Ileal Transposition Increases Pancreatic β Cell Mass and Decreases β Cell Senescence in Diet-Induced Obese Rats.

Abstract:
BACKGROUND
Ileal transposition (IT) is a surgical procedure to investigate the role of the distal small intestine in metabolic improvements induced by bariatric/metabolic surgery, which has been applied to some human cases. We performed IT in diet-induced obese rats to investigate the effect of IT on glucose metabolism and β cell senescence.

METHODS
Sprague-Dawley rats were fed high-fat diet (60% of total calories from fat) for 12 weeks and randomized into either IT or sham surgery. In the IT group, the distal ileal segment located between 5 and 15 cm proximal to the ileocecal valve was transposed 10 cm distal to the Treitz ligament isoperistaltically. In the sham surgery group, 3 corresponding transections of the intestine were made at the same locations as in IT and reattached in situ. β cell senescence was examined by the expression of two markers in vivo, p53BP1 and p16.

RESULTS
IT did not have a significant effect on body weight and insulin sensitivity, but postprandial insulin secretion was significantly increased. Glucagon-like peptide-1 (GLP-1) and peptide YY secretion were also increased after IT. The histology of the transposed ileum showed distinct hypertrophy with increased GLP-1 positive enteroendocrine cells. Pancreatic β cell area was significantly increased in the IT group. The percentage of p16 or p53BP1 positive senescent β cells was significantly lower in the IT group versus the sham group.

CONCLUSIONS
IT improved glucose tolerance in diet-induced obese rats mainly through augmented insulin secretion. This improvement was associated with attenuated β cell senescence.

Ahn|Chang Ho|CH|
Choi|Eun Hye|EH|
Oh|Tae Jung|TJ|
Cho|Young Min|YM|0000-0002-2331-6126

Ileal transposition
β cell mass
β cell senescence
Glucagon-like peptide-1


Stepparents and parenting stress: the roles of gender, marital quality, and views about gender roles.

Abstract: Previous research suggests that stepparenting can be stressful, although the mechanisms that contribute to the experience of parenting stress in stepfamilies are less clear. This study examines gender, marital quality, and views about gendered family roles as correlates of parenting stress among 310 stepmothers, stepfathers, and biological mothers and fathers. Findings suggest that stepparents, and especially stepmothers, experience higher levels of parenting stress than biological parents. Findings also suggest that less traditional views about gendered family roles and higher dyadic adjustment are associated with lower parenting stress for stepparents, particularly in combination. Stepparents reporting both of these protective factors were indistinguishable in terms of parenting stress from biological parents. These findings indicate potential pathways to mitigate the stress associated with stepparenting.

Parenting stress
Gender
Marital quality
Stepfamily


Ultrasensitive and visual detection of tetracycline based on dual-recognition units constructed multicolor fluorescent nano-probe.

Abstract: Ultrasensitive and visual detection of tetracycline antibiotic (TC) residues is of great significance to public health and environmental safety. A novel dual-response ratiometric fluorescent nano-probe (SiQDs-Cit-Eu) has been elaborately tailored for the determination and on-site visual assay of tetracycline, by grafting citric acid and europium (Eu3+) ions onto the surface of silicon quantum dots (SiQDs). The blue-emissive SiQDs (λem = 455 nm) fabricated by a one-step facile method act as both scaffold for coordination with Eu3+ ions and recognition unit for TC owing to the inner filter effect (IFE). The coordinate unsaturated red-fluorescent Eu3+ ions (λem = 617 nm) bond to the surface of SiQDs, serving as the specific recognition element for TC due to the antenna effect. In the presence of TC, the as-synthesized nano-probe exhibits double (λem = 455 and 617 nm) and reverse response signals which are accompanied by a marked color change from blue to purple, and then red, thus achieving ultra-high sensitivity with a detection limit of 7.1 nM and instant visual detection of TC in real samples (milk, honey, lake and river water). Furthermore, smartphone-assisted point-of-care testing platform is also constructed based on nano-probe-immobilized test paper by using the color scanning APP.

Zhang|Lina|L| Wang|Yuli|Y| Jia|Lei|L| Bi|Ning|N| Bie|Hongyan|H| Chen|Xiangzhen|X| Zhang|Chuanxiang|C| Xu|Jun|J|

Tetracycline
Ratiometric fluorescence
Silicon quantum dots
Europium(III) ion
Smartphone sensing


Mobile vs fixed-bearing total knee arthroplasty performed by a single surgeon: a 4- to 6.5-year randomized, prospective, controlled, double-blinded study.

Abstract: The superiority between posterior-stabilized mobile-bearing and fixed-bearing designs still remains controversial. Fifty-six consecutive patients undergoing primary, unilateral knee arthroplasty for osteoarthritis were randomly assigned to receive either a mobile-bearing (29 patients) or fixed-bearing (27 patients) prosthesis. We report the results at 4 to 6.5 years (mean, 5.5) follow-up. The Knee Society knee scores, pain scores, functional scores and Oxford knee scores were not statistically different (P > 0.05) between the two groups. Mean postoperative range-of-motion of mobile-bearing knees was significantly greater than that of fixed-bearing knees (127º versus 111º, P = 0.011). 72% of patients could sit cross legged, 48% could sit on the floor, and 17% could squat. Kaplan-Meier survival rate was 100%. No spin-out of mobile bearing was observed. The radiological analysis showed no osteolysis or implant loosening.

total knee arthroplasty
posterior-stabilized mobile-bearing
osteoarthritis
fixed-bearing knee


Is Shunt Evaluation Useful in Children With Intraventricular Shunts With Seizures?

Abstract:
BACKGROUND
Seizures are a common presenting symptom to the emergency department (ED) in children with intraventricular shunts (IVS). The incidence of shunt malfunction and the yield of imaging studies in children with IVS presenting with seizures is unknown.

OBJECTIVES
We assessed the utility and diagnostic yield of evaluation for shunt malfunction in patients with IVS with seizure and identified clinical predictors for shunt malfunction in these children.

METHODS
We performed a retrospective review of children aged zero to 21 years of age with IVS who presented to the ED with seizure between 2011 and 2015. Demographic, clinical, laboratory and radiological data were collected. Shunt malfunction was diagnosed based on whether a shunt revision was performed during the hospitalization.

RESULTS
We evaluated 408 ED visits (median age: six years [IQR: 3, 11], males 61.5%) for IVS with seizures. Few visits were for first seizure (37; 9.1%) or for status epilepticus (46 visits; 11.3%). Computerized tomography head was performed in 318 patients (95.2%), of which 32 scans (10.6%) were suggestive of shunt malfunction. A shunt series was performed in 302 (90.4%) and was suggestive of shunt malfunction in eight (2.6%) patients. Shunt malfunction was diagnosed in 40 of 408 visits (9.8%). Only a history of multiple (≥3) shunt revisions was significantly associated with shunt malfunction. There was no association between number, type, or prior history of seizures and shunt malfunction.

CONCLUSION
Our study demonstrates a low yield of imaging studies for the evaluation of shunt malfunction in children with IVS with seizures, and shunt malfunction is an uncommon cause of seizures in these children.

Cohen|Anat|A| Agarwal|Rajkumar|R| Farooqi|Ahmad|A| Kannikeswaran|Nirupama|N|

D015898:Tomography Scanners, X-Ray Computed

Intraventricular shunts
Seizures
Computerized tomography head/brain
Hydrocephalus


Promises and pitfalls of synthetic chromosomes in plants.

Abstract: This review summarizes synthetic chromosome construction in plants and speculates on how they might be applied to various uses in the future, as well as the possible impact for synthetic biology. The procedures to construct foundational platforms for synthetic chromosomes in plants are described, together with some challenges to be overcome in growing such chromosomes and expanding their applications.

D022201:Chromosomes, Artificial
D032461:Chromosomes, Plant
D017343:Genes, Plant
D005813:Genes, Synthetic
D008967:Molecular Biology
D010944:Plants

plants
synthetic biology
artificial chromosomes
centromere
engineered minichromosomes
food security
genetic engineering


Chemiluminescence "signal-on-off" dual signals ratio biosensor based on single-stranded DNA functions as guy wires to detect EcoR V.

Abstract: Signal output mode is the important part of biosensor. In general, "signal on" and "signal off" are two common output modes. The development of dual signals-based ratio analysis as a powerful diagnostic tool has attracted widespread attention in the biosensor field in recent years. Dual signals ratio sensors with "signal on" and "signal off" are more favored because of their low background signal and better sensitivity and selectivity. In this study, inspired by the idea that EcoR V can cut specific sites of DNA to produce two corresponding fragments, and by using the capturing probe as guy wires, a reliable and sensitive method for EcoR V assay is developed based on the ratio of dual chemiluminescence (CL) signals for the first time. In particular, in the existence of the objective EcoR V, the substrate DNA would be degraded into two double stranded oligonucleotides with blunt ends which include the sequence I and the sequence II, then they can separately compete with two different corresponding capture probes on magnetic beads (MBs). One of capture probe hybridized with the sequence I containing more guanine (G) bases that reacted with the phenylglyoxal (PG) to produce chemical reaction which triggered a positive CL signal output I + CL as "signal-on"; another capture probe is priority to hybridize the sequence II, which triggered the weaker reporter DNA linked with horseradish peroxidase (HRP) probe to fall off the MBs, thereby outputting a negative CL signal I-CL as "signal-off". By comparing the linear relation and the correlation coefficient, the I-CL/I + CL ratio method has better linear relation (0.01-10 U/mL) and higher sensitivity (0.0045 U/mL). In addition, this developed strategy of high selectivity which can directly detect low concentration of target EcoR V in human serum, and thus this dual ratio biosensor might offer a promising detection approach for clinical diagnostics.

Yan|Xiluan|X| Shu|Qinglei|Q| Zhao|Kun|K| Xiao|Yipi|Y| Ai|Fanrong|F| Zheng|Xiangjuan|X|

Chemiluminescence
Dual Signals
Ratio Biosensor
EcoR V
DNA strand-displacement reactions


Influences of nitrite on paracetamol degradation in dielectric barrier discharge reactor.

Abstract: The frequent detection of paracetamol in natural water increased environmental concerns. The dielectric barrier discharge (DBD) technology is an effective paracetamol removing method, however, this research showed that the removal of paracetamol using DBD technology at 30 min dropped from 100% to 53.3% as the initial paracetamol concentration increased from 10 mg/L to 100 mg/L, due to the formation of more competitive intermediate products at higher paracetamol concentration. The removal of TOC was found to be much slower than that of paracetamol, as paracetamol was removed completely after 5 min treatment, the removal rate of TOC was 46.3% after 20 min treatment under 500 W discharge power and 50 mL/min air flow rate. The orthogonal experiment showed that the removal of TOC was significantly influenced by the treatment time, discharge power and recirculating flow rate, while less influenced by the discharge frequency. In the removal process of paracetamol, nitrite ion that generated during DBD treatment reacted with paracetamol to form an intermediate product of 3-nitro-4-acetamidophenol. The presence of nitrite ion retarded the removal of 3-nitro-4-acetamidophenol and thus the TOC, however, the nitrate ion did not. The degradation of paracetamol followed a sequence of 3-nitro-4-acetamidophenol, nitrosophenol/acetamide, N-methylacetamide, acetamide and small molecule organic acids in the DBD reactor, and these intermediates were finally oxidized to CO2, H2O and NO3-.

Nitrite
Paracetamol
Dielectric barrier discharge
TOC
Plasma


Design and development of engineered receptors for cell and tissue engineering.

Abstract: Advances in synthetic biology have provided genetic tools to reprogram cells to obtain desired cellular functions that include tools to enable the customization of cells to sense an extracellular signal and respond with a desired output. These include a variety of engineered receptors capable of transmembrane signaling that transmit information from outside of the cell to inside when specific ligands bind to them. Recent advances in synthetic receptor engineering have enabled the reprogramming of cell and tissue behavior, controlling cell fate decisions, and providing new vehicles for therapeutic delivery.

cell and tissue engineering
Synthetic biology
synthetic receptors
receptor engineering


Biosynthesis of Carnosine and Related Dipeptides in Vertebrates.

Abstract: Carnosine (β-alanyl-L-histidine) and its methylated derivatives: anserine (β-alanyl-Nπ- methyl-L-histidine) and balenine (β-alanyl-Nτ-methyl-L-histidine) are abundant constituents of excitable tissues of vertebrates. While carnosine and anserine are present at high concentrations and in variable proportions in skeletal muscle and brain of most vertebrates, balenine appears to be rather more abundant in marine mammals and certain reptilian species. Since the discovery of these compounds at the beginning of 20th century, numerous studies have been devoted to identification of the biochemical and physiological properties of carnosine and related dipeptides. These led to the discovery of the pHbuffering, metal-chelation and antioxidant, capabilities of carnosine and anserine, although no definitive ideas concerning their physiological role has yet been formulated. Only recently the molecular identities of the enzymes catalyzing synthesis of carnosine (carnosine synthase, EC 6.3.2.11) and anserine (carnosine N-methyltransferase, EC 2.1.1.22) have been elucidated, which has given a new insight into their metabolism in vertebrates. These findings have opened new research areas and provide authentic opportunities for understanding the biological function of these "enigmatic" dipeptides. This review aims to summarize recent advances in our knowledge concerning enzymes responsible for the biosynthesis of carnosine and related dipeptides and to evaluate their importance in vertebrate physiology.

biosynthesis
carnosine
Anserine
balenine
carnosine synthase
carnosine N-methyltransferase
CARNMT1
CARNS1
HNMT-like
UPF0586
homocarnosine.


Near-Field Thermophotovoltaic Conversion with High Electrical Power Density and Cell Efficiency above 14.

Abstract: A huge amount of thermal energy is available close to material surfaces in radiative and nonradiative states, which can be useful for matter characterization or energy harvesting. Even though a full class of novel nanoengineered devices has been predicted over the last two decades for exploiting near-field thermal photons, efficient near-field thermophotovoltaic conversion could not be achieved experimentally until now. Here, we realize a proof of principle by using a micrometer-sized indium antimonide photovoltaic cell cooled at 77 K and approached at nanometer distances from a hot (∼730 K) graphite microsphere emitter. We demonstrate a near-field power conversion efficiency of the cell above 14% and unprecedented electrical power density outputs (0.75 W cm-2), which are orders of magnitude larger than all previous attempts. These results highlight that near-field thermophotovoltaic converters are now competing with other thermal-to-electrical conversion devices and also pave the way for efficient photoelectric detection of near-field thermal photons.

thermophotovoltaics
conversion efficiency
Thermal radiation
nanoscale


Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate Immunity Against Pneumocystis Infection.

Abstract: Invasive fungal infections, including Pneumocystis Pneumonia (PcP), remain frequent life-threatening conditions of patients with adaptive immune defects. While innate immunity helps control pathogen growth early during infection, it is typically not sufficient for complete protection against Pneumocystis and other human fungal pathogens. Alveolar macrophages (AM) possess pattern recognition molecules capable of recognizing antigenic and structural determinants of Pneumocystis. However, this pathogen effectively evades innate immunity to infect both immunocompetent and immunosuppressed hosts, albeit with differing outcomes. During our studies of mouse models of PcP, the FVB/N strain was identified as unique because of its ability to mount a protective innate immune response against Pneumocystis infection. In contrast to other immunocompetent strains, which become transiently infected prior to the onset of adaptive immunity, FVB/N mice rapidly eradicated Pneumocystis before an adaptive immune response was triggered. Furthermore, FVB/N mice remained highly resistant to infection even in the absence of functional T cells. The effector mechanism of innate protection required the action of functional alveolar macrophages, and the adoptive transfer of resistant FVB/N AMs, but not susceptible CB.17 AMs, conferred protection to immunodeficient mice. Macrophage IFNγ receptor signaling was not required for innate resistance, and FVB/N macrophages were found to display markers of alternative activation. IFNγ reprogrammed resistant FVB/N macrophages to a permissive M1 biased phenotype through a mechanism that required direct activation of the macrophage IFNγR. These results demonstrate that appropriately programmed macrophages provide protective innate immunity against this opportunistic fungal pathogen, and suggest that modulating macrophage function may represent a feasible therapeutic strategy to enhance antifungal host defense. The identification of resistant and susceptible macrophages provides a novel platform to study not only the mechanisms of macrophage-mediated antifungal defense, but also the mechanisms by which Pneumocystis evades innate immunity.

Bhagwat|Samir P|SP|
Gigliotti|Francis|F|
Wang|Jing|J|
Wang|Zhengdong|Z|
Notter|Robert H|RH|
Murphy|Patrick S|PS|
Rivera-Escalera|Fátima|F|
Malone|Jane|J|
Jordan|Michael B|MB|
Elliott|Michael R|MR|
Wright|Terry W|TW|

D056704:Adaptive Immunity
D000818:Animals
D006801:Humans
D007113:Immunity, Innate
D007121:Immunocompetence
D016867:Immunocompromised Host
D008264:Macrophages
D016676:Macrophages, Alveolar
D008807:Mice, Inbred BALB C
D008810:Mice, Inbred C57BL
D008819:Mice, Nude
D016513:Mice, SCID
D016720:Pneumocystis Infections
D015398:Signal Transduction
D013601:T-Lymphocytes

alveolar macrophage
innate immunity
pneumocystis
fungal pathogens
mouse models


Identified OAS3 gene variants associated with coexistence of HBsAg and anti-HBs in chronic HBV infection.

Abstract: The underlying mechanism of coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen antibody (anti-HBs) is still controversial. To identify the host genetic factors related to this unusual clinical phenomenon, a two-stage study was conducted in the Chinese Han population. In the first stage, we performed a case-control (1:1) age- and gender-matched study of 101 cases with concurrent HBsAg and anti-HBs and 102 controls with negative HBsAg and positive anti-HBs using whole exome sequencing. In the second validation stage, we directly sequence the 16 exons on the OAS3 gene in two dependent cohorts of 48 cases and 200 controls. Although, in the first stage, a genome-wide association study of 58,563 polymorphism variants in 101 cases and 102 controls found no significant loci (P-value ≤ .05/58563), and neither locus achieved a conservative genome-wide significance threshold (P-value ≤ 5e-08), gene-based burden analysis showed that OAS3 gene rare variants were associated with the coexistence of HBsAg and anti-HBs. (P-value = 4.127e-06 ≤ 0.05/6994). A total of 16 rare variants were screened out from 21 cases and 3 controls. In the second validation stage, one case with a stop-gained rare variant was identified. Fisher's exact test of all 149 cases and 302 controls showed that the rare coding sequence mutations were more frequent in cases vs controls (P-value = 7.299e-09, OR = 17.27, 95% CI [5.01-58.72]). Protein-coding rare variations on the OAS3 gene are associated with the coexistence of HBsAg and anti-HBs in patients with chronic HBV infection in Chinese Han population.

Wang|S|S|
Wang|J|J|
Fan|M-J|MJ|
Li|T-Y|TY|
Pan|H|H|
Wang|X|X|
Liu|H-K|HK|
Lin|Q-F|QF|
Zhang|J-G|JG|
Guan|L-P|LP|
Zhernakova|D V|DV|
O'Brien|S J|SJ|
Feng|Z-R|ZR|
Chang|L|L|
Dai|E-H|EH|
Lu|J-H|JH|
Xi|H-L|HL|
Zeng|Z|Z|
Yu|Y-Y|YY|
Wang|B-B|BB|0000-0002-1597-5930

OAS3
coexistence of HBsAg and anti-HBs
whole exome sequencing
rare variants


Solving visual pollution with deep learning: A new nexus in environmental management.

Abstract: Visual pollution is a relatively new concern amidst the existing plethora of mainstream environmental pollution, recommending the necessity for research to conceptualize, formalize, quantify and assess it from different dimensions. The purpose of this study is to create a new field of automated visual pollutant classification, harnessing the technological prowess of the 21st century for applications in environmental management. From the wide range of visual pollutants, four categories have been considered viz. (i) billboards and signage, (ii) telephone and communication wires, (iii) network and communication towers and (iv) street litter. The deep learning model used in this study simulates the human learning experience in the context of image recognition for visual pollutant classification by training and testing a convolutional neural network with several layers of artificial neurons. Data augmentation using image processing techniques and a train-test split ratio of 80:20 have been used. Training accuracy of 95% and validation accuracy of 85% have been achieved by the deep learning model. The results indicate that the upper limit of accuracy i.e. the asymptote, depends on the dataset size for this type of task. This study has several applications in environmental management. For example, the deployment of the trained model for processing of video/live footage from smartphone applications, closed-circuit television and drones/unmanned aerial vehicles can be applied for both the removal and management of visual pollutants in the natural and built environment. Furthermore, generating the 'visual pollution score/index' of urban regions such as towns and cities will create a new 'metric/indicator' in the field of urban environmental management.

Ahmed|Nahian|N|
Islam|M Nazmul|MN|
Tuba|Ahmad Saraf|AS|
Mahdy|M R C|MRC|
Sujauddin|Mohammad|M|

Visual pollution
Deep learning
Environmental management
Pollutant classification
Image recognition
Convolutional neural network


Effects of aristolochic acid I and/or hypokalemia on tubular damage in C57BL/6 rat with aristolochic acid nephropathy.

Abstract:
Background/Aims
This study was designed to investigate the roles of aristolochic acid I (AA-I) and hypokalemia in acute aristolochic acid nephropathy (AAN).

METHODS
After an adaptation period (1 week), a total of 40 C57BL/6 mice (male, 8 weeks old) were divided into four groups: I (control group), II (low potassium [K] diet), III (normal K diet with administration of AA-I [10 mg/kg weight]), and IV (low K diet with AA-I). After collecting 24 hours of urine at 2 weeks, the mice were sacrificed, and their blood and kidneys were obtained to perform immunochemical staining and/or Western blot analysis.

RESULTS
Proteinuria, glycosuria, and increased fractional excretion of sodium and K were prominent in groups III and IV (p < 0.05). Diffuse swelling and poor staining of collecting duct epithelial cells were evident in the medullas of group II. Typical lesions of toxic acute tubular injury were prominent in the cortices of groups III and IV. Α-Smooth muscle actin (α-SMA) was higher in the cortices of the mice in groups III and IV versus group II (p < 0.05), and higher in the medullas of group IV than groups I and III (p < 0.05). E-cadherin was higher in the cortices of groups III and IV compared to group I (p < 0.05). The F4/80 value was higher in the cortices and medullas of groups II, III, and IV compared to group I (p < 0.05), particularly in the case of group II.

Conclusions
AA-I can induce acquired Fanconi syndrome in the acute stage of AAN. Macrophages appear to play a key role in the pathogenesis of AAN and hypokalemic nephropathy. It remains uncertain whether hypokalemia plays any role in AAN and hypokalemia.

Yi|Joo-Hark|JH| Han|Sang-Woong|SW| Kim|Wan-Young|WY| Kim|Jin|J| Park|Moon-Hyang|MH|

Aristolochic acid I
Hypokalemia
Macrophages
Balkan nephropathy


COVID-19 - Important considerations for developing and using a vaccine.

Abstract: The novel coronavirus SARS-CoV-2 after emerging in China has caused a global pandemic that is risking the lives of millions. COVID-19 has spread across the world at a very rapid rate raising concerns of capacity limitations and lack of unified responses at the global level, particularly from the world's most developed countries. The spread of further infection has been curtailed by lockdown and mass social distancing that has been enforced in most parts of the world. There are no clinical data yet suggesting that any available candidate vaccine will be effective for COVID-19 which will be a critical need for eventually preventing this disease. Extensive research is underway with some success in identification of monoclonal antibodies from COVID-19 recovered patients, which may inform on vaccine development. The clinical evaluations of COVID-19 vaccines need to follow standardized protocols that are essential for safeguarding humans. In absence of a vaccine or a widely available effective therapy, quarantine and other preventive measures are essential in curtailing the risk of pandemic spread.


Bilateral Lichen Striatus: A Case Report with Review of Literature.

Abstract: Lichen striatus is a self-limiting dermatosis presenting with sudden eruption of lichenoid papules along the lines of Blaschko. A 5-year-old girl presented with asymptomatic hypopigmented linear lesions over both upper limbs. The histopathological examination revealed spongiosis, vacuolar alteration of the basal layer and lymphocytic exocytosis with a mild-to-moderate perivascular mononuclear infiltrate in the dermis. Lichen striatus was diagnosed based upon the characteristic clinical and histopathological findings. The pathogenetic mechanism of bilateral lichen striatus is unknown at present, however, a somatic mutation in two different clones of cells can be a possibility.

Gupta|Aastha|A|
Gautam|Ram K|RK|
Bhardwaj|Minakshi|M|


Prevalence and associated factors of diabetic retinopathy in rural Korea: the Chungju metabolic disease cohort study.

Abstract: This study was aimed to investigate the prevalence of diabetic retinopathy and its associated factors in rural Korean patients with type 2 diabetes. A population-based, cross-sectional diabetic retinopathy survey was conducted from 2005 to 2006 in 1,298 eligible participants aged over 40 yr with type 2 diabetes identified in a rural area of Chungju, Korea. Diabetic retinopathy was diagnosed by a practicing ophthalmologist using funduscopy. The overall prevalence of diabetic retinopathy in the population was 18% and proliferative or severe non-proliferative form was found in 5.0% of the study subjects. The prevalence of retinopathy was 6.2% among those with newly diagnosed type 2 diabetes and 2.4% of them had a proliferative or severe non-proliferative diabetic retinopathy. The odds ratio of diabetic retinopathy increased with the duration of diabetes mellitus (5-10 yr: 5.2- fold; > 10 yr: 10-fold), postprandial glucose levels (> 180 mg/dL: 2.5-fold), and HbA1c levels (every 1% elevation: 1.34-fold). The overall prevalence of diabetic retinopathy in rural Korean patients was similar to or less than that of other Asian group studies. However, the number of patients with proliferative or severe non-proliferative diabetic retinopathy was still high and identified more frequently at the time of diagnosis. This emphasizes that regular screening for diabetic retinopathy and more aggressive management of glycemia can reduce the number of people who develop diabetic retinopathy.

Kim|Ji-Hyun|JH|
Kwon|Hyuk-Sang|HS|
Park|Yong-Moon|YM|
Lee|Jin-Hee|JH|
Kim|Man-Soo|MS|
Yoon|Kun-Ho|KH|
Lee|Won Chul|WC|
Cha|Bong-Yun|BY|
Son|Ho-Young|HY|

D000368:Aged
D001786:Blood Glucose
D015331:Cohort Studies
D003924:Diabetes Mellitus, Type 2
D003930:Diabetic Retinopathy
D005260:Female
D006442:Glycated Hemoglobin A
D006801:Humans
D008297:Male
D008875:Middle Aged
D016017:Odds Ratio
D015995:Prevalence
D056910:Republic of Korea
D012307:Risk Factors
D012424:Rural Population

Prevalence
Diabetic Retinopathy
Risk Factors


Prospective Prediction of Juvenile Homicide/Attempted Homicide among Early-Onset Juvenile Offenders.

Abstract: While homicide perpetrated by juveniles is a relatively rare occurrence, between 2010 and 2014, approximately 7%-8% of all murders involved a juvenile offender. Unfortunately, few studies have prospectively examined the predictors of homicide offending, with none examining first-time murder among a sample of adjudicated male and female youth. The current study employed data on 5908 juvenile offenders (70% male, 45% Black) first arrested at the age of 12 or younger to prospectively examine predictors of an arrest for homicide/attempted homicide by the age of 18. Among these early-onset offenders, males, Black youth, those living in households with family members with a history of mental illness, those engaging in self-mutilation, and those with elevated levels of anger/aggression (all measured by age 13) were more likely to be arrested for homicide/attempted homicide by age 18. These findings add to the scant scientific literature on the predictors of homicide, and illustrate potential avenues for intervention.

Baglivio|Michael T|MT|
Wolff|Kevin T|KT|

homicide
juvenile offending
murder
violence


The mechanism of polystyrene microplastics to affect arsenic volatilization in arsenic-contaminated paddy soils.

Abstract: Different concentrations and sizes of polystyrene microplastics (PS-MP) were added to low (25.9) and high (56.8) mg kg-1 As-contaminated soil to investigate the effects of PS-MP on soil As volatilization. Either S1 (10 μm) or S2 (0.1-1 μm) PS-MP was added to As-contaminated soil at 0.8%, which increased As volatilization by 13.7% and 7.4% in low As-contaminated soil; and 21.8% and 16.5% in high As-contaminated soil, respectively. The addition of PS-MP reduced the water-soluble (WS) As content, increased the non-specifically-sorbed (NSS), specifically-sorbed (SS) As content, soil catalase (CAT) and urease (UE) activities. The abundance of Proteobacteria and Firmicutes showed opposite trends to As volatilization, while the abundance of Bacteroidetes and arsM gene expression exhibited similar variability to As volatilization over the 7-week experiment. Therefore, we postulate that in As-contaminated soil, As volatilization was enhanced in the presence of PS-MP due to two possible mechanisms: 1) PS-MP affects the abundance of Proteobacteria, Firmicutes, Bacteroidetes, and arsM gene in soil; 2) PS-MP increases As volatilization via reducing soil nutrient and increasing the content of SS As. Our results highlighted the importance of investigating impacts of microplastics on the volatility of specific contaminants to implement effective environmental remediation strategies in polluted farmlands.

Dong|Youming|Y| Gao|Minling|M| Liu|Xuewei|X| Qiu|Weiwen|W| Song|Zhengguo|Z|

Polystyrene microplastic
Volatilization
As
Microbial
Species


The effects of menthol on exercise performance and thermal sensation: A meta-analysis.

Abstract:
OBJECTIVES
Menthol is an organic compound with non-thermal cooling properties that has been shown to relieve thermal strain associated with exercise in the heat; however, its effects on performance have not been systematically analysed. The aims were to determine the effects of menthol applied (1) internally and (2) externally on exercise performance and thermal sensation.

DESIGN
Meta-analysis METHODS: A search was performed using various databases in August 2018. The studies were screened using search criteria for eligibility. Thirteen peer-reviewed articles were identified for inclusion in a primary analysis on the effect of menthol on exercise performance; subsequently eleven of these articles were included in a secondary analysis on the effect of menthol on thermal sensation during exercise. A sub-analysis examining the application method was also performed.

RESULTS
Menthol improved overall exercise performance (Hedges' g=0.33, 95% CI -0.00, 0.65 P=0.05), demonstrating greater effects when applied internally (Hedges' g=0.40, 95% CI 0.04, 0.76, P=0.03). Thermal sensation was also lowered overall across all studies (Hedges' g=-0.54, 95% CI -0.67, -0.42, P<0.001).

CONCLUSIONS
Exercise performance can be improved by application of non-thermally cooling menthol, which also reduces perceptual measures of thermal sensation. Internal application appears to be the best strategy to improve performance.

Heat Cold Perception Sensory Thermoregulation


Glutamate-Cysteine Ligase Catalytic Subunit Attenuated Hepatitis C Virus-Related Liver Fibrosis and Suppressed Endoplasmic Reticulum Stress.

Abstract: The study aimed to clarify the role and molecular mechanism of glutamate-cysteine ligase catalytic subunit (GCLC) in modulating Hepatitis C virus (HCV)-related liver fibrosis. Twenty patients with HCV-related liver fibrosis and 15 healthy controls were enrolled. Differentially expressed plasma mRNAs were detected by digital gene expression profile analysis and validated by qRT-PCR. Hepatic histopathology was observed by H&E and Masson stained liver sections. The mRNA and protein expression of GCLC, endoplasmic reticulum (ER) stress markers, and inflammatory and fibrogenic factors were detected in liver tissues from patients with HCV-related hepatic fibrosis and HCV core protein-expressing LX-2. The GCLC-overexpressing LX-2 were established by transfecting puc19-GCLC plasmid. Then, glutathione and reactive oxygen species (ROS) levels were measured respectively by spectrophotometric diagnostic kit and dihydrodichlorofluorescein diacetate kit. GCLC were dramatically down-regulated in HCV-related fibrotic livers and activated HSCs, which companied with up-regulation of ER stress-related genes, including inositol-requiring 1 (IRE1) and glucose-regulated protein 78 (GRP78). Also, the proinflammatory and profibrogenic gene, including nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNFα), and transforming growth factor 1(TGFβ1), was highly upregulated. Overexpression of GCLC in hepatic stellate cells could suppress α-SMA and collagen I expression, produce hepatic GSH and reduce ROS, and down-regulate IRE1, GRP78, NF-κB, TNF-α, and TGFβ1 expression. GCLC was a negative regulatory factor in the development of HCV-related liver fibrosis and might be a potential therapeutic target for liver fibrosis.

Fu|Na|N| Li|Dongdong|D| Li|Wencong|W| Zhao|Wen|W| Zhang|Siyu|S| Liu|Lingdi|L| Zhao|Suxian|S| Du|Jinghua|J| Kong|Lingbo|L| Wang|Rongqi|R| Zhang|Yuguo|Y| Nan|Yuemin|Y|


Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents.

Abstract: A fungal strain, Drechmeria sp., was isolated from the root of Panax notoginseng. Totally, seven new indole diterpenoids, drechmerins A-G (1-7), were isolated from the fermentation broth of Drechmeria sp. together with four known analogues (8-11). Their structures were determined on the basis of 1D and 2D NMR and electronic circular dichroism (ECD) spectroscopic analyses as well as theoretical calculations. All the isolated compounds were evaluated for their antimicrobial activities against Candida albicans, Staphylococcus aureus, Bacillus cereus, B. subtillis, Pseudomonas aeruginosa, and Klebsiella pneumonia, respectively. Drechmerin B (2) displayed antimicrobial activity against C. albicans with an MIC value of 12.5 μg/mL. Molecular docking was used to investigate interactions of peptide deformylase with compounds 1-3, 5-7, 9, and 10.

Zhao|Jian-Chao|JC| Wang|Ya-Li|YL| Zhang|Tian-Yuan|TY| Chen|Zhong-Jian|ZJ| Yang|Tian-Mei|TM| Wu|Ying-Ying|YY| Sun|Cheng-Peng|CP| Ma|Xiao-Chi|XC| Zhang|Yi-Xuan|YX|

D000900:Anti-Bacterial Agents
D000890:Anti-Infective Agents
D002176:Candida albicans
D004224:Diterpenes
D006999:Hypocreales
D007211:Indoles
D008826:Microbial Sensitivity Tests
D015394:Molecular Structure
D011550:Pseudomonas aeruginosa
D013211:Staphylococcus aureus

Indole diterpenoids
Drechmeria sp.
Theoretical calculation
Antimicrobial activity


Determination of the ratio between mercaptalbumin and nonmercaptalbumin by HPLC with fluorescence probe specifically binding to albumin.

Abstract: A simple and selective HPLC-fluorescence (FL) method with FL probe, 4-[4-(4-dimethylaminophenyl)-5-phenyl-1H-imidazol-2-yl]benzoic acid methyl ester (DAPIM), for simultaneous determination of mercaptalbumin (HMA) and nonmercaptalbumin (HNA1) was developed. After HMA and HNA1 were separated on an ion-exchange column, they were on-line and post-column mixed with DAPIM. The DAPIM-albumin complex produces FL (λex 370nm and λem 510nm); however, DAPIM solution never gives the FL. Based on this mechanism, selective determination of HMA and HNA1 were achieved without any pretreatment and interfering peak. The proposed method was applied to the measurement of HMA and HNA1 in human serum of healthy volunteers and diabetes mellitus patients.

Ohyama|Kaname|K| Kishikawa|Naoya|N| Matsuo|Aya|A| Imazato|Takahiro|T| Ueki|Yukitaka|Y| Wada|Mitsuhiro|M| Nakashima|Kenichiro|K| Kuroda|Naotaka|N|

D002851:Chromatography, High Pressure Liquid

4-[4-(4-dimethylaminophenyl)-5-phenyl-1H-imidazol-2-yl]Benzoic acid methyl ester


A Fatty Acyl Coenzyme A Reductase Promotes Wax Ester Accumulation in Rhodococcus jostii RHA1.

Abstract: Many rhodococci are oleaginous and, as such, have considerable potential for the sustainable production of lipid-based commodity chemicals. Herein, we demonstrated that Rhodococcus jostii RHA1, a soil bacterium that catabolizes a wide range of organic compounds, produced wax esters (WEs) up to 0.0002% of its cellular dry weight during exponential growth on glucose. These WEs were fully saturated and contained primarily 31 to 34 carbon atoms. Moreover, they were present at higher levels during exponential growth than under lipid-accumulating conditions. Bioinformatics analyses revealed that RHA1 contains a gene encoding a putative fatty acyl coenzyme A (acyl-CoA) reductase (FcrA). The purified enzyme catalyzed the NADPH-dependent transformation of stearoyl-CoA to stearyl alcohol with a specific activity of 45 ± 3 nmol/mg · min and dodecanal to dodecanol with a specific activity of 5,300 ± 300 nmol/mg · min. Deletion of fcrA did not affect WE accumulation when grown in either carbon- or nitrogen-limited medium. However, the ΔfcrA mutant accumulated less than 20% of the amount of WEs as the wild-type strain under conditions of nitric oxide stress. A strain of RHA1 overproducing FcrA accumulated WEs to ∼13% cellular dry weight under lipid-accumulating conditions, and their acyl moieties had longer average chain lengths than those in wild-type cells (C17 versus C16). The results provide insight into the biosynthesis of WEs in rhodococci and facilitate the development of this genus for the production of high-value neutral lipids.IMPORTANCE Among the best-studied oleaginous bacteria, rhodococci have considerable potential for the sustainable production of lipid-based commodity chemicals, such as wax esters. However, many aspects of lipid synthesis in these bacteria are poorly understood. The current study identifies a key enzyme in wax ester synthesis in rhodococci and exploits it to significantly improve the yield of wax esters in bacteria. In so doing, this work contributes to the development of novel bioprocesses for an important class of oleochemicals that may ultimately allow us to phase out their unsustainable production from sources such as petroleum and palm oil.

Round|James|J|
Roccor|Raphael|R|
Li|Shu-Nan|SN|
Eltis|Lindsay D|LD|

wax esters
Rhodococcus
fatty acyl-CoA reductase
lipid accumulation
metabolic engineering


The irre cell recognition module (IRM) protein Kirre is required to form the reciprocal synaptic network of L4 neurons in the Drosophila lamina.

Abstract: Each neuropil module, or cartridge, in the fly's lamina has a fixed complement of cells. Of five types of monopolar cell interneurons, only L4 has collaterals that invade neighboring cartridges. In the proximal lamina, these collaterals form reciprocal synapses with both the L2 of their own cartridge and the L4 collateral branches from two other neighboring cartridges. During synaptogenesis, L4 collaterals strongly express the cell adhesion protein Kirre, a member of the irre cell recognition module (IRM) group of proteins ( Fischbach et al., 2009 , J Neurogenet, 23, 48-67). The authors show by mutant analysis and gene knockdown techniques that L4 neurons develop their lamina collaterals in the absence of this cell adhesion protein. Using electron microscopy (EM), the authors demonstrate, however, that without Kirre protein these L4 collaterals selectively form fewer synapses. The collaterals of L4 neurons of various genotypes reconstructed from serial-section EM revealed that the number of postsynaptic sites was dramatically reduced in the absence of Kirre, almost eliminating any synaptic input to L4 neurons. A significant reduction of presynaptic sites was also detected in kirre(0) mutants and gene knockdown flies using RNA interference. L4 neuron reciprocal synapses are thus almost eliminated. A presynaptic marker, Brp-short(GFP) confirmed these data using confocal microscopy. This study reveals that removing Kirre protein specifically disrupts the functional L4 synaptic network in the Drosophila lamina.

Lüthy|Kevin|K|
Ahrens|Birgit|B|
Rawal|Shilpa|S|
Lu|Zhiyuan|Z|
Tarnogorska|Dorota|D|
Meinertzhagen|Ian A|IA|
Fischbach|Karl-Friedrich|KF|

cell recognition
synapse
cell adhesion
Neph proteins
connectivity
neural circuit
optic lobe
visual system


Validation of Alexa-647-ATP as a powerful tool to study P2X receptor ligand binding and desensitization.

Abstract: Ion channel opening and desensitization is a fundamental process in neurotransmission. The ATP-gated P2X1 receptor (P2X1R) shows rapid and long-lasting desensitization upon agonist binding. This makes the electrophysiological investigation of its desensitization process, agonist unbinding, and recovery from desensitization a challenging task. Here, we show that the fluorescent agonist Alexa-647-ATP is a potent agonist at the P2X1R and a versatile tool to directly visualize agonist binding and unbinding. We demonstrate that the long-lasting desensitization of the P2X1R is due to both slow unbinding of agonist from the desensitized receptor and agonist mediated receptor internalization. Furthermore, the unbinding of the agonist Alexa-647-ATP from the desensitized receptor is accelerated in the continuous presence of competitive ligand. Modeling of our data indicates that three agonist molecules are required to drive the receptor into desensitization. Direct visualization of ligand unbinding from the desensitized receptor demonstrates the cooperativity of this process.

D000255:Adenosine Triphosphate
D000818:Animals
D002232:Carbocyanines
D004791:Enzyme Inhibitors
D005456:Fluorescent Dyes
D009865:Oocytes
D018408:Patch-Clamp Techniques
D011485:Protein Binding
D018075:RNA, Complementary
D051381:Rats
D058474:Receptors, Purinergic P2X1
D014982:Xenopus laevis

Alexa-647-ATP
Binding
Desensitization
Ion channel
P2X1 receptor
Allosteric interaction
MgORI
ORI
PAO
VCF
magnesium oocyte Ringer’s solution
oocyte ringer’s solution
phenyl arsine oxide
voltage clamp fluorometry


Protein kinase C signalling involved in prothoracicotropic hormone-stimulated prothoracic glands in the silkworm, Bombyx mori.

Abstract: In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)-stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37-kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37-kDa protein phosphorylation. PTTH-stimulated phosphorylation of the 37-kDa protein was markedly attenuated in the absence of Ca2+ . The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH-stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5'-monophosphate-activated protein kinase (AMPK) (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) did not affect PTTH-stimulated phosphorylation of the 37-kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC-dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH-stimulated phosphorylation of the 37-kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH-stimulated phosphorylation of the 37-kDa protein. PTTH-stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC-dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox-regulated PTTH-stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.

signalling
Bombyx mori
PKC
PTTH
phosphorylation
redox regulation
ecdysone


Bacterial synthesis of polysialic acid lactosides in recombinant Escherichia coli K-12.

Abstract: Bacterial polysialyltransferases (PSTs) are processive enzymes involved in the synthesis of polysialic capsular polysaccharides. They can also synthesize polysialic acid in vitro from disialylated and trisialylated lactoside acceptors, which are the carbohydrate moieties of GD3 and GT3 gangliosides, respectively. Here, we engineered a non-pathogenic Escherichia coli strain that overexpresses recombinant sialyltransferases and sialic acid synthesis genes and can convert an exogenous lactoside into polysialyl lactosides. Several PSTs were assayed for their ability to synthesize polysialyl lactosides in the recombinant strains. Fed-batch cultures produced α-2,8 polysialic acid or alternate α-2,8-2,9 polysialic acid in quantities reaching several grams per liter. Bacterial culture in the presence of propargyl-β-lactoside as the exogenous acceptor led to the production of conjugatable polysaccharides by means of copper-assisted click chemistry.

Richard|Emeline|E| Buon|Laurine|L| Drouillard|Sophie|S| Fort|Sébastien|S| Priem|Bernard|B|

D015971:Gene Expression Regulation, Enzymologic

polysialic acids
click chemistry
bacterial glycosylation
glyco-engineering


Changes in total phenolic and flavonoid content and antioxidative activities during production of juice concentrate from Asian pears (Pyrus pyrifolia Nakai).

Abstract: The total phenolic and flavonoid content and antioxidative activities during production of pear juice concentrate (PJC) from two cultivars, Hwasan and Niitaka, were investigated. The main processing steps in PJC production are washing, pressing, pasteurization, clarification, filtration, evaporation, and packaging. Total phenolic and flavonoid content of end-product PJC from Niitaka decreased by 53.11 and 46.47%, respectively, while those from Hwasan decreased by 55.46 and 36.09%, respectively, compared to the phenolic and flavonoid content of original fresh fruit. DPPH radical-scavenging activities, reducing power and nitrate radical-scavenging activities showed a similar tendency as total phenolic and flavonoid content; that is, they decreased in juice concentrate made from both cultivars. Also, antioxidant activities of press cake waste (skin and seeds) from Niitaka and Hwasan pears were higher than fresh pears. In conclusion, antioxidant levels were significantly affected during processing of PJC, especially during the pressing step in which press cake waste retains the seeds and skin.

Jiang|Gui-Hun|GH|
Nam|Seung-Hee|SH|
Yim|Sun-Hee|SH|
Kim|Young-Min|YM|
Gwak|Hyun Jung|HJ|
Eun|Jong-Bang|JB|

antioxidant activity
pear juice concentrate
press cake
Niitaka and Hwasan


Modulating eating behavior with transcranial direct current stimulation (tDCS): A systematic literature review on the impact of eating behavior traits.

Abstract: Transcranial direct current stimulation (tDCS) is becoming an increasingly popular technique for altering eating behaviors. Recent research suggests a possible eating behavior trait-dependent effect of tDCS. However, studies recruit participant populations with heterogeneous trait characteristics, including "healthy" individuals who do not present with eating behavior traits suggesting susceptibility to overconsumption. The present review considers the effects of tDCS across eating-related measures and explores whether a trait-dependent effect is evident across the literature. A literature search identified 28 articles using sham-controlled tDCS to modify eating-related measures. Random effects meta-analyses were performed, with subgroup analyses to identify differences between "healthy" and trait groups. Trivial overall effects (g = -0.12 to 0.09) of active versus sham tDCS were found. Subgroup analyses showed a more consistent effect for trait groups, with small and moderate effect size (g = -1.03 to 0.60), suggesting tDCS is dependent on participants' eating behavior traits. Larger effect sizes were found for those displaying traits associated with study outcomes (e.g., heightened food cravings). "Healthy" individuals appear to be unresponsive to stimulation. Based on this meta data, future work should recruit those with eating behavior trait susceptibilities to overconsumption, focusing on those who present with traits associated with the outcome of interest.

food craving
food consumption
food reward
non-invasive brain stimulation


Community-Based Interventions for Cardiovascular Disease Prevention in Low-and Middle-Income Countries: A Systematic Review.

Abstract: Objectives: To synthesize evidence on the effectiveness of community-based interventions for cardiovascular disease (CVD) prevention in low- and middle-income countries (LMICs) to inform design of effective strategies for CVD prevention. Methods: We searched MEDLINE, EMBASE, CINAHL, Cochrane register of controlled studies and PSYCINFO databases for studies published between January 2000 and June 2019. Other studies were identified from gray literature sources and review of reference lists of included studies. The primary outcomes for the review were those aimed at primary prevention of CVD targeting physical activity, diet, smoking and alcohol consumption. Results: Database searches yielded 15,885 articles and 94 articles were identified through snowball searching. After screening, the articles from LMICs were 32 emanating from 27 studies: 9 cluster randomized trials, eight randomized controlled trials and 10 controlled before and after studies. Community-based interventions successfully improved population knowledge on CVD and risk factors and influenced physical activity and dietary practices. Evidence of interventions on smoking cessation and reduced alcohol consumption was inconsistent. Conclusion: This evidence should inform policy makers in decision-making and prioritizing evidence-based interventions.

Ndejjo|Rawlance|R|
Hassen|Hamid Yimam|HY|
Wanyenze|Rhoda K|RK|
Musoke|David|D|
Nuwaha|Fred|F|
Abrams|Steven|S|
Bastiaens|Hilde|H|
Musinguzi|Geofrey|G|

community-based
cardiovascular disease
effectiveness
physical activity
diet
smoking
alcohol
knowledge


Cytocompatibility of a conductive nanofibrous carbon nanotube/poly (L-Lactic acid) composite scaffold intended for nerve tissue engineering.

Abstract: The purpose of this study was to fabricate a conductive aligned nanofibrous substrate and evaluate its suitability and cytocompatibility with neural cells for nerve tissue engineering purposes. In order to reach these goals, we first used electrospinning to fabricate single-walled carbon-nanotube (SWCNT) incorporated poly(L-lactic acid) (PLLA) nanofibrous scaffolds and then assessed its cytocompatibility with olfactory ensheathing glial cells (OEC). The plasma treated scaffolds were characterized using scanning electron microscopy and water contact angle. OECs were isolated from olfactory bulb of GFP Sprague-Dawley rats and characterized using OEC specific markers via immunocytochemistry and flow cytometery. The cytocompatibility of the conductive aligned nano-featured scaffold was assessed using microscopy and MTT assay. We indicate that doping of PLLA polymer with SWCNT can augment the aligned nanosized substrate with conductivity, making it favorable for nerve tissue engineering. Our results demonstrated that SWCNT/PLLA composite scaffold promote the adhesion, growth, survival and proliferation of OEC. Regarding the ideal physical, topographical and electrical properties of the scaffold and the neurotrophic and migratory features of the OECs, we suggest this scaffold and the cell/scaffold construct as a promising platform for cell delivery to neural defects in nerve tissue engineering approaches.

Kabiri|Mahboubeh|M| Oraee-Yazdani|Saeed|S| Dodel|Masumeh|M| Hanaee-Ahvaz|Hana|H| Soudi|Sara|S| Seyedjafari|Ehsan|E| Salehi|Mohammad|M| Soleimani|Masoud|M|

carbon nanotube
composite scaffold
Nerve tissue engineering
electrospun nanofiber
olfactory ensheathing cells


Roll-over shape of a prosthetic foot: a finite element evaluation and experimental validation.

Abstract: Prosthetic feet have generally been designed experimentally by adopting a trial-and-error technique. The objective of this research is to introduce a novel numerical approach for the a priori evaluation of the roll-over shape (ROS) of a prosthetic foot for application in its systematic design and development. The ROS was achieved numerically by employing a non-linear finite element model incorporating the augmented Lagrangian and multi-point constraint contact formulations, a hyperelastic material model and a higher-order strain definition. The Ottobock Solid Ankle Cushion Heel (SACH) foot was chosen to experimentally validate the numerical model. The geometry of the foot was evaluated from optical scans, and the material properties were obtained from uniaxial tensile, shear and volumetric compression tests. A new setup was designed for an improved experimental determination of the ROS, with the inclusion of an extended moment arm and variable loading. Error analysis of the radius of curvature of the ROS between the numerical and experimental results showed the percentage error to be 7.52%, thereby establishing the validity of the model. A numerical design model of this kind can be utilised to vary the input design parameters to arrive at a prosthetic foot with specified performance characteristics effectively and economically. Graphical abstract.

D001186:Artificial Limbs
D017076:Computer-Aided Design
D020342:Finite Element Analysis
D005528:Foot
D006801:Humans
D011474:Prosthesis Design

Foot
Artificial limbs
Finite element analysis
Gait
Walking


Development of corticospinal motor excitability and cortical silent period from mid-childhood to adulthood - a navigated TMS study.

Abstract:
OBJECTIVES
We characterized the maturation of the excitability of the motor cortex and corticospinal tract from childhood to adulthood using electric field (EF) navigated TMS and correlated the results with manual dexterity.

METHODS
Both hemispheres of healthy right-handed children (6-9 years, n=10), preadolescents (10-12 years, n=13), adolescents (14-17 years, n=12) and young adults (22-34 years, n=12) of both genders were examined. The optimal cortical representation site and resting motor threshold (rMT) were determined for the abductor pollicis brevis muscle. Motor-evoked potential (MEP) latencies and amplitudes in relaxed and active states, input-output curves and silent period (SP) durations were determined. Manual dexterity was assessed with the Box and Block Test.

RESULTS
rMT (in terms of maximal stimulator output or EF strength) decreased with age (P<0.001) and stabilized when reaching adolescence. The MEP amplitude (P=0.037) and latency increased (P<0.001) with age. Input-output curves showed age-dependent changes in several parameters. SP duration decreased with age (P<0.001), and demonstrated hemispheric asymmetry in the children (P=0.030). Manual dexterity correlated negatively with rMT (P<0.001).

DISCUSSION
The excitation/inhibition balance develops with age and correlates with manual dexterity. Strong corticospinal inhibition was observed in the children and this was found to decrease with age. Interhemispheric asymmetry was only observed for SP duration in the children. Knowledge of normal development is crucial for the understanding of developmental disabilities and using estimates of effective EF may be advantageous in future pediatric studies.

Säisänen|Laura|L| Julkunen|Petro|P| Lakka|Timo|T| Lindi|Virpi|V| Könönen|Mervi|M| Määttä|Sara|S|

Development
Excitability
Silent period
Motor cortex
Human maturation
Transcranial magnetic stimulation


Transcription Factors Drive Opposite Relationships between Gene Age and Tissue Specificity in Male and Female Drosophila Gonads.

Abstract: Evolutionarily young genes are usually preferentially expressed in the testis across species. Although it is known that older genes are generally more broadly expressed than younger genes, the properties that shaped this pattern are unknown. Older genes may gain expression across other tissues uniformly, or faster in certain tissues than others. Using Drosophila gene expression data, we confirmed previous findings that younger genes are disproportionately testis biased and older genes are disproportionately ovary biased. We found that the relationship between gene age and expression is stronger in the ovary than any other tissue and weakest in testis. We performed ATAC-seq on Drosophila testis and found that although genes of all ages are more likely to have open promoter chromatin in testis than in ovary, promoter chromatin alone does not explain the ovary bias of older genes. Instead, we found that upstream transcription factor (TF) expression is highly predictive of gene expression in ovary but not in testis. In the ovary, TF expression is more predictive of gene expression than open promoter chromatin, whereas testis gene expression is similarly influenced by both TF expression and open promoter chromatin. We propose that the testis is uniquely able to express younger genes controlled by relatively few TFs, whereas older genes with more TF partners are broadly expressed with peak expression most likely in the ovary. The testis allows widespread baseline expression that is relatively unresponsive to regulatory changes, whereas the ovary transcriptome is more responsive to trans-regulation and has a higher ceiling for gene expression.

Drosophila
testis
ovary
ATAC-seq
expression complexity
transcription factor expression


Risk factors for recurrence of Crohn's disease requiring surgery in patients receiving post-operative anti-tumor necrosis factor maintenance therapy.

Abstract:
OBJECTIVES
Anti-tumor necrosis factor (TNF) antibodies have shown efficacy in the prevention of recurrence of Crohn's disease after intestinal resection. However, some patients develop surgical recurrence despite this therapy. We aimed to evaluate the risk factors for recurrence of Crohn's disease requiring surgery while receiving post-operative anti-TNF therapy.

METHODS
We performed a retrospective evaluation of 164 patients who had received post-operative anti-TNF maintenance therapy between 2002 and 2016. We classified Crohn's disease-related re-operation as surgical recurrence and analyzed its risk factors using the Cox proportional hazard model.

RESULTS
Of the 164 participants, 128 had received infliximab and 36 had received adalimumab maintenance therapy. We obtained follow-up data over a mean of 60.2 months. The proportion of patients with surgical recurrence at 5 years was 14.9%. The only independent risk factor for surgical recurrence, which we identified was post-operative smoking habit (odds ratio, 5.03; 95% CI, 1.14-12.8; P=0.033).

CONCLUSIONS
Post-operative smoking may be a significant risk factor for post-operative surgical recurrence of Crohn's disease while receiving anti-TNF maintenance therapy.

Araki|Toshimitsu|T| Okita|Yoshiki|Y| Kondo|Satoru|S| Hiro|Junichiro|J| Toiyama|Yuji|Y| Inoue|Mikihiro|M| Ohi|Masaki|M| Inoue|Yasuhiro|Y| Uchida|Keiichi|K| Mohri|Yasuhiko|Y| Kusunoki|Masato|M|

recurrence
Crohn's disease
anti-TNF therapy
smoking
operation


Soft-tissue facial characteristics of attractive Chinese men compared to normal men.

Abstract:
OBJECTIVE
To compare the facial characteristics of attractive Chinese men with those of reference men.

MATERIALS AND METHODS
The three-dimensional coordinates of 50 facial landmarks were collected in 40 healthy reference men and in 40 "attractive" men, soft tissue facial angles, distances, areas, and volumes were computed and compared using analysis of variance.

RESULTS
When compared with reference men, attractive men shared several similar facial characteristics: relatively large forehead, reduced mandible, and rounded face. They had a more acute soft tissue profile, an increased upper facial width and middle facial depth, larger mouth, and more voluminous lips than reference men.

CONCLUSIONS
Attractive men had several facial characteristics suggesting babyness. Nonetheless, each group of men was characterized by a different development of these features. Esthetic reference values can be a useful tool for clinicians, but should always consider the characteristics of individual faces.

Wu|Feng|F| Li|Junfang|J| He|Hong|H| Huang|Na|N| Tang|Youchao|Y| Wang|Yuanqing|Y|


The human embryo, subjectivity and legal capacity. Notes in the light of art. 1 of the Italian law on "medically assisted procreation".

Abstract:
AIM
This paper aims to examine the legal status of the human embryo taking into consideration Article 1 of the Italian law on medically assisted procreation, which protects the human embryo, which is recognised as an individual holding the same rights as already born children. The progressive increase in legal decisions regarding reproductive technologies requires a re-examination of the traditional legal categories of "subjectivity" and legal capacity, and a deeper understanding of the status of the human embryo as a subject, or individua.

MATERIALS AND METHODS
The following sources were searched: Institutional websites, Research Centre for Social Investments reports, updated jurisprudence and Rulings of Italian Constitutional Court and European Court of Human Rights. In addition, also the following databases were searched: PubMed and Scopus, using the following keywords: medically assisted procreation (MAP) and embryo.

RESULTS
The authors believe that the best orientation is the modern principle of equality (non-discrimination); according to them, the need to protect unborn life requires therefore the consideration of interests which can no longer be confined to the solely patrimonial ones held by the embryo. The paper draws attention to a series of non-patrimonial interests, for whose protection the legal expert has to adopt innovative safeguarding techniques. In this context, there emerge some rights worthy of protection whose potential holders are as yet unborn.

Ricci|G|G|
Campanozzi|L L|LL|
Marinelli|S|S|
Midolo|E|E|
Ruggeri|L|L|

Embryo
Subject
Legal capacity
Artificial insemination
Equality principle
Human dignity
Right to life


Immunotherapies in chronic adhesive arachnoiditis - A case series and literature review.

Abstract: Chronic spinal adhesive arachnoiditis (CSAA) is a rare condition with limited therapeutic options. Surgical treatment proves effective in approximately 60% of cases. Conservative treatment options have not been extensively investigated. Here, we report the course of the disease, analyze the effect of immune treatments in patients with CSAA who were treated in the University Hospital Essen between 2015 and 2020, and conduct a literature review. Three out of four patients showed no improvement after treatment with corticosteroids, methotrexate, or plasmapheresis. All non-responders suffered from CSAA for several years, while one patient who had a disease duration of less than one month fully recovered. It is necessary to verify whether treatment at an early stage of the disease is better than treatment after chronic adhesion manifestation, as it interrupts the development of adhesions and all subsequent complications.

Hackert|Jana|J| Maßmann|Louisa|L| Sure|Ulrich|U| Forsting|Michael|M| Kleinschnitz|Christoph|C| Pul|Refik|R| Hagenacker|Tim|T|

CSAA, Chronic spinal adhesive arachnoiditis

ICD, International Statistical Classification of Diseases and Related Health Problems


Activation of muscarinic receptors in rat parotid acinar cells induces AQP5 trafficking to nuclei and apical plasma membrane.

Abstract:
BACKGROUND
The subcellular distribution of aquaporin-5 (AQP5) in rat parotid acinar cells in response to muscarinic acetylcholine receptor (mAChR) activation remains unclear.

METHODS
Immunoconfocal and immunoelectron microscopy were used to visualize the distribution of AQP5 in parotid acinar cells. Western blotting was used to analyze AQP5 levels in membranes. To clarify the characteristics of membrane domains associated with AQP5, detergent solubility and sucrose-density flotation experiments were performed.

RESULTS
Under control conditions, AQP5 was diffusely distributed on the apical plasma membrane (APM) and apical plasmalemmal region and throughout the cytoplasm. Upon mAChR activation, AQP5 was predominantly located in the nucleus, APM and lateral plasma membrane (LPM). Subsequently, localization of AQP5 in the nucleus, APM and LPM was decreased. Prolonged atropine treatment inhibited mAChR agonist-induced translocation of AQP5 to the nucleus, APM and LPM. AQP5 levels were enhanced in isolated nuclei and nuclear membranes prepared from parotid tissues incubated with mAChR agonist. mAChR agonist induced AQP5 levels in both soluble and insoluble nuclear fractions solubilized with Triton X-100 or Lubrol WX. Small amounts of AQP5 in nuclei were detected using low-density sucrose gradient. When AQP5 was present in the nuclear membrane, nuclear size decreased.

CONCLUSION
The activation of mAChR induced AQP5 translocation to the nucleus, APM and LPM, and AQP5 may trigger water transport across the nuclear membrane and plasma membrane in rat parotid acinar cells.

GENERAL SIGNIFICANCE
AQP5 translocates to the nuclear membrane and may trigger the movement of water, inducing shrinkage of the nucleus and the start of nuclear functions.

Cho|Gota|G|
Bragiel|Aneta M|AM|
Wang|Di|D|
Pieczonka|Tomasz D|TD|
Skowronski|Mariusz T|MT|
Shono|Masayuki|M|
Nielsen|Søren|S|
Ishikawa|Yasuko|Y|

D061354:Acinar Cells
D000818:Animals
D051402:Aquaporin 5
D002462:Cell Membrane
D002467:Cell Nucleus
D008297:Male
D021962:Membrane Microdomains
D009685:Nuclear Envelope
D010306:Parotid Gland
D021381:Protein Transport
D051381:Rats
D017208:Rats, Wistar
D011976:Receptors, Muscarinic

Acinar cells
Trafficking
Nuclei
Apical plasma membrane
Aquaporin-5
Parotid glands


Polyherbal formula (ASILACT®) induces Milk production in lactating rats through Upregulation of α-Lactalbumin and aquaporin expression.

Abstract:
BACKGROUND
Polyherbal formula (PHF) contains extract of Sauropus androgynous (L.) Merr., Trigonella foenum-graceum L., and Moringa oleifera Lam. considered to induce galactagogue activity. This research aimed to evaluate the galactagogue activity of PHF and its effects on α-lactalbumin (LALBA) as well as aquaporin (AQP) gene expression at messenger ribonucleic acid (mRNA) levels in mammary glands of lactating rats.

METHODS
Thirty lactating Wistar rats were randomly divided into five groups (n = 6), each has 7 pups. Group I was treated orally with distilled water as negative control. Groups II, III, and IV were orally administered with PHF at 26.25, 52.5 and 105 mg/kg/day, respectively. Group V was treated with domperidone 2.7 mg/kg/day, orally as positive control. The treatment was performed at third day until fifteenth day of parturition. The observed parameters include the galactagogue activity indicating by milk yield of lactating rats, the pup weight changes and lactating rats body weight changes during lactating period, mRNA expression of LALBA and AQP using quantitative Real Time Polymerase Chain Reaction (qRT-PCR) and histopathological analysis of mammary glands at the end of treatment period.

RESULT
The result showed that the PHF groups (52.5 and 105 mg/kg/day) and domperidone were significantly increased milk production of lactating rats (p < 0.05). The levels of mRNA expression of LALBA and AQPs were significantly upregulated by 105 mg/kg/day of PHF or 2.7 mg/kg of domperidone administration (p < 0.0001). Histopathological analysis of mammary glands shows that alveoli diameter was increase 14.59 and 19.33% at 105 mg/kg of PHF and 2.7 mg/kg of domperidone treatment, respectively.

CONCLUSION
The study suggested that PHF has potentially to induce galactagogue activity on lactating period through upregulation of LALBA and AQP genes at the mRNA level.

Aquaporin expression
Sauropus androgynous
Trigonella foenum-graceum
Moringa oleifera
Galactagogue activity
α-Lactalbumin expression


Modelling the growth kinetics of Listeria monocytogenes in pasta salads at different storage temperatures and packaging conditions.

Abstract: The aim of this study was to model Listeria monocytogenes growth kinetics in ready to eat full meal pasta salads, containing fresh and cooked ingredients. With this aim, laboratory prepared salads, representing two formulations of commercial pasta salads, were spiked with L. monocytogenes and tested under categorised packaging and storage temperature conditions. L. monocytogenes enumeration results collected in 15 different laboratory prepared salad datasets were analysed with primary and secondary models. The models showing the best fit to describe L. monocytogenes growth kinetics in the laboratory prepared salads were then validated within commercial pasta salads. Baranyi no-lag was the best primary model fitting datasets collected at 12 °C, whereas the exponential model gave the best results for datasets collected at 4 °C. The maximum microbial specific growth rate (μmax) mean values obtained at 4 and 12 °C for salads packaged under air packaging conditions were 0.008 ± 0.003 and 0.036 ± 0.006 log10 (cfu/g) h-1, respectively. At the same temperatures, the μmax mean values obtained under modified atmosphere were 0.005 ± 0.005 and 0.026 ± 0.005 log10 (cfu/g) h-1, respectively. The Gamma secondary model predicted the growth kinetics of L. monocytogenes at both temperatures and packaging conditions and the μmax at the optimum temperature and the optimum pH for Listeria growth (μopt) estimated by the model corresponded to 0.247 ± 0.009 log10 (cfu/g) h-1. Baranyi model without lag phase was used to generate growth kinetics under different scenarios. In the comparison of the predicted log10 concentrations respect to the observed ones the residues rarely exceeded 1 Log10 cfu/g. The selected models can be applied to describe the growth kinetics of L. monocytogenes in similar types of pasta salads with comparable pH, shelf life and storage conditions.

De Cesare|Alessandra|A|
Vitali|Silvia|S|
Tessema|Girum Tadesse|GT|
Trevisani|Marcello|M|
Fagereng|Tone Mathisen|TM|
Beaufort|Annie|A|
Manfreda|Gerardo|G|
Skjerdal|Taran|T|

D002611:Cheese
D003080:Cold Temperature
D003257:Consumer Product Safety
D005511:Food Handling
D005516:Food Microbiology
D018857:Food Packaging
D005519:Food Preservation
D061353:Food Storage
D007700:Kinetics
D008089:Listeria monocytogenes
D008461:Meat Products
D008962:Models, Theoretical
D014675:Vegetables

Listeria monocytogenes
pasta salads
Storage conditions
predictive models


A Series of Ferulic Acid Amides Reveals Unexpected Peroxiredoxin 1 Inhibitory Activity with in vivo Antidiabetic and Hypolipidemic Effects.

Abstract: Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats as confirmed by histopathological examinations. These results provide guidance for developing the current FAAs as new potential antidiabetic agents.

Yasmin|Sabina|S|
Cerchia|Carmen|C|
Badavath|Vishnu Nayak|VN|
Laghezza|Antonio|A|
Dal Piaz|Fabrizio|F|
Mondal|Susanta K|SK|
Atlı|Özlem|Ö|
Baysal|Merve|M|
Vadivelan|Sankaran|S|
Shankar|S|S|
Siddique|Mohd Usman Mohd|MUM|
Pattnaik|Ashok Kumar|AK|
Singh|Ravi Pratap|RP|
Loiodice|Fulvio|F|
Jayaprakash|Venkatesan|V|
Lavecchia|Antonio|A|0000-0002-2181-8026

Ferulic acid amides
Peroxiredoxin 1
Type 2 diabetes
Hyperglycemia
Hyperlipidemia


Dosing of antibacterial agents in obese adults: does one size fit all?

Abstract: Obesity is a global pandemic affecting 33% of adults in the United States. Obese persons receiving cefazolin or fluconazole have been shown to have worse outcomes with suboptimal dosing. Studies evaluating the safety of colistin, daptomycin, and vancomycin have shown increased weight or obesity may potentially increase toxicity. Many antimicrobials lack pharmacokinetic data to support dose individuation in obese persons, due in part to the lack of obese patients in drug development studies. A one size fits all approach to dose optimization for obese patients is not likely. Current expert opinion suggests some antimicrobials (i.e. vancomycin) be dosed according to total body weight, whereas others (i.e. aminoglycosides) require adjusted body weight for dose calculations. Yet other antimicrobials are reported to need no dose adjustment, largely based on studies using body mass index groups. Therefore, each drug should be individually evaluated to determine the proper dose for obese persons.

antibacterial
obesity
pharmacokinetics
body weight
dose adjustment
BMI


What is the fate of artificial urinary sphincters among men undergoing repetitive bladder cancer treatment?

Abstract:
Purpose
Functional characteristics and durability of the artificial urinary sphincter (AUS) among patients who develop bladder cancer has been poorly characterized. We sought to evaluate AUS outcomes among patients subsequently diagnosed with bladder cancer, in order to describe device survivability when subject to diagnostic and therapeutic procedures such as cystoscopy, transurethral resection, and cystectomy.

Materials and Methods
We retrospectively reviewed 1,803 male patients treated with AUS surgery at a single institution between 1983-2014. We describe AUS device outcomes among patients undergoing surveillance and treatment for bladder cancer.

Results
Following AUS placement, 14 (0.8%) patients were subsequently diagnosed with and treated for bladder cancer and 4 patients with bladder cancer undergoing treatment and screening, subsequently received AUS placement. The median follow-up from device placement was 7.2 years (interquartile range [IQR], 2.8-11.5), and the median time from AUS placement to bladder cancer diagnosis was 6 (IQR, 0-9). There were a total of 8 primary and 1 secondary devices failures. Despite a median of 2 diagnostic cystoscopies (IQR, 1-6) and 0 bladder tumor resections (IQR, 0-0) per patient following device implantation, only 1 (5.6%) patient experienced an iatrogenic erosion related to urethral manipulation. Among those undergoing cystectomy (n=4), 1 device was left in situ without complication.

Conclusions
Bladder cancer surveillance and treatment with an AUS device in place appears to confer minimal additional risk to AUS survival. Careful attention should be given to device deactivation and use of the smallest caliber instruments available to minimize the risk of iatrogenic urethral erosion.

Cystoscopy
Urinary bladder neoplasms
Urinary incontinence
Urinary sphincter, artificial


Adolescent trajectories of fine motor and coordination skills and risk for schizophrenia.

Abstract: Premorbid motor dysfunction is one of the earliest of developmental antecedents identified among individuals who develop schizophrenia in adulthood. However, among individuals with schizophrenia, premorbid motor dysfunction is not apparent at all stages of childhood development and may reduce with increasing age. Currently, little is known about the trajectories of motor development during adolescence among youth at-risk for the disorder. One hundred and one participants were assessed repeatedly, at approximately 24-month intervals (time 1, aged 9-12 years; time 2, 11-14 years; and time 3, 13-16 years), on the Purdue Pegboard assessment, comprising four subtests: Dominant Hand (DH), Non-Dominant Hand (NDH), Both Hands (BH), and Assembly. Fine motor and coordination skills development between ages 9-16 years was compared between youth characterised by a triad of developmental antecedents of schizophrenia (ASz, N = 32); youth with at least one affected relative with schizophrenia/schizoaffective disorder (FHx; N = 26); and typically developing youth without antecedents or family history (TD, N = 43). Longitudinal mixed models for repeated measures indicated significant motor skills improvements with age in TD youth on the Assembly subtest only. Relative to TD youth, we found evidence for developmental deficits (i.e., dysfunction that emerged early and remained stable) among ASz youth on DH and BH subtests, and among FHx youth on the Assembly subtest. ASz youth were characterised by a developmental delay on the Assembly subtest (i.e., initial performance decrement in middle childhood that caught up with peers' performance during adolescence). These divergences from normative motor development may reflect differences in structural and functional neural correlates.

Dickson|Hannah|H|
Roberts|Ruth E|RE|
To|Melody|M|
Wild|Kate|K|
Loh|Max|M|
Laurens|Kristin R|KR|

D020022:Genetic Predisposition to Disease

Antecedents
Motor development
Pegboard
Genetic high-risk
Psychosis
Psychotic-like experiences


Regulated structural transitions unleash the chaperone activity of αB-crystallin.

Abstract: The small heat shock protein αB-crystallin is an oligomeric molecular chaperone that binds aggregation-prone proteins. As a component of the proteostasis system, it is associated with cataract, neurodegenerative diseases, and myopathies. The structural determinants for the regulation of its chaperone function are still largely elusive. Combining different experimental approaches, we show that phosphorylation-induced destabilization of intersubunit interactions mediated by the N-terminal domain (NTD) results in the remodeling of the oligomer ensemble with an increase in smaller, activated species, predominantly 12-mers and 6-mers. Their 3D structures determined by cryo-electron microscopy and biochemical analyses reveal that the NTD in these species gains flexibility and solvent accessibility. These modulated properties are accompanied by an increase in chaperone activity in vivo and in vitro and a more efficient cooperation with the heat shock protein 70 system in client folding. Thus, the modulation of the structural flexibility of the NTD, as described here for phosphorylation, appears to regulate the chaperone activity of αB-crystallin rendering the NTD a conformational sensor for nonnative proteins.

Peschek|Jirka|J|
Braun|Nathalie|N|
Rohrberg|Julia|J|
Back|Katrin Christiane|KC|
Kriehuber|Thomas|T|
Kastenmüller|Andreas|A|
Weinkauf|Sevil|S|
Buchner|Johannes|J|

Hsp70
conditional disorder
posttranslational modification
sHsp
structure-function relationship


Characterization of patient head motion in otologic surgery: Implications for TEES.

Abstract:
PURPOSE
Middle ear disease is increasingly being managed via transcanal endoscopic ear surgery (TEES). A limitation of TEES is that it restricts the surgeon to single-handed dissection. One solution to this would be an endoscope holder to facilitate two-handed dissection. Current endoscope holders are stationary, and can cause potential damage from endoscope contact with the ossicles or ear canal if unintended head motion occurs from inadequate anesthetic. A dynamic device that could detect and react to patient motion would mitigate these concerns, but currently there is little formal characterization of the frequency, velocity and acceleration of unintended patient head motion during otologic procedures performed under general anesthesia. The present study aims to characterize intraoperative patient head motion kinematics during cases utilizing TEES.

MATERIALS AND METHODS
This is a prospective study of adults undergoing otologic procedures performed with general anesthesia and without paralysis. Head motion was characterized using a nine-axis inertial measurement unit (IMU), (LPMS-B2, Life Performance Research) mounted to each patient's forehead for the procedure duration.

RESULTS
Data was collected across 10 cases; 50% of patients were female and mean age was 50 ± 14 years. There was observed patient head motion in 40% of cases with maximum linear acceleration of 0.75 m/s2 and angular velocity of 12.50 degrees/s.

CONCLUSIONS
Patient movement during otologic procedures was commonly observed, demonstrating the need for a dynamic holder to allow two-handed TEES. Results from this study are the first objective characterization of patient head motion kinematics during otologic procedures performed under general anesthesia.

Berges|Alexandra J|AJ|
Razavi|Christopher|C|
Shahbazi|Mahya|M|
Taylor|Russell|R|
Carey|John P|JP|
Creighton|Francis X|FX|

Head motion
Otologic surgery
Kinematic
trans-Canal endoscopic ear surgery


Identification of Mob2, a novel regulator of larval neuromuscular junction morphology, in natural populations of Drosophila melanogaster.

Abstract: Although evolutionary changes must take place in neural connectivity and synaptic architecture as nervous systems become more complex, we lack understanding of the general principles and specific mechanisms by which these changes occur. Previously, we found that morphology of the larval neuromuscular junction (NMJ) varies extensively among different species of Drosophila but is relatively conserved within a species. To identify specific genes as candidates that might underlie phenotypic differences in NMJ morphology among Drosophila species, we performed a genetic analysis on one of two phenotypic variants we found among 20 natural isolates of Drosophila melanogaster. We discovered genetic polymorphisms for both positive and negative regulators of NMJ growth segregating within the variant line. Focusing on one subline, that displayed NMJ overgrowth, we mapped the phenotype to Mob2 [Monopolar spindle (Mps) one binding protein 2)], a gene encoding a Nuclear Dbf2 (Dumbbell formation 2)-Related (NDR) kinase activator. We confirmed this identification by transformation rescue experiments and showed that presynaptic expression of Mob2 is necessary and sufficient to regulate NMJ growth. Mob2 interacts in a dominant, dose-dependent manner with tricornered but not with warts, to cause NMJ overgrowth, suggesting that Mob2 specifically functions in combination with the former NDR kinase to regulate NMJ development. These results demonstrate the feasibility and utility of identifying genetic variants affecting NMJ morphology in natural populations of Drosophila. These variants can lead to discovery of new genes and molecular mechanisms that regulate NMJ development while also providing new information that can advance our understanding of mechanisms that underlie nervous system evolution.

D018507:Gene Expression Regulation, Developmental

D047908:Intracellular Signaling Peptides and Proteins

Synapse
behavior
natural variants
neural evolution
neurodevelopment


"I Was Raised in Addiction": Constructions of the Self and the Other in Discourses of Addiction and Recovery.

Abstract: The aim of this article is to address how conceptualizations of addiction shape the lived experiences of people who use drugs (PWUDs) during the current opioid epidemic. Using a discourse analytic approach, we examine interview transcripts from 27 PWUDs in rural Appalachian Ohio. We investigate the ways in which participants talk about their substance use, what these linguistic choices reveal about their conceptions of self and other PWUDs, and how participants' discursive caches might be constrained by or defined within broader social discourses. We highlight three subject positions enacted by participants during the interviews: addict as victim of circumstance, addict as good Samaritan, and addict as motivated for change. We argue participants leverage these positions to contrast themselves with a reified addict-other whose identity carries socially ascribed characteristics of being blameworthy, immoral, callous, and complicit. We implicate these processes in the perpetuation of intragroup stigma and discuss implications for intervention.

Sibley|Adams L|AL|0000-0001-5073-8677
Schalkoff|Christine A|CA|
Richard|Emma L|EL|
Piscalko|Hannah M|HM|
Brook|Daniel L|DL|
Lancaster|Kathryn E|KE|
Miller|William C|WC|
Go|Vivian F|VF|

D000701:Analgesics, Opioid
D001061:Appalachian Region
D016739:Behavior, Addictive
D006801:Humans
D057545:Social Stigma
D019966:Substance-Related Disorders

addiction
opioids
Ohio
stigma
discourse analysis
harm reduction
qualitative methods
rural health
substance use disorders


Potential Primary Endpoint for Exploratory Clinical Trial in Patients with Overactive Bladder: A Systematic Literature Review.

Abstract:
OBJECTIVES
To identify a potential primary endpoint in an early-phase exploratory trial among key overactive bladder (OAB) symptoms.

METHODS
Placebo-controlled double-blinding trials in patients with OAB were extracted for systematic literature review. The correlation between key OAB symptoms recorded in bladder diaries and coefficient of variation (CV) in each study were assessed.

RESULTS
Forty-one controlled trials were extracted for the present review. Mean number of urgency episodes in 24 h was substantially associated with mean number of urgency incontinence episodes in 24 h, mean volume voided per micturition, and mean number of micturitions in 24 h (Spearman's r = 0.725, -0.661, and 0.657, respectively). Mean number of micturitions in 24 h was also substantially associated with mean volume voided per micturition (Spearman's r = -0.674). Mean number of incontinence episodes in 24 h was substantially associated with mean number of urgency incontinence episodes in 24 h and mean volume voided per micturition (Spearman's r = 0.840 and -0.628, respectively). The median CV of mean volume voided per micturition in each trial was the smallest among all endpoints.

CONCLUSIONS
Our findings suggest that volume voided per micturition is a useful symptom for evaluating OAB candidate compounds in a small sample size and represents an effective primary endpoint, especially in exploratory clinical trials.

D016032:Randomized Controlled Trials as Topic

endpoint
overactive bladder
systematic literature review
randomized controlled trial


Educational outcomes of Helping Babies Breathe training at a community hospital in Honduras.

Abstract:
OBJECTIVES
Helping Babies Breathe is an evidence-based curriculum designed to teach basic neonatal resuscitation in low-resource countries. The purpose of this study was to evaluate the acquisition of knowledge and skills following this training and correlation of learner characteristics to performance in a Spanish-speaking setting.

METHODS
Thirty-one physicians and 39 nurses completed Helping Babies Breathe training at a Honduran community hospital. Trainee knowledge and skills were evaluated before and after the training using a multiple-choice questionnaire, bag-mask ventilation skills test, and two objective structured clinical exams (OSCEs). Linear mixed-effects models were used to analyze assessment scores pre- and post-training by profession (physician or nurse) while controlling for covariates.

RESULTS
Helping Babies Breathe training resulted in significant increases in mean scores for the multiple-choice question test, bag-mask ventilation skills test, and OSCE B. Time to initiation of effective bag-mask ventilation decreased from a mean of 74.8 to 68.4 s. Despite this improvement in bag-mask ventilation, only 42 % of participants were able to initiate effective bag-mask ventilation within the Golden Minute. Although physicians scored higher on the pre-test multiple-choice questions and bag-mask ventilation, nurses demonstrated a greater mean difference in scores after training. OSCE B scores pre- and post-training increased similarly between professions. Nurses' and physicians' performance in simulation was not significantly different after the training. Assessment scores and course feedback indicated a need for more skills practice, particularly with bag-mask ventilation.

CONCLUSIONS
When evaluated immediately after an initial workshop, Helping Babies Breathe training resulted in significant gains in neonatal resuscitation knowledge and skills. Following training, nurses, who commonly do not perform these skills in real-life situations, were able to perform at a similar level to physicians. Further studies are necessary to determine how to sustain this knowledge and skills over time, tailor the course to learner characteristics, and whether this training translates into improvements in clinical practice.

Seto|Teresa L|TL|
Tabangin|Meredith E|ME|
Josyula|Srirama|S|
Taylor|Kathryn K|KK|
Vasquez|Juan Carlos|JC|
Kamath-Rayne|Beena D|BD|

Educational outcomes
Helping Babies Breathe
Neonatal resuscitation


Upregulation of miRNA-154-5p prevents the tumorigenesis of osteosarcoma.

Abstract:
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone sarcoma in human worldwide. It has been shown that the level of microRNA-154-5p (miR-154-5p) was downregulated in human OS tissues. However, the mechanisms by which miR-154-5p regulates the proliferation, apoptosis and invasion in OS remain unclear. Thus, the present study aimed to investigate the role of miR-154-5p during the tumorigenesis of OS.

METHODS
The level of miR-154-5p in human OS tissues was detected by RT-qPCR. In addition, the effects of miR-154-5p on apoptosis and invasion of OS cells were assessed by flow cytometry and transwell assays, respectively. Meanwhile, the dual luciferase reporter system assay was performed to explore the interaction of miR-154-5p and E2F5.

RESULTS
The level of miR-154-5p was downregulated in OS tissues. Overexpression of miR-154-5p significantly inhibited the proliferation, migration and invasion of MG63 cells. In addition, upregulation of miR-154-5p obviously induced apoptosis in MG63 cells via upregulation of Bax and cleaved caspase 3, and downregulation of Bcl-2. Moreover, luciferase reporter assay identified that E2F5 was the binding target of miR-154-5p. Meanwhile, overexpression of miR-154-5p induced cell cycle arrest in MG63 cells via inhibiting the expressions of E2F5, Cyclin E1 and CDK2. Furthermore, in vivo assays indicated that overexpression of miR-154-5p notably inhibited the tumor growth in an OS xenograft model.

CONCLUSION
These results indicated that miR-154-5p may function as a potential tumor suppressor in OS. Therefore, miR-154-5p might be a novel therapeutic option for the treatment of OS.

Tian|Qing|Q| Gu|Yufan|Y| Wang|Feifei|F| Zhou|Lijun|L| Dai|Zhipeng|Z| Liu|Hongjian|H| Wu|Xuejian|X| Wang|Xinxing|X| Liu|Yong|Y| Chen|Songfeng|S| Han|Qicai|Q|

D015972:Gene Expression Regulation, Neoplastic

D023041:Xenograft Model Antitumor Assays


Structural and functional measures of marine microbial communities: An experiment to assess implications for oil spill management.

Abstract: Microbial communities are ecologically important in aquatic environments and impacts on microbes have the potential to affect a number of functional processes. We have amended seawater with a crude oil and assessed changes in species composition as well as a measure of functional diversity (the ability of the community to utilise different carbon sources) and the community level metabolic signature. We found that there was a degree of functional redundancy in the community we tested. Oiled assemblages became less diverse and more dominated by specialist hydrocarbon degraders, carbon source utilisation increased initially but there was no change in metabolic signature in this small scale laboratory experiment. This study supports the decision framework around management of oil spills. This package of methods has the potential to be used in the testing and selection of new dispersants for use in oil spill response.

Morris|Liz|L|
O'Brien|Allyson|A|
Natera|Siria H A|SHA|
Lutz|Adrian|A|
Roessner|Ute|U|
Long|Sara M|SM|

Hydrocarbon
16sDNA
Biolog Ecoplates
Diversity profiling
Metabolomics
Pollution


Interactions between Aβ oligomers and presynaptic cholinergic signaling: age-dependent effects on attentional capacities.

Abstract: Substantial evidence suggests that cerebral deposition of the neurotoxic fibrillar form of amyloid precursor protein, β-amyloid (Aβ), plays a critical role in the pathogenesis of Alzheimer's disease (AD). Yet, many aspects of AD pathology including the cognitive symptoms and selective vulnerability of cortically projecting basal forebrain (BF) cholinergic neurons are not well explained by this hypothesis. Specifically, it is not clear why cognitive decline appears early when the loss of BF cholinergic neurons and plaque deposition are manifested late in AD. Soluble oligomeric forms of Aβ are proposed to appear early in the pathology and to be better predictors of synaptic loss and cognitive deficits. The present study was designed to examine the impact of Aβ oligomers on attentional functions and presynaptic cholinergic transmission in young and aged rats. Chronic intracranial infusions of Aβ oligomers produced subtle decrements in the ability of rats to sustain attentional performance with time on task, irrespective of the age of the animals. However, Aβ oligomers produced robust detrimental effects on performance under conditions of enhanced attentional load in aged animals. In vivo electrochemical recordings show reduced depolarization-evoked cholinergic signals in Aβ-infused aged rats. Moreover, soluble Aβ disrupted the capacity of cholinergic synapses to clear exogenous choline from the extracellular space in both young and aged rats, reflecting impairments in the choline transport process that is critical for acetylcholine (ACh) synthesis and release. Although aging per se reduced the cross-sectional area of BF cholinergic neurons and presynaptic cholinergic proteins in the cortex, attentional performance and ACh release remained unaffected in aged rats infused with the control peptide. Taken together, these data suggest that soluble Aβ may marginally influence attentional functions at young ages primarily by interfering with the choline uptake processes. However, age-related weakening of the cholinergic system may synergistically interact with these disruptive presynaptic mechanisms to make this neurotransmitter system vulnerable to the toxic effects of oligomeric Aβ in robustly impeding attentional capacities.

Parikh|Vinay|V|
Bernard|Carcha S|CS|
Naughton|Sean X|SX|
Yegla|Brittney|B|

D050494:Vesicular Acetylcholine Transport Proteins

Presynaptic
Cholinergic
Attention
Alzheimer's disease
Aging
Soluble amyloid-beta