A cohort study of tibialis anterior tendon shortening in combination with calf muscle lengthening in spastic equinus in cerebral palsy.

Abstract: The aim of this study was to evaluate the outcome of combined tibialis anterior tendon shortening (TATS) and calf muscle-tendon lengthening (CMTL) in spastic equinus. Prospectively collected data was analysed in 26 patients with hemiplegic (n=13) and diplegic (n=13) cerebral palsy (CP) (GMFCS level I or II, 14 males, 12 females, age range 10-35 years; mean 16.8 years). All patients had pre-operative 3D gait analysis and a further analysis at a mean of 17.1 months (±5.6months) after surgery. None was lost to follow-up. Twenty-eight combined TATS and CMTL were undertaken and 19 patients had additional synchronous multilevel surgery. At follow-up 79% of patients had improved foot positioning at initial contact, whilst 68% reported improved fitting or reduced requirement of orthotic support. Statistically significant improvements were seen in the Movement Analysis Profile for ankle dorsi-/plantarflexion (4.15°, p=0.032), maximum ankle dorsiflexion during swing phase (11.68°, p<0.001), and Edinburgh Visual Gait Score (EVGS) (4.85, p=0.014). Diplegic patients had a greater improvement in the EVGS than hemiplegics (6.27 -vs- 2.21, p=0.024). The originators of combined TATS and CMTL showed that it improved foot positioning during gait. The present study has independently confirmed favourable outcomes in a similar patient population and added additional outcome measures, the EVGS, foot positioning at initial contact, and maximum ankle dorsiflexion during swing phase. Study limitations include short term follow-up in a heterogeneous population and that 19 patients had additional surgery. TATS combined with CMTL is a recommended option for spastic equinus in ambulatory patients with CP.

Tsang|S T J|STJ|
McMorran|D|D|
Robinson|L|L|
Herman|J|J|
Robb|J E|JE|
Gaston|M S|MS|


Pectins from cashew apple fruit (Anacardium occidentale): Extraction and chemical characterization.

Abstract: The cashew tree (Anacardium occidentale) is a tropical evergreen tree largely cultivated in Brazil, which produces the cashew apple, a peduncle rich in carbohydrates and considered an industrial waste of the nut production. Until now, there were no data available about the chemical structure of cell wall polysaccharides found in cashew apple. In this work, its pectic polysaccharides have been characterized through monosaccharide composition, HPSEC, methylation and 13C and 1H/13C HSQC-DEPT-NMR analyses. Highly methyl esterified homogalacturonan with a DE of 76% mixed with arabinogalactan were found. This latter was purified and presented a highly branched type II arabinogalactan (AG II) and small amounts of a type I rhamnogalacturonan in which the AG II could be anchored. These findings about the chemical structure of cashew apple pectins could contribute to develop future nutritional, biotechnological and pharmacological uses for this industrial waste from the cashew nut production.

Tamiello-Rosa|Camila Silva|CS|
Cantu-Jungles|Thaisa Moro|TM|
Iacomini|Marcello|M|
Cordeiro|Lucimara M C|LMC|

D019906:Nuclear Magnetic Resonance, Biomolecular

Pectins
Cashew apple
Polysaccharides
Arabinogalactan


Clinical outcomes in patients with isolated left ventricular noncompaction and heart failure.

Abstract:
BACKGROUND
We prospectively evaluated long-term clinical outcomes of patients diagnosed with isolated left ventricular noncompaction (ILVNC) and heart failure from a sub-Saharan African population.

METHODS AND RESULTS
Patients in this single-center study were followed at a tertiary care institution. Clinical follow-up was performed with the use of protocol-driven echocardiographic screening for ventricular thrombus every 4 months. Warfarin was maintained or initiated only if thrombus was detected with the use of echocardiography. Fifty-five patients were followed for 16.7 ± 5.9 (range 12-33) months. All individuals had left ventricular (LV) ejection fraction <50% (mean 29.6 ± 11.8%). Of the 55 patients, 7 (12.7%) died, and sudden cardiac death was the cause in 5 (71.4%). There were no differences in baseline clinical, echocardiographic, or electrocardiographic characteristics between survivors and nonsurvivors. Recurrent heart failure developed in 12 patients (21.8%); 1 patient developed a ventricular arrhythmia. No thromboembolic or major bleeding complications occurred in the 16 patients on warfarin; 1 episode of thromboembolism occurred in the 39 patients not on warfarin. Mean survival probability at 33 months was 0.64.

CONCLUSIONS
Sudden cardiac death was the most common cause of death in patients with ILVNC and heart failure. Recurrent heart failure occurred in 21.8% of patients. Development of LV thrombus and cardioembolism is uncommon in this population.

Peters|Ferande|F|
Khandheria|Bijoy K|BK|
Botha|Francois|F|
Libhaber|Elena|E|
Matioda|Hiral|H|
Dos Santos|Claudia|C|
Govender|Samantha|S|
Meel|Ruchika|R|
Essop|Mohammed R|MR|

Left ventricular noncompaction
heart failure
echocardiography
sudden cardiac death


Relationship Between Metabolic Disorders and Breast Cancer Incidence and Outcomes. Is There a Preventive and Therapeutic Role for Berberine?

Abstract: The association between obesity/overweight and carcinogenesis is a recognized highly complex and still partially unknown process. Nevertheless, these conditions are frequently related with several pathological states such as chronic inflammation, presence of dyslipidemia and insulin-resistance (metabolic disorders) which are now accepted features contributing to the increased hormonal-dependent cancer risk. Breast cancer incidence and outcome is strictly related to metabolic disorders. Thus, managing these emerging risk factors, should be a new and optimal strategy in breast cancer prevention and therapy. Unfortunately, the agents able to interfere with metabolic disorders, produce often light or serious side-effects and consequently their compliance and efficacy are weak. Some nutraceutical compounds seem to be an ideal option with the same activity and effectiveness to ordinary agents but with minor side effects. Berberine, an extraordinary medicinal herb, has been proven to have many clinical pharmacological effects, including lowering of blood glucose, increasing insulin sensitivity, and correcting lipid metabolism disorders. It has a comparable therapeutic effect to common drugs. It acts contemporarily on hyperlipidemia, hyperglycemia and insulin resistance without their related side effects and could be a real alternative in healthy high risk or affected breast cancer patients with metabolic disorders. This commentary examines the pathophysiology of metabolic disorders and its relationship to breast cancer. Moreover, it evaluates the possible role of berberine in the clinical practice.

breast cancer
berberine
Obesity
dyslipidemia
insulin-resistance
nutraceuticals
review


Hippocampal Transcriptomic Profiles: Subfield Vulnerability to Age and Cognitive Impairment.

Abstract: The current study employed next-generation RNA sequencing to examine gene expression differences related to brain aging, cognitive decline, and hippocampal subfields. Young and aged rats were trained on a spatial episodic memory task. Hippocampal regions CA1, CA3, and the dentate gyrus were isolated. Poly-A mRNA was examined using two different sequencing platforms, Illumina, and Ion Proton. The Illumina platform was used to generate seed lists of genes that were statistically differentially expressed across regions, ages, or in association with cognitive function. The gene lists were then retested using the data from the Ion Proton platform. The results indicate hippocampal subfield differences in gene expression and point to regional differences in vulnerability to aging. Aging was associated with increased expression of immune response-related genes, particularly in the dentate gyrus. For the memory task, impaired performance of aged animals was linked to the regulation of Ca2+ and synaptic function in region CA1. Finally, we provide a transcriptomic characterization of the three subfields regardless of age or cognitive status, highlighting and confirming a correspondence between cytoarchitectural boundaries and molecular profiling.

Ianov|Lara|L|
De Both|Matt|M|
Chawla|Monica K|MK|
Rani|Asha|A|
Kennedy|Andrew J|AJ|
Piras|Ignazio|I|
Day|Jeremy J|JJ|
Siniard|Ashley|A|
Kumar|Ashok|A|
Sweatt|J David|JD|
Barnes|Carol A|CA|
Huentelman|Matthew J|MJ|
Foster|Thomas C|TC|

aging
gene expression
Ion proton
cognitive function
Illumina HiSeq
hippocampus
transcription


A Comparison of Tumor-Associated and Non-Tumor-Associated Gastric Microbiota in Gastric Cancer Patients.

Abstract:
BACKGROUND
How gastric cancer (GC) incidence is associated with changes in the gastric microbiome has not been firmly established. The present study therefore aims to investigate the microbial communities present within the gastric mucosa of patients with superficial gastritis (SG) or GC.

METHODS
Paired tumor and paracancerous samples of the gastric mucosa were collected from 18 patients being surgically treated for GC and from 32 patients with SG being treated via gastroscopy. The gastric microbiome in these samples was then profiled via 16S rRNA sequencing, with a linear discriminant analysis effect size (LEfSe) approach used to identify and compare different bacteria, and with PICRUSt used for predictive functional analyses.

RESULTS
GC patients exhibited a distinct gastric microbiota profile from that observed in SG patients. These changes were evident in both tumor and paracancerous tissues from GC patients. Specifically, we found that 6 bacterial genera were specifically enriched in GC tissue samples relative to SG samples, while 18 genera were depleted in these same samples. Based on the differential abundance of these bacteria, we were able to calculate microbial dysbiosis index (MDI) values, which were significantly higher in GC patients than in SG patients. In addition, MDI values were negatively correlated with gastric Shannon index and were positively correlated with relative Helicobacter spp. abundance. Importantly, these MDI values were readily able to discriminate between GC and SG patient samples. Functional analysis suggested that GC patients were more likely to harbor a nitrosating microbial community.

CONCLUSIONS
GC patients exhibited a gastric microbiome profile distinct from that observed in SG patients, with these differences being evident in both tumor and paracancerous tissues. Differences in the relative abundance of Helicobacter spp. may be the primary driver of gastric dysbiosis in GC patients.

Wu|Zhen-Feng|ZF| Zou|Kun|K| Wu|Guan-Nan|GN| Jin|Zhao-Jia|ZJ| Xiang|Chun-Jie|CJ| Xu|Shuo|S| Wang|Yao-Hui|YH| Wu|Xiao-Yu|XY| Chen|Che|C| Xu|Zhe|Z| Li|Wei-Su|WS| Yao|Xue-Quan|XQ|0000-0002-3984-7255 Zhang|Jun-Feng|JF| Liu|Fu-Kun|FK|

Microbiota
Gastric cancer
Carcinogenesis
Stomach


Differential diagnoses, investigation, and management of a periocular swelling close to the nasolacrimal duct in a horse - A case report of Dacryops.

Abstract: To describe the differential diagnoses, investigation, and management of a periocular swelling close to the nasolacrimal duct in a horse that was consistent with a nasolacrimal duct dacryops (lacrimal cyst). A 16-year-old gelding, Connemara cross presented with a history of a periocular swelling rostroventral medial to the right eye that had been sampled by the referring veterinary surgeon. A cystic lesion was diagnosed following standing computed tomography. Surgical removal of the cystic lesion was performed, and the tissue was submitted for histopathologic and immunohistochemical examination. Surgical removal of the cyst was curative, and there was no recurrence of clinical signs 7 months later. There was a small amount of mineralized material in the center of the cyst. Histopathologic and immunohistochemical examination confirmed a nasolacrimal duct cyst. Dacryops can form in horses as well as other species and appears to have a favorable outcome if surgically removed.

dacryops
cyst
computed tomography
histopathology
equine
nasolacrimal system


Contribution of the xenograft bone plate-screw system in lumbar transpedicular stabilization: An in vivo study in dogs.

Abstract:
OBJECTIVES
Xenograft bone plate-screws (XBPSs) can be alternative tools in lumbar transpedicular stabilization (TS). The aim of this study was to show biomechanical and histopathological contribution of the XBPSs system in lumbar TS.

MATERIALS AND METHODS
Fifteen (n = 15) hybrid dog and ten (n = 10) L2-4 cadaveric specimens were included in the study. The dogs were separated according to surgical techniques: L3 laminectomy and bilateral facetectomy (LBF) in Group I (experimental group [EG I] (n = 5), L3 LBF plus TS with metal plate-screws (MPSs) in Group II (EG II) (n = 5), and L3 LBF plus TS with XBPSs in Group III (EG III) (n = 5). The cadaveric specimens were separated to L2-4 intact in Group I (CG I), (n = 5), and L3 LBF in Group II (CG II), (n = 5). The dogs were sacrificed at the end of 3rd month, and their L2-4 spinal segments were en bloc removed and prepared as in control groups. Flexion, extension, left-right bending, rotation, and compression tests were applied to all segments. Stiffness values were calculated and analyzed statistically. All dog segments were evaluated histopathologically.

RESULTS
XBPS system showed a higher average stiffness values for left bending, extension, flexion, and compression compared to MPS, but these differences were not statistically meaningful. XBPS system had superiority to the fusion formation, as well.

CONCLUSIONS
XBPSs provide stability and help the fusion formation, but this system does not have a biomechanical advantage over MPS system in TS.

Sarigul|Sani|S|
Salci|Hakan|H|
Lekesiz|Huseyin|H|
Dogan|Seref|S|
Ozcan|Resat|R|
Gorgul|Osman Sacit|OS|
Aksoy|Kaya|K|

xenograft bone plate-screw
transpedicular stabilization
Biomechanic
histopathology


Urrets-Zavalia syndrome (fixed and dilated pupil following penetrating keratoplasty for keratoconus) and its variants.

Abstract: Urrets-Zavalia Syndrome (UZS) was described 50 years ago as the appearance of a fixed and dilated pupil following penetrating keratoplasty for keratoconus in patients receiving atropine. The mechanism of UZS has still not been fully determined, but an acute increase in intraocular pressure and ischemia of the iris most probably play a major role. Fixed and dilated pupils also occur in association with other ophthalmic surgeries, such as lamellar keratoplasties, cataract surgery, and glaucoma procedures. Some have questioned the existence of this syndrome, as well as the linkage to keratoconus and use of mydriatics. We review the pathophysiology, etiology, and clinical presentation of fixed and dilated pupils following ophthalmic procedures.

Urrets-Zavalia syndrome
fixed and dilated pupil
penetrating keratoplasty
keratoconus
atropine
mydriatics


Metabolic complications of childhood obesity.

Abstract:
Context
Childhood obesity is a global health problem. A percentage of 2.3 of Indian boys and 2.5 of Indian girls are obese. Childhood obesity is associated with many morbidities like diabetes mellitus, coronary artery disease, musculoskeletal problems, and increased mortality.

Aims
The aim of this study is to estimate burden of metabolic complications of obesity in child and parents of obese children and compare it with normal-weight children.

Settings and Design
The study was done at a tertiary health center in northern India. It was a cross-sectional study.

Methods and Material
We enrolled 60 obese children and age- and sex-matched 26 controls, based on Indian Academy of Pediatrics (IAP)2015 body mass index (BMI) charts. Anthropometric parameters and metabolic complications in family were compared between cases and controls. Clinical markers of metabolic derangements and laboratory metabolic profile were assessed for obese children.

Statistical Analysis Used
Descriptive statistics was used to describe frequencies. Chi-square test and Mann-Whitney test and Spearman correlation were used for comparison.

Results
The prevalence of obesity and obesity-related complications was high in families of obese children. Ten percent of obese children had impaired fasting glucose and 30% had Haemoglobin A1c (HbA1c) in prediabetes category. Forty percent of obese children had dyslipidemia, 45% had transaminitis, and 46.7 were vitamin D deficient. A percentage of 41.7 of obese children had fatty liver on ultrasound.

Conclusions
The family health and child weight are linked through home environment and genetics. The metabolic complications of obesity prediabetes, dyslipidemia, fatty liver, and lower vitamin D level are common in childhood obesity. Regular screening and interventions of metabolic complications are essential for saving child's future health.

Munusamy|Jeyaraj|J| Yadav|Jaivinder|J| Kumar|Rakesh|R| Bhalla|Anil|A| Dayal|Devi|D|

metabolic complications
obesity
Child
lifestyle


Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions.

Abstract: Adverse drug reactions (ADRs) remain associated with significant mortality. Delayed hypersensitivity reactions (DHRs) that occur greater than 6 h following drug administration are T-cell mediated with many severe DHRs now associated with human leukocyte antigen (HLA) risk alleles, opening pathways for clinical prediction and prevention. However, incomplete negative predictive value (NPV), low positive predictive value (PPV), and a large number needed to test (NNT) to prevent one case have practically prevented large-scale and cost-effective screening implementation. Additional factors outside of HLA contributing to risk of severe T-cell-mediated DHRs include variation in drug metabolism, T-cell receptor (TCR) specificity, and, most recently, HLA-presented immunopeptidome-processing efficiencies via endoplasmic reticulum aminopeptidase (ERAP). Active research continues toward identification of other highly polymorphic factors likely to impose risk. These include those previously associated with T-cell-mediated HLA-associated infectious or auto-immune disease such as Killer cell immunoglobulin-like receptors (KIR), epistatically linked with HLA class I to regulate NK- and T-cell-mediated cytotoxic degranulation, and co-inhibitory signaling pathways for which therapeutic blockade in cancer immunotherapy is now associated with an increased incidence of DHRs. As such, the field now recognizes that susceptibility is not simply a static product of genetics but that individuals may experience dynamic risk, skewed toward immune activation through therapeutic interventions and epigenetic modifications driven by ecological exposures. This review provides an updated overview of current and proposed genetic factors thought to predispose risk for severe T-cell-mediated DHRs.

Li|Yueran|Y|
Deshpande|Pooja|P|
Hertzman|Rebecca J|RJ|
Palubinsky|Amy M|AM|
Gibson|Andrew|A|
Phillips|Elizabeth J|EJ|

delayed hypersensitivity
human leukocyte antigen
T-cell receptor
endoplasmic reticulum aminopeptidase
genetic risk
immune checkpoint


Development and validation of a Diabetes Risk Score for screening undiagnosed diabetes in Sri Lanka (SLDRISK).

Abstract:
BACKGROUND
Screening for undiagnosed diabetes is not widely undertaken due to the high costs and invasiveness of blood sampling. Simple non-invasive tools to identify high risk individuals can facilitate screening. The main objectives of this study are to develop and validate a risk score for screening undiagnosed diabetes among Sri Lankan adults and to compare its performance with the Cambridge Risk Score (CRS), the Indian Diabetes Risk Score (IDRS) and three other Asian risk scores.

METHODS
Data were available from a representative sample of 4276 adults without diagnosed diabetes. In a jack-knife approach two thirds of the sample was used for the development of the risk score and the remainder for the validation. Age, waist circumference, BMI, hypertension, balanitis or vulvitis, family history of diabetes, gestational diabetes, physical activity and osmotic symptoms were significantly associated with undiagnosed diabetes (age most to osmotic symptoms least). Individual scores were generated for these factors using the beta coefficient values obtained in multiple logistic regression. A cut-off value of sum = 31 was determined by ROC curve analysis.

RESULTS
The area under the ROC curve of the risk score for prevalent diabetes was 0.78 (CI 0.73-0.82). In the sample 36.3 % were above the cut-off of 31. A risk score above 31 gave a sensitivity, specificity, positive predictive value and negative predictive value of 77.9, 65.6, 9.4 and 98.3 % respectively. For Sri Lankans the AUC for the CRS and IDRS were 0.72 and 0.66 repectively.

CONCLUSIONS
This simple non-invasive screening tool can identify 80 % of undiagnosed diabetes by selecting 40 % of Sri Lankan adults for confirmatory blood investigations.

Katulanda|P|P|
Hill|N R|NR|
Stratton|I|I|
Sheriff|R|R|
De Silva|S D N|SD|
Matthews|D R|DR|

D000328:Adult
D000367:Age Factors
D001786:Blood Glucose
D015992:Body Mass Index
D015331:Cohort Studies
D003920:Diabetes Mellitus
D005260:Female
D006801:Humans
D006973:Hypertension
D016015:Logistic Models
D008297:Male
D008403:Mass Screening
D015995:Prevalence
D012372:ROC Curve
D018570:Risk Assessment
D012307:Risk Factors
D013188:Sri Lanka
D055105:Waist Circumference

Diabetes
Risk score
Screening
Sri Lanka
South Asian


Simultaneous improvements on nutrient and Mg recoveries of microalgal bioremediation for municipal wastewater and nickel laterite ore wastewater.

Abstract: Effects of different mixing ratios between synthetic municipal wastewater (MW) and magnesium (Mg2+)-enriched nickel laterite ore wastewater (NLOWW) on growth of Chlorella sorokiniana (C. sorokiniana), photosynthetic activities, cellular biocomposition, nutrient and Mg2+ removal were investigated in photobioreactors. In the culture without NLOWW, wrinkled cells were observed with low biomass production. The culture mixed with 0.13% NLOWW obtained 1.89-fold higher biomass yield, 3.77-fold enhanced photosynthetic activity (Fv/Fm value), and improved nutrient removal (nitrogen by 102.2%, phosphorus by 39.3%). However, excessive Mg2+ at 100% NLOWW produced highest reactive oxygen species suppressing microalgal growth. The Mg2+ removal capacity increased with NLOWW loading. Moreover, microalgal assimilation primarily contributed to nutrient removal while absorption was the dominant Mg2+ removal pathway. Carbohydrate content in biomass increased with Mg2+ loading. Finally, the approach for MW/NLOWW treatment was demonstrated as economically feasible with revenue of $75.6 per kilogram biomass through a comprehensive economic model.

Chen|Zhipeng|Z|
Qiu|Shuang|S|
Amadu|Ayesha Algade|AA|
Shen|Yeting|Y|
Wang|Lingfeng|L|
Wu|Zhengshuai|Z|
Ge|Shijian|S|

Wastewater
Magnesium
Biomass production
Nutrient removal
Microalgae


A Stab in the Dark: A Case Report of an Atypical Presentation of Giant Cell Arteritis (GCA).

Abstract: Background: Giant cell arteritis/temporal arteritis (GCA) is an inflammatory condition that affects large to medium vessels such as the aorta and its primary branches. Patients classically present with fatigue, fever, headache, jaw claudication and in severe cases, may suffer either transient (amaurosis fugax) or permanent visual loss. The reference standard for diagnosis is the temporal artery biopsy (TAB) and the mainstay of treatment is with immunosuppression. Our patient JG, presented with a range of non-specific symptoms that mimicked generalised sepsis, but was ultimately diagnosed with GCA through effective, methodical multi-disciplinary team (MDT) work. Clinical case: JG, an 81 year old gentleman, presented acutely with a 3-4 weeks history of fatigue, lethargy, pyrexia and a marked inflammatory response suggestive of a sepsis but without a clear primary source or clinical features of vasculitis. His inflammatory markers were markedly raised although his erythrocyte sedimentation rate (ESR) was not elevated. He was initially treated for sepsis of unknown origin however, body imaging after admission suggested a possible infection around a previous aortic graft site. This was refuted in subsequent 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET/CT) scanning. Microbiological, parasitic, as well as autoimmune assays were unremarkable. He underwent a TAB which was diagnostic for GCA and as a result, was started on oral corticosteroids with immediate symptom relief. He was discharged and followed up on an outpatient basis. Conclusions: This case highlights how a vasculitis can present with a range of non-specific symptoms that may resemble a fever of unknown origin (FUO)/sepsis that can lead to a delay in making the correct diagnosis. It also highlights the importance of considering a diagnosis of vasculitis in patients who present with a FUO where there is no clear focus of infection. Delays in diagnosis and management of these conditions can potentially lead to significant irreversible morbidity.

McCausland|Beth|B|
Desai|David|D|
Havard|David|D|
Kaur|Yasmin|Y|
Yener|Asalet|A|
Bradley|Emma|E|
Patel|Harnish P|HP|0000-0002-0081-1802

giant cell arteritis
temporal arteritis
temporal artery biopsy
non-specific symptoms
sepsis
FDG-PET/CT
inflammation
multidisciplinary team working


High prevalence of anti-Toxoplasma gondii antibodies in beef cattle in Midwestern Brazil.

Abstract: The present study aimed to determine the seroprevalence of anti-Toxoplasma gondii antibodies using an indirect immunofluorescence assay (IFA-IgG) in 3,814 cows aged ≥ 24 months belonging to 353 beef farms in the Mato Grosso state. Additionally, we aimed to identify the possible risk factors associated with seropositivity in Mato Grosso, which encompasses three biomes (Amazon, Cerrado, and Pantanal) of Brazil. Analysis of 3,814 samples observed that 1,307 animals were positive for anti-T. gondii antibodies (IFA-IgG ≥ 64), with an animal-level seroprevalence of 34.27%. Herd-level seroprevalence was 92.07%. In the animal-level model, cows raised in the Amazon and Pantanal biomes and breed studies on European and Zebu or hybrid were found to be at risk for T. gondii seropositivity. Prevalence of anti-T. gondii antibodies in cows destined for human consumption was found to be widely distributed throughout the entire study area. Further studies are required to assess the impact of beef in the possible transmission of toxoplasmosis to humans residing in the region and establish additional control measures for this protozoan mainly on beef herds raised in the Amazon and Pantanal biomes, where the highest values of seroprevalence were observed.

Maia|Maerle Oliveira|MO|
de Almeida|Sayanne Luns Hatum|SLH|
Schmidt|Ana Carolina|AC|
de Oliveira|Anderson Castro Soares|ACS|
de Aguiar|Daniel Moura|DM|
Dos Santos-Doni|Thaís Rabelo|TR|
de Campos Pacheco|Richard|R|

Antibodies
Beef cattle
Toxoplasmosis
Zoonosis


Two novel lanthanide(III) organic frameworks based on a biphenyltetracarboxylate ligand: synthesis, structure and magnetic and luminescence properties.

Abstract: Two new two-dimensional lanthanide coordination polymers, namely poly[[tetra-μ2-acetato-tetraaquabis(μ4-biphenyl-3,3',5,5'-tetracarboxylato)tetrakis(dimethylacetamide)tetraterbium(III)] pentahydrate], {[Tb4(C16H6O8)2(C2H3O2)4(C4H9NO)4(H2O)4]·5H2O}n, (1), and poly[[tetra-μ2-acetato-tetraaquabis(μ5-biphenyl-3,3',5,5'-tetracarboxylato)tetrakis(dimethylacetamide)tetraeuropium(III)] tetrahydrate], {[Eu4(C16H6O8)2(C2H3O2)4(C4H9NO)4(H2O)4]·4H2O}n, (2), have been synthesized from biphenyl-3,3',5,5'-tetracarboxylic acid (H4bpt) and Ln(NO3)3·6H2O (Ln = Tb and Eu) under solvothermal conditions. Single-crystal X-ray structure analysis shows that the two compounds are isostructural and crystallize in the monoclinic P21/n space group. The crystal structures are constructed from bpt4- ligands (as linkers) and {Ln2(μ2-CH3COO)2} building units (as nodes), which topological analysis shows to be a (4,6)-connected network with sql topology. Compounds (1) and (2) have been characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and fluorescence analysis in the solid state. In addition, a magnetic investigation shows the presence of antiferromagnetic interactions in compound (1).

Hao|Hongguo|H| Wang|Yuchen|Y| Yuan|Suxian|S| Li|Dacheng|D| Sun|Junshan|J|

luminescence properties
crystal structure
SQUEEZE
europium(III)
magnetic properties
terbium(III)
tetracarboxylate
two-dimensional coordination polymers


Re-examination of two diatom reference genomes using long-read sequencing.

Abstract:
BACKGROUND
The marine diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum are valuable model organisms for exploring the evolution, diversity and ecology of this important algal group. Their reference genomes, published in 2004 and 2008, respectively, were the product of traditional Sanger sequencing. In the case of T. pseudonana, optical restriction site mapping was employed to further clarify and contextualize chromosome-level scaffolds. While both genomes are considered highly accurate and reasonably contiguous, they still contain many unresolved regions and unordered/unlinked scaffolds.

RESULTS
We have used Oxford Nanopore Technologies long-read sequencing to update and validate the quality and contiguity of the T. pseudonana and P. tricornutum genomes. Fine-scale assessment of our long-read derived genome assemblies allowed us to resolve previously uncertain genomic regions, further characterize complex structural variation, and re-evaluate the repetitive DNA content of both genomes. We also identified 1862 previously undescribed genes in T. pseudonana. In P. tricornutum, we used transposable element detection software to identify 33 novel copia-type LTR-RT insertions, indicating ongoing activity and rapid expansion of this superfamily as the organism continues to be maintained in culture. Finally, Bionano optical mapping of P. tricornutum chromosomes was combined with long-read sequence data to explore the potential of long-read sequencing and optical mapping for resolving haplotypes.

CONCLUSION
Despite its potential to yield highly contiguous scaffolds, long-read sequencing is not a panacea. Even for relatively small nuclear genomes such as those investigated herein, repetitive DNA sequences cause problems for current genome assembly algorithms. Determining whether a long-read derived genomic assembly is 'better' than one produced using traditional sequence data is not straightforward. Our revised reference genomes for P. tricornutum and T. pseudonana nevertheless provide additional insight into the structure and evolution of both genomes, thereby providing a more robust foundation for future diatom research.

Filloramo|Gina V|GV|
Curtis|Bruce A|BA|
Blanche|Emma|E|
Archibald|John M|JM|

Thalassiosira pseudonana
Phaeodactylum tricornutum
Bionano optical mapping
Diatom genomics
Long-terminal repeat retrotransposons
Oxford Nanopore long-read sequencing


Effect of Photobiomodulation in Rescuing Lipopolysaccharide-Induced Dopaminergic Cell Loss in the Male Sprague-Dawley Rat.

Abstract: Photobiomodulation (PBM) provides neuroprotection against dopaminergic cell death and associated motor deficits in rodent and primate models of Parkinson's disease (PD). However, it has not yet been tested in the lipopolysaccharide (LPS) model of PD, which leads to dopaminergic cell death through microglia-evoked neuroinflammation. We investigated whether transcranial PBM could protect against dopaminergic cell death within the substantia nigra in male Sprague-Dawley rats following supranigral LPS injection. PBM fully protected rats from 10 µg LPS which would have otherwise caused 15% cell loss, but there was no significant neuroprotection at a 20 µg dose that led to a 50% lesion. Cell loss at this dose varied according to the precise site of injection and correlated with increased local numbers of highly inflammatory amoeboid microglia. Twenty microgram LPS caused motor deficits in the cylinder, adjusted stepping and rotarod tests that correlated with dopaminergic cell loss. While PBM caused no significant improvement at the group level, motor performance on all three tests no longer correlated with the lesion size caused by 20 µg LPS in PBM-treated rats, suggesting extranigral motor improvements in some animals. These results provide support for PBM as a successful neuroprotective therapy against the inflammatory component of early PD, provided inflammation has not reached a devastating level, as well as potential benefits in other motor circuitries.

Lipopolysaccharide
neuroinflammation
microglia
Parkinson’s disease
low-level light therapy


Myocardial ischemia in the absence of obstructive coronary lesion: The role of post-stress diastolic dysfunction in detecting early coronary atherosclerosis.

Abstract:
BACKGROUND
The interactions between non-obstructive coronary atherosclerosis (<50% stenosis) and myocardial perfusion and functional parameters on myocardial perfusion imaging (MPI) have never been evaluated.

METHODS AND RESULTS
One-hundred and ninety-five patients were submitted to stress-rest MPI and invasive coronary angiography. The presence of obstructive coronary lesions (>50% stenosis) was excluded. The summed stress score (SSS) was calculated in every patient. Moreover, the left ventricular (LV) ejection fraction (EF) and peak filling rate (PFR) were computed from gated MPI images as measures of systolic and diastolic functions. Sixty/195 patients (31%) showed the presence of non-obstructive atherosclerosis (>20% and <50% diameter reduction). Interestingly, they presented a higher SSS than those with normal coronary arteries (P < 0.001) despite a similar myocardial scar burden. If compared to patients with normal coronary arteries, those with non-obstructive atherosclerosis showed more abnormal post-stress PFR values (2.5 ± 0.9 vs 2.9 ± 0.8, P = 0.004), despite a similar EF. On multivariate analysis, the presence non-obstructive atherosclerosis was the only significant predictor (P = 0.026) of post-stress LV diastolic impairment, independently from perfusion parameters.

CONCLUSIONS
In patients without anatomically significant coronary lesions, the development of post-stress LV diastolic dysfunction on MPI associates with the presence of non-obstructive atherosclerosis on coronary angiography.

Gimelli|Alessia|A|
Liga|Riccardo|R|
Pasanisi|Emilio Maria|EM|
Casagranda|Mirta|M|
Marzullo|Paolo|P|

Diastolic dysfunction
coronary atherosclerosis
CZT
SPECT
ischemic heart disease


Measuring Secretion of Capsidiol in Leaf Tissues of Nicotiana benthamiana.

Abstract: Plant species produce a wide variety of antimicrobial metabolites to protect themselves against potential pathogens in natural environments. Phytoalexins are low molecular weight compounds produced by plants in response to attempted attacks of pathogens. Accumulation of phytoalexins in attacked plant tissues can inhibit the growth of penetrating pathogens. Thus phytoalexins play a major role in post-invasion defense against pathogens. Major phytoalexins produced by Solanaceous plants are sesquiterpenoids such as capsidiol produced by Nicotiana and Capsicum species, and rishitin produced by Solanum species, which are synthesized in the cytosol and secreted into the intercellular space of plant tissues. We previously reported that deficiency in capsidiol secretion causes enhanced susceptibility of Nicotiana benthamiana to potato late blight pathogen, Phytophthora infestans. Here, we describe a practical protocol to measure the secreted capsidiol in N. benthamiana.

Secretion
Capsidiol
Nicotiana benthamiana
Phytoalexins
Transporter


Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

Abstract: Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P < 0.001). HDV is not uncommon in Egypt. HBV genotype-D was associated with HDV genotype-IIb. Delta infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk.

Fouad|Rabab|R|
Abdo|Mahmoud|M|
Eldeen|Hadeel Gamal|HG|
Sabry|Dina|D|
Atef|Mira|M|
Ahmed|Rasha|R|
Zayed|Naglaa|N|

D020133:Reverse Transcriptase Polymerase Chain Reaction


Endoscope-assisted, minimally invasive evacuation of sub-acute/chronic epidural hematoma: Novelty or paradox of Theseus?

Abstract:
BACKGROUND
Sub-acute/chronic epidural hematoma (EDH) may present with nagging symptoms of headache, nausea, vomiting, lethargy, etc. We attempted to offer a minimally invasive, single burr hole, endoscope-assisted evacuation of EDHs instead of a conventional craniotomy.

METHODS
Seven patients with sub-acute/chronic EDH (six supratentorial and one infratentorial) presented to us 3 to 7 days after low-velocity road traffic accidents with complaints of headache and lethargy. The EDH volumes measured between 20 to 50 ml, and the patients were operated on using a single burr hole made through a small incision. We used 0-, 30- and 70-degree, angulated, rigid, high-definition endoscopes to identify and evacuate the organized clots in the extradural space. Flexible catheters were used for suction and irrigation. After achieving hemostasis, the dura was hitched back to the burr hole site. The wound was closed over a negative suction drain.

RESULTS
All patients had prompt recovery from symptoms. Postoperative CT scans showed complete or near complete evacuation of the hematomas. The hospital stay and analgesic requirements were minimal. There was no infective complication or conversion to conventional open surgery. The average time for surgery was 77.8 min, and average blood loss was 328.5 ml.

CONCLUSION
Endoscope-assisted evacuation of sub-acute/chronic EDH is a novel concept, which offers quick relief from symptoms in a minimally invasive fashion and a cosmetically acceptable way. None of the standard principles of surgery are hampered. It avoids extensive dissection of the temporalis or sub-occipital muscles. However, achieving hemostasis can be difficult. Further study and better equipment will validate the procedure.

Minimally invasive
Sub-acute/chronic EDH
Endoscopic EDH
Single burr hole surgery for EDH


An Activatable Afterglow/MRI Bimodal Nanoprobe with Fast Response to H2 S for In Vivo Imaging of Acute Hepatitis.

Abstract: Accurate detection of hepatic hydrogen sulfide (H2 S) to monitor H2 S-related enzymes' activity is critical for acute hepatitis diagnosis, but remains a challenge due to the dynamic and transient nature of H2 S. Here, we report a H2 S-activatable near-infrared afterglow/MRI bimodal probe F1-GdNP, which shows an "always-on" MRI signal and "off-on" afterglow signal toward H2 S. F1-GdNP shows fast response, high sensitivity and specificity toward H2 S, permitting afterglow imaging of H2 S and evaluation of cystathionine γ-lyase (CSE)'s activity in living mice. We further employ the high spatial-resolution MRI signal of F1-GdNP to track its delivery and accumulation in liver. Importantly, F1-GdNP offers a high signal-to-background ratio (SBR=86.2±12.0) to sensitively report on the increased hepatic H2 S level in the acute hepatitis mice via afterglow imaging, which correlated well with the upregulated CSE activity in the liver, showcasing the good potential of F1-GdNP for monitoring of acute hepatitis process in vivo.

afterglow
MRI
acute hepatitis
hydrogen sulfide
cystathionine γ-lyase


Obstructive Jaundice Due to Tuberculosis of Distal CBD and Periampullary Region Mimickcholangiocarcinoma.

Abstract: Abdominal tuberculosis (TB) commonly affects the intestinal tract, lymph nodes, peritoneum, and solid organs in varying combinations. Hepatobiliary or pancreatic TB is rare and the preoperative diagnosis is difficult. Though rare, there have been a few citations of intrahepatic tuberculosis, but isolated bile duct tuberculosis is extremely rare. Here we report a case of obstructive jaundice which was initially thought to be due to lower-end cholangiocarcinoma but postoperatively it was found to be tuberculosis.

Ray|Sumantra|S|
Chatterjee|Sajib|S|
Saha|Asis Kumar|AK|
Samanta|Saugata|S|

obstructive jaundice
tuberculosis
Bile ducts


Progressive metabolic impairment underlies the novel nematicidal action of fluensulfone on the potato cyst nematode Globodera pallida.

Abstract:
BACKGROUND
Fluensulfone is a new nematicide with an excellent profile of selective toxicity against plant parasitic nematodes. Here, its effects on the physiology and biochemistry of the potato cyst nematode Globodera pallida have been investigated and comparisons made with its effect on the life-span of the free-living nematode Caenorhabditis elegans to provide insight into its mode of action and its selective toxicity.

RESULTS
Fluensulfone exerts acute effects (≤1h; ≥100μM) on stylet thrusting and motility of hatched second stage G. pallida juveniles (J2s). Chronic exposure to lower concentrations of fluensulfone (≥3days; ≤30μM), reveals a slowly developing metabolic insult in which G. pallida J2s sequentially exhibit a reduction in motility, loss of a metabolic marker for cell viability, high lipid content and tissue degeneration prior to death. These effects are absent in adults and dauers of the model genetic nematode Caenorhabditis elegans.

CONCLUSION
The nematicidal action of fluensulfone follows a time-course which progresses from an early impact on motility through to an accumulating metabolic impairment, an inability to access lipid stores and death.

Kearn|James|J| Lilley|Catherine|C| Urwin|Peter|P| O'Connor|Vincent|V| Holden-Dye|Lindy|L|

Metabolism
Plant parasitic nematode
Stylet
Motility
Hatching
Lipid


Nurses' information practice in municipal health care-A web-like landscape.

Abstract:
AIM
To uncover the characteristics of nurses' information practice in municipal health care and to address how, when and why various pieces of information are produced, shared and managed.

BACKGROUND
Nursing documentation in the electronic patient record has repeatedly been found unsatisfactory. Little is known about how the information practice of nurses in municipal health care actually is borne out. In order to understand why nursing documentation continues to fail at living up to the expected requirements, a better understanding of nurses' information practice is needed.

DESIGN
A qualitative observational field study. The study complied with the Consolidated Criteria for Reporting Qualitative Research.

METHODS
Empirical data were collected in three Norwegian municipalities through participant observations and individual interviews with 17 registered nurses on regular day shifts. The data were analysed through thematic content analysis.

RESULTS
Nurses' information practice in municipal health care can be described as complex. The complexity is reflected in four themes that emerged from the data: (1) web of information sources, (2) knowing the patient and information redundancy, (3) asynchronous information practice and (4) compensatory workarounds.

CONCLUSIONS
The complex and asynchronous nature of nurses' information practice affected both how and when information was produced, recorded and shared. When available systems lacked functions the nurses wanted, they created compensatory workarounds. Although electronic patient record was an important part of their information practice, nurses in long-term care often knew their patients well, which meant that a lot of information about the patients was in their heads, and that searching for information in the electronic patient record sometimes seemed redundant.

RELEVANCE TO CLINICAL PRACTICE
This study provides contextual knowledge that might be valuable (a) in the further development of information systems tailored to meet nurses' information needs and (b) when studying patient safety in relation to nurses' information practice.

information practice
nursing documentation
electronic patient records
patient safety
continuity of care


Primary care visits increase utilization of evidence-based preventative health measures.

Abstract:
BACKGROUND
Primary care visits can serve many purposes and potentially influence health behaviors. Although previous studies suggest that increasing primary care provider numbers may be beneficial, the mechanism responsible for the association is unclear, and have not linked primary care access to specific preventative interventions. We investigated the association between the number of times patients accessed their primary care provider team and the likelihood they received selected preventative health interventions.

METHODS
Patients with complete data sets from Sanford Health were categorized based on the number of primary care visits they received in a specified time period and the preventative health interventions they received. Patient characteristics were used in a propensity analysis to control for variables. Relative risks and 95% confidence intervals were calculated to estimate the likelihood of obtaining preventative measures based on number of primary care visits compared with patients who had no primary care visits during the specified time period.

RESULTS
The likelihood of a patient receiving three specified preventative interventions was increased by 127% for vaccination, 122% for colonoscopy, and 75% for mammography if the patient had ≥ 1 primary care visit per year. More primary care visits correlated with increasing frequency of vaccinations, but increased primary care visits beyond one did not correlate with increasing frequency of mammography or colonoscopy.

CONCLUSIONS
One or more primary care visits per year is associated with increased likelihood of specific evidence-based preventative care interventions that improve longitudinal health outcomes and decrease healthcare costs. Increasing efforts to track and increase the number of primary care visits by clinics and health systems may improve patient compliance with select preventative measures.

Hostetter|Jeffrey|J|
Schwarz|Nolan|N|
Klug|Marilyn|M|
Wynne|Joshua|J|
Basson|Marc D|MD|0000-0001-9696-2789

Primary care
Vaccination
Colonoscopy
Mammography
Wellness visits


Evaluation of sperm nuclear integrity in patients with different percentages of decapitated sperm in ejaculates.

Abstract: The decapitated sperm defect is a rare type of teratozoospermia responsible for male infertility. Spermatozoa from patients affected by this syndrome are used for intracytoplasmic sperm injection (ICSI) although little is known about their DNA integrity. This study evaluated sperm nuclear alterations in four patients and ten fertile men (control group). Sperm samples were examined by light, transmission electron and high-magnification contrast microscopy and analysed after terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling, aniline blue staining and fluorescence in-situ hybridization. Spermatozoa from patients presented varying degrees of decapitation, along with morphological and ultrastructural head abnormalities. Whereas the proportion of spermatozoa with fragmented DNA and numerical chromosome abnormalities was similar in patients 1-3 and controls, the percentage of spermatozoa with hypocondensed chromatin was higher in patients 1-3 than in fertile men. Patient 4 presented a distinct phenotype, with an increased proportion of flagellated spermatozoa with DNA strand breaks as well as increased aneuploidy and diploidy rates compared with controls and with patients 1-3. No successful pregnancy resulted from ICSI although embryos were obtained for three patients. The morphological defects and the nuclear alterations observed in spermatozoa of patients with the decapitated sperm syndrome may have contributed to ICSI failures.

Rondanino|Christine|C| Duchesne|Véronique|V| Escalier|Denise|D| Jumeau|Fanny|F| Verhaeghe|France|F| Peers|Marie-Claire|MC| Mitchell|Valérie|V| Rives|Nathalie|N|

DNA fragmentation
aneuploidy rates
chromatin condensation
decapitated spermatozoa
sperm nucleus


Practice pattern of ileal pouch surveillance in academic medical centers in the United States.

Abstract:
OBJECTIVE
There is no consensus on whether, when and how to surveil an ileal pouch. The aims of this study were to evaluate experts' opinions and practice patterns on pouch surveillance and to determine if they were associated with detection of neoplasia.

METHODS
Eligible physicians were identified by searching the literature in MEDLINE and the physician list of the Crohn's and Colitis Foundation of America and surveying by questionnaire.

RESULTS
Fifty-two eligible participants from 32 tertiary institutions were identified. Forty-one physicians (79%) felt that surveillance pouchoscopy was necessary, and 36 (69%) believed that pouchoscopy with biopsy was effective for the detection of neoplasia. Great variation exists with regard to the frequency of surveillance pouchoscopy. Eighteen physicians (35%) reported the detection of a total of 4 pouch dysplasias and 15 pouch cancers within the previous 5 years. The follow-up number of ileal pouches per year was significantly higher in the neoplasia detection group (50 vs 25, P = 0.041). Those who reported detecting neoplasia took even fewer biopsies from the ileal pouch body during the pouchoscopy examination (>3 biopsies per location, 44% vs 82%, P = 0.005). Multivariable analysis showed that the number of patients with ileal pouches followed up per year was the only independent factor associated with the detection of pouch neoplasia (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.1-2.1; P = 0.005).

CONCLUSION
Most experts agree with performing pouchoscopy and biopsy for surveillance of ileal pouch neoplasia, although the optimal interval varies greatly. The detection of pouch neoplasia appears to be related to patient volume and physician experience.

Gu|Jinyu|J|
Remzi|Feza H|FH|
Lian|Lei|L|
Shen|Bo|B|

neoplasia
ileal pouch-anal anastomosis
restorative proctocolectomy
ulcerative colitis


Moderating effect of self-efficacy on the relation between behavior problems in persons with dementia and the distress they cause in caregivers.

Abstract:
INTRODUCTION
Behavioral and psychological symptoms in dementia (BPSD) are the principal sources of stress in caregivers. The aim of the present work is to analyze the moderating effect of self-efficacy for managing BPSD on the distress these problems generate in family caregivers.

METHOD
The participants were 231 family caregivers of people with dementia. We assessed the frequency and caregiver distress associated with three dimensions of BPSD (depressive, disruptive and memory problems). In addition, we assessed the moderating effect of self-efficacy for dealing with BPSD in the relationship between the dementia patient's frequency of BPSD and caregiver distress through hierarchical regression analyses, one for each of the dimensions of BPSD.

RESULTS
We found a moderating effect of self-efficacy on the relation between the frequency of BPSD and the distress in caregivers for the dimensions of depressive and disruptive behaviors. Caregivers having to deal with a high frequency of behavior problems but with high levels of self-efficacy presented significantly lower levels of distress associated with depressive and disruptive behavior problems compared to those caregivers with low levels of self-efficacy. No differences in the effects of self-efficacy were found for distress levels of caregivers who dealt with low frequency of BPSD. Also, we did not find a moderating effect of self-efficacy on the relation between the frequency of memory problems and caregivers' distress.

CONCLUSIONS
The results suggest that self-efficacy for managing BPSD attenuates the relation between the frequency of behavior problems – both disruptive and depressive – and the distress they cause in caregivers.

Nogales-González|C|C|
Romero-Moreno|R|R|
Losada|A|A|
Márquez-González|M|M|
Zarit|S H|SH|

D011569:Psychiatric Status Rating Scales

behavioral and psychological symptoms in dementia (BPSD)


Quantitative Assessment of Shotgun Metagenomics and 16S rDNA Amplicon Sequencing in the Study of Human Gut Microbiome.

Abstract: The analysis of microbiota composition in humans, animals, and built environments is important because of emerging roles and applications in a broad range of disease and ecological phenotypes. Next Generation Sequencing is the current method of choice to characterize microbial community composition. The taxonomic profile of a microbial community can be obtained either by shotgun analysis of random DNA fragments or through 16S ribosomal RNA gene (rDNA) amplicon sequencing. It has been previously shown that the 16S rDNA amplicon sequencing approach yields quantitatively and qualitatively different results compared to shotgun metagenomics when the two techniques are used to assess microbial community composition on the same samples. However, most of such comparisons were either based on the recovery of 16S rDNA sequences in the shotgun metagenomics data or limited to a single microbiome or synthetic samples. Direct comparison of shotgun metagenomics and 16S rDNA amplicon sequencing on the same samples was performed only once in the recent literature, suggesting that the two methods yield comparable results. Here, we set out to compare the outcome of these two alternative approaches to the microbiome characterization in human gut microbiomes from stool samples. To this end, we processed six different samples with both techniques. We report here that shotgun next generation sequencing metagenomics allows much deeper characterization of the microbiome complexity, allowing identification of a larger number of species for each sample, compared to 16S rDNA amplicon sequencing. Further comparative studies in independent samples are called for.

Laudadio|Ilaria|I| Fulci|Valerio|V| Palone|Francesca|F| Stronati|Laura|L| Cucchiara|Salvatore|S| Carissimi|Claudia|C|

shotgun metagenomics
metagenomics
16S rDNA amplicon sequencing
human gut microbiome
next generation sequencing
Crohn disease


Main nutrient patterns are associated with prospective weight change in adults from 10 European countries.

Abstract:
PURPOSE
Various food patterns have been associated with weight change in adults, but it is unknown which combinations of nutrients may account for such observations. We investigated associations between main nutrient patterns and prospective weight change in adults.

METHODS
This study includes 235,880 participants, 25-70 years old, recruited between 1992 and 2000 in 10 European countries. Intakes of 23 nutrients were estimated from country-specific validated dietary questionnaires using the harmonized EPIC Nutrient DataBase. Four nutrient patterns, explaining 67 % of the total variance of nutrient intakes, were previously identified from principal component analysis. Body weight was measured at recruitment and self-reported 5 years later. The relationship between nutrient patterns and annual weight change was examined separately for men and women using linear mixed models with random effect according to center controlling for confounders.

RESULTS
Mean weight gain was 460 g/year (SD 950) and 420 g/year (SD 940) for men and women, respectively. The annual differences in weight gain per one SD increase in the pattern scores were as follows: principal component (PC) 1, characterized by nutrients from plant food sources, was inversely associated with weight gain in men (-22 g/year; 95 % CI -33 to -10) and women (-18 g/year; 95 % CI -26 to -11). In contrast, PC4, characterized by protein, vitamin B2, phosphorus, and calcium, was associated with a weight gain of +41 g/year (95 % CI +2 to +80) and +88 g/year (95 % CI +36 to +140) in men and women, respectively. Associations with PC2, a pattern driven by many micro-nutrients, and with PC3, a pattern driven by vitamin D, were less consistent and/or non-significant.

CONCLUSIONS
We identified two main nutrient patterns that are associated with moderate but significant long-term differences in weight gain in adults.

Freisling|Heinz|H|
Pisa|Pedro T|PT|
Ferrari|Pietro|P|
Byrnes|Graham|G|
Moskal|Aurelie|A|
Dahm|Christina C|CC|
Vergnaud|Anne-Claire|AC|
Boutron-Ruault|Marie-Christine|MC|
Fagherazzi|Guy|G|
Cadeau|Claire|C|
Kühn|Tilman|T|
Neamat-Allah|Jasmine|J|
Buijsse|Brian|B|
Boeing|Heiner|H|
Halkjær|Jytte|J|
Tjonneland|Anne|A|
Hansen|Camilla P|CP|
Quirós|J Ramón|JR|
Travier|Noémie|N|
Molina-Montes|Esther|E|
Amiano|Pilar|P|
Huerta|José M|JM|
Barricarte|Aurelio|A|
Khaw|Kay-Tee|KT|
Wareham|Nicholas|N|
Key|Tim J|TJ|
Romaguera|Dora|D|
Lu|Yunxia|Y|
Lassale|Camille M|CM|
Naska|Androniki|A|
Orfanos|Philippos|P|
Trichopoulou|Antonia|A|
Masala|Giovanna|G|
Pala|Valeria|V|
Berrino|Franco|F|
Tumino|Rosario|R|
Ricceri|Fulvio|F|
de Magistris|Maria Santucci|MS|
Bueno-de-Mesquita|H Bas|HB|
Ocké|Marga C|MC|
Sonestedt|Emily|E|
Ericson|Ulrika|U|
Johansson|Mattias|M|
Skeie|Guri|G|
Weiderpass|Elisabete|E|
Braaten|Tonje|T|
Peeters|Petra H M|PH|
Slimani|Nadia|N|

Nutrients
Weight gain
Dietary patterns
Energy balance
Obesity
Public health


A neural classification method for supporting the creation of BioVerbNet.

Abstract:
BACKGROUND
VerbNet, an extensive computational verb lexicon for English, has proved useful for supporting a wide range of Natural Language Processing tasks requiring information about the behaviour and meaning of verbs. Biomedical text processing and mining could benefit from a similar resource. We take the first step towards the development of BioVerbNet: A VerbNet specifically aimed at describing verbs in the area of biomedicine. Because VerbNet-style classification is extremely time consuming, we start from a small manual classification of biomedical verbs and apply a state-of-the-art neural representation model, specifically developed for class-based optimization, to expand the classification with new verbs, using all the PubMed abstracts and the full articles in the PubMed Central Open Access subset as data.

RESULTS
Direct evaluation of the resulting classification against BioSimVerb (verb similarity judgement data in biomedicine) shows promising results when representation learning is performed using verb class-based contexts. Human validation by linguists and biologists reveals that the automatically expanded classification is highly accurate. Including novel, valid member verbs and classes, our method can be used to facilitate cost-effective development of BioVerbNet.

CONCLUSION
This work constitutes the first effort on applying a state-of-the-art architecture for neural representation learning to biomedical verb classification. While we discuss future optimization of the method, our promising results suggest that the automatic classification released with this article can be used to readily support application tasks in biomedicine.

Chiu|Billy|B|0000-0001-6683-3249 Majewska|Olga|O| Pyysalo|Sampo|S| Wey|Laura|L| Stenius|Ulla|U| Korhonen|Anna|A| Palmer|Martha|M|

D035843:Biomedical Research
D057225:Data Mining
D000069550:Machine Learning
D009323:Natural Language Processing
D039781:PubMed


Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial.

Abstract:
BACKGROUND AND OBJECTIVES
Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence.

STUDY DESIGN
Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs' cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage.

RESULTS
Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 [25.9%] vs. placebo, n = 22 [42%]); needed less additional medication, and had lower mortality (topiramate, n = 5 [9.2%] vs. placebo, n = 10 [19.2%]); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found.

CONCLUSIONS
Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.

Nuñez-Ramiro|Antonio|A|
Benavente-Fernández|Isabel|I|
Valverde|Eva|E|
Cordeiro|Malaika|M|
Blanco|Dorotea|D|
Boix|Hector|H|
Cabañas|Fernando|F|
Chaffanel|Mercedes|M|
Fernández-Colomer|Belén|B|
Fernández-Lorenzo|Jose Ramón|JR|
Kuligowski|Julia|J|
Loureiro|Begoña|B|
Moral-Pumarega|Maria Teresa|MT|
Pavón|Antonio|A|
Sánchez-Illana|Angel|A|
Tofé|Inés|I|
Hervás|David|D|
García-Robles|Ana|A|
Parra-Llorca|Anna|A|
Cernada|Maria|M|
Martinez-Rodilla|Juan|J|
Lorente-Pozo|Sheila|S|
Llorens|Roberto|R|
Marqués|Remedios|R|
Vento|Máximo|M|
|||

D003131:Combined Modality Therapy
D004311:Double-Blind Method
D005260:Female
D006801:Humans
D007036:Hypothermia, Induced
D020925:Hypoxia-Ischemia, Brain
D007231:Infant, Newborn
D016015:Logistic Models
D008279:Magnetic Resonance Imaging
D008297:Male
D018696:Neuroprotective Agents
D000077236:Topiramate

Hypoxic-ischemic encephalopathy
Seizures
Anaerobic metabolism
Hyperexcitability
Oxidative stress biomarkers


Multidisciplinary Clinics for Colorectal Cancer Care Reduces Treatment Time.

Abstract:
INTRODUCTION
Management of locally advanced and metastatic colorectal cancer (CRC) requires the expertise of multiple specialists. Multidisciplinary clinics (MDCs) are a working model designed to facilitate delivery of coordinated care. The present study evaluated the effects of MDC on the time to treatment (TTT).

PATIENTS AND METHODS
Patients with CRC or locally advanced anal cancer who were evaluated at a single-institution MDC from January 2014 to October 2015 were identified from an institutional registry. The clinical characteristics and timelines for various aspects of treatment were retrospectively reviewed and recorded. A control population of patients not evaluated at the MDC was matched 1:2 by disease and the number of treating specialties. The primary endpoints were the TTT from diagnosis and the TTT from the first consultation.

RESULTS
A total of 105 patients were included: 35 were evaluated at the MDC and 70 were controls. The MDC patients experienced a 7.8-day shorter TTT from the first consultation (21.5 vs. 29.3 days; P = .01). The difference was greater for patients visiting 3 departments (21.3 vs. 30.6 days; P < .001). Patients requiring neoadjuvant chemoradiation accounted for most of the decreased interval compared with those requiring surgery alone as their first treatment. The proportion of patients initiating treatment within 3 weeks from the first consultation was greater for those seen in the MDC (57.1% vs. 30% for controls; P = .01).

CONCLUSION
Implementation of a multidisciplinary CRC clinic yielded decreased intervals from the first consultation to treatment in our institution. Focusing efforts to increase MDC usage will improve treatment efficiency and improve patient access.

Kozak|Vanessa N|VN|
Khorana|Alok A|AA|
Amarnath|Sudha|S|
Glass|Katherine E|KE|
Kalady|Matthew F|MF|

Time to treatment
Colon cancer
Process improvement
Rectal cancer
Timely care


Activity dependent CAM cleavage and neurotransmission.

Abstract: Spatially localized proteolysis represents an elegant means by which neuronal activity dependent changes in synaptic structure, and thus experience dependent learning and memory, can be achieved. In vitro and in vivo studies suggest that matrix metalloproteinase and adamalysin activity is concentrated at the cell surface, and emerging evidence suggests that increased peri-synaptic expression, release and/or activation of these proteinases occurs with enhanced excitatory neurotransmission. Synaptically expressed cell adhesion molecules (CAMs) could therefore represent important targets for neuronal activity-dependent proteolysis. Several CAM subtypes are expressed at the synapse, and their cleavage can influence the efficacy of synaptic transmission through a variety of non-mutually exclusive mechanisms. In the following review, we discuss mechanisms that regulate neuronal activity-dependent synaptic CAM shedding, including those that may be calcium dependent. We also highlight CAM targets of activity-dependent proteolysis including neuroligin and intercellular adhesion molecule-5 (ICAM-5). We include discussion focused on potential consequences of synaptic CAM shedding, with an emphasis on interactions between soluble CAM cleavage products and specific pre- and post-synaptic receptors.

Conant|Katherine|K|
Allen|Megan|M|
Lim|Seung T|ST|

CAM
adhesion
MMP
dendritic spine
glutamate
metalloproteases


Anterior Cruciate Ligament Reconstruction with Hamstring Tendons Has no Deleterious Effect on Hip Extension Strength.

Abstract:
Background
Hamstring tendons are secondary hip extensors. Their harvest for graft in anterior cruciate ligament (ACL) reconstruction may create deleterious effect on hip extension strength. This is of particular importance in sports that need powerful hip extension force like climbing and sprinting. Due to scarcity of a comprehensive study in this area, we designed this prospective study to evaluate hip extension strength following ACL reconstruction using different types of grafts.

Methods
Fifty eight patients were enrolled in this prospective non-randomized case control study to compare isokinetic hip extension strength following ACL reconstruction with different graft types. Twenty patients in group A (both Semitendinosus and Gracilis tendons autograft (ST-G)), 14 patients in group B (Tibialis Posterior tendon allograft (Allograft)), 12 patients in group C (bone-patellar tendon-bone autograft (BPTB)) and 12 patients in group D (only semitendinosus autograft (ST)) were studied. Hip extension strength was tested post-operatively at three- and six-month periods using a Biodex isokinetic testing machine at a speed of 30 degree per second in operated (cases) and non-operated (controls) limbs.

Results
There was a significant increase in hip extension force between three and six month intervals in all four groups and in both operated (case) and non-operated (control) limbs (P<0.05, 95% CI). However, there was more increase in case limbs in comparison to control limbs. There was no significant difference in hip extension strength among all four groups (both in case and control limbs) in the third- and the sixth-month post-operative tests.

Conclusion
Graft type had no effect on hip extension strength following ACL reconstruction, and the harvest of one or both hamstrings had no deleterious effect on hip extension force.

Level of evidence
III.

Hadi|Hosseinali|H| Bagherifar|Abolfazl|A| Tayebi|Fereshte|F| Ansaria|Majid|M| Shahsavaripour|Ali|A| Qomashi|Iman|I| Jabalameli|Mahmoud|M|

Anterior cruciate ligament
Hip extension
Isokinetic testing


Temporal Change of the Content of 10 Oligosaccharides in the Milk of Chinese Urban Mothers.

Abstract: Breastfed infants tend to be less prone to infections and may have improved cognitive benefits compared to formula-fed infants. Human milk oligosaccharides (HMO) are the third most abundant component of human milk, but are absent from formulae. They may be partially responsible for the benefits of breastfeeding. In this cross-sectional observational study, the HMO composition of milk from Chinese mothers was studied to determine the impact of stage of lactation, mode of delivery and geographical location. The content of 10 HMO was measured by HPLC in 446 milk samples from mothers living in three different cities in China. Around 21% of the samples contained levels of 2'-fucosyllactose (2'-FL) below the limit of quantification, which is similar to the frequency of fucosyltransferase-2 non-secretors in other populations, but 2'-FL was detected in all samples. Levels of most of the HMO studied decreased during the course of lactation, but the level of 3-fucosyllactose increased. Levels of 2'-FL and 3-fucosyllactose seem to be strongly correlated, suggesting some sort of mechanism for co-regulation. Levels of 6'-sialyllactose were higher than those of 3'-sialyllactose at early stages of lactation, but beyond 2-4 months, 3'-sialyllactose was predominant. Neither mode of delivery nor geographical location had any impact on HMO composition.

Austin|Sean|S|
De Castro|Carlos A|CA|
Bénet|Thierry|T|
Hou|Yangfeng|Y|
Sun|Henan|H|
Thakkar|Sagar K|SK|
Vinyes-Pares|Gerard|G|
Zhang|Yumei|Y|
Wang|Peiyu|P|

D002851:Chromatography, High Pressure Liquid

human milk oligosaccharides
lactation
HPLC
fucosyllactose
lacto-N-fucosylpentaose
lacto-N-neotetraose
lacto-N-tetraose
sialyllactose


Intraplantar injection of tetrahydrobiopterin induces nociception in mice.

Abstract: Tetrahydrobiopterin (BH4) is implicated in the development and maintenance of chronic pain. After injury/inflammation, the biosynthesis of BH4 is markedly increased in sensory neurons, and the pharmacological and genetic inhibition of BH4 shows analgesic effects in pre-clinical animal pain models. Intrathecal injections of BH4 have been shown to induce and enhance pain-like behaviours in rats, suggesting that under chronic pain conditions BH4 may act by facilitating central sensitisation. So far it is unknown whether BH4 acts on peripheral sites of the somatosensory system or whether BH4 per se provokes nociceptive pain behaviours. The purpose of this study was therefore to investigate the acute nociceptive effects of intraplantar injection of BH4. BH4 was found to induce dose-dependent licking/biting of the paw lasting 5 min, which was not observed following an injection of biopterin (inactive BH4 metabolite). Paw swelling, measured as paw thickness and weight, was not observed after BH4 injection. To explore possible mechanisms of action of BH4, the effect of local pre-treatment with indomethacin, Nω-nitro-L-arginine methyl ester, Nω-nitro-L-arginine, capsazepine and ruthenium red was tested. Morphine served as a positive control. Intraplantar pre-injection of morphine dose-dependently inhibited BH4-induced nociception, while none of the other compounds showed any statistical significant antinociception. These results suggest that BH4 exhibits nociceptive properties at peripheral sites of the somatosensory system, proposing an as yet unexplored involvement of BH4 in peripheral nociceptive processes. However, this appears not to be mediated through nitric oxide and prostaglandin release or by activation of the transient receptor potential vanilloid 1.

Nasser|Arafat|A|
Ali|Sawsan|S|
Wilsbech|Signe|S|
Bjerrum|Ole J|OJ|
Møller|Lisbeth B|LB|

BH4
Pain
Mouse behaviour
Nitric oxide inhibition
PGE(2) inhibition
TRPV1 antagonists


Des-Arg9-bradykinin causes kinin B1 receptor mediated endothelium-independent contractions in endotoxin-treated porcine coronary arteries.

Abstract: This study examined responses of isolated pig coronary arteries after kinin B1 receptor induction by endotoxin. Des-Arg9-bradykinin (DBK) induced concentration-dependent, endothelium-independent contractions in lipopolysaccharide (LPS)-treated but not untreated arterial rings. The B1-receptor antagonist SSR240612, but not the B2-receptor antagonist HOE140, prevented the endothelium-independent contractions to DBK. The DBK-induced contractions were blocked by indomethacin (nonselective cyclooxygenase [COX] inhibitor), celecoxib (selective COX-2 inhibitor), and terbogrel (thromboxane-prostanoid [TP] receptor antagonist) but not valeryl salicylate (selective COX-1 inhibitor), AH6809 (an E prostanoid [EP] and PGD2 receptor [DP1] receptor antagonist), AL 8810 (a selective PGF2α [FP] receptor antagonist), or RO1138452 (a selective I prostanoid [IP] receptor antagonist). They were attenuated by N-(p-amylcinnamoyl) anthranilic acid (ACA), and by DETCA plus tiron but not by l-NAME. Quantitative RT-PCR revealed excessive up-regulations of mRNA expressions of B1 receptors, COX-2, and thromboxane A synthase 1 (TBXAS1) following LPS incubation, but not of B2 receptors or COX-1. The present data demonstrate that B1 receptors are coupled to COX-2 in causing endothelium-independent contractions in endotoxin-treated pig coronary arteries. Accordingly, kinin B1 receptor induction during inflammation may have a pathological significance in the vasculature, particular in coronary arteries with dysfunctional endothelial cells.

More|Amar S|AS|
Kim|Hye Min|HM|
Khang|Gilson|G|
Hildebrandt|Tobias|T|
Bernlöhr|Christian|C|
Doods|Henri|H|
Vanhoutte|Paul M|PM|
Wu|Dongmei|D|

D065169:Bradykinin B1 Receptor Antagonists

Kinin B1 receptor
Cyclooxygenase-2
Vascular contraction
Vascular inflammation


Nicotine deprivation elevates neural representation of smoking-related cues in object-sensitive visual cortex: a proof of concept study.

Abstract:
OBJECTIVE
In the current study, we use functional magnetic resonance imaging (fMRI) and multi-voxel pattern analysis (MVPA) to investigate whether tobacco addiction biases basic visual processing in favour of smoking-related images. We hypothesize that the neural representation of smoking-related stimuli in the lateral occipital complex (LOC) is elevated after a period of nicotine deprivation compared to a satiated state, but that this is not the case for object categories unrelated to smoking.

METHODS
Current smokers (≥10 cigarettes a day) underwent two fMRI scanning sessions: one after 10 h of nicotine abstinence and the other one after smoking ad libitum. Regional blood oxygenated level-dependent (BOLD) response was measured while participants were presented with 24 blocks of 8 colour-matched pictures of cigarettes, pencils or chairs. The functional data of 10 participants were analysed through a pattern classification approach.

RESULTS
In bilateral LOC clusters, the classifier was able to discriminate between patterns of activity elicited by visually similar smoking-related (cigarettes) and neutral objects (pencils) above empirically estimated chance levels only during deprivation (mean = 61.0%, chance (permutations) = 50.0%, p = .01) but not during satiation (mean = 53.5%, chance (permutations) = 49.9%, ns.). For all other stimulus contrasts, there was no difference in discriminability between the deprived and satiated conditions.

CONCLUSION
The discriminability between smoking and non-smoking visual objects was elevated in object-selective brain region LOC after a period of nicotine abstinence. This indicates that attention bias likely affects basic visual object processing.

Nicotine deprivation
Lateral occipital complex
Pattern classification
Attention bias
Smoking cues


"Technoference" and Implications for Mothers' and Fathers' Couple and Coparenting Relationship Quality.

Abstract: Technology devices are widely used today, creating opportunities to connect and communicate with distant others while also potentially disrupting communication and interactions between those who are physically present (i.e., technoference or phubbing). These disruptions in couple and coparenting relationships have the potential to negatively impact relationship outcomes. In this two-part study of 182 married/cohabiting couples from the Daily Family Life Project and 239 couples from the Couple Well-Being Project, we examined the role of technoference in couple and coparenting relationship quality and potential gender differences utilizing dyadic data. We found that greater technoference related to greater conflict over technology use, and greater conflict predicted lower relationship satisfaction and poorer perceptions of coparenting quality (Study 1). Using a more diverse sample (Study 2), we again found support for the main pathways tested in our first study, suggesting that results found in Study 1 and in previous work are not artifacts of sampling. As satisfaction, support, and agreement among relationship partners and parents are often critical to relationship health and family cohesion, it is important for couples and families to evaluate, monitor, and be willing to adapt their technology usage patterns so that these patterns do not cause conflict and possibly relationship deterioration over time.

McDaniel|Brandon T|BT|
Galovan|Adam M|AM|
Cravens|Jaclyn D|JD|
Drouin|Michelle|M|

coparenting
relationship quality
couple relationships
media use
phone addiction
smartphones


Controlling persister cells of Pseudomonas aeruginosa PDO300 by (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one.

Abstract: Pseudomonas aeruginosa is a major pathogen causing chronic pulmonary infections; for example, 80% of cystic fibrosis patients get infected by this bacterium as the disease progresses. Such chronic infections are challenging because P. aeruginosa exhibits high-level tolerance to antibiotics by forming biofilms (multicellular structures attached to surfaces), by entering dormancy and forming antibiotic tolerant persister cells, and by conversion to the mucoid phenotype. Recently, we reported that a synthetic quorum sensing inhibitor, (Z)-4-bromo-5-(bromomethylene)-3-methylfuran-2(5H)-one (BF8), can sensitize both planktonic and biofilm-associated persister cells of P. aeruginosa PAO1 to antibiotics at the concentrations non-inhibitory to its growth. In this study, we further characterized the effects of this compound on the mucoid strain P. aeruginosa PDO300. BF8 was found to reduce persistence during the growth of PDO300 and effectively kill the persister cells isolated from PDO300 cultures. In addition to planktonic cells, BF8 was also found to inhibit biofilm formation of PDO300 and reduce associated persistence. These findings broaden the activities of this class of compounds and indicate that BF8 also has other targets in P. aeruginosa in addition to quorum sensing.

D015107:4-Butyrolactone
D000900:Anti-Bacterial Agents
D018441:Biofilms
D004361:Drug Tolerance
D015394:Molecular Structure
D011550:Pseudomonas aeruginosa
D053038:Quorum Sensing

Persister
Pseudomonas aeruginosa
Biofilm
Antibiotic tolerance
Mucoid
Quorum sensing


Chronic kidney disease and neurological disorders: are uraemic toxins the missing piece of the puzzle?

Abstract: Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.

Liabeuf|Sophie|S|0000-0001-5384-9006
Pepin|Marion|M|
Franssen|Casper F M|CFM|
Viggiano|Davide|D|
Carriazo|Sol|S|0000-0002-6697-5279
Gansevoort|Ron T|RT|
Gesualdo|Loreto|L|
Hafez|Gaye|G|0000-0002-0837-634X
Malyszko|Jolanta|J|
Mayer|Christopher|C|
Nitsch|Dorothea|D|
Ortiz|Alberto|A|0000-0002-9805-9523
Pešić|Vesna|V|
Wiecek|Andrzej|A|
Massy|Ziad A|ZA|
|||

uraemic toxins
CKD
cardiovascular
indoxyl sulphate
stroke


Simulation on different response characteristics of aerosol particle number concentration and mass concentration to emission changes over mainland China.

Abstract:
In this study, Nested Air Quality Prediction Modeling System with Advance Particle Microphysics module (NAQPMS+APM) is applied to simulate the response characteristics of aerosol particle number concentration and mass concentration to emission changes over mainland China. It is the first attempt to investigate the response of both aerosol mass concentration and number concentration to emission changes using a chemical transport model with detailed aerosol microphysics over mainland China. Results indicate that the response characteristics are obviously different between aerosol particle number concentration and mass concentration. Generally, the response of number concentration shows a more heterogeneous spatial distribution than that of mass concentration. Furthermore, number concentration has a higher sensitivity not only to primary particles emission but also to precursor gases than that of mass concentration. Aerosol particle mass concentration exhibits a consistent trend with the emission change and yet aerosol number concentration does not. Due to the nonlinearity of aerosol microphysical processes, reduction of primary particles emission does not necessarily lead to an obvious decrease of aerosol number concentration and it even increases the aerosol number concentration. Over Central-Eastern China (CEC), the most polluted regions in China, reducing primary particles emission rather than precursor gas emissions is more effective in reducing particles number concentration. By contrast, the opposite is true over the northwestern China. The features of fine particles pollution revealed in this study are associated with the spatial differences in China's population, geography, climate and economy. Considering the more adverse effects of ultrafine particles on human health and the spatial distribution of population, making different measures in controlling particles number concentration from that controlling mass concentration in different regions over mainland China is indicated.

MAIN FINDINGS
FPN concentration responds more heterogeneously to emission than FPM. Spatial difference of response of FPN to emission is distinguished by a boundary line.

Chen|Xueshun|X| Wang|Zifa|Z| Li|Jie|J| Yang|Wenyi|W| Chen|Huansheng|H| Wang|Zhe|Z| Hao|Jianqi|J| Ge|Baozhu|B| Wang|Dawei|D| Huang|Huili|H|

Number concentration
Mass concentration
Emission change
NAQPMS+APM
Aerosol microphysics


32 Years of Ultrasonic-Assisted Lipoplasty (U.A.L.): From Aesthetic to Obesity.

Abstract: In this article, we tried to take stock of the state of the art in ultrasonic-assisted lipoplasty focusing on its most recent technologic advances and in the newest clinical applications, such as overweight, obesity, breast surgery and regenerative medicine. Great space was devoted to the analysis and clarification of the most common myths and legends related to this intriguing technique.

Zocchi|Michele L|ML|
Vindigni|Vincenzo|V|
Bassetto|Franco|F|

Obesity
Adipose-derived stem cells (ADSCs)
Liposuction (SAL)
Ultrasonic mega lipoplasty (UML)
Ultrasonic-assisted lipoplasty (UAL)


The signs of ocular-surface disorders after switching from latanoprost to tafluprost/timolol fixed combination: a prospective study.

Abstract:
PURPOSE
To evaluate the ocular-surface safety of a 0.001% benzalkonium chloride-containing tafluprost/timolol fixed combination (TTFC) in patients with primary open-angle glaucoma (POAG) or ocular hypertension who have inadequate intraocular pressure (IOP) control with latanoprost monotherapy.

METHODS
This study is a multicenter, prospective, single-arm, open-label clinical study. Patients with POAG or ocular hypertension who have inadequate IOP control with latanoprost monotherapy were considered eligible. After providing informed consent, patients continued latanoprost monotherapy for 12 weeks, followed by a switch to TTFC. We evaluated the extent of ocular-surface damage using superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), hyperemia score, IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate at 0, 4, and 12 weeks after switching.

RESULTS
A total of 68 patients were enrolled, of whom, 64 patients were included in the final analysis. No significant changes in SPK score, TBUT, or hyperemia score were observed at 4 and 12 weeks compared with week 0. IOP decreased significantly at 4 (13.9±2.5 mmHg) and 12 (14.1±2.5 mmHg) weeks, relative to week 0 (15.3±2.7 mmHg). No significant changes in either SBP or DBP were observed during the study, although patients' mean heart rate decreased significantly after switching to TTFC. Adverse drug reactions to TTFC occurred in seven patients including two incidences of asthma and one of arrhythmia, and no events were serious.

CONCLUSION
The ocular-surface safety of TTFC is not significantly different to that of latanoprost. Furthermore, switching from latanoprost to TTFC in patients with insufficient IOP control has additive IOP-lowering effects. TTFC is an effective approach for patients receiving latanoprost monotherapy who require more intensive IOP reduction.

Okumichi|Hideaki|H| Kiuchi|Yoshiaki|Y| Baba|Tetsuya|T| Kanamoto|Takashi|T| Naito|Tomoko|T| Nakakura|Shunsuke|S| Tabuchi|Hitoshi|H| Nii|Hiroki|H| Sueoka|Chie|C| Sugimoto|Yosuke|Y|

latanoprost
tafluprost/timolol fixed combination
ocular-surface safety
glaucoma
intraocular pressure


Leptin activates cytosolic calcium responses through protein kinase-C dependent mechanism in immortalized RFamide-related peptide-3 neurons.

Abstract: RFamide-related peptide-3 (RFRP-3), a mammalian ortholog of avian gonadotropin-inhibitory hormone (GnIH), seems to be an important regulator of the hypothalamus-pituitary-gonadal (HPG) reproductive axis. Leptin, a permissive hormonal regulator of fertility, provides energy signal to brain. According to current view, leptin does not act directly on gonadotrophin-releasing hormone (GnRH) neurons. RFRP-3 neurons have been shown to express leptin receptors. The goal of the present study was to examine whether leptin acts through RFRP-3 neurons to modulate activity of the GnRH neurons. For this aim, the effects of leptin on intracellular free Ca(2+) levels ([Ca(2+)]i) in RFRP-3 neurons were investigated by using in vitro calcium imaging system. In the present study, rHypoE-7 cell line was used as a model to explore the effects of leptin on RFRP-3 neurons. rHypoE-7 cells were placed on glass coverslip and loaded with 1 μM Fura-2 AM. [Ca(2+)]i responses were quantified by the changes in 340/380 ratio. Leptin (0.1-10 μM) caused increases in [Ca(2+)]i in a dose-dependent manner. The changes in [Ca(2+)]i were significantly attenuated by pre-treatment with protein kinase C inhibitor. These results demonstrate that leptin activates intracellular calcium signaling in RFRP-3 neurons through PKC-dependent pathway, and thus leptin may exert its effect on GnRH neurons by means of RFRP-3 cells.

Ozcan|Mete|M| Saatci|Tugrul|T| Ayar|Ahmet|A| Canpolat|Sinan|S| Kelestimur|Haluk|H|

Leptin
Protein kinase-C
RFamide-related peptide-3 neurons
Calcium signaling


Left Ventricular Remodeling in Patients with Primary Aldosteronism: A Prospective Cardiac Magnetic Resonance Imaging Study.

Abstract:
OBJECTIVE
This study used cardiac magnetic resonance imaging (MRI) to compare the characteristics of left ventricular remodeling in patients with primary aldosteronism (PA) with those of patients with essential hypertension (EH) and healthy controls (HCs).

MATERIALS AND METHODS
This prospective study enrolled 35 patients with PA, in addition to 35 age- and sex-matched patients with EH, and 35 age- and sex-matched HCs, all of whom underwent comprehensive clinical and cardiac MRI examinations. The analysis of variance was used to detect the differences in the characteristics of left ventricular remodeling among the three groups. Univariable and multivariable linear regression analyses were used to determine the relationships between left ventricular remodeling and the physiological variables.

RESULTS
The left ventricular end-diastolic volume index (EDVi) (mean ± standard deviation [SD]: 85.1 ± 13.0 mL/m² for PA, 75.9 ± 14.3 mL/m² for EH, and 77.3 ± 12.8 mL/m² for HC; p = 0.010), left ventricular end-systolic volume index (ESVi) (mean ± SD: 35.2 ± 9.8 mL/m² for PA, 30.7 ± 8.1 mL/m² for EH, and 29.5 ± 7.0 mL/m² for HC; p = 0.013), left ventricular mass index (mean ± SD: 65.8 ± 16.5 g/m² for PA, 56.9 ± 12.1 g/m² for EH, and 44.1 ± 8.9 g/m² for HC; p < 0.001), and native T1 (mean ± SD: 1224 ± 39 ms for PA, 1201 ± 47 ms for EH, and 1200 ± 44 ms for HC; p = 0.041) values were higher in the PA group compared to the EH and HC groups. Multivariable linear regression demonstrated that log (plasma aldosterone-to-renin ratio) was independently correlated with EDVi and ESVi. Plasma aldosterone was independently correlated with native T1.

CONCLUSION
Patients with PA showed a greater degree of ventricular hypertrophy and enlargement, as well as myocardial fibrosis, compared to those with EH. Cardiac MRI T1 mapping can detect left ventricular myocardial fibrosis in patients with PA.

Ventricular remodeling
Magnetic resonance imaging
Essential hypertension
Hyperaldosteronism


Slow climate mode reconciles historical and model-based estimates of climate sensitivity.

Abstract: The latest Intergovernmental Panel on Climate Change Assessment Report widened the equilibrium climate sensitivity (ECS) range from 2° to 4.5°C to an updated range of 1.5° to 4.5°C in order to account for the lack of consensus between estimates based on models and historical observations. The historical ECS estimates range from 1.5° to 3°C and are derived assuming a linear radiative response to warming. A Bayesian methodology applied to 24 models, however, documents curvature in the radiative response to warming from an evolving contribution of interannual to centennial modes of radiative response. Centennial modes display stronger amplifying feedbacks and ultimately contribute 28 to 68% (90% credible interval) of equilibrium warming, yet they comprise only 1 to 7% of current warming. Accounting for these unresolved centennial contributions brings historical records into agreement with model-derived ECS estimates.

Climate Sensitivity
Bayesian Inference
Climate Feedbacks
Radiative Forcing


Redox regulation of soluble guanylyl cyclase.

Abstract: The nitric oxide/soluble guanylyl cyclase (NO-sGC) signaling pathway regulates the cardiovascular, neuronal, and gastrointestinal systems. Impaired sGC signaling can result in disease and system-wide organ failure. This review seeks to examine the redox control of sGC through heme and cysteine regulation while discussing therapeutic drugs that target various conditions. Heme regulation involves mechanisms of insertion of the heme moiety into the sGC protein, the molecules and proteins that control switching between the oxidized (Fe3+) and reduced states (Fe2+), and the activity of heme degradation. Modifications to cysteine residues by S-nitrosation on the α1 and β1 subunits of sGC have been shown to be important in sGC signaling. Moreover, redox balance and localization of sGC is thought to control downstream effects. In response to altered sGC activity due to changes in the redox state, many therapeutic drugs have been developed to target decreased NO-sGC signaling. The importance and relevance of sGC continues to grow as sGC dysregulation leads to numerous disease conditions.

Shah|Rohan C|RC|
Sanker|Subramaniam|S|
Wood|Katherine C|KC|
Durgin|Brittany G|BG|
Straub|Adam C|AC|

Redox
Soluble guanylyl cyclase
Heme
Therapeutics
Localization
Thiol


How specific is too specific? B-cell responses to viral infections reveal the importance of breadth over depth.

Abstract: Influenza virus infection induces robust and highly protective B-cell responses. Knowledge gained from the analysis of such protective humoral responses can provide important clues for the design of successful vaccines and vaccination approaches and also provides a window into the regulation of fundamental aspects of B-cell responses that may not be at play when responses to non-replicating agents are studied. Here, I review features of the B-cell response to viruses, with emphasis on influenza virus infection, a highly localized infection of respiratory tract epithelial cells, and a response that is directed against a virus that continuously undergoes genetic changes to its surface spike protein, a major target of neutralizing antibodies. Two aspects of the B-cell response to influenza are discussed here, namely polyreactive natural antibodies and the role and function of germinal center responses. Both these features of the B-cell response raise the question of how important antibody fine-specificity is for long-term protection from infection. As outlined, the pathogenesis of influenza virus and the nature of the antiviral B-cell response seem to emphasize repertoire diversity over affinity maturation as driving forces behind the influenza-specific B-cell immunity.

germinal centers
B-1 cells
antibody repertoire
antiviral immunity
extrafollicular foci
plasma cells


Translating stem cell research to cardiac disease therapies: pitfalls and prospects for improvement.

Abstract: Over the past 2 decades, there have been numerous stem cell studies focused on cardiac diseases, ranging from proof-of-concept to phase 2 trials. This series of papers focuses on the legacy of these studies and the outlook for future treatment of cardiac diseases with stem cell therapies. The first section by Drs. Rosen and Myerburg is an independent review that analyzes the basic science and translational strategies supporting the rapid advance of stem cell technology to the clinic, the philosophies behind them, trial designs, and means for going forward that may impact favorably on progress. The second and third sections were collected as responses to the initial section of this review. The commentary by Drs. Francis and Cole discusses the review by Drs. Rosen and Myerburg and details how trial outcomes can be affected by noise, poor trial design (particularly the absence of blinding), and normal human tendencies toward optimism and denial. The final, independent paper by Dr. Marbán takes a different perspective concerning the potential for positive impact of stem cell research applied to heart disease and future prospects for its clinical application. (Compiled by the JACC editors).

Rosen|Michael R|MR|
Myerburg|Robert J|RJ|
Francis|Darrel P|DP|
Cole|Graham D|GD|
Marbán|Eduardo|E|

stem cell research
heart diseases
cell-based therapy
research design
stem cell transplantation
tissue-based therapy


The three-dimensional structure and recognition mechanism of Manduca sexta peptidoglycan recognition protein-1.

Abstract: Peptidoglycan recognition proteins (PGRPs) recognize bacteria through their unique cell wall constituent, peptidoglycans (PGs). PGRPs are conserved from insects to mammals and all function in antibacterial defense. In the tobacco hornworm Manduca sexta, PGRP1 and microbe binding protein (MBP) interact with PGs and hemolymph protease-14 precursor (proHP14) to yield active HP14. HP14 triggers a serine protease network that produces active phenoloxidase (PO), Spätzle, and other cytokines to stimulate immune responses. PGRP1 binds preferentially to diaminopimelic acid (DAP)-PGs of Gram-negative bacteria and Gram-positive Bacillus and Clostridium species than Lys-PGs of other Gram-positive bacteria. In this study, we synthesized DAP- and Lys-muramyl pentapeptide (MPP) and monitored their associations with M. sexta PGRP1 by surface plasmon resonance. The Kd values (0.57 μM for DAP-MPP and 45.6 μM for Lys-MPP) agree with the differential recognition of DAP- and Lys-PGs. To reveal its structural basis, we produced the PGRP1 in insect cells and determined its structure at a resolution of 2.1 Å. The protein adopts a fold similar to those from other PGRPs with a classical L-shaped PG-binding groove. A unique loop lining the shallow groove suggests a different ligand-binding mechanism. In summary, this study provided new insights into the PG recognition by PGRPs, a critical first step that initiates the serine protease cascade.

Hu|Yingxia|Y| Cao|Xiaolong|X| Li|Xiuru|X| Wang|Yang|Y| Boons|Geert-Jan|GJ| Deng|Junpeng|J| Jiang|Haobo|H|

D000818:Animals
D002352:Carrier Proteins
D019476:Insect Proteins
D018402:Manduca
D062105:Molecular Docking Simulation
D010457:Peptidoglycan
D017433:Protein Structure, Secondary
D051192:Receptors, Pattern Recognition
D020349:Surface Plasmon Resonance

Serine protease
Hemolymph protein
Insect immunity
Melanization
Pattern recognition
Prophenoloxidase activation