGFR over time.

ANALYTICAL APPROACH
Cluster analysis was used to group patients with similar morphologic characteristics. Glomerular descriptors and patient clusters were assessed for associations with outcomes using adjusted Cox models and linear mixed models. Messenger RNA from glomerular tissue was used to assess differentially expressed genes between clusters and identify genes associated with individual descriptors driving cluster membership.

RESULTS
Three clusters were identified: X (N=56), Y (N=68), and Z (N=97). Clusters Y and Z had higher probabilities of proteinuria remission (HR [95% CI]= 1.95 [0.99, 3.85] and 3.29 [1.52, 7.13], respectively), lower hazards of disease progression 0.22 [0.08, 0.57] and 0.11 [0.03, 0.45], respectively), and lower loss of eGFR over time compared with X. Cluster X had 1920 differentially expressed genes compared to Y+Z, which reflected activation of pathways of immune response and inflammation. Six descriptors driving the clusters individually correlated with clinical outcomes and gene expression.

LIMITATIONS
Low prevalence of some descriptors and biopsy at a single time point.

CONCLUSIONS
The NDPSS allows for categorization of FSGS/MCD patients into clinically and biologically relevant subgroups, and uncovers histologic parameters associated with clinical outcomes and molecular signatures not included in current classification systems.

Hodgin|Jeffrey B|JB|
Mariani|Laura H|LH|
Zee|Jarcy|J|
Liu|Qian|Q|
Smith|Abigail R|AR|
Eddy|Sean|S|
Hartman|John|J|
Hamidi|Habib|H|
Gaut|Joseph P|JP|
Palmer|Matthew B|MB|
Nast|Cynthia C|CC|
Chang|Anthony|A|
Hewitt|Stephen|S|
Gillespie|Brenda W|BW|
Kretzler|Matthias|M|
Holzman|Lawrence B|LB|
Barisoni|Laura|L|
|||

clinical outcomes
transcriptomics
nephrotic syndrome
proteinuria
gene expression
glomerular disease
molecular analysis
morphologic features
renal pathology


Mapping the anode surface-electrolyte interphase: investigating a life limiting process of lithium primary batteries.

Abstract: Cathode solubility in batteries can lead to decreased and unpredictable long-term battery behavior due to transition metal deposition on the negative electrode such that it no longer supports high current. Analysis of negative electrodes from cells containing vanadium oxide or phosphorus oxide based cathode systems retrieved after long-term testing was conducted. This report demonstrates the use of synchrotron based X-ray microfluorescence (XRμF) to map negative battery electrodes in conjunction with microbeam X-ray absorption spectroscopy (μXAS) to determine the oxidation states of the metal centers resident in the solid electrolyte interphase (SEI) and at the electrode surface. Based on the empirical findings, a conceptual model for the location of metal ions in the SEI and their role in impacting lithium ion mobility at the electrode surfaces is proposed.

Bock|David C|DC|
Tappero|Ryan V|RV|
Takeuchi|Kenneth J|KJ|
Marschilok|Amy C|AC|
Takeuchi|Esther S|ES|

solid electrolyte interphase
X-ray microfluorescence mapping
lithium battery
silver vanadium oxide
silver vanadium phosphorus oxide


Capturing patients, missing inequities: Data standardization on sexual orientation and gender identity across unequal clinical contexts.

Abstract: In effort to address fundamental causes and reduce health disparities, public programs increasingly mandate sites of care to capture patient data on social and behavioral domains within Electronic Health Records (EHRs). Data reporting drawing from EHRs plays an essential role in public management of social problems, and data on social factors are commonly cited as foundational for eliminating health inequities. Yet one major shortcoming of these data-centered initiatives is their limited attention to social context, including the institutional conditions of biomedical stratification and variation of care provision across clinical settings. In this article, we leverage comparative fieldwork to examine provider and system responses to mandated data collection on patient sexual orientation and gender identity (SOGI), highlighting unequal clinical contexts as they appear across a large county safety-net institution and an LGBTQ-oriented health organization. Although point of care data collection is commonly justified for governance in the aggregate (e.g., disparity monitoring), we find standardized data on social domains presents a double-edged sword in clinical settings: formal categories promote visibility where certain issues remain hidden, yet constrain clinical utility in sites with greater knowledge and experience with related topics. We further illustrate how data standardization captures patient identities yet fundamentally misses these unequal contexts, resulting in limited attenuation of inequity despite broad expectations of clinical change. By revealing the often-invisible contexts of care that elude standard measurement, our findings underline the strengths of qualitative social science in accounting for the complex dynamics of enduring social problems. We call for deeper engagement with the unequal contexts of biomedical stratification, especially in light of increasing pressure to quantify the social amidst the rising tide of data-driven care.

Electronic health records
Health inequity
Clinical settings
Data analytics
Gender and sexual minority
LGBTQ health
Social determinants
United States


The relationship between the latency period, infection markers, and oxidant and antioxidant states in women with preterm premature rupture of membranes.

Abstract:
BACKGROUND
A major cause of perinatal morbidity and mortality has been reported to be preterm premature rupture of membranes (PPROM). Our objective was to evaluate oxidant-antioxidant balance, infection parameters, time interval between rupture of membranes and delivery (latency period), and the relationship among all these parameters.

METHODS
Seventy-five cases with PPROM between 24 and 34 gestational weeks were included in the study. A control group of 41 women who gave birth at term were considered as the control group. The relationship among maternal plasma total oxidative stress (TOS), malondialdehyde (MDA), total antioxidant status (TAS), leukocyte counts, CRP, vitamin C and E levels, gestational week, neonatal birthweight, and latency period was evaluated.

RESULTS
In cases with PPROM, rupture occurred at an average of 29.4 gestational weeks and premature babies were born at an average of 31.6 gestational weeks. The mortality rate of babies born to PPROM women was 18.7% (14/75) died at or following birth. In the PPROM group, TOS, MDA, and leukocyte counts were found to be significantly higher compared to the control group (p < 0.001). Besides, a significant negative correlation was detected among the latency period, TOS, CRP, and leukocyte counts (p < 0.05).

CONCLUSIONS
Appropriate treatment protocols that strengthen antioxidant defense systems and taking into consideration the signs of infection can decrease the incidence of PPROM and/or mortality rates of babies born to PPROM women.

D005322:Fetal Membranes, Premature Rupture

Latency period
Oxidant and antioxidant states
PPROM
Inflammatory marker


Differential Gene Expression in Red Imported Fire Ant (Solenopsis invicta) (Hymenoptera: Formicidae) Larval and Pupal Stages.

Abstract: Solenopsis invicta Buren is an invasive ant species that has been introduced to multiple continents. One such area, the southern United States, has a history of multiple control projects using chemical pesticides over varying ranges, often resulting in non-target effects across trophic levels. With the advent of next generation sequencing and RNAi technology, novel investigations and new control methods are possible. A robust genome-guided transcriptome assembly was used to investigate gene expression differences between S. invicta larvae and pupae. These life stages differ in many physiological processes; of special importance is the vital role of S. invicta larvae as the colonies' "communal gut". Differentially expressed transcripts were identified related to many important physiological processes, including digestion, development, cell regulation and hormone signaling. This dataset provides essential developmental knowledge that reveals the dramatic changes in gene expression associated with social insect life stage roles, and can be leveraged using RNAi to develop effective control methods.

Allen|Margaret L|ML|0000-0002-4758-1290
Rhoades|Joshua H|JH|
Sparks|Michael E|ME|0000-0001-6251-8559
Grodowitz|Michael J|MJ|

transcriptome
differential expression
digestion
RNA-Seq
fire ant brood


Documenting and visualising progress towards Universal Health Coverage of insulin and blood glucose test strips for people with diabetes.

Abstract:
AIMS
Global governments have committed to achieve Universal Health Coverage (UHC), ensuring access to quality and affordable healthcare for all. This is fundamental for those with type 1 diabetes mellitus, who require daily access to both insulin and blood glucose test strips to survive. This group risks being left behind by global initiatives that fail to consider these particular needs.

METHODS
A questionnaire was distributed to key informants in 37 less-resourced countries. Seven high-income countries were also included for comparison. We drew on a WHO framework developed to assess progress towards UHC to create scales on three dimensions: population covered, services provided and direct costs. A fourth dimension, availability, was added. Results were grouped into six patterns and visually displayed with radar graphs.

RESULTS
65% of the less-resourced national health systems provided insulin, with medians of 67% for service provision (equating to Human Regular and NPH), 55% direct costs covered, and 75% availability. Test strips were only provided in 14% of the less-resourced systems, with medians 42% (less than two strips per day), 76%, and 88% respectively. Six patterns of provision were identified. Progress correlated with income level, yet some low-income countries are achieving provision for insulin and test strips for those enrolled in health insurance schemes.

CONCLUSION
No less-resourced country had even near-complete coverage for insulin, and coverage was worse for test strips. This study demonstrates the utility of this framework which could be developed as a means of tracking progress in meeting the needs of people with diabetes.

Klatman|Emma Louise|EL|
McKee|Martin|M|
Ogle|Graham David|GD|

Universal Health Coverage
Insulin
Diabetes
Type 1 diabetes
Blood glucose monitoring
Sustainable development goals


Taxonomic and nomenclatural changes in three species of Pterostichus Bonelli (Coleoptera: Carabidae) from the Far East.

Abstract: The ground beetle genus Pterostichus Bonelli has diversified in regions including the Far East, but taxonomic issues remain even at the species level. This study presents taxonomic and nomenclatural changes in three species of Pterostichus from the Far East: P. (Petrophilus) eximius Morawitz, P. (Lenapterus) wellschmiedi Kirschenhofer, and P. (L.) subrugosus Straneo. The analyses are based on comparative studies of the endophallus of male genitalia, which is taxonomically useful in Carabidae but has not been examined in these species. The first species, P. eximius, has been treated as a monotypic species that is widely distributed in Eastern Siberia, the Russian Far East, and adjacent regions, but our results revealed that populations from Rishiri-tô and the Sakhalin islands are distinct from the nominotypical population from Transbaikalia. The name for the Sakhalin population, which was synonymized with P. eximius, is reinstated as subspecies P. eximius sachalinensis stat. nov., and the Rishiri-tô population is described as Pterostichus eximius rishiridakensis ssp. nov. Conspecificity (syn. nov.) was confirmed for P. wellschmiedi, which was described from southern Sakhalin, and P. marginatus Matsumura, which was described earlier from southern Sakhalin. No conspicuous differences in the endophallus structure were found between P. subrugosus, which was described from Hokkaidô, and P. marginatus, although differences are recognized in the elytral sculptures and in the metallic luster of the dorsal surface. The taxon was thus downgraded to subspecies P. marginatus subrugosus stat. nov.

Coleoptera, biogeography, comparative morphology, male genitalia, new status, new subspecies, new synonym, phylogeny


Association of nucleotide excision repair pathway gene polymorphisms with gastric cancer and atrophic gastritis risks.

Abstract: Polymorphisms of NER genes could change NER ability, thereby altering individual susceptibility to GC. We systematically analyzed 39 SNPs of 8 key genes of NER pathway in 2686 subjects including 898 gastric cancer (GC), 851 atrophic gastritis (AG) and 937 controls (CON) in northern Chinese. SNP genotyping were performed using Sequenom MassARRAY platform. The results demonstrated that DDB2 rs830083 GG genotype was significantly associated with increased GC risk compared with wild-type CC (OR=2.32, P= 6.62 × 10-9); XPC rs2607775 CG genotype conferred a 1.73 increased odds of GC risk than non-cancer subjects compared with wild-type CC (OR=1.73, P= 3.04 × 10-4). The combined detection of these two polymorphisms demonstrated even higher GC risk (OR=3.05). Haplotype analysis suggested that DDB2 rs2029298-rs326222-rs3781619-rs830083 GTAG haplotype was significantly associated with disease risk in each step of CON→AG→GC development (AG vs. CON: OR=2.88, P= 7.51 × 10-7; GC vs. AG: OR=2.90, P=5.68 × 10-15; GC vs. CON: OR=8.42, P=2.22 × 10-15); DDB2 GTAC haplotype was associated with reduced risk of GC compared with CON (OR=0.63, P= 8.31 × 10-12). XPC rs1870134-rs2228000-rs2228001-rs2470352-rs2607775 GCAAG haplotype conferred increased risk of GC compared with AG (OR=1.88, P= 6.98 × 10-4). XPA rs2808668 and drinking, DDB2 rs326222, rs3781619, rs830083 and smoking demonstrated significant interactions in AG; XPC rs2607775 had significant interaction with smoking in GC. In conclusion, NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors. The detection of NER pathway polymorphisms such as DDB2 and XPC might be applied in the prediction of GC risk and personalized prevention in the future. NER pathway polymorphisms especially in "damage incision" step were significantly associated with GC risk and had interactions with environment factors, which might be applied in the prediction of GC risk and personalized prevention in the future.

Liu|Jingwei|J| Sun|Liping|L| Xu|Qian|Q| Tu|Huakang|H| He|Caiyun|C| Xing|Chengzhong|C| Yuan|Yuan|Y|

D020022:Genetic Predisposition to Disease

D060888:Real-Time Polymerase Chain Reaction

nucleotide excision repair
polymorphism
gastric cancer


Topics and structure in preoperative nursing consultations with patients undergoing colorectal cancer surgery.

Abstract:
BACKGROUND
The preoperative education, which occurs in preoperative patient consultations, is an important part of the surgical nurse's profession. These consultations may be the building blocks of a partnership that facilitates communication between patient and nurse.

AIM
The aim of the study was to describe topics and structure and documentation in preoperative nursing consultations with patients undergoing surgery for colorectal cancer.

METHOD
The study was based on analysis of consultations between seven patients and nurses at a Swedish university hospital. The preplanned preoperative consultations were audio-recorded and transcribed verbatim. The structure of the consultations was described in terms of phases and the text was analysed according to a manifest content analysis RESULTS: The consultations were structured on an agenda that was used variously and communicating different topics in an equally varied manner. Seven main topics were found: Health status, Preparation before surgery, Discovery, Tumour, Operation, Symptoms and Recovery after surgery. The topic structure disclosed a high number of subtopics. The main topics 'Discovery', 'Tumour' and 'Symptoms' were only raised by patients and occupied only 11% of the discursive space. Documentation was sparse and included mainly task-oriented procedures rather than patients' worries and concerns.

CONCLUSION
There was no clear structure regarding preoperative consultation purpose and content. Using closed questions instead of open is a hindrance of developing a dialogue and thus patient participation. Preoperative consultation practice needs to be strengthened to include explicit communication of the consultations' purpose and agenda, with nurses actively discussing and responding to patients' concerns and sensitive issues. The results of the study facilitate the development of methods and structure to support person-centred communication where the patient is given space to get help with the difficult issues he/she may have when undergoing surgery.

Pettersson|Monica E|ME|
Öhlén|Joakim|J|
Friberg|Febe|F|
Hydén|Lars-Christer|LC|
Carlsson|Eva|E|

cancer
communication
patient participation
care
health education
narrative
nurse-patient interaction
qualitative approaches


Biochemical Markers for the Diagnosis of Mitochondrial Fatty Acid Oxidation Diseases.

Abstract: Mitochondrial fatty acid β-oxidation (FAO) contributes a large proportion to the body's energy needs in fasting and in situations of metabolic stress. Most tissues use energy from fatty acids, particularly the heart, skeletal muscle and the liver. In the brain, ketone bodies formed from FAO in the liver are used as the main source of energy. The mitochondrial fatty acid oxidation disorders (FAODs), which include the carnitine system defects, constitute a group of diseases with several types and subtypes and with variable clinical spectrum and prognosis, from paucisymptomatic cases to more severe affectations, with a 5% rate of sudden death in childhood, and with fasting hypoketotic hypoglycemia frequently occurring. The implementation of newborn screening programs has resulted in new challenges in diagnosis, with the detection of new phenotypes as well as carriers and false positive cases. In this article, a review of the biochemical markers used for the diagnosis of FAODs is presented. The analysis of acylcarnitines by MS/MS contributes to improving the biochemical diagnosis, both in affected patients and in newborn screening, but acylglycines, organic acids, and other metabolites are also reported. Moreover, this review recommends caution, and outlines the differences in the interpretation of the biomarkers depending on age, clinical situation and types of samples or techniques.

carnitine
newborn screening
acylcarnitines
acylglycines
fatty acid β-oxidation diseases
mass spectrometry


M6A Classification Combined With Tumor Microenvironment Immune Characteristics Analysis of Bladder Cancer.

Abstract:
Background
Studies have shown that N6-methyl adenosine (m6A) plays an important role in cancer progression; however, the underlying mechanism of m6A modification in tumor microenvironment (TME) cell infiltration of bladder cancer remains unclear. This study aimed to investigate the role of m6A modification in TME cell infiltration of bladder cancer.

Methods
The RNA expression profile and clinical data of bladder cancer were obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We assessed the m6A modification patterns of 664 bladder cancer samples based on 20 m6A regulators through unsupervised clustering analysis and systematically linked m6A modification patterns to TME cell infiltration characteristics. Gene ontology and gene set variation analyses were conducted to analyze the underlying mechanism based on the assessment of m6A methylation regulators. Principal component analysis was used to construct the m6A score to quantify m6A modification patterns of bladder cancer.

Results
The genetic and expression alterations in m6A regulators were highly heterogeneous between normal and bladder tissues. Three m6A modification patterns were identified. The cell infiltration characteristics were highly consistent with the three immune phenotypes, including immune rejection, immune inflammation, and immune desert. The biological functions of three m6A modification patterns were different. Cox regression analyses revealed that the m6A score was an independent signature with patient prognosis (HR = 1.198, 95% CI: 1.031-1.390). Patients with a low-m6A score were characterized by increased tumor mutation burden, PD-L1 expression, and poorer survival. Patients in the low-m6A score group also showed significant immune responses and clinical benefits in the CTLA-4 immunotherapy cohort (p =0.0069).

Conclusions
The m6A methylation modification was related to the formation of TME heterogeneity and complexity. Assessing the m6A modification pattern of individual bladder cancer will improve the understanding of TME infiltration characteristics.

Zhu|Huili|H| Jia|Xiaocan|X| Wang|Yuping|Y| Song|Zhijuan|Z| Wang|Nana|N| Yang|Yongli|Y| Shi|Xuezhong|X|

m6A
tumor microenvironment
bladder cancer
mutation burden
immunotherapy


Tumor Growth and Cell Proliferation Rate in Human Oral Cancer.

Abstract:
BACKGROUND AND AIMS
Oral squamous cell cancer (SCC) has a high rate of morbidity and an overall 5-year survival rate for patients of 50%, statistics that have not changed in the last half century. A better understanding of the biological nature of this aggressive disease is mandatory. The two most studied human oral cancer cell lines-SCC-15 and SCC-25-share some biological characteristics but differ in others and may serve as a platform for further oral SCC analysis. We compared their basic carcinogenic characteristics, cellular proliferation rate and tumor growth, and discussed results according to available data from the literature and our own previous studies.

METHODS
We examined doubling time both in vitro and in vivo of the SCC-15 and SCC-25 cell lines. After seeding the exact same number of cells in a six-well dish we counted them daily. To confirm doubling time differences in cells, we progressed to an in vivo model in nude mice using male 9- to 10-week-old BALB/c-nu/nu mice.

RESULTS
In both models (in vitro and in vivo) SCC-15 multiplied faster than SCC-25 cell line. In vivo the difference was more than double and in vitro this change was 24%.

CONCLUSION
Both SCC-15 and SCC-25 cell lines are suitable for further exploration of the oral carcinogenesis process. Based on our currently presented results and on the available literature, it seems that SCC-15 has an increased potential for local tumor growth and cell proliferation, whereas SCC-25 has a higher potential for invasion and metastasis.

D000818:Animals
D002294:Carcinoma, Squamous Cell
D045744:Cell Line, Tumor
D049109:Cell Proliferation
D006801:Humans
D008297:Male
D008807:Mice, Inbred BALB C
D008819:Mice, Nude
D009062:Mouth Neoplasms

Tumor growth
Cell proliferation
Oral cancer
Doubling time


Timing of manipulation under anaesthesia for stiffness after total knee arthroplasty.

Abstract: Stiffness following total knee arthroplasty (TKA) is a debilitating condition for the patient with limitation of functional outcome. There are various causes of stiffness, which can be classified as pre-operative, per-operative and post-operative. Arthrofibrosis is one of the causes, which can be managed in different ways, and manipulation under anaesthesia (MUA) is routinely performed as the first line of management. The timing of MUA is often debated. We review the paper by Issa et al., which looks at the effect of timing of manipulation on a stiff TKA. They conclude that early manipulation within 12 weeks of performing the TKA had a higher mean flexion gain (36.5°), higher final range of motion (ROM) (119°) and higher knee society score (89 points) compared to those performed after 12 weeks which were 17°, 95° and 84 points respectively. Other studies have also reinforced the idea that early manipulation within 12 weeks has a better outcome than those performed after 12 weeks. There may still be a benefit of manipulation until 26 weeks after which open arthrolysis may be needed to improve ROM.

Mamarelis|Georgios|G|
Sunil-Kumar|Karadi Hari|KH|
Khanduja|Vikas|V|

manipulation
stiffness
knee arthroplasty
Arthrofibrosis


Passive bilateral leg cycling with concomitant regional circulatory occlusion for testing mechanoreflex-metaboreflex interactions in humans.

Abstract:
PURPOSE
The exercise pressor reflex (EPR) plays a fundamental role in physiological reactions to exercise in humans and in the pathophysiology of cardiovascular disorders. There is no "gold standard" method for EPR assessment; therefore, we propose a new protocol for testing interactions between the muscle mechanoreflex and metaboreflex (major components of EPR).

METHODS
Thirty-four healthy subjects (mean age [± standard deviation] 24 ± 4 years, 22 men) were enrolled in the study. During the study, the hemodynamic and ventilatory parameters of these subjects were continuously monitored using our proposed assessment method. This assessment method consists of an initial 5-min rest period (baseline) followed by 5 min of passive cycling (PC) on an automated cycle ergometer (mechanoreceptor stimulation), after which tourniquet cuffs located bilaterally on the upper thighs are inflated for 3 min to evoke venous and arterial regional circulatory occlusion (CO) during PC (metaboreceptor stimulation). Deflation of the tourniquet cuffs is followed by a second 5 min of PC and finally by a 5-min recovery time. The control test comprises a 5-min rest period, followed by 3 min of CO only and a final 5-min recovery.

RESULTS
Mean arterial pressure (MAP) and minute ventilation (MV) increased significantly during PC (MAP: from 90 ± 9.3 to 95 ± 9.7 mmHg; MV: from 11.5 ± 2.5 to 13.5 ± 2.9 L/min; both p < 0.05) and again when CO was applied (MAP: from 95 ± 9.7 to 101 ± 11.0 mmHg; MV: from 13.5 ± 2.9 to 14.8 ± 3.8 L/min; both p < 0.05). In the control test there was a slight increase in MAP during CO (from 92 ± 10.5 to 94 ± 10.0 mmHg; p < 0.05) and no changes in the ventilatory parameters.

CONCLUSION
Bilateral leg passive cycling with concomitant circulatory occlusion is a new, simple and effective method for testing interactions between the mechanoreflex and metaboreflex in humans.

Circulatory occlusion
Exercise pressor reflex
Passive cycling
Mechanoreceptors
Metaboreceptors


Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist.

Abstract: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are highly effective at lowering hemoglobin A1c (HbA1c) and facilitating weight loss. Four agents in the GLP-1 RA class, albiglutide, liraglutide, dulaglutide, and semaglutide, also have cardioprotective effects. However, subcutaneous administration of these agents remains a major reason for their underutilization. A new coformulation of semaglutide with sodium N-[8-(2-hydroxybenzoyl) amino caprylate (SNAC) is the first oral GLP-1 RA reviewed by the U.S. Food and Drug Administration (FDA). The SNAC technology prevents destruction of semaglutide in the stomach and facilitates transcellular absorption through the gastric membrane enabling semaglutide to reach systemic circulation intact. The oral formulation of semaglutide was studied in the PIONEER trials, demonstrating similar efficacy to the presently available GLP-1 RAs with regard to HbA1c lowering and weight loss. Although the PIONEER 6 trial suggests positive effects on cardiovascular mortality with oral semaglutide, these benefits may not fully be appreciated until the completion of the SOUL trial.

Bucheit|John D|JD|
Pamulapati|Lauren G|LG|
Carter|Nicole|N|
Malloy|Kevin|K|
Dixon|Dave L|DL|
Sisson|Evan M|EM|

Semaglutide
SNAC technology
PIONEER trials
Oral GLP-1 receptor agonists


The effect of infant-directed speech on early multimodal communicative production in Spanish and Basque.

Abstract: We analyzed the effect of infant-directed speech (IDS) on multimodal communicative production of children at the beginning of the second year of life in two different languages: Spanish and Basque. Twelve Spanish and twelve Basque children aged between 12 and 15 months observed two versions of an audiovisual story: one version was narrated with IDS and the other with adult-directed speech (ADS). We analyzed the use of gaze and the communicative behaviors produced by children. The time spent looking at the story increases in the IDS condition regardless of the language of the narration. Children produced more multimodal communicative behaviors while watching the IDS version both in Spanish and in Basque. These results suggest that IDS increases attention and social engagement promoting joint attention episodes.

DE Pablo|Irati|I|
Murillo|Eva|E|
Romero|Asier|A|

infant-directed speech
multimodal communication
gestures
language development
vocalizations


Impact of ripening inhibitors on molecular transport of antimicrobial components from essential oil nanoemulsions.

Abstract: The objective of this study was to provide insights into the mechanisms involved in the mass transport of antimicrobial compounds from essential oil nanoemulsions to bacterial cell membranes. Origanum oil-in-water nanoemulsions were produced using spontaneous emulsification by titrating a mixture of essential oil, ripening inhibitor, and surfactant (Tween 80) into 5 mM sodium citrate buffer (pH 3.5). Stable nanoemulsions containing relatively small droplets (d < 60 nm) were produced using this low-energy method. The nature of the ripening inhibitor used in the oil phase of the nanoemulsions affected the antimicrobial activity of the nanoemulsions: corn (LCT) > medium-chain triglycerides (MCT). Differences in antimicrobial activity were attributed to the differences in the rate of transfer of hydrophobic antimicrobial constituents from the nanoemulsion to the MCT emulsion, which was used to mimic the hydrophobic region of the bacterial cell membranes. Each antimicrobial nanoemulsion was separated from the MCT emulsion by a dialysis tubing. Dialysis tubing with two different pore sizes was used, one excluding nanoemulsion droplet and micelle delivery, allowing the delivery of antimicrobial compounds only through the aqueous phase and the other by both the aqueous phase and micelles. For origanum oil nanoemulsions, the delivery of all antimicrobial agents occurred more efficiently when micelles were present.

Ryu|Victor|V|
Corradini|Maria G|MG|
McClements|David J|DJ|
McLandsborough|Lynne|L|

Antimicrobial
Nanoemulsion
Micelle
Origanum oil
Minimum inhibitory concentration
Ostwald ripening inhibitor
Partitioning
Salmonella
Thymus capitatus


Immediate effects of thoracic spinal mobilisation on erector spinae muscle activity and pain in patients with thoracic spine pain: a preliminary randomised controlled trial.

Abstract:
OBJECTIVES
To investigate the activity of the thoracic erector spinae muscles and perceived pain intensity immediately after central postero-anterior (PA) mobilisation of the thoracic spine.

DESIGN
Randomised, placebo-controlled, experimental design.

PARTICIPANTS AND INTERVENTIONS
Thirty-four participants with non-specific thoracic pain were randomised to the experimental group [grade III central PA mobilisation performed for 3minutes at the level of the seventh thoracic vertebra (T7)] or the placebo group (less than grade I central PA mobilisation performed for 3minutes at T7).

MAIN OUTCOME MEASURES
Before and immediately after PA mobilisation, surface electromyography (EMG) was recorded from the thoracic erector spinae muscles as the participants performed 10° spine extension from a prone position for 10seconds. Each participant rated their pain intensity as an investigator performed grade III central PA over the most symptomatic thoracic segment, and the pressure pain threshold (PPT) was evaluated bilaterally over the erector spinae muscles.

RESULTS
The EMG amplitude of thoracic erector spinae activity was reduced significantly after the intervention in the experimental group (P<0.05), but not in the placebo group. The difference between the groups was significant {pre-post change: placebo -14 [standard deviation (SD) 50]mV, experimental 28 (SD 48)mV; mean difference -42mV; 95% confidence interval of the difference -76 to 7; P<0.05} albeit small (Grissom=0.44). However, both groups showed a significant reduction in pain immediately after the intervention, and both groups showed a similar pre-post change in PPT.

CONCLUSION
These preliminary findings indicate that grade III central mobilisation over the most symptomatic thoracic segment reduces thoracic erector spinae activity during extension of the trunk in people with non-specific thoracic spine pain.

CLINICAL TRIAL REGISTRATION NUMBER
ISRCTN47601528.

Pecos-Martín|D|D|
de Melo Aroeira|A E|AE|
Verás Silva|R L|RL|
Martínez de Tejada Pozo|G|G|
Rodríguez Solano|L M|LM|
Plaza-Manzano|G|G|
Gallego-Izquierdo|T|T|
Falla|D|D|

Mobilisation
Thoracic pain
Electromyography
Manual therapy
Musculoskeletal pain


Non-metal sensory electrode design and protocol of DNA-nucleobases in living cells exposed to oxidative stresses.

Abstract: Sensory protocols for evaluation of DNA distortion due to exposure to various harmful chemicals and environments in living cells are needed for research and clinical investigations. Here, a design of non-metal sensory (NMS) electrode was built by using boron-doped carbon spherules for detection of DNA nucleobases, namely, guanine (Gu), adenine (Ad), and thymine (Th) in living cells. The key-electrode based nanoscale NMS structures lead to voids with a facile diffusion, and strong binding events of the DNA nucleobases. Furthermore, the NMS geometric structures would significantly create electrode surfaces with numerous centrally active sites, curvature topographies, and anisotropic spherules. The NMS shows potential as sensitive protocol for DNA-nucleobases in living cells exposed to oxidative stresses. In one-step signaling assay, NMS shows high signaling transduction of Gu-, Ad-, and Th-DNA nucleobases targets with ultra-sensitive and low detection limits of 3.0, 0.36, and 0.34 nM, respectively, and a wide linear range of up to 1 μM. The NMS design and protocol show evidence of the role of surface construction features and B-atoms incorporated into the graphitic carbon network for creating abundant active sites with facile electron diffusion and heavily target loads along with within-/out-plane circular spheres. Indeed NMS, with spherule-rich interstitial surfaces can be used for sensitive and selective evaluation of damaged-DNA to various dysfunctional metabolism in the human body.

Emran|Mohammed Y|MY|
El-Safty|Sherif A|SA|
Selim|Mahmoud M|MM|
Minowa|Takashi|T|
Elmarakbi|Ahmed|A|
Shenashen|Mohamed A|MA|

DNA-Nucleobases
Living cells
Oxidative stresses
Boron-doped carbon spherules
Guanine
Adenine
Thymine
Electrochemical sensor


Study on the aerobic remediation of Ni(II) by Pseudomonas hibiscicola strain L1 interaction with nitrate.

Abstract: Aerobic denitrifying bacteria have the potential to remove the co-pollutants Ni(II) and nitrate in industrial wastewater. In this study, aerobic denitrifying bacteria with significant Ni(II) removal efficiency was isolated from the biological reaction tank and named as Pseudomonas hibiscicola L1 strain after 16 S rRNA identification analysis. The removal of ever-increasing Ni(II) and NO3--N wastewater under aerobic conditions by strain L1 was discussed. The experimental results showed that strain L1 removed 84% of Ni(II) and 81% of COD, with the use of 34.8 mg L-1 of nitrogen source and without nitrite accumulation yet. Strain L1 had remarkable activity (OD600 = 0.51-0.56 (p < 0.05)) at 20 mg L-1 of Ni(II) and 100 mg L-1 of NO3--N. It was found that high Ni(II) gradients (2-10 mg L-1) had little effect on nitrate removal ratio (35-34% (p > 0.05), and the removal ratios of Ni(II) was enhanced (from 42% to 83% (p < 0.05)) by increasing nitrate (25-100 mg L-1). Also, the results indicated that strain L1 could reduce Ni(II) and nitrate under different pH (6-9); electron donor-glucose, sodium acetate, sodium succinate and trisodium citrate; C/N (5-20) and coexisting ions (Cu(II) and Zn(II)). Notably, the nitrogen balance analysis showed 32.4% of TN was lost nitrogen and 19.7% of TN was assimilated for cell growth, which indicated aerobic denitrification process of strain L1. Meanwhile, characterization technology (SEM, FTIR, and XRD) showed Ni(II) was bioadsorbed in the form of Ni(NH2)2, NiCO3, and Ni(OH)2·2H2O through surface functional groups. This research provides new microbial method for the simultaneous removal of nitrate and Ni(II) in wastewater.

An|Qiang|Q| Deng|Shuman|S| Liu|Meng|M| Li|Zheng|Z| Wu|Danqing|D| Wang|Tuo|T| Chen|Xuemei|X|

Denitrification
Ni(II) biosorption
Ni(II) precipitation
Pseudomonas sp.
metal resistance


Managing plastic waste disposal by assessing consumers' recycling behavior: the case of a densely populated developing country.

Abstract: The rapid increase in urbanization has given rise to the need of proper waste management. Within municipal waste, the plastic waste is a growing concern which is causing severe harm to our ecosystem. If ignored, this problem will have harmful effects on both human and wildlife. Therefore, this study aims to find out the factors that influence the recycling behavior patterns of consumers regarding plastic waste. The variables from the theory of planned behavior were adopted to study the behavior of consumers toward recycling plastic waste. The data was collected from 243 residents of Karachi-metropolitan city of Pakistan. The partial least square-structural equation modelling was applied to analyze the data. The findings of the current study reveal that different consumers' attributes and attitudes trigger different types of recycling behavior when it comes to waste disposal. Pressure from family and friends and perceived behavioral control trigger the behavior of reselling the waste plastic products while consumer's awareness of consequences and personal attitude toward proper waste disposal leads to reuse or donating that product to someone who can use that plastic product. The understanding of these consumer attributes may help to shape the behavioral outcomes in order to manage waste disposal. This study will be beneficial for business managers looking to improve reverse logistics as well as government/municipal policy makers and academics/researchers who are interested in a solution-oriented study.

Plastic waste
Theory of planned behavior
Attitude
Resell
Awareness of consequences
Reuse
Donate


Correlation of magnetic resonance imaging optic nerve parameters to optical coherence tomography and the visual field in glaucoma.

Abstract:
BACKGROUND
To determine the viability of using magnetic resonance imaging measurement of optic nerve morphology as an objective analysis of glaucomatous damage.

DESIGN
Retrospective study conducted at Tohoku University Hospital.

PARTICIPANTS
Thirty-eight eyes of 19 patients with open-angle glaucoma.

METHODS
Patients were scanned with T2-weighted and 3-T diffusion tensor magnetic resonance imaging, and parameters of the optic nerve, including fractional anisotropy, apparent diffusion coefficient and cross-sectional area, were determined. Conventional parameters of glaucomatous damage, including circumpapillary and macular retinal nerve fibre layer thickness, and mean deviation and average total deviation of the central 16 test points from the Humphrey Field Analyzer, were then compared with the magnetic resonance imaging-derived parameters. Spearman's coefficient of correlation was calculated to determine the significance of the correlation.

MAIN OUTCOME MEASURE
Correlation coefficient between the magnetic resonance imaging parameters and the parameters of glaucomatous damage.

RESULTS
Mean deviation was significantly correlated with all magnetic resonance imaging parameters (fractional anisotropy: r = 0.53, apparent diffusion coefficient: r = -0.44, cross-sectional area: r = 0.70). Circumpapillary retinal nerve fibre layer thickness was significantly correlated with fractional anisotropy (r = 0.60) and cross-sectional area (r = 0.47), but not apparent diffusion coefficient (r = -0.29). Central macular function and macular retinal nerve fibre layer thickness were also significantly correlated with magnetic resonance imaging parameters.

CONCLUSIONS
Optic nerve magnetic resonance imaging parameters were significantly correlated to glaucomatous damage. Magnetic resonance imaging analysis of the optic nerve may, thus, have value as an objective instrument to assess glaucomatous degeneration, including the function of the macula.

Omodaka|Kazuko|K| Murata|Takaki|T| Sato|Shiho|S| Takahashi|Mai|M| Tatewaki|Yasuko|Y| Nagasaka|Tatsuo|T| Doi|Hiroshi|H| Araie|Makoto|M| Takahashi|Shoki|S| Nakazawa|Toru|T|

D038524:Diffusion Magnetic Resonance Imaging

glaucoma
macular function
MRI
objective examination


ABCB4 disease mimicking morbus Wilson: A potential diagnostic pitfall.

Abstract:
INTRODUCTION
Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare autosomal recessive cholestatic liver disorder caused by genetic deficiency of ATP-binding cassette subfamily B member 4 (ABCB4), a hepatocanalicular floppase translocating phospholipids from the inner to the outer leaflet of the canalicular membrane lipid bilayer. PFIC3 is characterised by production of hydrophilic bile with lithogenic properties which is harmful to the hepatobiliary epithelia. Chronic cholestasis in some patients may be accompanied by excessive accumulation of copper in the liver and by increased urinary copper excretion, the findings mimicking Wilson disease (WD).

METHODS AND RESULTS
We report an 11 y/o male patient with growth retardation, mild craniofacial dysmorphic features and chronic liver disease, initially diagnosed and treated as WD. Whereas genetic testing for WD was negative, further molecular and histopathological analysis revealed two novel mutations (c.833+1G>T and c.1798T>A) in ABCB4 and complete absence of the ABCB4/MDR3 protein in the liver, determining PFIC3 as the correct diagnosis.

CONCLUSION
PFIC3 and WD display pleomorphic and sometimes overlapping clinical and laboratory features, which may pose a differential diagnostic problem. Since the patient management in WD and PFIC3 differs significantly, an early and accurate diagnosis is crucial for optimising of therapeutic approach and prevention of possible complications.

Sticova|Eva|E| Neroldova|Magdalena|M| Kotalova|Radana|R| Subhanova|Iva|I| Jirsa|Milan|M|

D018435:ATP Binding Cassette Transporter, Subfamily B

progressive familial intrahepatic cholestasis type 3


Mini-Mental State Examination: new normative values on subjects in Southern Italy.

Abstract:
OBJECTIVE
The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77-85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies.

METHODS
MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance.

RESULTS
The mean raw MMSE score was 27.78 (SD = 1.80) (range 22-30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms.

CONCLUSIONS
(1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia.

D000073216:Mental Status and Dementia Tests

Mini-Mental State Examination
MMSE
Dementia
Alzheimer’s disease
Cognitive screening tool


Identification of spoilage by Alicyclobacillus bacteria in tomato-based products by UHPLC-MS/MS.

Abstract: In recent years, there have been some cases of alteration of tomato derivatives by Alicyclobacilli spp. The spoilage was reported by consumers who felt odors and abnormal tastes ("bad") of products. In this work, an untarget approach with Q-Exactive™ Quadrupole-Orbitrap Mass Spectrometer has been used to identify metabolites associated with the alteration of tomato puree by Alicyclobacillus bacteria. The study was carried out on tomato puree found positive for the presence of Alicyclobacillus spores. The germination and growth of native spores were induced through incubation at 65°C under static conditions for 5 days. For microbial concentration below 100 ufc/mL, negative growth was considered. The samples arising from incubation were submitted to UHPL-HRMS/MS analysis. To find compounds related to microbial growth, data obtained by UHPLC-MS/MS analysis were processed with Thermo Fisher Compound Discoverer™ 2.0 software. We compared samples grouped according to microbial growth: positive growth vs negative growth. Five compounds were identified and confirmed by analysis performed on authentic standards. To other compounds, we have assigned a putative identity. The HRMS approach using Q-Exactive™ Quadrupole-Orbitrap Mass Spectrometer has proven to be an important and powerful tool for identification of compounds which could be used as marker molecules in cases of suspected spoilage by Alicyclobacillus bacteria in tomato derivatives.

D002851:Chromatography, High Pressure Liquid

Alicyclobacillus bacteria
untarget approach
Q-Exactive
metabolites
tomato puree


Lower trapezius transfer with Achilles tendon augmentation: indication and clinical results.

Abstract: Lower trapezius tendon transfer with Achilles tendon allograft augmentation may be used to treat patients with lack of active external rotation following shoulder paralysis or massive irreparable posterosuperior rotator cuff tears. In the setting of shoulder paralysis, the integrity of the ipsilateral lower trapezius may be compromised. In this instance, the contralateral lower trapezius may be used with reasonable results. In the setting of irreparable rotator cuff tears, the procedure may be performed through an open or arthroscopically assisted technique. The latter avoids the need for an acromial osteotomy and risk of nonunion associated with repair of the osteotomy. Both are effective in reversing pseudoparesis or pseudoparalysis. Advanced degenerative changes have an effect on outcomes, resulting in less pain improvement, decreased range of motion, and greater need for reoperation with conversion to reverse total shoulder arthroplasty. Nonetheless, the lower trapezius tendon transfer is an effective option for restoring active external rotation with relatively consistent results.

Aibinder|William R|WR|
Elhassan|Bassem T|BT|

Tendon transfer
External rotation
Rotator cuff tear
Pseudoparalysis
Shoulder injuries


Biocompatible In Situ Polymerization of Multipurpose Polyacrylamide-Based Hydrogels on Skin via Silver Ion Catalyzation.

Abstract: Free radical polymerization is a mature method and can be used for preparing multifunctional hydrogels by simply changing the commercial monomers, but the harsh and time-consuming initiation conditions restrict its injectable ability, which further limits its application in the biomedical field. Though some catalysts can be used to accelerate the polymerization, their application is restrained by the biotoxicity. Hence, finding a biocompatible catalyzer for in situ free radical polymerization of hydrogels has a great prospect in biomedical application but is still challenging. In this study, we discovered that silver ions could catalyze free radical polymerization under ambient by transforming hydrone into hydroxyl radicals in the presence of ammonium persulfate, and the in situ-formed hydrogels prepared by this way showed great histocompatibility, hemocompatibility, cytocompatibility, and immunocompatibility. Benefitting from its convenience and biocompatibility, the in situ polymerization of polyacrylamide-based hydrogels for tissue adhesion, wound dressing, and conductive materials on the skin could be realized by simply blending diverse ingredients. Furthermore, this discovery may be a step toward the in situ-polymerized hydrogels for biomedical applications.

biocompatibility
silver ions
catalyzer
free radical polymerization
injectable hydrogel


Neuroprotective Effect of β-secretase Inhibitory Peptide from Pacific Hake (Merluccius productus) Fish Protein Hydrolysate.

Abstract:
BACKGROUND
Various methodologies have been employed for the therapeutic interpolation of the progressive brain disorder Alzheimer's disease. Thus, β-secretase inhibition is significant to prevent disease progression in the early stages.

OBJECTIVE
This study seeks to purify and characterize a novel β-secretase inhibitory peptide from Pacific hake enzymatic hydrolysate.

METHODS
A potent β-secretase inhibitory peptide was isolated by sequential purifications using Sephadex G-25 column chromatography and octadecylsilane (ODS) C18 reversed-phase HPLC. A total of seven peptides were synthesized using the isolated peptide sequences. SH-SY5Y cells stably transfected with the human ''Swedish'' amyloid precursor protein (APP) mutation APP695 (SH-SY5YAPP695swe) were used as an in-vitro model system to investigate the effect of Leu-Asn peptide on APP processing.

RESULTS
The β-secretase inhibitory activity (IC50) of the purified peptide (Ser-Leu-Ala-Phe-Val-Asp- Asp-Val-Leu-Asn) from fish protein hydrolysate was 18.65 μM and dipeptide Leu-Asn was the most potent β-secretase inhibitor (IC50 value = 8.82 µM). When comparing all the seven peptides, the inhibition pattern of Leu-Asn dipeptide was found to be competitive by Lineweaver-Burk plot and Dixon plot (Ki value = 4.24 µM). The 24 h treatment with Leu-Asn peptide in SH-SY5Y cells resulted in reducing the β-amyloid (Aβ) production in a dose-dependent manner.

CONCLUSION
Therefore, the results of this study suggest that β-secretase inhibitory peptides derived from marine organisms could be potential candidates to develop nutraceuticals or pharmaceuticals as antidementia agents.

Lee|Jung Kwon|JK|
Li-Chan|Eunice C Y|ECY|
Cheung|Imelda W Y|IWY|
Jeon|You-Jin|YJ|
Ko|Ju-Young|JY|
Byun|Hee-Guk|HG|

D053829:Amyloid Precursor Protein Secretases


Incremental Prognostic Value of Apparent Diffusion Coefficient Histogram Analysis in Head and Neck Squamous Cell Carcinoma.

Abstract:
RATIONALE AND OBJECTIVES
We aimed to investigate the incremental prognostic value of apparent diffusion coefficient (ADC) histogram analysis in patients with head and neck squamous cell carcinoma (HNSCC) and integrate it into a multivariate prognostic model.

MATERIALS AND METHODS
A retrospective review of magnetic resonance imaging findings was conducted in patients with pathologically confirmed HNSCC between June 2012 and December 2015. For each tumor, six histogram parameters were derived: the 10th, 50th, and 90th percentiles of ADC (ADC10, ADC50, and ADC90); mean ADC values (ADCmean); kurtosis; and skewness. The clinical variables included age, sex, smoking status, tumor volume, and tumor node metastasis stage. The association of these histogram and clinical variables with overall survival (OS) was determined. Further validation of the histogram parameters as independent biomarkers was performed using multivariate Cox proportional hazard models combined with clinical variables, which was compared to the clinical model. Models were assessed with C index and receiver operating characteristic curve analyses for the 12- and 36-month OS.

RESULTS
Ninety-six patients were eligible for analysis. Median follow-up was 877 days (range, 54-1516 days). A total of 29 patients died during follow-up (30%). Patients with higher ADC values (ADC10 > 0.958 × 10-3 mm2/s, ADC50 > 1.089 × 10-3 mm2/s, ADC90 > 1.152 × 10-3 mm2/s, ADCmean > 1.047 × 10-3 mm2/s) and lower kurtosis (≤0.967) were significant predictors of poor OS (P < .100 for all). After adjusting for sex and tumor node metastasis stage, the ADC90 and kurtosis are both significant predictors of OS with hazard ratios = 1.00 (95% confidence interval: 1.001-1.004) and 0.58 (95% confidence interval: 0.37-0.90), respectively. By adding the ADC parameters into the clinical model, the C index and diagnostic accuracies for the 12- and 36-month OS showed significant improvement.

CONCLUSIONS
ADC histogram analysis has incremental prognostic value in patients with HNSCC and increases the performance of a multivariable prognostic model in addition to clinical variables.

Li|Xiaoxia|X| Yuan|Ying|Y| Ren|Jiliang|J| Shi|Yiqian|Y| Tao|Xiaofeng|X|

D000077195:Squamous Cell Carcinoma of Head and Neck

histogram analysis
Head and neck squamous cell carcinoma
diffusion-weighted imaging


High frequency electroporation efficiency is under control of membrane capacitive charging and voltage potential relaxation.

Abstract: The study presents the proof of concept for a possibility to achieve a better electroporation in the MHz pulse repetition frequency (PRF) region compared to the conventional low frequency protocols. The 200ns×10 pulses bursts of 10-14kV/cm have been used to permeabilize Chinese hamster ovary (CHO) cells in a wide range (1Hz-1MHz) of PRF. The permeabilization efficiency was evaluated using fluorescent dye assay (propidium iodide) and flow cytometry. It was determined that a threshold PRF exists when the relaxation of the cell transmembrane potential is longer than the delay between the consequent pulses, which results in accumulation of the charge on the membrane. For the CHO cells and 0.1S/m electroporation medium, this phenomenon is detectable in the 0.5-1MHz range. It was shown that the PRF is an important parameter that could be used for flexible control of electroporation efficiency in the high frequency range.

Novickij|Vitalij|V| Ruzgys|Paulius|P| Grainys|Audrius|A| Šatkauskas|Saulius|S|

MHz
Propidium iodide
Transmembrane potential
Cell polarization
Membrane permeabilization


Time-to-isolation guided titration of freeze duration in 3rd generation short-tip cryoballoon pulmonary vein isolation - Comparable clinical outcome and shorter procedure duration.

Abstract:
BACKGROUND
The optimal freeze duration in cryoballoon pulmonary vein isolation (PVI) is unknown. The 3rd generation cryoballoon facilitates observation of the time-to-isolation (TTI) and thereby enables individualized cryoenergy titration. To evaluate the efficacy of an individualized freeze duration we compared the clinical outcome of patients treated with a TTI-guided ablation protocol to the outcome of patients treated with a fixed ablation protocol.

METHODS
We compared 100 patients treated with the 3rd generation cryoballoon applying a TTI-based protocol (TTI group) to 100 patients treated by a fixed freeze protocol (fixed group). In the fixed group a 240s freeze cycle was followed by a 240s bonus freeze after acute PV isolation. In the TTI group freeze duration was 180s if TTI was ≥30s and reduced to only 120s, if TTI was <30s. In case of a TTI >60s a 180s bonus freeze was applied.

RESULTS
Freedom from atrial arrhythmia recurrence off class I/III antiarrhythmic drugs after one year was not different between the TTI group (73.6%) and the fixed group (75.7%; p=0.75). Mean procedure duration was 85.8±27.3min in the TTI group compared to 115.7±27.1min in the fixed group (p<0.001). Mean fluoroscopy time was 17.5±6.6min in the TTI group and 22.5±9.8min in the fixed group (p<0.001).

CONCLUSIONS
TTI-guided cryoenergy titration leads to reduced procedure duration and fluoroscopy time and appears to be as effective as a fixed ablation strategy. A single 2-minute freeze seems to be sufficient in case of short TTI.

Pott|Alexander|A| Kraft|Christoph|C| Stephan|Tilman|T| Petscher|Kerstin|K| Rottbauer|Wolfgang|W| Dahme|Tillman|T|

Time-to-isolation
Cryoballoon
Ablation
2-Minute freeze
Atrial fibrillation
Short tip


Disappearance of Anti-Thyroid Autoantibodies following Thymectomy in Patients with Myasthenia Gravis.

Abstract:
Objectives
The thymus plays a central role in immune tolerance, which prevents autoimmunity. Myasthenia gravis (MG) is commonly associated with thymoma or thymus hyperplasia, and it can coexist with autoimmune thyroid diseases. However, the role of the thymus in thyroid autoimmunity remains to be clarified, which we investigated here.

Study Design
The study design entailed the inclusion of consecutive MG patients and the measurement of anti-thyroid autoantibodies at baseline and, limited to autoantibody-positive patients, also at 24 and 48 weeks. One hundred and seven MG patients were studied. The main outcome measure was the behaviour of anti-thyroglobulin autoantibodies (TgAbs) and anti-thyroperoxidase autoantibodies (TPOAbs) over time in relation to thymectomy.

Results
Serum TgAbs and/or TPOAbs were detected in ∼20% of patients in the absence of thyroid dysfunction. The prevalence of positive serum TgAbs and/or TPOAbs decreased significantly (p = 0.002) over the follow-up period in patients who underwent thymectomy, but not in patients who were not thymectomized. When the analysis was restricted to TgAbs or TPOAbs, findings were similar. On the same line, there was a general trend towards a reduction in the serum concentrations of anti-thyroid autoantibodies in patients who underwent thymectomy, which was significant for TPOAbs (p = 0.009).

Conclusions
Our findings suggest a role of the thymus in the maintenance of humoral thyroid autoimmunity.

Rotondo Dottore|Giovanna|G|
Leo|Marenza|M|
Ricciardi|Roberta|R|
Maestri|Michelangelo|M|
Bucci|Ilaria|I|
Lucchi|Marco|M|
Melfi|Franca|F|
Guida|Melania|M|
De Rosa|Anna|A|
Petrucci|Loredana|L|
Ionni|Ilaria|I|
Lanzolla|Giulia|G|
Nicolì|Francesca|F|
Mantuano|Michele|M|
Ricci|Debora|D|
Latrofa|Francesco|F|
Mariotti|Stefano|S|
Marcocci|Claudio|C|
Marinò|Michele|M|

Anti-thyroid autoantibodies
Thymectomy
Myasthenia gravis
Thymus
Anti-thyroglobulin autoantibodies
Anti-thyroperoxidase autoantibodies


Exploration of the Stanford Integrated Psychosocial Assessment for Transplantation With Psychosocial and Medical Outcomes in Kidney and Kidney-Pancreas Transplant Recipients.

Abstract:
INTRODUCTION
The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a psychometric instrument designed to assess patient risk for transplant. We investigated the association between SIPAT scores and demographic data with psychosocial and medical outcomes within a diverse kidney/kidney-pancreas transplant population.

DESIGN
The SIPAT was administered to all pretransplant candidates. A retrospective review of transplanted patients who had at least 6 months of follow-up was completed.

RESULTS
The sample included 136 patients: male (n = 77 [57%]) with a mean age of 47 years old. Thirty-eight percent were black (n = 51), 55% had less than a high school education (n = 74), and 65% had low socioeconomic status (n = 89). Statistical difference was found among SIPAT scores and substance use and support system instability (P = .035, P = .012). Females (P = .012) and patients with a history of psychopathology (P = .002) developed or had a relapse of psychopathology following transplant. Patients with more than a high school education (P = .025) and who were less than 30 years (P = .026) had higher rejection incidence rates. Risk factors for rehospitalizations included Hispanic race, diabetes, and low socioeconomic status (P = .036, P = .038, P = .014). African American/Black and male patients had higher incidence of infection events (P = .032, P = .049). Mortality and treatment nonadherence were not significantly associated with SIPAT scores or demographic variables.

CONCLUSION
The SIPAT was associated with posttransplant substance use and support system instability, while demographic variables were associated with the development and/or relapse of psychopathology, graft loss, rejection, infection events, and medical rehospitalizations. Revision of the SIPAT to include additional demographic components may lend to improved prediction of transplant outcomes.

Chen|Gloria|G|0000-0002-4517-9070
Bell|Cynthia S|CS|
Loughhead|Penelope|P|
Ibeche|Bashar|B|
Bynon|John S|JS|
Hall|David R|DR|
De Golovine|Aleksandra|A|
Edwards|Angelina|A|
Dar|Wasim A|WA|

D000328:Adult
D001741:African Americans
D000367:Age Factors
D003920:Diabetes Mellitus
D004522:Educational Status
D005006:Ethnicity
D005260:Female
D006084:Graft Rejection
D006085:Graft Survival
D006630:Hispanic or Latino
D006801:Humans
D015994:Incidence
D007239:Infections
D016030:Kidney Transplantation
D008297:Male
D001523:Mental Disorders
D008875:Middle Aged
D016035:Pancreas Transplantation
D010349:Patient Compliance
D010359:Patient Readmission
D057234:Preoperative Period
D011594:Psychometrics
D012189:Retrospective Studies
D012923:Social Class
D012944:Social Support
D019966:Substance-Related Disorders
D066027:Transplant Recipients
D044465:Whites

kidney (allograft) function/dysfunction
recipient selection
risk assessment/risk stratification


Change in quality of life among community-dwelling older adults: population-based longitudinal study.

Abstract:
PURPOSE
This population-based study aimed to determine 5-year change in multidimensional QoL among community-dwelling older people, and to identify predictors of QoL change among demographic, socioeconomic, and health characteristics.

METHODS
Data of the 2011 and 2016 annual assessments of 1845 older men and women (age range 68-77 years) from the Lc65 + cohort study were used. QoL was assessed using a 28-item instrument yielding a QoL overall score and seven domain-specific QoL subscores. Additional ratings of QoL included a single item (excellent; very good; good; fair; poor), expected QoL in 1 year (better; worse; same as today), and retrospective assessment of QoL 5-year change (better; worse; same as 5 years ago). The predictors of 5-year change in the QoL score were assessed using linear regression, controlling for baseline QoL score.

RESULTS
All prospective and retrospective indicators of QoL converged towards a slight deterioration over 5 years. QoL subscores significantly decreased in domains "Close entourage" (P = 0.004), "Social and cultural life" (P < 0.001), "Esteem and recognition" (P = 0.001), "Health and mobility" (P < 0.001), and "Autonomy" (P < 0.001), whereas "Material resources" (P = 0.345) and "Feeling of safety" (P = 0.380) remained stable. A stronger decrease in QoL was observed in the most vulnerable profiles at baseline in terms of demographic, socioeconomic, and health characteristics. Changes in depressive symptoms and in disability-either worsening or improving-predicted QoL change in the expected direction.

CONCLUSIONS
Age-related decline in QoL may be limited through the prevention of disability and depressive symptoms, and more generally by devoting special attention to vulnerable profiles.

Quality of life
Cohort studies
Epidemiology of ageing
Gerontology


19F-NMR Diastereotopic Signals in Two N-CHF₂ Derivatives of (4S,7R)-7,8,8-Trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole.

Abstract: In this paper, we report the anisochrony of the fluorine atoms of a CHF₂ group when linked to a pyrazole ring. The pyrazole is part of (4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole also known as (4S,7R)-campho[2,3-c]pyrazole, which has two stereogenic centers. Gauge-Independent Atomic Orbital (GIAO)/Becke, 3-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,f) calculated 19F chemical shifts of the minimum energy conformations satisfactorily agree with the experimental data. The energy differences between minima need to consider solvent effects (continuum model) to be satisfactorily reproduced.

D005461:Fluorine
D007191:Indazoles
D009682:Magnetic Resonance Spectroscopy
D008958:Models, Molecular
D008968:Molecular Conformation
D015394:Molecular Structure

diastereotopic anisochrony pyrazoles 19F‐NMR B3LYP GIAO PCM indazoles


The use of smartphone-derived location data to evaluate participation following critical illness: A pilot observational cohort study.

Abstract:
BACKGROUND
Disability is common following critical illness, impacting the quality of life of survivors, and is difficult to measure. 'Participation' can be quantified as involvement in life outside of their home requiring movement from their home to other locations. Participation restriction is a key element of disability, and following critical illness, participation may be diminished. It may be possible to quantify this change using pre-existing smartphone data.

OBJECTIVES
The feasibility of extracting location data from smartphones of survivors of intensive care unit (ICU) admission and assessing participation, using location-based outcomes, during recovery from critical illness was evaluated.

METHODS
Fifty consecutively admitted, consenting adult survivors of non-elective admission to ICU of greater than 48-h duration were recruited to a prospective observational cohort study where they were followed up at 3 and 6 months following discharge. The feasibility of extracting location data from survivors' smartphones and creating location-derived outcomes assessing participation was investigated over three 28-d study periods: pre-ICU admission and at 3 and 6 months following discharge. The following were calculated: time spent at home; the number of destinations visited; linear distance travelled; and two 'activity spaces', a minimum convex polygon and standard deviation ellipse.

RESULTS
Results are median [interquartile range] or n (%). The number of successful extractions was 9/50 (18%), 12/39 (31%), and 13/33 (39%); the percentage of time spent at home was 61 [56-68]%, 77 [66-87]%, and 67 [58-77]% (P = 0.16); the number of destinations visited was 34 [18-64], 38 [22-63], and 65 [46-88] (P = 0.02); linear distance travelled was 367 [56-788], 251 [114-323], and 747 [326-933] km over 28 d (P = 0.02), pre-ICU admission and at 3 and 6 months following ICU discharge, respectively. Activity spaces were successfully created.

CONCLUSION
Limited smartphone ownership, missing data, and time-consuming data extraction limit current implementation of mass extraction of location data from patients' smartphones to aid prognostication or measure outcomes. The number of journeys taken and the linear distance travelled increased between 3 and 6 months, suggesting participation may improve over time.

Gluck|Samuel|S|
Andrawos|Alice|A|
Summers|Matthew J|MJ|
Lange|Jarrod|J|
Chapman|Marianne J|MJ|
Finnis|Mark E|ME|
Deane|Adam M|AM|

Critical illness
Smartphone
Outcomes
Global position system
Technology


Metabolic Rate in Adolescent Athletes: The Development and Validation of New Equations, and Comparison to Previous Models.

Abstract: We sought to assess the accuracy of current or developing new prediction equations for resting metabolic rate (RMR) in adolescent athletes. RMR was assessed via indirect calorimetry, alongside known predictors (body composition via dual-energy X-ray absorptiometry, height, age, and sex) and hypothesized predictors (race and maturation status assessed via years to peak height velocity), in a diverse cohort of adolescent athletes (n = 126, 77% male, body mass = 72.8 ± 16.6 kg, height = 176.2 ± 10.5 cm, age = 16.5 ± 1.4 years). Predictive equations were produced and cross-validated using repeated k-fold cross-validation by stepwise multiple linear regression (10 folds, 100 repeats). Performance of the developed equations was compared with several published equations. Seven of the eight published equations examined performed poorly, underestimating RMR in >75% to >90% of cases. Root mean square error of the six equations ranged from 176 to 373, mean absolute error ranged from 115 to 373 kcal, and mean absolute error SD ranged from 103 to 185 kcal. Only the Schofield equation performed reasonably well, underestimating RMR in 51% of cases. A one- and two-compartment model were developed, both r2 of .83, root mean square error of 147, and mean absolute error of 114 ± 26 and 117 ± 25 kcal for the one- and two-compartment model, respectively. Based on the models' performance, as well as visual inspection of residual plots, the following model predicts RMR in adolescent athletes with better precision than previous models; RMR = 11.1 × body mass (kg) + 8.4 × height (cm) - (340 male or 537 female).

Reale|Reid J|RJ|
Roberts|Timothy J|TJ|
Lee|Khalil A|KA|
Bonsignore|Justina L|JL|
Anderson|Melissa L|ML|

prediction
energy expenditure
youth athlete


Bacteria Etiological Agents Causing Lower Respiratory Tract Infections and Their Resistance Patterns.

Abstract:
BACKGROUND
Lower respiratory tract infections (LTRIs) are among the most common infectious diseases with potential life-threatening complications.

METHODS
The study consisted of 426 patients with suspected LTRIs from mid and far western region of Nepal between September 2011 and July 2014. The specimens were collected and processed according to the standard microbiological methods at the Central Laboratory of Microbiology of Nepalgunj Medical College, Nepal.

RESULTS
Among the isolated Gram-positive organisms, Streptococcus pneumonia (n = 30, 51.7%) was the most predominant pathogen, followed by Staphylococcus aureus (n = 28, 48.3%). Among the isolated Gram-negative organisms, Pseudomonas aeruginosa (n = 71, 35.32%) was the most predominant pathogen, followed by Haemophilus influenzae (n = 68, 33.83%), Klebsiella pneumonia (n = 36, 17.19%), and Escherichia coli (n = 26, 12.94%). The pattern of resistance varied regarding the bacteria species, and there were multi-resistant isolates. Also, a significant difference (P value less than 0.05) was observed between males and females for each type of bacterial species. Among 259 isolates, 86 (33.20%) were from children aged 1-10 years, which were statistically significant (P valuse less than 0.05) compared to the other age groups.

CONCLUSIONS
P. aeruginosa and H. influenzae (Gram-negative) and S. pnemoniae (Gram-positive) were the most common bacterial isolates recovered from LTRIs. Age group of 1-10 years old was at a higher risk. Many isolates showed appreciable levels of antibiotic resistance due to antibiotic abuse. There is a need to increase surveillance and develop better strategies to curb the increasing prevalence of LRTI in this region of Nepal.

D024901:Drug Resistance, Multiple, Bacterial

Nepal
Antimicrobial drug resistance
Bacterial infections
Respiratory system


Children with type 1 diabetes of early age at onset - immune and metabolic phenotypes.

Abstract: Objectives We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes. Methods Comparative study of two groups of T1D children: EAO (≤5 years) and later age at onset (LAO; >5 years), regarding the presence of other autoimmune (AI) diseases, diabetes ketoacidosis and immunologic profile at onset and metabolic data 1 year after diagnosis. Statistical analysis was performed with significance set for p < 0.05. Results The study included 137 children (EAO = 52, mean age 3.6 ± 1.5 [mean ± standard deviation (SD)] and LAO = 85, mean age 10.4 ± 2.9). EAO was more associated with concomitant AI diseases (p = 0.032). Despite no differences in disease onset, EAO presented with lower C-peptide levels (p = 0.01) and higher absolute lymphocyte number (p < 0.0001), with an inverse correlation between these two variables (p = 0.028). Additionally, the EAO group had a higher frequency of serum detection of three antibodies (Abs) (p = 0.0008), specifically insulin Abs (p = 0.0001). One year after diagnosis, EAO had higher total daily insulin (TDI) dose (p = 0.008), despite similar hemoglobin A1c (HbA1c). Conclusions Our data show an association of EAO T1D with more AI diseases, higher number of Abs, lower initial insulin reservoir and higher insulin requirements 1 year after diagnosis. In this group, immune imbalance seems more evident and disease progression faster, probably reflecting distinct "immune environment" with different ages at disease onset. Further studies in the field of immunogenetics and immune tolerance are required, to improve patient stratification and find novel targets for therapeutic intervention.

type 1 diabetes
autoantibodies
early onset
innate immunity
β-cells


Protocol for assessing and predicting acute respiratory decline in hospitalized patients.

Abstract: This protocol aids both new and experienced researchers in designing retrospective clinical and translational studies of acute respiratory decline in hospitalized patients. This protocol addresses (1) the basics of respiratory failure and electronic health record research, (2) defining patient cohorts as "mild, progressive, or severe" instead of "ICU versus non-ICU", (3) adapting physiological indices, and (4) using biomarker trends. We apply these approaches to inflammatory biomarkers in COVID-19, but this protocol can be applied to any progressive respiratory failure study. For complete details on the use and execution of this protocol, please refer to Mueller et al. (2020).

Crowley|Conor P|CP|
Merriam|Louis T|LT|
Mueller|Alisa A|AA|
Tamura|Tomoyoshi|T|
DeGrado|Jeremy R|JR|
Haider|Hibah|H|
Salciccioli|Justin D|JD|
Kim|Edy Y|EY|

Clinical Protocol
Health Sciences
Immunology


A longitudinal study investigating the prevalence of Staphylococcus aureus genotype B in seasonally communal dairy herds.

Abstract: Staphylococcus aureus is a major mastitis-causing pathogen. Various genotypes have been recently identified in Switzerland but Staph. aureus genotype B (GTB) was the only genotype associated with high within-herd prevalence. The risk of introducing this Staph. aureus genotype into a herd may be increased by frequent animal movements. This may also be the case when cows from different herds of origin are commingled and share their milking equipment for a limited period of time. The aim of the present study was to determine the prevalence of Staph. aureus GTB in seasonally communal dairy herds before and after a summer period when dairy farming is characterized by mixing cows from different herds of origin in 1 communal operation. In addition, the environment was investigated to identify potential Staph. aureus GTB reservoirs relevant for transmission of the disease. A total of 829 cows from 110 herds of origin in 9 communal operations were included in the study. Composite milk samples were collected from all cows during the first or second milking after arrival at the communal operation and again shortly before the end of the season. Swab samples from the environment, involved personnel, and herding dogs present were collected before the cows arrived. At the end of the season, sampling of personnel was repeated. All samples were analyzed for the presence of Staph. aureus GTB using an established quantitative PCR. At the beginning of the season, Staph. aureus GTB-positive cows were identified in 7 out of 9 communal operations and the within-communal operation prevalence ranged from 2.2 to 38.9%. At the second sampling, all communal operations were Staph. aureus GTB positive, showing within-communal operation prevalence from 1 to 72.1%. The between-herd of origin prevalence increased from 27.3 to 56.6% and the cow-level prevalence increased from 11.2% at the beginning of the season to 29.6% at the end of the season. On 3 different communal operations, Staph. aureus GTB-positive swabs from seasonally employed personnel were identified at the end of the season. The results indicate that Staph. aureus GTB can easily spread in communal operations when cows from different herds of origin are mixed during the summer season. Effective management measures need to be designed to prevent the spread of Staph. aureus GTB in seasonally communal herds.

Voelk|V|V|
Graber|H U|HU|
van den Borne|B H P|BH|
Sartori|C|C|
Steiner|A|A|
Bodmer|M|M|
Haerdi-Landerer|M C|MC|

Staphylococcus aureus
communal herd
biosecurity
epidemiology


The natural product fucoidan ameliorates hepatic ischemia-reperfusion injury in mice.

Abstract: Fucoidan is a sulfated polysaccharide based predominantly on l-fucose, and has several biologic functions. Reactive oxygen species-mediated apoptosis and autophagy and release of related inflammatory factors have important roles in hepatic ischemia-reperfusion injury (IR). Here, the effect of fucoidan on hepatic IR was investigated. Mice were randomized into sham, IR, and fucoidan (20, 40mg/kg for 14days) groups. Samples were collected to assess biochemical indicators, hepatocyte damage and levels of proteins related to signaling pathways at different time points. Fucoidan had no effect on normal liver tissue, but inhibited the increases in alanine aminotransferase, aspartate transaminase, inflammatory factors, and the hepatocyte damage caused by IR. Also, apoptosis and autophagy via the activated JAK2/STAT1 pathway were attenuated by fucoidan to protect against hepatic injury. In conclusion, fucoidan ameliorates hepatic IR injury in mice via JAK2/STAT1-mediated apoptosis and autophagy. Inhibition of this pathway may be associated with reduced release of related inflammatory cytokines, especially interferon-γ.

Li|Jingjing|J| Zhang|QingHui|Q| Li|Sainan|S| Dai|Weiqi|W| Feng|Jiao|J| Wu|Liwei|L| Liu|Tong|T| Chen|Kan|K| Xia|Yujing|Y| Lu|Jie|J| Zhou|Yingqun|Y| Fan|Xiaoming|X| Guo|Chuanyong|C|

Fucoidan
Hepatic ischemia reperfusion
Interferon-gamma


Adipokines promote chronic kidney disease.

Abstract: The rapid growth in obesity worldwide contributes to an increase in metabolic syndrome and obesity-related kidney disease with an enhanced increased risk for chronic kidney disease, finally progressing to end-stage renal disease. Adipose tissue is a highly active endocrine organ secreting numerous factors that contribute to renal and cardiovascular complications. In renal damage, various adipokines are involved through mediating endothelial dysfunction, inducing oxidative stress and inflammation as well as stimulating renal sympathetic nervous activity, and it reduces cancellous bone but conversely increases cortical bone. Adipokines may also be involved in the development of renal anaemia. A balance exists between more protective adipokines (adiponectin) and factors mediating pathophysiological effects (angiotensin II, TNFα). Obesity may cause a disruption of this delicate balance, thereby inducing renal disease. Consequently, weight reduction and lifestyle changes affecting all components of the metabolic syndrome are essential to disrupt this vicious cycle.

adipokine
kidney disease
endothelial dysfunction
oxidative stress
inflammation


Pulsed UV laser light on Escherichia coli and Saccharomyces cerevisiae suspended in non-alcoholic beer.

Abstract:
BACKGROUND
The aim of this study was to investigate the effect of pulsed ultra-violet (UV) irradiation on inactivation of beer spoilage microorganisms. UV irradiation is nowadays cost effective enough to compete with traditional biological, physical, and chemical treatment technologies and has become an alternative to such methods.

MATERIAL AND METHODS
Photoinactivation effects of pulsed UV laser with the wavelengths of 355 and 266 nm, which inactivate typical prokaryotic (Escherichia coli) and eukaryotic (Saccharomyces cerevisiae) microorganisms, were examined with different doses and exposure times.

RESULTS
A dose of 100 J/cm(2) of the 355 nm pulsed UV laser was able to reduce about 1 to 2 log (88.75%) of E.coli with the population of 1.6×10(8) colony-forming units (CFU/ml), and 97% of 3.2×10(7), 3×10(6), 5.5×10(5), and 9×10(4) CFU/ml. In the case of 266 nm, more than 99% reduction in E. coli serial dilutions was inactivated, using 10 J/cm(2) with exception of 7×10(4) CFU/ml which was not detected any bacterial growth using 5 J/cm2. In addition, 50, 40, and 20 J/cm(2) energy were used successfully to inactivate S. cerevisiae at the populations of 5.4×10(6), 7×10(5), 5×10(4) and 4×10(3) CFU/ml, respectively. As a result, pulsed UV Laser with 266 nm was strong enough to inactivate a high titer of bacterial and yeast indicator standards suspended in non-alcoholic beer in comparison with 355nm doses.

CONCLUSION
Results indicate that pulsed UV technology, in principle, is an attractive alternative to conventional methods for the inactivation of indicator microorganisms and has potential in irradiation of unpasteurized beer.

Hosseini|Sm|S| Azar-Daryany|Mk|M| Massudi|R|R| Elikaei|A|A|

Pulsed UV laser light
non-alcoholic Beer
Inactivation
E. coli
S. cerevisiae


Novel seM-types of Streptococcus equi subsp. equi identified in isolates circulating in Argentina.

Abstract:
BACKGROUND
Strangles is a worldwide infectious disease caused by Streptococcus equi subsp. equi that affects the upper respiratory tract of horses. Streptococcus equi subsp. equi characterisation by seM-typing is internationally used for epidemiological studies and comparison of isolates.

OBJECTIVES
To identify and to compare the seM-types of Argentinian isolates of Streptococcus equi subsp. equi.

STUDY DESIGN
Investigation of bacterial isolates using molecular and phylogenetic approaches.

METHODS
A total of 59 Argentinian isolates of Streptococcus equi subsp. equi obtained between 2007 and 2019 were studied by seM-typing. The sequence similarity of Argentinian seM-types and the other alleles available on the seM database was determined using BLAST and phylogenetic analysis was performed using the Neighbour-Joining algorithm. The amino acid sequences were predicted and compared with the predicted amino acid sequence of the reference strain 4047 using the MEGA 7 software and PROVEAN tool.

RESULTS
Eight seM-types were found among the isolates. Only one of them (seM-61) has been previously reported and the other seven alleles (seM-129, seM-130, seM-131, seM-132, seM-133, seM-134 and seM-135) were novel seM sequences. High genetic similarity was observed among the Argentinian seM-types, with the exception of seM-130. No functional effects of amino acid differences were predicted.

MAIN LIMITATIONS
The number of related and unrelated isolates per year.

CONCLUSIONS
Seven novel seM-types and seM-61 that were previously reported in Brazil were circulating in Argentina which were identified as circulating in Argentinian horses between 2007 and 2019. The high genetic similarity among the Argentinian and Brazilian seM-types suggests that there is a geographical distribution of strain types. The geographical restriction of strains is likely to reflect the movement of horses between different equine disciplines and neighbouring countries.

seM-types
Streptococcus equi subsp. equi
Argentina
strangles
horse
genotypes


Bilateral ovarian maldescent: Unusual cause of infertility - A case report and literature review.

Abstract: Infertility due to ovarian maldescent is extremely rare and diagnosis can be challenging in the absence of uterine anomalies. We present a case of infertility due to bilateral ovarian maldescent with normal uterine anatomy who conceived after in vitro fertilization and did not require removal of the ovaries. A 19-year-old woman presented with primary infertility. After three failed cycles of ovulation induction/intrauterine insemination and one failed cycle of fresh embryo transfer, the patient underwent laparoscopy, which showed bilateral ovaries above the pelvic brim. The patient conceived after second in vitro fertilization and delivered at 34 weeks. Accurate diagnosis of ovarian maldescent in a patient of unexplained infertility and normal uterus is crucial for successful follicular aspiration and infertility treatment. It is important to counsel patients about the benign nature of this rare entity and future fertility.

Garg|D|D| Grazi|R|R| Kankanala|N|N| Melzer-Ross|K|K|

ovarian maldescent
infertility
in vitro fertilization
intrauterine insemination