Analysis of 21 X-chromosome polymorphisms in urban and rural populations in Salta province (north-western Argentina).

Abstract: Population genetic data for 21 X-chromosome markers (Alu insertions and STRs) are reported for two populations (rural and urban) in Salta province (north-western Argentina). New variants are described, confirming the complexity and variability of some markers in this set. Results reveal Salta populations harbor a high Native American component, despite their self-recognized European ancestry. Notwithstanding the high genetic similarity of both populations, the rural sample seems to have maintained a larger Amerindian legacy. Data further show these X-linked markers, especially STRs, are highly informative in Salta populations and, therefore, can contribute to the development of a local database for forensic purposes in north-western Argentina.

Ferragut|J F|JF|
Bassitta|M|M|
Torrens|V|V|
Albeza|V|V|
Acreche|N|N|
Castro|J A|JA|
Ramon|C|C|
Picornell|A|A|

D001118:Argentina
D041321:Chromosomes, Human, X
D005787:Gene Frequency
D014644:Genetic Variation
D005828:Genetics, Population
D006801:Humans
D007199:Indians, South American
D011110:Polymorphism, Genetic
D012424:Rural Population
D014505:Urban Population

X-chromosome
Salta
Alu insertions
Calchaqui Valleys
Investigator Argus X-12 kit
North-western Argentina (NWA)
X-STR


Biodegradable, Flexible, and Transparent Conducting Silver Nanowires/Polylactide Film with High Performance for Optoelectronic Devices.

Abstract: As a synthetic renewable and biodegradable material, the application of polylactide (PLA) in the green flexible electronics has attracted intensive attention due to the increasingly serious issue of electronic waste. Unfortunately, the development of PLA-based optoelectronic devices is greatly hindered by the poor heat resistance and mechanical property of PLA. To overcome these limitations, herein, we report a facile and promising route to fabricate silver nanowires/PLA (AgNW/PLA) film with largely improved properties by utilizing the stereocomplex (SC) crystallization between poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA). Through embedding the AgNW networks into the PLLA:PDLA blend matrix via a transfer method, the AgNW/PLLA:PDLA film with both high transparency and excellent conductivity was obtained. Compared with the AgNW/PLLA film, the formation of SC crystallites in the composites matrix could significantly enhance not only heat resistance but also mechanical strength of the AgNW/PLLA:PDLA film. Exceptionally, the AgNW/PLLA:PDLA film exhibited superior flexibility and could maintain excellent electrical conductivity stability even under the condition of 10,000 repeated bending cycles and 100 tape test cycles. In addition, the organic light-emitting diodes (OLEDs) with the AgNW/PLLA:PDLA films as electrodes were successfully fabricated in this work for the first time and they exhibited highly flexible, luminous, as well as hydrolytic degradation properties. This work could provide a low-cost and environment-friendly avenue towards fabricating high-performanced PLA-based biodegradable electronics.

Wang|Junjun|J| Yu|Junsheng|J|0000-0002-7484-8114 Bai|Dongyu|D|0000-0003-4647-217X Li|Zhuobin|Z| Liu|Huili|H| Li|Ying|Y|0000-0003-2343-0233 Chen|Shanyong|S| Cheng|Jiang|J| Li|Lu|L|

silver nanowires
polylactide
stereocomplex
green optoelectronic devices


Neuropeptide Localization in Lymnaea stagnalis: From the Central Nervous System to Subcellular Compartments.

Abstract: Due to the relatively small number of neurons (few tens of thousands), the well-established multipurpose model organism Lymnaea stagnalis, great pond snail, has been extensively used to study the functioning of the nervous system. Unlike the more complex brains of higher organisms, L. stagnalis has a relatively simple central nervous system (CNS) with well-defined circuits (e.g., feeding, locomotion, learning, and memory) and identified individual neurons (e.g., cerebral giant cell, CGC), which generate behavioral patterns. Accumulating information from electrophysiological experiments maps the network of neuronal connections and the neuronal circuits responsible for basic life functions. Chemical signaling between synaptic-coupled neurons is underpinned by neurotransmitters and neuropeptides. This review looks at the rapidly expanding contributions of mass spectrometry (MS) to neuropeptide discovery and identification at different granularity of CNS organization. Abundances and distributions of neuropeptides in the whole CNS, eleven interconnected ganglia, neuronal clusters, single neurons, and subcellular compartments are captured by MS imaging and single cell analysis techniques. Combining neuropeptide expression and electrophysiological data, and aided by genomic and transcriptomic information, the molecular basis of CNS-controlled biological functions is increasingly revealed.

Wood|Ellen A|EA|
Stopka|Sylwia A|SA|
Zhang|Linwen|L|
Mattson|Sara|S|
Maasz|Gabor|G|
Pirger|Zsolt|Z|
Vertes|Akos|A|

neuropeptide
Lymnaea stagnalis
central nervous system
mass spectrometry
single neuron analysis


Propensity score weighting for a continuous exposure with multilevel data.

Abstract: Propensity score methods (e.g., matching, weighting, subclassification) provide a statistical approach for balancing dissimilar exposure groups on baseline covariates. These methods were developed in the context of data with no hierarchical structure or clustering. Yet in many applications the data have a clustered structure that is of substantive importance, such as when individuals are nested within healthcare providers or within schools. Recent work has extended propensity score methods to a multilevel setting, primarily focusing on binary exposures. In this paper, we focus on propensity score weighting for a continuous, rather than binary, exposure in a multilevel setting. Using simulations, we compare several specifications of the propensity score: a random effects model, a fixed effects model, and a single-level model. Additionally, our simulations compare the performance of marginal versus cluster-mean stabilized propensity score weights. In our results, regression specifications that accounted for the multilevel structure reduced bias, particularly when cluster-level confounders were omitted. Furthermore, cluster mean weights outperformed marginal weights.

Schuler|Megan S|MS|
Chu|Wanghuan|W|
Coffman|Donna|D|

propensity score
continuous exposure
multilevel data
observational study


iHIVARNA phase IIa, a randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of iHIVARNA-01 in chronically HIV-infected patients under stable combined antiretroviral therapy.

Abstract:
BACKGROUND
HIV therapeutic vaccination aims to improve the immune responses against HIV in order to control viral replication without the need for combined antiretroviral therapy (cART). iHIVARNA-01 is a novel vaccine combining mRNA delivery and T-cell immunogen (HTI) based on conserved targets of effective antiviral T-cell responses. In addition, it holds adequate stimuli required for activating antigen presenting cells (APC)s and co-activating specific T-cells (TriMix), including human CD40L, constitutively active TLR4 (caTLR4) and CD70. We propose that in-vivo targeting of dendritic cells (DCs) by direct administration of a HIV mRNA encoding these immune modulating proteins might be an attractive alternative to target DCs in vitro.

METHODS/DESIGN
This is a phase-IIa, randomized, double-blinded, placebo-controlled, multicenter study in chronically HIV-1 infected patients under stable cART. One of the three study arms is randomly allocated to subjects. Three vaccinations with either HIVACAT T-cell immunogen (HTI)-TriMix (iHIVARNA-01), TriMix or water for injection (WFI) (weeks 0, 2 and 4) are administered by intranodal injection in the inguinal region. Two weeks after the last immunization (week 6) cART is stopped for 12 weeks. The two primary endpoints are: (1) safety and tolerability of intranodal iHIVARNA-01 vaccination compared with TriMix or WFI and (2) induced immunogenicity, i.e., increase in the frequency of HIV-specific T-cell responses between baseline, week 6 and 12 weeks after treatment interruption in iHIVARNA-01-treated patients as compared to the control groups, immunized with TriMix-mRNA or WFI measured by an IFNγ ELISPOT assay. Secondary endpoints include the evaluation of time to viral rebound, plasma viral load (pVL) at w18, the proportion of patients with control of viral load, induction of T-cell responses to new HIV epitopes, polyfunctionality of HIV-specific T-cells, CD8+ T-cell in-vitro HIV suppressive capacity, the effect on viral reservoir (measured by proviral DNA and cell-associated RNA), assessment of viral immune escape by mutation and mRNA expression profiles of host immune genes.

DISCUSSION
This trial aims to direct target DC in situ with mRNA encoding HTI and TriMix for co-stimulation. Intranodal injection circumvents laborious DC isolation and handling in the laboratory. The trial extends on the safety results of a phase-I dose-escalating trial. This candidate vaccine could complement or even replace cART for chronic HIV infection and could be applicable to improve the care and cost of HIV infection.

TRIAL REGISTRATION
EudraCT 2016-002724-83 (22 September 2016); ClinicalTrials.gov, ID: NCT02888756 . Registered on 23 August 2016.

D016915:AIDS Vaccines
D019380:Anti-HIV Agents
D002908:Chronic Disease
D003713:Dendritic Cells
D004311:Double-Blind Method
D015658:HIV Infections
D006801:Humans
D008213:Lymphocyte Activation
D012333:RNA, Messenger
D013601:T-Lymphocytes
D014611:Vaccination

Therapeutic vaccine
TriMix
HIV-1
Reservoir
Antigen-presenting cell
Functional cure
Immunotherapy
Lymph node


Effect of yoga on chronic non-specific neck pain: An unconditional growth model.

Abstract:
OBJECTIVE
Chronic neck pain is a common problem that affects approximately half of the population. Conventional treatments such as medication and exercise have shown limited analgesic effects. This analysis is based on an original study that was conducted to investigate the physical and behavioral effects of a 9-week Iyengar yoga course on chronic non-specific neck pain. This secondary analysis uses linear mixed models to investigate the individual trajectories of pain intensity in participants before, during and after the Iyengar yoga course.

METHOD
Participants with chronic non-specific neck pain were selected for the study. The participants suffered from neck pain for at least 5 days per week for at least the preceding 3 months, with a mean neck pain intensity (NPI) of 40 mm or more on a Visual Analog Scale of 100 mm. The participants were randomized to either a yoga group (23) or to a self-directed exercise group (24). The mean age of the participants in the yoga group was 46, and ranged from 19 to 59. The participants in the yoga group participated in an Iyengar yoga program designed to treat chronic non-specific neck pain. Our current analysis only includes participants who were initially randomized into the yoga group. The average weekly neck pain intensity at baseline, during and post intervention, comprising 11 total time points, was used to construct the growth models. We performed a step-up linear mixed model analysis to investigate change in NPI during the yoga intervention. We fit nested models using restricted maximum-likelihood estimation (REML), tested fixed effects with Wald test p-values and random effects with the likelihood ratio test. We constructed 10 REML models.

RESULTS
The model that fit the data best was an unconditional random quadratic growth model, with a first-order auto-regressive structure specified for the residual R matrix. Participants in the yoga group showed significant variation in NPI. They demonstrated variation in their intercepts, in their linear rates of change, and most tellingly, in their quadratic rates of change.

CONCLUSIONS
While all participants benefitted from the yoga intervention, the degree to which they benefitted varied. Additionally, they did not experience a consistent rate of reduction in NPI - their NPI fluctuated, either increasing and then decreasing, or vice-versa. We comment on the clinical and research implications of our findings.

Allende|Santiago|S| Anandan|Anita|A| Lauche|Romy|R| Cramer|Holger|H|

D016032:Randomized Controlled Trials as Topic

Yoga
Neck pain
Pain
Growth model
Linear mixed model
Mixed model
Longitudinal
Mixed procedure
Randomized trial
Repeated measures
Unconditional growth curve model
Variance components model


Genetic Variants Associated with Cancer Pain and Response to Opioid Analgesics: Implications for Precision Pain Management.

Abstract:
OBJECTIVE
To review the current knowledge on the association of genetic variants with cancer pain.

DATA SOURCES
Data-based publications and review articles retrieved from PubMed, CINAHL, and Web of Science, as well as an additional search in Google Scholar.

CONCLUSION
Genetic variability can influence differential pain perception and response to opioids in cancer patients, which will have implications in the optimal personalized treatment of cancer pain. More studies are warranted to replicate findings.

IMPLICATIONS FOR NURSING PRACTICE
Nurses are poised to educate patients on biomarker testing and interpretation and to use precision pain management strategies based on this information.

Yang|Gee Su|GS|
Barnes|Natalie M|NM|
Lyon|Debra E|DE|
Dorsey|Susan G|SG|

D000701:Analgesics, Opioid
D000072716:Cancer Pain
D014644:Genetic Variation
D006801:Humans
D009369:Neoplasms
D059408:Pain Management
D057285:Precision Medicine

Genetic variant
Cancer
Pain
Biomarker
Genetic polymorphism
Precision medicine


Why equal treatment is not always equitable: the impact of existing ethnic health inequalities in cost-effectiveness modeling.

Abstract:
BACKGROUND
A critical first step toward incorporating equity into cost-effectiveness analyses is to appropriately model interventions by population subgroups. In this paper we use a standardized treatment intervention to examine the impact of using ethnic-specific (Māori and non-Māori) data in cost-utility analyses for three cancers.

METHODS
We estimate gains in health-adjusted life years (HALYs) for a simple intervention (20% reduction in excess cancer mortality) for lung, female breast, and colon cancers, using Markov modeling. Base models include ethnic-specific cancer incidence with other parameters either turned off or set to non-Māori levels for both groups. Subsequent models add ethnic-specific cancer survival, morbidity, and life expectancy. Costs include intervention and downstream health system costs.

RESULTS
For the three cancers, including existing inequalities in background parameters (population mortality and comorbidities) for Māori attributes less value to a year of life saved compared to non-Māori and lowers the relative health gains for Māori. In contrast, ethnic inequalities in cancer parameters have less predictable effects. Despite Māori having higher excess mortality from all three cancers, modeled health gains for Māori were less from the lung cancer intervention than for non-Māori but higher for the breast and colon interventions.

CONCLUSIONS
Cost-effectiveness modeling is a useful tool in the prioritization of health services. But there are important (and sometimes counterintuitive) implications of including ethnic-specific background and disease parameters. In order to avoid perpetuating existing ethnic inequalities in health, such analyses should be undertaken with care.

McLeod|Melissa|M| Blakely|Tony|T| Kvizhinadze|Giorgi|G| Harris|Ricci|R|

Ethnicity
Equity
Māori
Cost effectiveness
Heterogeneity
New Zealand


Otolaryngology consultation tracheostomies and complex patient population.

Abstract:
PURPOSE
To assess for the differences in patients undergoing tracheostomy by the otolaryngology consult service versus other specialties.

MATERIALS AND METHODS
A series of 1035 tracheostomies performed at our institution from January 2013 through November 2015 was retrospectively reviewed. Patient-related factors that contribute to procedural difficulty were reviewed.

RESULTS
805 consecutive tracheostomies were included. Otolaryngology performed 176/805 (21.8%) tracheostomies as a consulting service. Morbidly obese patients were three times as likely to be referred to otolaryngology as other services (adjusted OR: 3.23; 95% CI: 2.21-4.72). Mean BMI was 36.38kg/m2 for Consults vs. 28.69kg/m2 for Others and morbidly obese patients had a mean BMI of 49.84kg/m2 vs. 42.68kg/m2 for Consults and Others respectively (p<0.001). Patients with upper airway compromise (8.5% of Consults vs. 1.6% for Others) had 5.5 times higher odds to be performed by otolaryngology (adjusted OR: 5.46; 95% CI: 2.24-13.28). Otolaryngology performed 81.8% of awake tracheostomies (n=9/11). There were significantly higher proportions of patients with diabetes, renal, pulmonary and cardiovascular disease in the Consults groups vs. Others (p<0.05).

CONCLUSIONS
More complex tracheostomies are being referred to and performed by otolaryngology at our institution. Difficult and challenging tracheostomies seem to be the "standard" for otolaryngologists.

Alfonso|Kristan P|KP|
Kaufman|Michael R|MR|
Dressler|Emily V|EV|
Liu|Meng|M|
Aouad|Rony K|RK|

Otolaryngology
Awake tracheostomy
Comorbidities
Morbid obesity
Open tracheostomy
Percutaneous tracheostomy


Effect of anemia on hepatotoxicity of HAART in HIV patients in Benin city.

Abstract:
BACKGROUND
Hepatotoxicity is a relevant adverse effect of highly active antiretroviral Treatment owing to its frequency, and it can cause interruption of therapy, hepatitis, and death. There is dearth of information on hepatotoxicity arising from highly active antiretroviral therapy (HAART) in anemic patients. Anemia is the most common symptom in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. We studied the effect of anemia on hepatotoxicity in HIV patients who were about to start HAART, attending clinic, or in the medical wards.

MATERIALS AND METHODS
This was a prospective study in which patients were recruited consecutively and followed up for 24 weeks.

RESULTS
In all, 84 patients were recruited and 42 were enrolled as controls. The mean ages of the cases and controls were 35.2±9.9 and 35.5±9.0 years, respectively. The age range of the cases was 18-68 years with a median age of 31.5 years, whereas the mean age of the controls was 20-57 years with a median age of 33.5 years. There was no difference (t=0.197, df=124, and P=0.844). There were 61 females (72.6%) and 23 males (27.4%) in the cases, whereas in the controls, there were 34 females (81.0%) and 8 males (19.0%). Among the cases, 30 (35.7%) were anemic, while 54 (64.3%) were not anemic. Six (20%) of the anemic patients had hepatotoxicity, and 9 (16.7%) of the patients with normal packed cell volume had hepatotoxicity. Among the controls, all 42 (100%) patients had normal packed cell volume. Four (9.5%) of the patients had hepatotoxicity. There was no association between hepatotoxicity and anemia (χ(2) =3.243, df=2, P=0.198).

CONCLUSION
Anemia did not affect hepatotoxicity of HAART in this study.

hepatotoxicity of highly active antiretroviral treatment


Proanthocyanidin protects against acute zearalenone-induced testicular oxidative damage in male mice.

Abstract: Zearalenone (ZEN) exerts a major effect on human and animal health and has led to serious worldwide economic problems. In this study, we investigated whether proanthocyanidin (PC) can prevent ZEN-induced testicular oxidative damage in male mice and explored the underlying mechanism. Kunming mice were injected with ZEN (40 mg kg-1) on the 11th day after intragastric administration of PC (75 or 150 mg/kg) for 10 days; the sperm quality of mice was then analysed statistically. Additionally, testicular morphology parameters related to oxidative damage, apoptosis and the expression of endoplasmic reticulum (ER) stress-related genes (GRP78, CHOP and XBP-1) were all measured. Results showed that ZEN exposure significantly reduced the sperm density, improved the sperm aberration rate, increased the MDA level and reduced SOD and GSH-Px activities. Meanwhile, ZEN was attributed to the downregulation of the expressions of the gene and protein of Bcl-2 and upregulation of the expressions of the gene and protein of Bax and caspase-3. ZEN exposure also upregulated the mRNA expression of GRP78, CHOP and XBP-1; however, PC pre-treatment reduced ZEN-induced oxidative damage and tended to maintain normal testicular morphology. Furthermore, PC pre-treatment substantially downregulated the expressions of the GRP78, CHOP and XBP-1 and upregulated the expression of the Bcl-2 gene. In conclusion, PC, due to its anti-oxidative ability, could ameliorate ZEN-induced testicular reproductive toxicity in male mice by decreasing ER stress and testicular cell apoptosis.

Long|Miao|M| Yang|Shuhua|S| Zhang|Yi|Y| Li|Peng|P| Han|Jianxin|J| Dong|Shuang|S| Chen|Xinliang|X| He|Jianbin|J|

D000091342:Endoplasmic Reticulum Chaperone BiP

Proanthocyanidin
Oxidative damage
Apoptosis
Mice testis
Zearaleone


Growth hormone receptor antagonism with pegvisomant in insulin resistant non-diabetic men: A phase II pilot study.

Abstract: Background: Growth hormone (GH) is known to affect insulin and glucose metabolism.  Blocking its effects in acromegalic patients improves diabetes and glucose metabolism. We aimed to determine the effect of pegvisomant, a GH receptor antagonist, on insulin resistance, endogenous glucose production (EGP) and lipolysis in insulin resistant non-diabetic men.  Methods: Four men between the ages of 18-62 with a BMI of 18-35kg/m 2, with insulin resistance as defined by a HOMA-IR > 2.77, were treated for four weeks with pegvisomant 20 mg daily.  Inpatient metabolic assessments were performed before and after treatment. The main outcome measurements were: change after pegvisomant therapy in insulin sensitivity as measured by hyperinsulinemic euglycemic clamp; and EGP and lipolysis assessed by stable isotope tracer techniques. Results: Insulin like growth factor-1 (IGF-1) concentrations decreased from 134.0 ± 41.5 (mean ± SD) to 72.0 ± 11.7 ng/mL (p = 0.04) after 4 weeks of therapy. Whole body insulin sensitivity index (M/I 3.2 ± 1.3 vs. 3.4 ± 2.4; P = 0.82), as well as suppression of EGP (89.7 ± 26.9 vs. 83.5 ± 21.6%; p = 0.10) and Ra glycerol (59.4 ± 22.1% vs. 61.2 ± 14.4%; p = 0.67) during the clamp were not changed significantly with pegvisomant treatment. Conclusions: Blockade of the GH receptor with pegvisomant for four weeks had no significant effect on insulin/glucose metabolism in a small phase II pilot study of non-diabetic insulin resistant participants without acromegaly.

Lee|Ada P|AP|
Mulligan|Kathleen|K|
Schambelan|Morris|M|
Murphy|Elizabeth J|EJ|
Weiss|Ethan J|EJ|0000-0001-9936-5816

Growth Hormone
Pegvisomant
Insulin resistance
Metabolism
Prediabetes


Effects of temperature and feeding frequency on ingestion and growth for rare minnow.

Abstract: Water temperature and feeding frequency are two important components in feeding strategy that directly affect the growth and physiology of fishes. The rare minnow (Gobiocypris rarus) has been cultured for decades in the laboratory as an experimental fish and is widely used in environmental science research. An 8-week factorial feeding experiment was conducted on juvenile rare minnows to investigate the interaction between water temperature (ambient, 20, 24, 28°C) and feeding frequency (one, two, three meals per day) on growth performance, feed utilization, gut evacuation and adaptability to variable environmental conditions. Groups fed three times a day at 28°C attained the maximum final body weight, followed by those fed two times a day at 24°C. There was an obvious curvilinear relationship between specific growth rate and temperature. Increased temperature significantly promoted food consumption and growth rate, but there were no benefits on growth by feeding multiple times at temperatures of 18°C or lower. Temperature and feeding frequency also affected gut evacuation rates: high temperature and frequency lead to fast evacuation. These results show that the optimal temperature and feeding frequency for rare minnow is 24°C and two meals a day for maximal growth, feeding efficiency, and daily management. The findings also suggest that the rare minnow has the ability to rapidly adapt to changing culture conditions by adjusting physiological activities in the short term.

Temperature
Feeding frequency
Growth
Rare minnow (Gobiocypris rarus)
Evacuation


Low Cost MR Compatible Haptic Stimulation with Application to fMRI Neurofeedback.

Abstract: The most common feedback displays in the fMRI environment are visual, e.g., in which participants try to increase or decrease the level of a thermometer. However, haptic feedback is increasingly valued in computer interaction tasks, particularly for real-time fMRI feedback. fMRI-neurofeedback is a clinical intervention that has not yet taken advantage of this trend. Here we describe a low-cost, user-friendly, MR-compatible system that can provide graded haptic vibrotactile stimulation in an initial application to fMRI neurofeedback. We also present a feasibility demonstration showing that we could successfully set up the system and obtain data in the context of a neurofeedback paradigm. We conclude that vibrotactile stimulation using this low-cost system is a viable method of feedback presentation, and encourage neurofeedback researchers to incorporate this type of feedback into their studies.

Young|Kymberly D|KD|
Prause|Nicole|N|
Lazzaro|Sarah|S|
Siegle|Greg J|GJ|

haptic
fMRI neurofeedback
amygdala
vibration


Adaptation to Chronic Nutritional Stress Leads to Reduced Dependence on Microbiota in Drosophila melanogaster.

Abstract: Numerous studies have shown that animal nutrition is tightly linked to gut microbiota, especially under nutritional stress. In Drosophila melanogaster, microbiota are known to promote juvenile growth, development, and survival on poor diets, mainly through enhanced digestion leading to changes in hormonal signaling. Here, we show that this reliance on microbiota is greatly reduced in replicated Drosophila populations that became genetically adapted to a poor larval diet in the course of over 170 generations of experimental evolution. Protein and polysaccharide digestion in these poor-diet-adapted populations became much less dependent on colonization with microbiota. This was accompanied by changes in expression levels of dFOXO transcription factor, a key regulator of cell growth and survival, and many of its targets. These evolutionary changes in the expression of dFOXO targets to a large degree mimic the response of the same genes to microbiota, suggesting that the evolutionary adaptation to poor diet acted on mechanisms that normally mediate the response to microbiota. Our study suggests that some metazoans have retained the evolutionary potential to adapt their physiology such that association with microbiota may become optional rather than essential.IMPORTANCE Animals depend on gut microbiota for various metabolic tasks, particularly under conditions of nutritional stress, a relationship usually regarded as an inherent aspect of animal physiology. Here, we use experimental evolution in fly populations to show that the degree of host dependence on microbiota can substantially and rapidly change as the host population evolves in response to poor diet. Our results suggest that, although microbiota may initially greatly facilitate coping with suboptimal diets, chronic nutritional stress experienced over multiple generations leads to evolutionary adaptation in physiology and gut digestive properties that reduces dependence on the microbiota for growth and survival. Thus, despite its ancient evolutionary history, the reliance of animal hosts on their microbial partners can be surprisingly flexible and may be relaxed by short-term evolution.

Erkosar|Berra|B|
Kolly|Sylvain|S|
van der Meer|Jan R|JR|
Kawecki|Tadeusz J|TJ|

D000824:Animal Nutritional Physiological Phenomena

adaptation
nutritional stress
microbiota
Drosophila
digestion
experimental evolution
dFOXO
juvenile development


Clerodane diterpenoids from Scutellaria formosana with inhibitory effects on NO production and interactions with iNOS protein.

Abstract: A phytochemical study on Scutellaria formosana afforded five previously undescribed spiro-diterpenoids, scutellapenes A-E. The structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of these compounds were established by the time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Scutellapenes B-E possess a spiro-diterpenoid skeleton. All of the compounds showed inhibitory effects on LPS-induced nitric oxide (NO) production in murine microglial BV-2 cells. The further molecular docking studies revealed that these bioactive compounds had strong interactions with the iNOS protein.

Wang|Peixia|P| Liu|Feng|F| Yang|Xueyuan|X| Liang|Yue|Y| Li|Shen|S| Su|Guochen|G| Jin|Da-Qing|DQ| Ohizumi|Yasushi|Y| Xu|Jing|J| Guo|Yuanqiang|Y|

Scutellaria formosana
iNOS
Spiro-diterpenoids
Molecular docking
Labiatae
NO inhibitors


Biomimetic Water-Responsive Self-Healing Epoxy with Tunable Properties.

Abstract: As dynamic cross-linking networks are intrinsically weaker than permanent covalent networks, it is a big challenge to obtain a stiff self-healing polymer using reversible networks. Inspired by the self-healable and mechanically adaptive nature of sea cucumber, we design a water-responsive self-healing polymer system with reversible and permanent covalent networks by cross-linking poly(propylene glycol) with boroxine and epoxy. This double cross-linked structure is self-healing due to the boroxine reversible network as well as showing a room-temperature tensile modulus of 1059 MPa and a tensile stress of 37 MPa, on a par with classic thermosets. The dynamic boroxine bonds provide the self-healing response and enable up to 80% recovery in modulus and tensile strength upon water contact. The system shows superior adhesion to metal substrates by comparison with the commercial epoxy-based structural adhesive. Besides, this system can change modulus from a stiff thermoset to soft rubber (by a factor of 150) upon water stimulus, enabling potential applications of either direct or transform printing for micro/nanofabrication. Moreover, by incorporating conductive nanofillers, it becomes feasible to fabricate self-healing and versatile strain/stress sensors based on a single thermoset, with potential applications in wearable electronics for human healthcare.

water-responsive
self-healing
epoxy
boroxine
strain sensors


Survey of Leptospira spp. and Brucella abortus in Free-Ranging Armadillos from Pantanal, Brazil.

Abstract: Out of the 20 recognized species of armadillos in the world, 11 are found in Brazil, and five of them are found in Pantanal, one of the world's largest wetlands. Beef cattle (Bos taurus) farming is the main economic activity in this region, which promotes intense wildlife-livestock contact and increases the likelihood of pathogen exposure, including to agents with zoonotic and economic relevance. Previous studies demonstrated that several wildlife species in Pantanal have been exposed to Brucella abortus and Leptospira spp.; however, little is known regarding the exposure and/or prevalence of zoonotic pathogens in armadillos. We used conventional PCR, the rose Bengal test (RBT), and the microscopic agglutination test (MAT) to investigate the exposure to and infection by Brucella spp. and Leptospira spp. using blood samples from four species of armadillos: nine-banded armadillo (Dasypus novemcinctus, n=2), southern naked-tailed armadillo (Cabassous unicinctus, n=8), yellow armadillo (Euphractus sexcinctus, n=16), and giant armadillo (Priodontes maximus, n=22), captured in Nhecolândia, Pantanal, Brazil. Samples were PCR- and RBT-negative for Brucella spp. infection and exposure. However, MAT revealed a Leptospira spp. seroprevalence of 31% (5/16; 95% confidence interval [CI]=0.11-0.58) in yellow armadillo and 18% (4/22; 95% CI=0.05-0.40) in giant armadillo specimens to serogroups Autumnalis, Cynopteri, and Pomona, with titers ranging from 200 to 1,600. Our results contribute to the understanding of zoonotic pathogens in armadillos in Pantanal and reinforce the importance of wildlife health surveillance in this area.

Dalazen|Gislaine Taimara|GT|
de Souza Filho|Antonio Francisco|AF|
Sanchez Sarmiento|Angélica Maria|AM|
Fuentes-Castillo|Danny|D|
Gattamorta|Marco Aurélio|MA|
Kluyber|Danilo|D|
Jean Desbiez|Arnaud Léonard|AL|
Heinemann|Marcos Bryan|MB|
Matushima|Eliana Reiko|ER|

Dasypus novemcinctus
Cabassous unicinctus
Euphractus sexcinctus
Priodontes maximus
Nhecolândia
Cingulata
Xenarthra


Towards fast and reliable simultaneous EEG-fMRI analysis of epilepsy with automatic spike detection.

Abstract:
OBJECTIVE
The process of manually marking up epileptic spikes for simultaneous electroencephalogram (EEG) and resting state functional MRI (rsfMRI) analysis in epilepsy studies is a tedious and subjective task for a human expert. The aim of this study was to evaluate whether automatic EEG spike detection can facilitate EEG-rsfMRI analysis, and to assess its potential as a clinical tool in epilepsy.

METHODS
We implemented a fast algorithm for detection of uniform interictal epileptiform discharges (IEDs) in one-hour scalp EEG recordings of 19 refractory focal epilepsy datasets (from 16 patients) who underwent a simultaneous EEG-rsfMRI recording. Our method was based on matched filtering of an IED template (derived from human markup) used to automatically detect other 'similar' EEG events. We compared simultaneous EEG-rsfMRI results between automatic IED detection and standard analysis with human EEG markup only.

RESULTS
In contrast to human markup, automatic IED detection takes a much shorter time to detect IEDs and export an output text file containing spike timings. In 13/19 focal epilepsy datasets, statistical EEG-rsfMRI maps based on automatic spike detection method were comparable with human markup, and in 6/19 focal epilepsy cases automatic spike detection revealed additional brain regions not seen with human EEG markup. Additional events detected by our automated method independently revealed similar patterns of activation to a human markup. Overall, automatic IED detection provides greater statistical power in EEG-rsfMRI analysis compared to human markup in a short timeframe.

CONCLUSIONS
Automatic spike detection is a simple and fast method that can reproduce comparable and, in some cases, even superior results compared to the common practice of manual EEG markup in EEG-rsfMRI analysis of epilepsy.

SIGNIFICANCE
Our study shows that IED detection algorithms can be effectively used in epilepsy clinical settings. This work further helps in translating EEG-rsfMRI research into a fast, reliable and easy-to-use clinical tool for epileptologists.

Omidvarnia|Amir|A|
Kowalczyk|Magdalena A|MA|
Pedersen|Mangor|M|
Jackson|Graeme D|GD|

Spike detection
EEG
Focal epilepsy
Matched filtering
Interictal discharge
fMRI


Nanogels as potential nanomedicine carrier for treatment of cancer: A mini review of the state of the art.

Abstract: Nanogels are being explored as drug delivery agents for targeting cancer due to their easy tailoring properties and ability to efficiently encapsulate therapeutics of diverse nature through simple mechanisms. Nanogels are proficiently internalized by the target cells, avoid accumulating in nontarget tissues thereby lower the therapeutic dosage and minimize harmful side effects. However, there is an urgent need for relevant clinical data from nanogels so as to allow translation of the nanogel concept into a viable therapeutic application for the treatment of cancer. This review highlights some of the recent progress in nanogels as a carrier in the field of nanomedicine for the treatment of cancer. The present review critically analyzes the use of extracellular pH targeting for nanogels, siRNA delivery, PEGylated nanogels, multi-responsive nanogels and intracellular delivery of nanogels for improved therapy of cancer.

siRNA
PEGylated nanogels
Intracellular delivery
Nanogel carriers
Stimuli-responsive nanogels
Tumor extracellular pH targeting


Sequence symmetry analysis in pharmacovigilance and pharmacoepidemiologic studies.

Abstract: Sequence symmetry analysis (SSA) is a method for detecting adverse drug events by utilizing computerized claims data. The method has been increasingly used to investigate safety concerns of medications and as a pharmacovigilance tool to identify unsuspected side effects. Validation studies have indicated that SSA has moderate sensitivity and high specificity and has robust performance. In this review we present the conceptual framework of SSA and discuss advantages and potential pitfalls of the method in practice. SSA is based on analyzing the sequences of medications; if one medication (drug B) is more often initiated after another medication (drug A) than before, it may be an indication of an adverse effect of drug A. The main advantage of the method is that it requires a minimal dataset and is computationally efficient. By design, SSA controls time-constant confounders. However, the validity of SSA may be affected by time-varying confounders, as well as by time trends in the occurrence of exposure or outcome events. Trend effects may be adjusted by modeling the expected sequence ratio in the absence of a true association. There is a potential for false positive or negative results and careful consideration should be given to potential sources of bias when interpreting the results of SSA studies.

Lai|Edward Chia-Cheng|EC|
Pratt|Nicole|N|
Hsieh|Cheng-Yang|CY|
Lin|Swu-Jane|SJ|
Pottegård|Anton|A|
Roughead|Elizabeth E|EE|
Kao Yang|Yea-Huei|YH|
Hallas|Jesper|J|

D016907:Adverse Drug Reaction Reporting Systems

D064420:Drug-Related Side Effects and Adverse Reactions

Sequence symmetry analysis
Pharmacovigilance
Pharmacoepidemiology
Case-based design
Self-control method
Signal detection


Structural basis for loading and inhibition of a bacterial T6SS phospholipase effector by the VgrG spike.

Abstract: The bacterial type VI secretion system (T6SS) is a macromolecular machine that injects effectors into prokaryotic and eukaryotic cells. The mode of action of the T6SS is similar to contractile phages: the contraction of a sheath structure pushes a tube topped by a spike into target cells. Effectors are loaded onto the spike or confined into the tube. In enteroaggregative Escherichia coli, the Tle1 phospholipase binds the C-terminal extension of the VgrG trimeric spike. Here, we purify the VgrG-Tle1 complex and show that a VgrG trimer binds three Tle1 monomers and inhibits their activity. Using covalent cross-linking coupled to high-resolution mass spectrometry, we provide information on the sites of contact and further identify the requirement for a Tle1 N-terminal secretion sequence in complex formation. Finally, we report the 2.6-Å-resolution cryo-electron microscopy tri-dimensional structure of the (VgrG)3 -(Tle1)3 complex revealing how the effector binds its cargo, and how VgrG inhibits Tle1 phospholipase activity. The inhibition of Tle1 phospholipase activity once bound to VgrG suggests that Tle1 dissociation from VgrG is required upon delivery.

D004926:Escherichia coli
D029968:Escherichia coli Proteins
D010740:Phospholipases
D000069376:Type VI Secretion Systems

type VI secretion system
cryo-electron microscopy
bacterial competition
bacterial toxin
protein secretion


Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson's disease: historical overview and future prospects.

Abstract: Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro-Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987, we detected PREP activity in human cerebrospinal fluid (CSF) using highly sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl-coumarin amide as a new synthetic substrate, and found a marked decrease in its activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) as compared with its level in control patients without neurological diseases. In 2013, Hannula et al. found co-localization of PREP with α-synuclein in the postmortem PD brain. Several recent studies also suggest that the level of PREP in the brain of PD patients may be related to dopamine (DA) cell death via promotion of α-synuclein oligomerization and that inhibitors of PREP may play a neuroprotective role in PD. Although the relationship between another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II) and dipeptidyl peptidase IV (DPP IV), and α-synuclein in the PD brain is not yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was significantly increased in PD patients. This review discusses the possibility of PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.

Dipeptidyl peptidase II/dipeptidyl peptidase IV ratio


Assessing the Multivariate Relationship between the Human Infant Intestinal Exfoliated Cell Transcriptome (Exfoliome) and Microbiome in Response to Diet.

Abstract: Gut microbiota and the host exist in a mutualistic relationship, with the functional composition of the microbiota strongly influencing the health and well-being of the host. In addition to the standard differential expression analysis of host genes to assess the complex cross-talk between environment (diet), microbiome, and host intestinal physiology, data-driven integrative approaches are needed to identify potential biomarkers of both host genes and microbial communities that characterize these interactions. Our findings demonstrate that the complementary application of univariate differential gene expression analysis and multivariate approaches such as sparse Canonical Correlation Analysis (sCCA) and sparse Principal Components Analysis (sPCA) can be used to integrate data from both the healthy infant gut microbial community and host transcriptome (exfoliome) using stool derived exfoliated cells shed from the gut. These approaches reveal host genes and microbial functional categories related to the feeding phenotype of the infants. Our findings also confirm that combinatorial noninvasive -omic approaches provide an integrative genomics-based perspective of neonatal host-gut microbiome interactions.

infant
exfoliome
microbiota
sparse canonical correlation analysis
sparse principal components analysis
breast milk


Lying to patients with dementia: Attitudes versus behaviours in nurses.

Abstract:
BACKGROUND
Using lies, in dementia care, reveals a common practice far beyond the diagnosis and prognosis, extending to the entire care process.

OBJECTIVES
In this article, we report results about the attitude and the behaviour of nurses towards the use of lies to patients with dementia.

RESEARCH DESIGN
An epidemiological cross-sectional study was conducted between September 2016 and February 2017 in 12 elderly residential facilities and in the geriatric, psychiatric and neurological wards of six specialised hospitals of Italy's Campania Region.

PARTICIPANTS
In all, 106 nurses compiled an attitude questionnaire (A) where the main question was 'Do you think it is ethically acceptable to use lies to patients with dementia?', instead 106 nurses compiled a behaviour questionnaire (B), where the main question was 'Have you ever used lies to patients with dementia?'

ETHICAL CONSIDERATIONS
Using lies in dementia care, although topic ethically still controversial, reveals a common practice far beyond the diagnosis and prognosis, extending to the entire care process.

FINDINGS
Only a small percentage of the interviewed nurses stated that they never used lies/that it is never acceptable to use lies (behaviour 10.4% and attitude 12.3%; p = 0.66). The situation in which nurses were more oriented to use lies was 'to prevent or reduce aggressive behaviors'. Indeed, only the 6.7% in the attitude group and 3.8% in the behaviour group were against using lies. On the contrary, the case in which the nurses were less oriented to use lies was 'to avoid wasting time giving explanations', in this situation were against using lies the 51.0% of the behaviour group and the 44.6% of the attitude group.

CONCLUSION
Our results, according to other studies, support the hypothesis of a low propensity of nurses to ethical reflection about use of lies. In our country, the implementation of guidelines about a correct use of lie in the relationship between health operators and patients would be desirable.

Cantone|Daniela|D|
Attena|Francesco|F|
Cerrone|Sabrina|S|
Fabozzi|Antonio|A|
Rossiello|Riccardo|R|
Spagnoli|Laura|L|
Pelullo|Concetta Paola|CP|


COVID-19 is spatial: Ensuring that mobile Big Data is used for social good.

Abstract: The mobility restrictions related to COVID-19 pandemic have resulted in the biggest disruption to individual mobilities in modern times. The crisis is clearly spatial in nature, and examining the geographical aspect is important in understanding the broad implications of the pandemic. The avalanche of mobile Big Data makes it possible to study the spatial effects of the crisis with spatiotemporal detail at the national and global scales. However, the current crisis also highlights serious limitations in the readiness to take the advantage of mobile Big Data for social good, both within and beyond the interests of health sector. We propose two strategical pathways for the future use of mobile Big Data for societal impact assessment, addressing access to both raw mobile Big Data as well as aggregated data products. Both pathways require careful considerations of privacy issues, harmonized and transparent methodologies, and attention to the representativeness, reliability and continuity of data. The goal is to be better prepared to use mobile Big Data in future crises.

mobile phone data, social media data, privacy


An analysis of deep vein thrombosis in burn patients (part II): A randomized and controlled study of thrombo-prophylaxis with low molecular weight heparin.

Abstract:
INTRODUCTION
Morbidity and mortality from venous thrombo-embolism (VTE) remains a significant problem for trauma and medical patients and there are established guidelines for prophylaxis in these patients. However, the efficacy and safety of VTE prophylaxis in thermally injured patients continue to be elusive as it has never been studied in a prospective, randomized fashion. Selective use of VTE prophylaxis, for high risk patients, is practiced by some burn units even if objective evidence is lacking for majority of risk factors enunciated in burn patients. Differing demographics and wound management techniques are other confounding factors mandating more prospective studies to evaluate the need and role of chemoprophylaxis for deep vein thrombosis (DVT) prevention in burn patients. Ours is the first prospective, randomized, controlled study which seeks to identify risk factors for DVT in our patients, and evaluate the role of routine chemoprophylaxis and its complications.

METHODS
The study design (sample size, inclusion/exclusion criteria, randomization, methodology and statistical methods) is detailed in part-1 of this two part manuscript.

RESULTS
Doppler ultrasound (DUS) identified DVT in four out of 50 patients (8% incidence) forming the control group. DVT was not detected in any of the patients on prophylaxis (0% incidence). This difference was found to be statistically significant (p value-0.021). Patients with DVT had significantly higher %TBSA, prolonged immobility and a longer duration of stay as compared to patients without DVT in the control group. Only one patient on enoxaparin prophylaxis developed mild epistaxis which resolved spontaneously. Fifteen patients died during the study out of which two had DVT but none showed autopsy evidence of pulmonary embolism.

CONCLUSION
With a moderate risk of developing DVT (8%) and a complication rate of only 2% with chemoprophylaxis, we feel that routine prophylaxis has the potential to decrease the incidence of VTE, without associated complications, in the moderate to high risk category.

Ahuja|Rajeev B|RB|
Bansal|Priya|P|
Pradhan|Gaurav S|GS|
Subberwal|Manju|M|

Deep vein thrombosis
DVT in burns
DVT prophylaxis


Breakthrough Infections of SARS-CoV-2 Gamma Variant in Fully Vaccinated Gold Miners, French Guiana, 2021.

Abstract: An outbreak of severe acute respiratory syndrome coronavirus 2 caused by the Gamma variant of concern infected 24/44 (55%) employees of a gold mine in French Guiana (87% symptomatic, no severe forms). The attack rate was 60% (15/25) among fully vaccinated miners and 75% (3/4) among unvaccinated miners without a history of infection.

Vignier|Nicolas|N| Bérot|Vincent|V| Bonnave|Nathalie|N| Peugny|Sandrine|S| Ballet|Mathilde|M| Jacoud|Estelle|E| Michaud|Céline|C| Gaillet|Mélanie|M| Djossou|Félix|F| Blanchet|Denis|D| Lavergne|Anne|A| Demar|Magalie|M| Nacher|Mathieu|M| Rousset|Dominique|D| Epelboin|Loïc|L|


Morpho-Molecular Metabolic Analysis and Classification of Human Pituitary Gland and Adenoma Biopsies Based on Multimodal Optical Imaging.

Abstract: Pituitary adenomas count among the most common intracranial tumors. During pituitary oncogenesis structural, textural, metabolic and molecular changes occur which can be revealed with our integrated ultrahigh-resolution multimodal imaging approach including optical coherence tomography (OCT), multiphoton microscopy (MPM) and line scan Raman microspectroscopy (LSRM) on an unprecedented cellular level in a label-free manner. We investigated 5 pituitary gland and 25 adenoma biopsies, including lactotroph, null cell, gonadotroph, somatotroph and mammosomatotroph as well as corticotroph. First-level binary classification for discrimination of pituitary gland and adenomas was performed by feature extraction via radiomic analysis on OCT and MPM images and achieved an accuracy of 88%. Second-level multi-class classification was performed based on molecular analysis of the specimen via LSRM to discriminate pituitary adenomas subtypes with accuracies of up to 99%. Chemical compounds such as lipids, proteins, collagen, DNA and carotenoids and their relation could be identified as relevant biomarkers, and their spatial distribution visualized to provide deeper insight into the chemical properties of pituitary adenomas. Thereby, the aim of the current work was to assess a unique label-free and non-invasive multimodal optical imaging platform for pituitary tissue imaging and to perform a multiparametric morpho-molecular metabolic analysis and classification.

pituitary gland and adenomas
multimodal imaging
optical coherence tomography
multiphoton microscopy
radiomics
Raman spectroscopy
image analysis
second harmonic generation
two-photon excitation fluorescence


De novo C3 glomerulonephritis in a renal allograft.

Abstract: C3 glomerulonephritis (C3GN) is a recently described, rare glomerular disease characterized by predominant or sole glomerular C3 deposits. Morphologic features of C3GN are similar to those of dense deposit disease (DDD); however, ribbon-like intramembranous electron-dense deposits are absent in the former. We report a case of de novo C3GN in a renal allograft with morphologic transformation to DDD. A 6-year-old boy presented with congenital left renal agenesis and right ureteropelvic junction obstruction. The patient underwent pyeloplasty but experienced recurrent urinary tract infections. At the age of 22 years, he received a renal allograft from a living related donor. C3GN was diagnosed after 1 year of transplantation; initial histology showed minimal mesangiopathy and this progressed to mesangial proliferation and membranoproliferative features over the next 7 years. Serum creatinine levels were stabilized with anti-rejection treatments for combating repeated episodes of acute rejection; however, glomerular and tubular band-like electron-dense deposits became evident.

Nahm|Ji Hae|JH|
Song|Seung Hwan|SH|
Kim|Yu Seun|YS|
Cheong|Hae-Il|HI|
Lim|Beom Jin|BJ|
Kim|Beom Seok|BS|
Jeong|Hyeon Joo|HJ|

C3 glomerulonephritis
dense deposit disease
rejection
kidney transplant


Synthesis, biological evaluation and molecular docking study of 1-amino-2-aroylnaphthalenes against prostate cancer.

Abstract: A series of functionalized naphthalene was synthesized and screened against human prostate cancer cell line (PC-3). The in vitro antiproliferative activity of the synthesized compounds was evaluated by monitoring their cytotoxic effects against PC-3 cells by using MTT assay. We observed that compound 5f resulted in more than 50% cell death at 14 µM. Treatment of PC-3 cells with 5f provides apoptosis by flow cytometry. Western blotting showed decreased expression of pro-caspase 8 and 9. Our study shows that cancer cell treated with 5f has higher concentration of reactive oxygen species as compare to untreated sample, which facilitate cancerous cell to enter apoptosis. Exact mechanism by which ROS is generated after 5f treatment is still under study. Molecular docking study further strengthens the results obtained from in vitro experiments. Compound 5f can be considered as a promising leads for anticancer agent against prostate cancer cells due to its potent cytotoxic activity and apoptotic effect.

Rai|Reeta|R|
Dutta|Roshan Kumar|RK|
Singh|Surjeet|S|
Yadav|Dharmendra Kumar|DK|
Kumari|Seema|S|
Singh|Harpreet|H|
Gupta|Rinkoo Devi|RD|
Pratap|Ramendra|R|

D004354:Drug Screening Assays, Antitumor

Prostate cancer
Naphthalene
Cytotoxicity
Apoptosis
Oxidative damage


Neonatal sepsis in a tertiary care center in central India: microbiological profile, antimicrobial sensitivity pattern and outcome.

Abstract:
INTRODUCTION
Neonatal mortality is increasingly recognized as an important global public health challenge. The spectrum of organisms that cause neonatal sepsis changes over time and varies from region to another. This study was conducted to determine the profile, antibiotic sensitivity pattern of bacterial isolates and outcome of confirmed neonatal sepsis in a tertiary care center.

STUDY DESIGN
All blood culture reports (n = 285), obtained during the study period (January 2012-September 2012) from the neonatal intensive care unit were analyzed.

RESULTS
Blood culture positivity rate was 22.1% (67/285). Seventy-three percent babies were outborn. Sixty-two percent babies were preterm and 80% were low birth weight. Thirty-six (57%) babies had early onset and remaining 27 (43%) had late onset neonatal sepsis. Blood culture isolates included Gram-negative bacilli (38/67, 56.7%), Gram-positive cocci (20/67, 29.8%), and Candida species (9/67, 13.4%). Staphylococci and Klebsiellae were the most common organisms responsible for infections, accounting for 25.4% (17/67) and 19.4% (13/67) of the isolates, respectively. All Gram positive isolates were sensitive to vancomycin, while 50-65% Gram negative isolates were sensitive to amikacin, ciprofloxacin and meropenem. Fifty-eight percent babies were discharged after completion of the antibiotic therapy, while 28.6% babies expired.

CONCLUSION
Multidrug resistant Gram negative isolates pose serious challenge, particularly in setting of emerging resistance to fluoroquinolones and carbepenems.

Mehar|V|V| Yadav|D|D| Somani|P|P| Bhatambare|G|G| Mulye|S|S| Singh|K|K|

D024901:Drug Resistance, Multiple, Bacterial

Microbiological profile
antimicrobial sensitivity pattern
Staphylococci
Klebsiellae
Candiada


Solitary median maxillary central incisor in association with hemifacial microsomia: A rare case report and review of literature.

Abstract: Solitary median maxillary central incisor (SMMCI) is a rare dental anomaly. It is estimated to occur in 1:50,000 live births. The SMMCI tooth differs from the normal central incisor in that the crown form is symmetric and it develops and erupts precisely in the midline of the maxillary dental arch in both primary and permanent dentitions. Presence of SMMCI with hemifacial microsomia (HFM) is a very rare clinical condition. We report a case of HFM in a male of Indian origin who presented with SMMCI in both primary and permanent dentitions. The association of HFM with SMMCI may be due to defective development of neural crest cells and/or lack of space in maxilla.

Utreja|Ashok|A|
Zahid|Syed Naved|SN|
Gupta|Richa|R|

solitary median maxillary central incisor


Pain measurement in the National Social Life, Health, and Aging Project: presence, intensity, and location.

Abstract:
OBJECTIVES
To describe the rationale for the pain presence, location, and intensity measures in the National Social Life, Health and Aging Project (NSHAP).

METHOD
Responses to the pain presence, location (pain map), and intensity (verbal descriptor scale) items were analyzed by gender and age (62-69, 70-79, and 80-91). Pain intensity was dichotomized (none to mild vs moderate or higher) and compared by demographics, physical function, mood, and self-rated health. All analyses used Wald tests to compare sample means.

RESULTS
Participants completed the pain presence (n = 2,430/2,799), location (n = 2,558/2,799), and intensity (n = 2,589/2,799) items. Pain items varied by gender with women reporting more head, arm, hip/buttock, leg, and foot pain compared to men, (p < .05) at each individual site. Women also reported more intense pain compared to men-2.13 versus 1.94, respectively (p < .05). Pain items demonstrated remarkable similarity among age cohorts. Health indicators were significant and in the expected direction (p < .001). An increase in comorbidity, ADL and IADL dependence, worse self-rated health, and more depressive symptoms were each significantly more common among participants who reported moderate or greater pain compared to none to mild pain.

DISCUSSION
Pain presence, location, and intensity measures were successfully integrated into NSHAP Wave 2 and exhibit construct and external validity.

Shega|Joseph W|JW|
Tiedt|Andrew D|AD|
Grant|Kaelin|K|
Dale|William|W|


Beneficial Bacteria Identified for the Control of Botrytis cinerea in Petunia Greenhouse Production.

Abstract: Botrytis cinerea infects most major greenhouse crops worldwide. With its increasing resistance to conventional fungicides and the movement of the greenhouse industry toward more sustainable production practices, alternative methods of control are needed. The objective of this study was to evaluate a collection of 60 bacterial strains through both a dual-culture assay and greenhouse trials to identify strains with biocontrol activity against B. cinerea. For the dual-culture assay, each bacterial strain was streaked on potato dextrose agar medium with B. cinerea. The B. cinerea growth reduction and the zone of inhibition were measured. Thirty-five strains reduced the growth of B. cinerea. All strains were also tested in an initial greenhouse trial in which Petunia × hybrida 'Carpet Red Bright' was sprayed and drenched with the bacteria biweekly for 6 weeks. All open flowers were tagged, and plants were inoculated with B. cinerea (1 × 104 conidia per 1 ml). Disease severity indices calculated from the daily flower gray mold severity ratings of all tagged flowers were used to identify the seven top-performing strains. These seven strains were then evaluated in a greenhouse validation trial. The methods were similar to those of the initial greenhouse trials except that replicate numbers were increased. Three strains (Pseudomonas protegens AP54, Pseudomonas chlororaphis 14B11, and Pseudomonas fluorescens 89F1) were selected for the ability to reduce B. cinerea infection in a greenhouse production setting. These strains can be used in future studies to develop additional biocontrol products for the management of B. cinerea in floriculture crops.

bacteria
biocontrol
gray mold
Pseudomonas
floriculture
botrytis blight
fungus


The Role of Peritoneal Dialysis in the Treatment of Acute Kidney Injury in Patients With Acute-on-Chronic Liver Failure: A Prospective Brazilian Study.

Abstract: This study aimed to explore the role of peritoneal dialysis (PD) in acute-on-chronic liver disease (ACLD) in relation to metabolic and fluid control and outcome. Fifty-three patients were treated by PD (prescribed Kt/V = 0.40/session), with a flexible catheter, tidal modality, using a cycler and lactate as a buffer. The mean age was 64.8 ± 13.4 years, model of end stage liver disease (MELD) was 31 ± 6, 58.5% were in the intensive care unit, 58.5% needed intravenous inotropic agents including terlipressin, 69.5% were on mechanical ventilation, alcoholic liver disease was the main cause of cirrhosis and the main dialysis indications were uremia and hypervolemia. Blood urea and creatinine levels stabilized after four sessions at around 50 and 2.5 mg/dL, respectively. Negative fluid balance (FB) and ultrafiltration (UF) increased progressively and stabilized around 3.0 L and -2.7 L/day, respectively. Weekly-delivered Kt/V was 2.7 ± 0.37, and 71.7% of patients died. Five factors met the criteria for inclusion in the multivariable analysis. Logistic regression identified as risk factors associated with Acute Kidney Injury (AKI) in ACLD patients: MELD (OR = 1.14, CI 95% = 1.09-2.16, p = 0.001), nephrotoxic AKI (OR = 0.79, CI 95% = 0.61-0.93, p = 0.02), mechanical ventilation (OR = 1.49, CI 95% = 1.14-2.97, p < 0.001), and positive fluid balance (FB) after two PD sessions (OR = 1.08, CI 95% = 1.03-1.91, p = 0.007). These factors were significantly associated with death. In conclusion, our study suggests that careful prescription may contribute to providing adequate treatment for most Acute-on-Chronic Liver Failure (ACLF) patients without contraindications for PD use, allowing adequate metabolic and fluid control, with no increase in the number of infectious or mechanical complications. MELD, mechanical complications and FB were factors associated with mortality, while nephrotoxic AKI was a protective factor. Further studies are needed to better investigate the role of PD in ACLF patients with AKI.

Ponce|Daniela|D|
Zamoner|Welder|W|
Dias|Dayana Bitencourt|DB|
Pires da Rocha|Erica|E|
Kojima|Christiane|C|
Balbi|André Luís|AL|

peritoneal dialysis
acute kidney injury
acute-on-chronic liver disease
mortality
liver cirrhosis


An explainable supervised machine learning predictor of acute kidney injury after adult deceased donor liver transplantation.

Abstract:
BACKGROUND
Early prediction of acute kidney injury (AKI) after liver transplantation (LT) facilitates timely recognition and intervention. We aimed to build a risk predictor of post-LT AKI via supervised machine learning and visualize the mechanism driving within to assist clinical decision-making.

METHODS
Data of 894 cases that underwent liver transplantation from January 2015 to September 2019 were collected, covering demographics, donor characteristics, etiology, peri-operative laboratory results, co-morbidities and medications. The primary outcome was new-onset AKI after LT according to Kidney Disease Improving Global Outcomes guidelines. Predicting performance of five classifiers including logistic regression, support vector machine, random forest, gradient boosting machine (GBM) and adaptive boosting were respectively evaluated by the area under the receiver-operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. Model with the best performance was validated in an independent dataset involving 195 adult LT cases from October 2019 to March 2021. SHapley Additive exPlanations (SHAP) method was applied to evaluate feature importance and explain the predictions made by ML algorithms.

RESULTS
430 AKI cases (55.1%) were diagnosed out of 780 included cases. The GBM model achieved the highest AUC (0.76, CI 0.70 to 0.82), F1-score (0.73, CI 0.66 to 0.79) and sensitivity (0.74, CI 0.66 to 0.8) in the internal validation set, and a comparable AUC (0.75, CI 0.67 to 0.81) in the external validation set. High preoperative indirect bilirubin, low intraoperative urine output, long anesthesia time, low preoperative platelets, and graft steatosis graded NASH CRN 1 and above were revealed by SHAP method the top 5 important variables contributing to the diagnosis of post-LT AKI made by GBM model.

CONCLUSIONS
Our GBM-based predictor of post-LT AKI provides a highly interoperable tool across institutions to assist decision-making after LT.

Zhang|Yihan|Y| Yang|Dong|D| Liu|Zifeng|Z| Chen|Chaojin|C| Ge|Mian|M| Li|Xiang|X| Luo|Tongsen|T| Wu|Zhengdong|Z| Shi|Chenguang|C| Wang|Bohan|B| Huang|Xiaoshuai|X| Zhang|Xiaodong|X| Zhou|Shaoli|S| Hei|Ziqing|Z|0000-0002-1256-5899

D058186:Acute Kidney Injury
D000328:Adult
D006801:Humans
D016031:Liver Transplantation
D019520:Living Donors
D000069550:Machine Learning
D018570:Risk Assessment
D000069553:Supervised Machine Learning

Liver transplant
Gradient boosting machine
Artificial intelligence
Big data
Clinical assisting tool
Kidney dysfunction
Perioperative medicine
Prognostic predictor
SHAP value
SHapley Additive exPlaination methods


Machine Learning Based Metagenomic Prediction of Inflammatory Bowel Disease.

Abstract: In this study, we investigate faecal microbiota composition, in an attempt to evaluate performance of classification algorithms in identifying Inflammatory Bowel Disease (IBD) and its two types: Crohn's disease (CD) and ulcerative colitis (UC). From many investigated algorithms, a random forest (RF) classifier was selected for detailed evaluation in three-class (CD versus UC versus nonIBD) classification task and two binary (nonIBD versus IBD and CD versus UC) classification tasks. We dealt with class imbalance, performed extensive parameter search, dimensionality reduction and two-level classification. In three-class classification, our best model reaches F1 score of 91% in average, which confirms the strong connection of IBD and gastrointestinal microbiome. Among most important features in three-class classification are species Staphylococcus hominis, Porphyromonas endodontalis, Slackia piriformis and genus Bacteroidetes.

Mihajlović|Andrea|A| Mladenović|Katarina|K| Lončar-Turukalo|Tatjana|T| Brdar|Sanja|S|

D039903:Actinobacteria
D041963:Bacteroidetes
D003093:Colitis, Ulcerative
D003424:Crohn Disease
D000069196:Gastrointestinal Microbiome
D006801:Humans
D015212:Inflammatory Bowel Diseases
D000069550:Machine Learning
D045202:Porphyromonas endodontalis
D041181:Staphylococcus hominis

machine learning
imbalance
microbiome
feature selection


Preparation of Yolk-Shell-Structured Cox Fe1-x P with Enhanced OER Performance.

Abstract: The design and development of low-cost, highly efficient, and stable electrocatalysts to take the place of noble-metal catalysts for the oxygen evolution reaction (OER) remain a significant challenge. Herein, the synthesis of yolk-shell-structured binary transition metal phosphide Cox Fe1-x P with different Co/Fe ratios by phosphidation of a cobalt ferrite precursor is reported. The as-synthesized Cox Fe1-x P catalysts were used for the OER. All yolk-shell Cox Fe1-x P catalysts with different Co/Fe ratios showed much better performance than the corresponding solid catalyst. The formation of Co oxides on the catalyst surface during OER and the optimal Co/Fe ratio were found to be critical to their activity. Among the as-prepared Cox Fe1-x P catalysts, that with a Co/Fe ratio of 0.47/0.53 (Co0.47 Fe0.53 P) exhibited the best performance. Co0.47 Fe0.53 P has an overpotential of 277 mV at a current density of 10 mA cm-2 , a Tafel slope of 37 mV dec-1 , and superior stability in alkaline medium. The outstanding performance is partly ascribed to the transfer of valence electrons from Co to P and Fe. The Co0.47 Fe0.53 P matrix with excellent conductivity and Fe phosphate that is stable on the surface of the catalyst are also helpful for the OER performance. In addition, the yolk-shell structure of Co0.47 Fe0.53 P increases the contact area between electrolyte and catalyst. These characteristics of Co0.47 Fe0.53 P greatly improve its OER performance. This optimized binary transition metal phosphide provides a new approach for the design of nonprecious-metal electrocatalysts.

transition metals
phosphides
yolk-shell structures
electrochemistry
template synthesis


Evaluation of a multiplex real-time PCR kit Amplidiag® Bacterial GE in the detection of bacterial pathogens from stool samples.

Abstract: This study evaluated the performance of a new commercially available multiplex real-time PCR kit Amplidiag® Bacterial GE in the systematic screening of bacterial pathogens causing gastroenteritis. Stool samples from 1168 patients were analyzed with Amplidiag® Bacterial GE, stool culture, and molecular reference tests, and the sensitivity and specificity of Amplidiag® Bacterial GE were determined by comparing the results to the reference tests. The evaluation showed good performance for Amplidiag® Bacterial GE: sensitivity and specificity of the test was 100/99.7% for Salmonella, 100/99.8% for Yersinia, 98.8/99.2% for Campylobacter, 92.9/100% for Shigella/EIEC, 100/99.9% for EHEC, 92.9/99.8% for ETEC, 98.9/99.2% for EPEC, and 100/99.8% EAEC, respectively. When compared with stool culture, Amplidiag® Bacterial GE was found to be more sensitive. This study suggests that Amplidiag® Bacterial GE is suitable for screening bacterial pathogens from stool samples. However, this study only demonstrates the performance of Amplidiag® Bacterial GE in low endemic settings, as the number of positive findings in this study was relatively low.

Rintala|Anniina|A| Munukka|Eveliina|E| Weintraub|Andrej|A| Ullberg|Måns|M| Eerola|Erkki|E|

D060885:Multiplex Polymerase Chain Reaction

Multiplex real-time PCR
Bacterial gastroenteritis
Diarrhea
Molecular diagnostics


It Does Not Follow: Evaluating the One-Off Publication Bias Critiques by Francis (2012a, 2012b, 2012c, 2012d, 2012e, in press).

Abstract: Francis (2012a, 2012b, 2012c, 2012d, 2012e, in press) attacks individual papers through critiques that apply faulty logic to analyses ironically biased by cherry picking. However well intentioned, the critiques are probably counterproductive to their stipulated goal and certainly unfair to the targeted authors.


ABCG2 C421A polymorphisms affect exposure of the epidermal growth factor receptor inhibitor gefitinib.

Abstract: ATP-binding castle protein G2 (ABCG2) is thought to inhibit the activities of certain gefitinib transporters, thereby affecting drug pharmacokinetics. The C421A polymorphism affects the function and expression of ABCG2 on the cell membrane. Previous studies have shown that proton-pump inhibitors (PPIs) inhibit gefitinib absorption, as well as the function of ABCG2. We evaluated the plasma concentrations of gefitinib in patients with and without the ABCG2 C421A polymorphism, who were or were not taking PPIs. In total, 61 patients with advanced epidermal-growth-factor-positive non-small-cell lung cancer were enrolled in this study. They were treated with gefitinib at a dose of 250 mg per day. Plasma gefitinib concentration and ABCG2 C421A status were determined after 2 weeks. The patients were divided into CC- and CA/AA genotype groups. We compared the trough and peak gefitinib levels and the area under the curve (AUC) values for 24-h gefitinib concentrations. We also compared these parameters among four groups distinguished according to the presence or absence of the polymorphism and PPI use. The mean trough gefitinib level and AUC value for 24-h gefitinib concentration were significantly lower in the CA/AA group compared to the CC group (mean trough level: 333.2 vs. 454.5 ng/mL, respectively, P = 0.021; AUC: 9949.9 vs. 13,085.4 ng・h/mL, respectively, P = 0.034). Among patients taking PPIs, the mean trough gefitinib level was significantly lower in the CA/AA group than the CC group (220.1 vs. 340.5 ng/mL, respectively, P = 0.033). The CA/AA-type of ABCG2 C421A polymorphism may be associated with lower gefitinib plasma concentrations.

D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2

ABCG2
Gefitinib
Non-small-cell lung cancer
EGFR mutation


Intraparenchymal leiomyoma of the breast: a case report.

Abstract: We report the case of a 27-year-old female with intraparenchymal leiomyoma of the breast. This case is interesting not only because intraparenchymal leiomyoma of the breast is a rare benign non-epithelial tumor, but also because it is never found in women at such an early age. We explain all the aspects of this case in this report with its radiologic, histopathologic and immunohistochemical findings.

Shah|Sumit D|SD|
Gupta|Arnab|A|
Roy|Sarvasti|S|
Mukhopadhyay|Supti|S|

Intraparenchymal leiomyoma
Leiomyoma
Breast neoplasm


Dehydroepiandrosterone and Dehydroepiandrosterone-Sulfate and Emotional Processing.

Abstract: Steroid hormones are important regulators of brain development, physiological function, and behavior. Among them, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) also do modulate emotional processing and may have mood enhancement effects. This chapter reviews the studies that bear relation to DHEA and DHEAS [DHEA(S)] and brain emotional processing and behavior. A brief introduction to the mechanisms of action and variations of DHEA(S) levels throughout life has also been forward in this chapter. Higher DHEA(S) levels may reduce activity in brain regions involved in the generation of negative emotions and modulate activity in regions involved in regulatory processes. At the electrophysiological level, higher DHEA-to-cortisol and DHEAS-to-DHEA ratios were related to shorter P300 latencies and shorter P300 amplitudes during the processing of negative stimuli, suggesting less interference of negative stimuli with the task and less processing of the negative information, which in turn may suggest a protective mechanism against negative information overload. Present knowledge indicates that DHEA(S) may play a role in cortical development and plasticity, protecting against negative affect and depression, and at the same time enhancing attention and overall working memory, possibly at the cost of a reduction in emotional processing, emotional memory, and social understanding.

Dehydroepiandrosterone
Dehydroepiandrosterone-sulfate
Emotion processing
Depression
Attention
Emotional memory
Cortisol
Event-related potentials
Neuroimaging


Initial group dietary education compared to individual education in gestational diabetes mellitus management: Do outcomes differ?

Abstract:
AIMS
To assess the effectiveness of Initial Group versus Initial Individual GDM dietary education in terms of insulin requirements and pregnancy outcomes.

METHODS
A retrospective audit of clinical data was conducted where English speaking women who received initial education in a group setting (01-2-2012 to 01-2-2014) (Group), were compared to women who received initial individual education with a dietitian (1-2-2010 to 31-1-2012) (Individual), all followed by one individual dietitian appointment. The same dietary information was provided in both settings. Data collected included: attendance rates, insulin requirements, maternal weight gain, and rates of adverse birth outcomes. Data were compared by t-test or Chi-squared test. Multivariable logistic regression analysis was conducted to determine independent predictors of insulin therapy.

RESULTS
Of 743 women; (362 Group and 381 Individual), Group women had a lower HbA1c at GDM diagnosis 5.3 ± 0.6% versus 5.5 ± 0.5% (34 ± 6.6 mmol/mol versus 37 ± 5.5 mmol/mol p < 0.0001). There were no other differences in baseline characteristics. More Group women required insulin (42.0% versus 34.6%, p = 0.048). Group education was found to be an independent predictor of insulin therapy (OR = 1.9 [1.29, 2.75] p < 0.001).

CONCLUSIONS
Despite adjusting for all known potential confounders, unlike Individual education, Group education remained a significant predictor of insulin therapy (but resulted in similar therapeutic and pregnancy outcomes to Individual education).

Barnes|Robyn A|RA|
Ross|Glynis P|GP|
Jalaludin|Bin B|BB|
Flack|Jeff R|JR|

Gestational diabetes
Outcome
Pregnancy
Medical Nutrition Therapy
Nutrition
Nutrition education


Sex-dependent association of urate on the patterns of striatal dopamine depletion in Parkinson's disease.

Abstract:
BACKGROUND AND PURPOSE
The aim was to investigate the relationship between the serum urate (UA) levels and patterns of striatal dopamine depletion in patients with de novo Parkinson's disease (PD).

METHODS
In all, 167 de novo PD patients who underwent 18 F-fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane positron emission tomography scans were enrolled. After quantifying dopamine transporter (DAT) availability in each striatal subregion, sex-dependent patterns of striatal dopamine depletion were analysed by measuring (i) dopamine depletion in the other striatal subregions and posterior putamen (intersubregional ratio, ISR) and (ii) the interhemispheric asymmetry of dopamine depletion in the posterior putamen (asymmetric ratio, AR).

RESULTS
The interaction analysis revealed a significant interaction effect of sex and serum UA levels on the ISR but not on the AR. The ISR was negatively correlated with the serum UA levels in all patients with PD (r = -0.156, P = 0.045), and this association was more prominent in male PD patients (r = -0.422, P < 0.001). However, no significant association between the AR and serum UA levels was found in any of the patients. In addition, serum UA levels were significantly associated with DAT availability in the posterior putamen on both the more affected side (r = 0.312, P = 0.005) and the less affected side (r = 0.312, P = 0.005) only in male PD patients.

CONCLUSIONS
The present study demonstrated the potentially close sex-specific relationship between the serum UA levels and the anterior-posterior gradient of DAT patterns, suggesting a sex-specific protective effect of UA on nigrostriatal dopaminergic neurons in de novo PD.

D050483:Dopamine Plasma Membrane Transport Proteins

urate
dopamine transporter
sex
Parkinson’s disease


Challenges in studying preimplantation embryo-maternal interaction in cattle.

Abstract: A comprehensive understanding of the complex embryo-maternal interactions during the preimplantation period requires the analysis of the very early stages of pregnancy encompassing early embryonic development, maternal recognition and the events leading to implantation. Despite the fact that embryo development until blastocyst stage is somewhat autonomous (i.e., does not require contact with the maternal reproductive tract and can be successfully recapitulated in vitro), many studies on ruminant embryo production have focused on the fundamental question of why: (i) only 30%-40% of immature oocytes develop to the blastocyst stage and (ii) the quality of such blastocysts continually lags behind that of blastocysts produced in vivo. Clear evidence indicates that in vitro culture conditions are far from optimal with deficiencies being manifested in short- and long-term effects on the embryo. Thus, enhanced knowledge of mechanisms controlling embryo-maternal interactions would allow the design of novel strategies to improve in vitro embryo conditions and reproductive outcomes in cattle.

Rodríguez-Alonso|Beatriz|B|
Sánchez|José María|JM|
González|Encina|E|
Lonergan|Patrick|P|
Rizos|Dimitrios|D|

Embryo-maternal interaction
Embryo
In vitro
In vivo
Oviduct
Uterus


Specific role of taurine in the 8-brominated-2'-deoxyguanosine formation.

Abstract: At the sites of inflammation, hypohalous acids, such as hypochlorous acid and hypobromous acid (HOBr), are produced by myeloperoxidase. These hypohalous acids rapidly react with the primary amino groups to produce haloamines, which are relatively stable and can diffuse long distances and cross the plasma membrane. In this study, we examined the effects of taurine, the most abundant free amino acid in the leukocyte cytosol, on the hypohalous acid-dependent formation of 8-chloro-2'-deoxyguanosine (8-CldG) and 8-bromo-2'-deoxyguanosine (8-BrdG). The reaction of taurine with HOBr yielded taurine bromamine, which is the most stable among other bromamines of amino acids. Taurine also enhanced the bromination of only dG among the four 2'-deoxynucleosides, whereas it inhibited the 8-CldG formation. The specificity of taurine for the enhanced formation of halogenated dG is completely different from that of nicotine, an enhancer of chlorination. The amount of dibrominated taurine (taurine dibromamine) closely correlated with the formation of 8-BrdG, suggesting that taurine dibromamine might be a plausible mediator for the dG bromination in vivo.

Asahi|Takashi|T| Nakamura|Yoshimasa|Y| Kato|Yoji|Y| Osawa|Toshihiko|T|

D002851:Chromatography, High Pressure Liquid

Taurine
Hypobromous acid
Bromamine
Nicotine
8-bromo-2′-deoxyguanosine


Comparing the Effects of Agnugol and Metformin on Oligomenorrhea in Patients with Polycystic Ovary Syndrome: A Randomized Clinical Trial.

Abstract:
INTRODUCTION
Polycystic Ovarian Syndrome (PCOS) is the most common endocrinopathy and cause of oligomenorrhea in women.

AIM
The present study was conducted with the aim to compare the effect of Agnugol and Metformin drugs on oligomenorrhea in patients with PCOS.

MATERIALS AND METHODS
This study was a clinical trial on 120 women with PCOS and had oligomenorrhea, referring to a gynaecology clinic Fatemieh, Hamadan city, Iran, 2015. Women were randomly divided into 2 groups using permutation blocks (getting the medications Agnugol and Metformin) and were treated with drugs Agnugol and Metformin for 3 months. Data collection included demographic questionnaire and check list was designed and completed before and at the end of interventions, by both groups. To analyse the data, descriptive statistics, chi-square tests, t-test, ANOVA with repeated measures was used.

RESULTS
The mean and SD of age was 39.45±4.60 for women taking Agnugol and 38.466±0.84 for those taking Metformin. Based on the results between the subjects, the two groups were not significantly different in terms of menstruation length, cycle intervals, or the number of pads, meaning that the two drugs had similar effects on menstrual cycle regulation, menstruation length and the number of pads. More side effects were reported in the group using Metformin.

CONCLUSION
Agnugol and Metformin drugs in the treatment of oligomenorrhea patients with PCOS have the same effect. Since Metformin is a chemical drug with side effects, Agnugol can be presented as its herbal alternative to treat oligomenorrhea.

Shayan|Arezoo|A|
Masoumi|Seyedeh Zahra|SZ|
Shobeiri|Fatemeh|F|
Tohidi|Shahin|S|
Khalili|Arash|A|

Endocrinopathy
Menstruation
Chemical drug
Herbal drug


Enhanced electro kinetic- pseudo-Fenton degradation of pyrene-contaminated soil using Fe3O4 magnetic nanoparticles: A data set.

Abstract: The aim of the data were to increase the treatment efficiency of pyrene from soil using Nano catalysts magnetite iron oxide (Fe3O4) and combined with electro kinetic. Soil provided with 100 mg/kg concentration and removal of pyrene done with EK-Fenton process. Nano catalyst was synthesized via a facile co-precipitation method and characterized by FTIR, XRD, SEM, EDX, VSM techniques. The effects of some operational parameters include catalyst dosage, pH, hydrogen peroxide concentration and the voltage were studied on the removal efficiency of pyrene. Results indicated the removal efficiency was obtained 87% under optimal conditions (pH = 3, Nano catalyst dosage= 1 g/l, H2O2=10 mM and voltage 30 V). Electrokinetic Fenton process can be as efficient and effective method for the removal of pyrene from contaminated soil using Nano Catalyst Fe3O4 introduced in optimal conditions.

Asgharzadeh|Fatemeh|F|
Moradi|Masoud|M|
Jonidi Jafari|Ahmad|A|
Esrafili|Ali|A|
Tahergorabi|Mahsa|M|
Rezaei Kalantari|Roshanak|R|

Soil
EK-pseudo-Fenton process
Fe3O4 nanoparticle


Pharmacokinetics and Tissue Distribution of Folate-Decorated Human Serum Albumin Loaded With Nano-Hydroxycamptothecin for Tumor Targeting.

Abstract: The goal of this work is to develop the method of preparing folate (FA)-decorated human serum albumin (HSA) loaded with nano-hydroxycamptothecin (nHCPT) nanoparticles (NPs) (FA-HSA-nHCPT-NPs) and to explore its antitumor activity in vivo and in vitro. FA-HSA-nHCPT-NPs were obtained by preparing nHCPT by a high-pressure homogenization technique followed with an anti-solvent method. The drug-loading efficiency of the FA-HSA-nHCPT-NPs was 7.8%. We adopted the human breast cancer cells (FA receptor-expressing MCF-7 cells) and BALB/c mice inoculated with human MCF-7 cells to determine the antitumor activity of FA-HSA-nHCPT-NPs in vitro and in vivo, respectively. The antitumor activity of FA-HSA-nHCPT-NPs was stronger than that of the raw HCPT in both conditions. Tissue distribution analysis showed that the FA-HSA-nHCPT-NPs carried more HCPT to tumors than the raw HCPT. The tumor inhibitory rate of FA-HSA-nHCPT-NPs was much higher compared with the raw HCPT. Th7us, the FA-HSA-nHCPT-NPs could serve as a viable delivery system with an obvious target effect on tumor.

Wang|Wenchao|W| Liang|Hui|H| Sun|Baihe|B| Xu|Jialin|J| Zeng|Zhen|Z| Zhao|Xiaojun|X| Li|Qingyong|Q|

D023041:Xenograft Model Antitumor Assays

tissue distribution
folate-decorated human serum albumin
hydroxycamptothecin
targeted delivery system


Updating insights into the rehydration of dairy-based powder and the achievement of functionality.

Abstract: Dairy-based powder had considerable development in the recent decade. Meanwhile, the increased variety of dairy-based powder led to the complex difficulties of rehydrating dairy-based powder, which could be the poor wetting or dissolution of powder. To solve these various difficulties, previous studies investigated the rehydration of powder by mechanical and chemical methods on facilitating rehydration, while strategies were designed to improve the rate-limiting rehydration steps of different powder. In this review, special emphasis is paid to the surface and structure of the dairy-based powder, which was accountable for understanding rehydration and the rate-limiting step. Besides, the advantage and disadvantage of methods employed in rehydration were described and compared. The achievement of the powder functionality was finally discussed and correlated with the rehydration methods. It was found that the surface and structure of dairy-based powder were decided by the components and production of powder. Post-drying methods like agglomeration and coating can tailor the surface and structure of powder afterwards to obtain better rehydration. The merit of the mechanical method is that it can be applied to rehydrate dairy-based powder without any addition of chemicals. Regarding chemical methods, calcium chelation is proved to be an effective chemical in rehydration casein-based powder.

Rehydration
dairy-based powder
functionality
calcium
cavitation
powder matrix


Trauma, subjectivity and subjectality.

Abstract: Taking a critical stand on contemporary trends in psychoanalysis regarding trauma, the author addresses the problem of psychic trauma mainly in terms of how it affects the patient's status as a subject. After reexamining the notions of subject and subjectivity, the author illustrates the usefulness of the notion of "subjectality," defined as a critical moment of subjectivity, necessary for processing the consequences of trauma. A clinical illustration is provided.

trauma
subjectality
subjectality
Ferenczi
Laplanche
analytic method
subjectivity


What does it mean to be a 'picky eater'? A qualitative study of food related identities and practices.

Abstract: Picky eaters are defined as those who consume an inadequate variety of food through rejection of a substantial amount of food stuffs that are both familiar and unfamiliar. Picky eating is a relatively recent theoretical concept and while there is increasing concern within public health over the lack of diversity in some children's diets, adult picky eaters remain an under researched group. This paper reports on the findings of a qualitative study on the routine food choices and practices of 26 families in Sandwell, West Midlands, UK. Photo elicitation and go-along interview data collection methods were used to capture habitual food related behaviours and served to describe the practices of nine individuals who self identified or were described as picky eaters. A thematic analysis revealed that those with the food related identity of picky eater had very restricted diets and experienced strong emotional and physical reactions to certain foods. For some this could be a distressing and alienating experience that hindered their ability to engage in episodes of social eating. Further research is needed to illuminate the specific practices of adult picky eaters, how this impacts on their lives, and how possible interventions might seek to address the challenges they face.

Thompson|Claire|C| Cummins|Steven|S| Brown|Tim|T| Kyle|Rosemary|R|

Picky eaters
Identity
Adults
Food practices


Epigenetic mechanisms of macrophage activation in type 2 diabetes.

Abstract: The alarming rise of obesity and type 2 diabetes (T2D) has put a tremendous strain on global healthcare systems. Over the past decade extensive research has focused on the role of macrophages as key mediators of inflammation in T2D. The inflammatory environment in the obese adipose tissue and pancreatic β-cell islets creates and perpetuates imbalanced inflammatory macrophage activation. Consequences of this chronic low-grade inflammation include insulin resistance in the adipose tissue and pancreatic β-cell dysfunction. Recently, the emerging field of epigenetics has provided new insights into the pathogenesis of T2D, while also affording potential new opportunities for treatment. In macrophages, epigenetic mechanisms are increasingly being recognized as crucial controllers of their phenotype. Here, we first describe the role of macrophages in T2D. Then we elaborate on epigenetic mechanisms that regulate macrophage activation, thereby focusing on T2D. Next, we highlight how diabetic conditions such as hyperlipidemia and hyperglycemia could induce epigenetic changes that promote an inflammatory macrophage phenotype. In conclusion we discuss possible therapeutic interventions by targeting macrophage epigenetics and speculate on future research directions.

Ahmed|Mohamed|M|
de Winther|Menno P J|MPJ|
Van den Bossche|Jan|J|

Epigenetics
Macrophage activation
Type 2 diabetes
Obesity
Inflammation


IRF2BPL gene mutation: Expanding on neurologic phenotypes.

Abstract: Heterozygous loss of function variants in the IRF2BPL are a newly described cause of neurodevelopmental disabilities and epilepsy. As of 2019, fewer than 20 patients have been described in the published literature. This article reports an additional case of a patient with a pathogenic IRF2BPL variant and offers a comprehensive review of the published cases of individuals with IRF2BPL variants, in order to help expand the phenotype. The patient has a history of infantile spasms evolving into drug-resistant epilepsy with underlying epileptic encephalopathy consistent with Lennox-Gastaut syndrome. While at the extreme end of the spectrum, his phenotype is consistent with those previously described. Our literature review highlights the wide range of phenotypes exhibited by those with diseases related to IRF2BPL gene variants. This article also briefly discusses other comorbidities seen in the patient and those previously reported. While the molecular underpinnings of the role of IRF2BPL gene in the central nervous system are newly established, the specifics of its effects elsewhere have yet to be delineated. Furthermore, its pathogenesis in other organ systems is not yet understood and could be of importance from a management perspective.

Shelkowitz|Emily|E|0000-0003-1911-1846
Singh|Jasleen K|JK|
Larson|Austin|A|
Elias|Ellen R|ER|

D020022:Genetic Predisposition to Disease

IRF2BPL gene mutation
epilepsy
developmental regression
intellectual disability


The effect of vitrification of immature bovine oocytes to the subsequent in vitro development and gene expression.

Abstract: Immature bovine oocytes were vitrified using the cryotop method and their post-warming survivability and capability to undergo in vitro maturation, fertilization and subsequent embryonic development were evaluated. In addition throughout the embryonic 2-cell, 4-cell, morula and blastocyst stages, the expression of four developmentally important genes (Cx43, CDH1, DNMT1 and HSPA14) was analysed using the real-time polymerase chain reaction (PCR). Immature oocytes (n = 550) were randomly assigned to non-vitrified (fresh) or cryotop vitrification groups using ethylene glycol (EG) with 1,2 propanediol (PROH) or dimethylsulphoxide (DMSO). After warming, oocytes survivability, embryo cleavage and embryonic developmental rates were not statistically different between the two cryoprotectants groups. However, the DMSO group had a lower (P < 0.05) oocyte maturation rate compared with the fresh and PROH groups. For morula and blastocyst rates, the DMSO group achieved a lower (P < 0.05) morula rate compared with the fresh group, while at the blastocyst stage, there were no differences between fresh and both cryoprotectants groups. For molecular analysis, at the 4-cell stage, most studied genes showed an inconsistent pattern of expression either from the PROH or DMSO groups. Noteworthily, these differences were limited at the morula and blastocyst stages. In conclusion, the cryotop method is sufficient for vitrification of immature bovine oocytes, both for embryonic developmental competence and at the molecular level. Moreover, PROH showed some advantage over DMSO as a cryoprotectant.

Faheem|Marwa S|MS|
Baron|E|E|
Carvalhais|I|I|
Chaveiro|A|A|
Pavani|K|K|
da Silva|F Moreira|FM|

D018507:Gene Expression Regulation, Developmental

Cryotop
Cryoprotectants
Cryopreservation
In vitro fertilization
Real-time quantitative PCR


Colorectal Cancer: Personalized Therapy.

Abstract:
BACKGROUND
Colorectal cancer (CRC) is the second most common type of cancer in the Western world. The treatment of this disease has evolved greatly, particularly for patients with metastatic disease. The advent of combination chemotherapy plus targeted agents has led to more curative resections and improved survival rates in these patients. A deeper understanding of the mechanisms of tumorigenesis has facilitated tumor characterization, prognosis and patient stratification, bringing us one step closer towards personalized medicine.

SUMMARY
There are two main pathways of CRC development: (1) chromosomal instability, also known as the classical adenoma-carcinoma sequence, and (2) microsatellite instability, caused by a defective mismatch repair (dMMR) system. Analysis of these pathways has uncovered key prognostic and predictive biomarkers to guide patient selection and treatment strategy. This review summarizes the current treatment regimens and recent advances in the personalized therapy of CRC.

KEY MESSAGE
Understanding of the mechanisms of CRC pathogenesis has led to new developments in tumor characterization, patient stratification, prognosis and treatment, bringing us closer to personalized therapy.

PRACTICAL IMPLICATIONS
In the adjuvant setting, the treatment decision is driven by clinical and histopathological factors. dMMR status is one of the most robust positive prognostic factors in resected colon cancer. More and more guidelines recommend refraining from adjuvant chemotherapy in patients with dMMR. In the metastatic setting, the introduction of effective compounds, including agents that target the epidermal growth factor receptor and vascular endothelial growth factor pathways, has significantly improved survival. The presence of wild-type KRAS and NRAS (all RAS) is a positive predictive factor for epidermal growth factor receptor antibody treatment. Therefore, analysis of all RAS status is recommended for all patients with metastatic disease prior to the initiation of first-line chemotherapy.

Colorectal cancer
Personalized therapy
Microsatellite instability
Adjuvant therapy
Palliative therapy


Analysis and Quantification of Glucosinolates.

Abstract: Recent advances in liquid chromatography and mass spectrometry have made it possible to increase the throughput of phytochemical analyses at high sensitivity. These improvements have made it more feasible to monitor metabolic processes at the metabolite level. Glucosinolates, the primary defense compounds in the model plant Arabidopsis thaliana, in particular, have gained increasing attention as model compounds for quantitative genetics and metabolic regulation. Depending on the plant species, tissue, glucosinolate content, complexity of the glucosinolate profile, and, most importantly, the overall purpose of the experiment, different choices need to be made regarding the methods of extraction and analysis. In this chapter, we describe different approaches for the analysis of glucosinolates and highlight advantages, disadvantages, and technical pitfalls. © 2016 by John Wiley & Sons, Inc.

Crocoll|Christoph|C|
Halkier|Barbara Ann|BA|
Burow|Meike|M|

glucosinolates
chromatography
mass spectrometry
metabolite profiling
plant specialized metabolism