Tbx18 is essential for normal development of vasculature network and glomerular mesangium in the mammalian kidney.

Abstract: Tbx18 has been shown to be essential for ureteral development. However, it remains unclear whether it plays a direct role in kidney development. Here we addressed this by focusing on examining the pattern and contribution of Tbx18+ cells in the kidney and its role in kidney vascular development. Expression studies and genetic lineage tracing revealed that Tbx18 is expressed in renal capsule, vascular smooth muscle cells and pericytes and glomerular mesangial cells in the kidney and that Tbx18-expressing progenitors contribute to these cell types. Examination of Tbx18(-/-) kidneys revealed large reduction in vasculature density and dilation of glomerular capillary loops. While SMA+ cells were reduced in the mutant, PDGFRβ+ cells were seen in early capillary loop renal corpuscles in the mutant, but fewer than in the controls, and further development of the mesangium failed. Analysis of kidney explants cultured from E12.5 excluded the possibility that the defects observed in the mutant were caused by ureter obstruction. Reduced proliferation in glomerular tuft and increased apoptosis in perivascular mesenchyme were observed in Tbx18(-/-) kidneys. Thus, our analyses have identified a novel role of Tbx18 in kidney vasculature development.

Xu|Jinshu|J| Nie|Xuguang|X| Cai|Xiaoqiang|X| Cai|Chen-Leng|CL| Xu|Pin-Xian|PX|

D020797:Receptor, Platelet-Derived Growth Factor beta

Tbx18
Glomerular mesangium
Kidney
Perivascular mesenchyme
Interstitium
Stromal cell
Vasculogenesis


Sub-CMC solubilization of n-alkanes by rhamnolipid biosurfactant: the Influence of rhamnolipid molecular structure.

Abstract: Solubilization of n-alkanes by dirhamnolipid (diRL) biosurfactant at sub-critical micelle concentrations (sub-CMC) was studied and the results were compared to that for monorhamnolipid (monoRL) obtained in our prior study. The results show that the apparent solubility of the four alkanes (decane, dodecane, tetradecane and hexadecane) increases linearly with the increase of diRL concentration at diRL concentrations below CMC. The solubilization potential of diRL indicated by molar solubilization ratio (MSR) is higher at sub-CMC than at hyper-CMC concentrations (0.43 vs 0.03, 7.91 vs 0.02, 5.16 vs 1.98 and 3.71 vs 1.26 for decane, dodecane, tetradecane and hexadecane, respectively). The maximum access at the surface of the alkane-rhamnolipid aggregates (Гmax) is smaller for diRL than for monoRL (2.47 vs 3.09, 2.35 vs 2.86, 2.26 vs 3.60, and 2.01 vs 4.09 mol/m2 for decane, dodecane, tetradecane and hexadecane, respectively). In addition, more significant impact of surface access change on the size of the aggregates were observed for diRL, indicating that the difference in the structure of polar group between diRL and monoRL (one more rhamnose ring in diRL polar group) has influence on alkane-solubilization behavior. Due to the smaller access at the surface of the aggregates, diRL can produce larger number of aggregates than monoRL in the solution and thus show higher solubilization efficiency of dodecane, tetradecane and hexadecane. The findings of the study add to the knowledge of solubilization of hydrophobic organic compounds by surfactants and contribute to application of rhamnolipid biosurfactant in the area of remediation.

Yang|Xin|X| Tan|Fei|F| Zhong|Hua|H| Liu|Guansheng|G| Ahmad|Zulfiqar|Z| Liang|Qinghua|Q|

Solubilization
n-alkanes
Dirhamnolipid
Monorhamnolipid
aggregate
Surface excess


Association of hsa-mir-328-3p Expression in Whole Blood With Optical Density of Retinal Pigment Epithelial Cells.

Abstract:
AIM
To investigate the association of the pair box 6 gene (PAX6) and hsa-miR-328-3p with optical density of macular pigment.

MATERIALS AND METHODS
We evaluated 112 individuals (34 with moderate myopia, eight with high-degree myopia, and 70 healthy individuals). The optical density of macular pigment was measured using single-wavelength reflectometry. DNA and RNA were extracted from whole blood samples. Expression of hsa-miR-328-3p and genotyping of single-nucleotide polymorphism of PAX6 (rs662702) were performed using Applied Biosystems 7900HT real-time polymerase chain reaction system. Optical density of retinal pigment epithelial cells was evaluated using Fundus plus camera.

RESULTS
In the group with myopia, with increasing ∆Ct hsa-miR-328-3p, the median optical density of the retinal pigment epithelium decreased statistically significantly (p<0.032). No statistically significant association was found between SNP rs662702 genotype variant of the PAX6 gene and the optical density of the retinal pigment epithelium.

CONCLUSION
The increased expression of hsa-miR-328-3p in the blood indicates a decrease in the optical density of the retinal pigment epithelium in those with myopia.

Kunceviciene|Edita|E| Budiene|Brigita|B| Smalinskiene|Alina|A| Vilkeviciute|Alvita|A| Liutkeviciene|Rasa|R|

D004847:Epithelial Cells
D006801:Humans
D035683:MicroRNAs
D000071841:PAX6 Transcription Factor
D055213:Retinal Pigment Epithelium
D012168:Retinal Pigments


Sustained intravitreal delivery of dexamethasone using an injectable and biodegradable thermogel.

Abstract: Delivery of therapeutic agents to posterior segment of the eyes is challenging due to the anatomy and physiology of ocular barriers and thus long-acting implantable formulations are much desired. In this study, a thermogelling system composed of two poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was developed as an injectable matrix for intravitreal drug delivery. The thermogel was prepared by mixing a sol and a precipitate of PLGA-PEG-PLGA triblock copolymers with different block ratios, among which a hydrophobic glucocorticoid, dexamethasone (DEX), was incorporated. The DEX-loaded thermogel was a low-viscous liquid at low temperature and formed a non-flowing gel at body temperature. The in vitro release rate of DEX from the thermogel could be conveniently modulated by varying the mixing ratio of the two copolymers. The long-lasting intraocular residence of the thermogel was demonstrated by intravitreal injection of a fluorescence-labeled thermogel to rabbits. Compared with a DEX suspension, the intravitreal retention time of DEX increased from a dozen hours to over 1week when being loaded in the thermogel. Additionally, intravitreal administration of the thermogel did not impair the morphology of retina and cornea. This study reveals that the injectable PLGA-PEG-PLGA thermogel is a biocompatible carrier for sustained delivery of bioactive agents into the eyes, and provides an alternative approach for treatment of posterior segment diseases.

Zhang|Li|L| Shen|Wenjia|W| Luan|Jiabin|J| Yang|Dongxiao|D| Wei|Gang|G| Yu|Lin|L| Lu|Weiyue|W| Ding|Jiandong|J|

Dexamethasone
Thermogel
Triblock copolymer
Intravitreal injection
Intraocular drug delivery


Do glucocorticoids mediate the link between environmental conditions and telomere dynamics in wild vertebrates? A review.

Abstract: Following the discoveries of telomeres and of their implications in terms of health and ageing, there has been a growing interest into the study of telomere dynamics in wild vertebrates. Telomeres are repeated sequences of non-coding DNA located at the terminal ends of chromosomes and they play a major role in maintaining chromosome stability. Importantly, telomeres shorten over time and shorter telomeres seem to be related with lower survival in vertebrates. Because of this potential link with longevity, it is crucial to understand not only the ecological determinants of telomere dynamics but also the regulatory endocrine mechanisms that may mediate the effect of the environment on telomeres. In this paper, we review the relationships that link environmental conditions, glucocorticoids (GC, the main hormonal mediator of allostasis) and telomere length in vertebrates. First, we review current knowledge about the determinants of inter-individual variations in telomere length. We emphasize the potential strong impact of environmental stressors and predictable life-history events on telomere dynamics. Despite recent progress, we still lack crucial basic data to fully understand the costs of several life-history stages and biotic and abiotic factors on telomere length. Second, we review the link that exists between GCs, oxidative stress and telomere dynamics in vertebrates. Although circulating GC levels may be closely and functionally linked with telomere dynamics, data are still scarce and somewhat contradictory. Further laboratory and field studies are therefore needed not only to better assess the proximate link between GC levels and telomere dynamics, but also to ultimately understand to what extent GCs and telomere length could be informative to measure the fitness costs of specific life-history stages and environmental conditions. Finally, we highlight the importance of exploring the functional links that may exist between coping styles, the GC stress response, and telomere dynamics in a life-history framework. To conclude, we raise new hypotheses regarding the potential of the GC stress response to drive the trade-off between immediate survival and telomere protection.

Angelier|Frédéric|F| Costantini|David|D| Blévin|Pierre|P| Chastel|Olivier|O|

Telomere
Oxidative stress
Stress
Corticosterone
Cortisol
HPA axis
Telomerase


Effectiveness of recombinant zoster vaccine (RZV) in patients with inflammatory bowel disease.

Abstract:
BACKGROUND AND AIMS
Patients with Inflammatory bowel disease (IBD) are at an increased risk of developing herpes zoster (HZ). The effectiveness of the recombinant zoster vaccine (RZV) in patients with IBD is unknown.

METHODS
In this retrospective cohort study using Explorys (October 2017-April 2020; IBM Corporation, Somers, NY, USA), the effectiveness of RZV for the prevention of HZ in patients with IBD ≥ 50 years was compared to general population aged ≥ 50 years. Rates of de-novo HZ were compared between patients with IBD and the general population and stratified by number of RZV doses received. Results are presented as odds ratios (OR) with 95% confidence intervals (CI).

RESULTS
The overall proportion of IBD patients ≥ 50 years who received HZ vaccination with the live zoster vaccine (ZVL) or RZV was low (n = 11320, out of 112,200 IBD patients in the cohort). A total of 1670 patients received RZV. Receipt of the RZV resulted in a significantly lower rate of HZ in IBD patients (OR 0.36, 95% CI 0.23-0.56) compared to the general population (OR 0.74, 95% CI 0.59-0.92). However, despite vaccination, patients with IBD who received the RZV were still 3-times more likely to develop HZ during the study follow up period compared to the general population receiving the RZV (OR 3.06, 95% CI 1.87-5.02) and unvaccinated IBD patients were 6-times more likely to develop HZ compared to general population (OR 6.21, 95% CI 6.02-6.41).

CONCLUSION
The recombinant zoster vaccine is effective in reducing the risk of HZ in patients with IBD compared to the general population. During our follow up period, patients with IBD, however, still remain at an increased risk for HZ despite vaccination.

Kochhar|Gursimran S|GS|
Desai|Aakash|A|
Caldera DO|Freddy|F|
El Hachem|Sandra|S|
Aoun|Elie|E|
Sandhu|Dalbir|D|
Mohan|Babu P|BP|
Dulai|Parambir S|PS|
Farraye|Francis A|FA|

D006562:Herpes Zoster
D053061:Herpes Zoster Vaccine
D014645:Herpesvirus 3, Human
D006801:Humans
D015212:Inflammatory Bowel Diseases
D012189:Retrospective Studies

Vaccination
Inflammatory bowel disease
Immunity
Shingles


Pulmonary artery reconstruction with a tailor-made bovine pericardial conduit following sleeve resection of a long segmental pulmonary artery for the treatment of lung cancer: technical details of the dog-ear method for adjusting diameter during vascular anastomosis.

Abstract: Sleeve resection of the pulmonary artery (PA) is always required for lung-sparing operations in which half or more of the vessel circumference is infiltrated by the primary tumor or metastatic hilar nodes. Following sleeve resection, conduit reconstruction may be indicated if there is excessive distance between the two vascular stumps, because there is a high degree of tension when repaired by direct anastomosis. We herein present a case of PA reconstruction using a tailor-made bovine pericardial conduit after sleeve resection of PA during lung cancer surgery. The length of resection was longer than 3 cm, and the difference in diameter between the conduit and peripheral PA stump was larger than 0.5 cm. We describe the surgical and oncological merits of a bovine pericardial conduit, and provide details of our reconstruction technique, focusing on adjustment of diameter between the conduit and peripheral PA (dog-ear method).

Pulmonary arteries
Lung cancer surgery
Revascularization
Surgery/techniques
Surgical equipment


Short day length enhances physiological resilience of the immune system against 2-deoxy-d-glucose-induced metabolic stress in a tropical seasonal breeder Funambulus pennanti.

Abstract: Studies demonstrate the importance of metabolic resources in the regulation of reproduction and immune functions in seasonal breeders. In this regard, the restricted energy availability can be considered as an environmental variable that may act as a seasonal stressor and can lead to compromised immune functions. The present study explored the effect of photoperiodic variation in the regulation of immune function under metabolic stress condition. The T-cell-dependent immune response in a tropical seasonal breeder Funambulus pennanti was studied following the inhibition of cellular glucose utilization with 2-deoxy-d-glucose (2-DG). 2-DG treatment resulted in the suppression of general (e.g., proliferative response of lymphocytes) and antigen-specific [anti-keyhole limpet hemocyanin IgG titer and delayed-type hypersensitivity response] T-cell responses with an activation of the hypothalamic-pituitary-adrenal axis, which was evident from the increased levels of plasma corticosterone. 2-DG administration increased the production of inflammatory cytokines [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and decreased the autocrine T-cell growth factor IL-2. The immunocompromising effect of 2-DG administration was retarded in animals exposed to short photoperiods compared with the control and long photoperiod-exposed groups. This finding suggested that short photoperiodic conditions enhanced the resilience of the immune system, possibly by diverting metabolic resources from the reproductive organs toward the immune system. In addition, melatonin may have facilitated the energy "trade-off" between reproductive and immune mechanisms, thereby providing an advantage to the seasonal breeders for their survival during stressful environmental conditions.

Stress
Photoperiod
2-Deoxy-d-glucose
Melatonin
Immune status


Malassezia japonica is part of the cutaneous microbiome of free-ranging golden-headed lion tamarins (Leontopithecus chrysomelas - Kuhl, 1820).

Abstract: We investigated Malassezia spp. in external ear canal and haircoat of free-ranging golden-headed lion tamarins (Leontopithecus chrysomelas). A total of 199 animals were restrained, and 597 clinical samples were collected. After the amplification of the 26S ribosomal gene by polymerase chain reaction (PCR), the RFLP technique was performed. Two additional PCR protocols were performed in 10 randomly selected strains. Malassezia sp. was isolated in 38.2% (76/199) of the animals and 14.6% (87/597) of the samples; all strains were lipodependent. The 10 sequenced strains showed a high identity with Malassezia japonica, species described in man, but not in animals, so far.

Coutinho|Selene Dall' Acqua|SDA|
Sacristán|Carlos|C|
Bueno|Marina Galvão|MG|
Marigo|Juliana|J|
Pissinatti|Alcides|A|
Kierulff|Maria Cecilia|MC|
Catão-Dias|José Luiz|JL|

Malassezia japonica
microbiome
golden-headed lion tamarin
Leontopithecus chrysomelas
Malassezia sp


Dynamic multi-coil tailored excitation for transmit B1 correction at 7 Tesla.

Abstract:
PURPOSE
Tailored excitation (TEx) based on interspersing multiple radio frequency pulses with linear gradient and higher-order shim pulses can be used to obtain uniform flip angle in the presence of large radio frequency transmission (B 1+) inhomogeneity. Here, an implementation of dynamic, multislice tailored excitation using the recently developed multi-coil nonlinear shim hardware (MC-DTEx) is reported.

METHODS
MC-DTEx was developed and tested both in a phantom and in vivo at 7 T, and its efficacy was quantitatively assessed. Predicted outcomes of MC-DTEx and DTEx based on spherical harmonic shims (SH-DTEx) were also compared.

RESULTS
For a planned 30 ° flip angle, in a phantom, the standard deviation in excitation improved from 28% (regular excitation) to 12% with MC-DTEx. The SD in in vivo excitation improved from 22 to 12%. The improvements achieved with experimental MC-DTEx closely matched the theoretical predictions. Simulations further showed that MC-DTEx outperforms SH-DTEx for both scenarios.

CONCLUSION
Successful implementation of multislice MC-DTEx is presented and is shown to be capable of homogenizing excitation over more than twofold B 1+ variations. Its benefits over SH-DTEx are also demonstrated. A distinct advantage of MC hardware over SH shim hardware is the absence of significant eddy current effects, which allows for a straightforward, multislice implementation of MC-DTEx. Magn Reson Med 76:83-93, 2016. © 2015 Wiley Periodicals, Inc.

Umesh Rudrapatna|S|S|
Juchem|Christoph|C|
Nixon|Terence W|TW|
de Graaf|Robin A|RA|

multi-coil
radio frequency
B1 shimming
DYNAMITE
dynamic shimming
wavelength effects


Increased risk of cardiovascular events in patients with herpes zoster: a population-based study.

Abstract: The association between herpes zoster and cardiovascular complications remains vague with limited study on the association between these two disorders. This study evaluated the risk of cardiovascular diseases in patients with herpes zoster. From insurance claims data of Taiwan, 19,483 patients with herpes zoster diagnosed in 1998-2008 and 77,932 subjects without herpes zoster were identified in this study. Both cohorts were followed up until the end of 2010 to measure the incidence of arrhythmia and coronary artery disease. The incidence rate ratio and adjusted hazard ratio (HR) of the cardiovascular complications with 95% confidence interval (CI) were estimated. The incidence of arrhythmia was 1.17-fold greater in the herpes zoster cohort than in the non-herpes zoster cohort (13.2 vs. 11.3 per 1,000 person-years), with an adjusted HR of 1.16 (P < 0.01). The coronary artery disease incidence in the herpes zoster cohort was 1.16-fold higher than that in the non-herpes zoster cohort (9.02 vs. 7.83 per 1,000 person-years), with an adjusted HR of 1.11 (P < 0.01). Over the stratified follow-up years, adjusted HRs were 1.22 (95% CI = 1.12-1.34) for arrhythmia and 1.14 (95% CI = 1.02-1.28) for coronary artery disease within 2 years after herpes zoster diagnosis. The risk measured for these disorders declined over time. Comorbidities of hypertension, diabetes, and hyperlipidemia also contributed to these cardiovascular disorders with greater extent. It is concluded that the contribution of herpes zoster to the risk of arrhythmia and cardiovascular diseases is less strong than that of hypertension, diabetes, and hyperlipidemia.

Wu|Po-yuan|PY| Lin|Cheng-Li|CL| Sung|Fung-Chang|FC| Chou|Tzu-Chieh|TC| Lee|Yuan-Teh|YT|

herpes zoster
arrhythmia
coronary artery disease
retrospective cohort study


Locking versus non-locking plate fixation in the management of mandibular fractures: a meta-analysis.

Abstract: The aim of the present study was to test whether there is a significant difference in the clinical outcomes between locking and non-locking plate fixation in the management of mandibular fractures. An electronic search without time or language restrictions was undertaken in December 2013. Eligible studies were clinical human studies, either randomized or not. The search strategy identified 10 publications. The I(2) statistic was used to express the percentage of the total variation across studies due to heterogeneity. The inverse variance method was used for the random-effects model in the case of heterogeneity being detected, or the fixed-effects model in the case of heterogeneity not being detected. The estimates of an intervention were expressed as the risk ratio (RR) with 95% confidence interval. Eight studies were judged to be at high risk of bias, whereas two studies were considered at moderate risk of bias. There was no statistically significant effect on the outcome of postoperative infection (P=0.17), malocclusion (P=0.15), hardware failure (P=0.77), hardware removal (P=0.95), wound dehiscence (P=0.98), or paraesthesia (P=0.20) in favour of locking plate fixation. The test for overall effect showed that the difference between the procedures did not significantly affect the incidence of postoperative complications (P=0.21), with RR 0.79 (95% CI 0.54-1.14).

D010043:Outcome and Process Assessment, Health Care

non-locking plate
mandibular fracture
meta-analysis
locking plate
complications
standard plate


The evolution and adaptive potential of transcriptional variation in sticklebacks--signatures of selection and widespread heritability.

Abstract: Evidence implicating differential gene expression as a significant driver of evolutionary novelty continues to accumulate, but our understanding of the underlying sources of variation in expression, both environmental and genetic, is wanting. Heritability in particular may be underestimated when inferred from genetic mapping studies, the predominant "genetical genomics" approach to the study of expression variation. Such uncertainty represents a fundamental limitation to testing for adaptive evolution at the transcriptomic level. By studying the inheritance of expression levels in 10,495 genes (10,527 splice variants) in a threespine stickleback pedigree consisting of 563 individuals, half of which were subjected to a thermal treatment, we show that 74-98% of transcripts exhibit significant additive genetic variance. Dominance variance is also prevalent (41-99% of transcripts), and genetic sources of variation seem to play a more significant role in expression variance in the liver than a key environmental variable, temperature. Among-population comparisons suggest that the majority of differential expression in the liver is likely due to neutral divergence; however, we also show that signatures of directional selection may be more prevalent than those of stabilizing selection. This predominantly aligns with the neutral model of evolution for gene expression but also suggests that natural selection may still act on transcriptional variation in the wild. As genetic variation both within- and among-populations ultimately defines adaptive potential, these results indicate that broad adaptive potential may be found within the transcriptome.

Leder|Erica H|EH|
McCairns|R J Scott|RJ|
Leinonen|Tuomas|T|
Cano|José M|JM|
Viitaniemi|Heidi M|HM|
Nikinmaa|Mikko|M|
Primmer|Craig R|CR|
Merilä|Juha|J|

gene expression
transcriptome
Gasterosteus aculeatus
QST
microarray
quantitative genetics


Effects of Arteriovenous Fistula Ligation on Cardiac Structure and Function in Kidney Transplant Recipients.

Abstract:
BACKGROUND
Cardiovascular morbidity and mortality remain high in recipients of a kidney transplant. The persistence of a patent arteriovenous fistula (AVF) after transplantation may contribute to ongoing maladaptive cardiovascular remodeling. The ability to reverse this maladaptive remodeling by ligation of this AVF is unknown. We conducted the first randomized controlled trial to evaluate the effect of AVF ligation on cardiac structure and function in stable kidney transplant recipients.

METHODS
In this randomized controlled trial, kidney transplant recipients (>12 months after transplantation with stable graft function) were randomized to AVF ligation or no intervention. All participants underwent cardiac magnetic resonance imaging at baseline and at 6 months. The primary outcome was the change in left ventricular (LV) mass. Secondary outcomes included changes in LV volumes, left and right atrial areas, LV ejection fraction, NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, cardiac output/index, brachial flows (ipsilateral to AVF), and pulmonary artery velocity.

RESULTS
A total of 93 patients were screened, of whom 64 met the inclusion criteria and were randomized to the AVF ligation (n=33) or control (n=31) group. Fifty-four participants completed the study: 27 in the AVF ligation group and 27 in the control group. On the second cardiac magnetic resonance scan, a mean decrease of 22.1 g (95% CI, 15.0-29.1) was observed in LV mass in the AVF ligation group compared with a small increase of 1.2 g (95% CI, -4.8 to 7.2) in the control group ( P<0.001). Significant decreases in LV end-diastolic volumes, LV end-systolic volumes, cardiac output, cardiac index, atrial volumes, and NT-proBNP were also seen in the AVF closure group ( P<0.01). No significant changes were observed in LV ejection fraction ( P=0.93) and pulmonary artery velocity ( P=0.07). No significant complications were noted after AVF ligation. No changes in estimated glomerular filtration rate or systolic and diastolic blood pressures were observed between cardiac magnetic resonance scans.

CONCLUSIONS
Elective ligation of patent AVF in adults with stable kidney transplant function resulted in clinically significant reduction of LV myocardial mass.

CLINICAL TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au . Unique Identifier: ACTRN12613001302741.

Rao|Nitesh N|NN|
Stokes|Michael B|MB|
Rajwani|Adil|A|
Ullah|Shahid|S|
Williams|Kerry|K|
King|David|D|
Macaulay|Ewan|E|
Russell|Christine H|CH|
Olakkengil|Santosh|S|
Carroll|Robert P|RP|
Faull|Randall J|RJ|
Teo|Karen S L|KSL|
McDonald|Stephen P|SP|
Worthley|Matthew I|MI|
Coates|P Toby|PT|

D000368:Aged
D001166:Arteriovenous Shunt, Surgical
D015415:Biomarkers
D005260:Female
D005919:Glomerular Filtration Rate
D006439:Hemodynamics
D006801:Humans
D017379:Hypertrophy, Left Ventricular
D007676:Kidney Failure, Chronic
D016030:Kidney Transplantation
D008026:Ligation
D008279:Magnetic Resonance Imaging
D008297:Male
D008875:Middle Aged
D020097:Natriuretic Peptide, Brain
D010446:Peptide Fragments
D011446:Prospective Studies
D020127:Recovery of Function
D006435:Renal Dialysis
D013021:South Australia
D013318:Stroke Volume
D013997:Time Factors
D016896:Treatment Outcome
D016277:Ventricular Function, Left
D020257:Ventricular Remodeling

arteriovenous fistula
kidney transplantation
magnetic resonance imaging
heart ventricles


Comparison of safety between high and low doses of sulbactam/ampicillin: A retrospective observational study in Japanese patients with pneumonia.

Abstract: Although 12 g/day sulbactam/ampicillin (SBT/ABPC) is approved in Japan, differences in the frequency of adverse effects induced by conventional (≤6 g/day) and high (≥9 g/day) doses remain unclear. We performed a retrospective observational study on SBT/ABPC-treated hospitalized adult patients with pneumonia from October 2015 to January 2018 to compare the safety between high and low doses. Patients were divided into high-dose (≥9 g/day, n = 200) and low-dose (≤6 g/day, n = 246) groups. We used logistic regression to determine propensity scores for the high-dose and low-dose groups and compared the incidence of adverse effects after propensity score adjustment (n = 200 in each group). Following propensity score adjustment, the frequency of elevated alanine aminotransferase (ALT) level was still significantly higher in the high-dose group than in the low-dose group (21% versus 11%, p = 0.006). In contrast, the frequencies of elevated alkaline phosphatase, aspartate aminotransferase, and serum creatinine levels and decreased white blood cell and platelet counts, and incidence of anemia, were not. Changes in blood urea nitrogen levels, erythrocyte count, and hematocrit were not significantly different between the two dose groups. There were two cases of rash reported to the Pharmaceuticals and Medical Devices Agency as an adverse effect in the high-dose group. Thirty-day mortality rates were not significantly different after propensity score adjustment. Our analysis suggests that an increase in the ALT grade was more frequent in patients treated with a daily dose of SBT/ABPC of ≥9 g.

Imanishi|Kaori|K| Nakakura|Ichiro|I| Miyabe|Takashi|T| Sako|Rumi|R| Yamauchi|Kazutaka|K|

Safety
Sulbactam/ampicillin
Hematological parameter
Hepatic dysfunction
High dose
Kidney dysfunction


The effects of anesthetic agents on pupillary function during general anesthesia using the automated infrared quantitative pupillometer.

Abstract: Pupil reactivity can be used to evaluate central nervous system function and can be measured using a quantitative pupillometer. However, whether anesthetic agents affect the accuracy of the technique remains unclear. We examined the effects of anesthetic agents on pupillary reactivity. Thirty-five patients scheduled for breast or thyroid surgery were enrolled in the study. Patients were divided into four groups based on the technique used to maintain anesthesia: a sevoflurane-remifentanil (SEV/REM) group, a sevoflurane (SEV) group, a desflurane-remifentanil (DES/REM) group, and a propofol-remifentanil (PRO/REM) group. We measured maximum resting pupil size (MAX), reduction pupil size ratio (%CH), latency duration (LAT) and neurological pupil index (NPi). A marked reduction in MAX and %CH compared with baseline was observed in all groups, but LAT was unchanged during surgery. NPi reduced within the first hour of surgery in the SEV/REM, SEV, and DES/REM groups, but was not significantly different in the PRO/REM group. Compared with the PRO/REM group, mean %CH and NPi in patients anesthetized with SEV/REM, SEV or DES/REM were markedly lower at 1 h after surgery had commenced. There was no correlation between NPi and bispectral index. Fentanyl given alone decreased pupil size and %CH in light reflex, but did not change the NPi. NPi was decreased by inhalational anesthesia not but intravenous anesthesia. The difference in pupil reactivity between inhalational anesthetic and propofol may indicate differences in the alteration of midbrain reflexs in patients under inhalational or intravenous anesthesia.

Shirozu|Kazuhiro|K| Setoguchi|Hidekazu|H| Tokuda|Kentaro|K| Karashima|Yuji|Y| Ikeda|Mizuko|M| Kubo|Makoto|M| Nakamura|Katsuya|K| Hoka|Sumio|S|

Quantitative pupillometer
Pupil reactivity
NPi


The Width of the Surgical Margin Does Not Influence Outcomes in Extremity and Truncal Soft Tissue Sarcoma Treated With Radiotherapy.

Abstract:
BACKGROUND AND OBJECTIVES
It is unclear whether the quantitative width of the surgical margin influences outcomes in patients with extremity and truncal soft tissue sarcoma (STS) treated with radiotherapy (RT).

METHODS
We performed a retrospective review of 382 patients with localized extremity or truncal STS who underwent limb-sparing surgery and RT from 1983 to 2010, and we analyzed the significance of resection margin status and quantitative margin width on outcomes.

RESULTS
Surgical margins were positive in 68 (18%) patients and negative in 314 (82%) patients. For those patients with a reported quantitative margin width (n = 235), the width of the negative margin was ≤1 mm (n = 128), >1 mm and ≤5 mm (n = 79), and >5 mm (n = 28). At a median follow-up of 82 months, the local recurrence rates were 5.4% and 11.8% for margin-negative and margin-positive patients, respectively. There were no differences in the rates of local or distant recurrence nor of any survival outcome based on the quantitative width of the surgical margin, provided that it was negative.

CONCLUSIONS
In patients undergoing RT and limb-sparing surgery for STS, achieving a negative margin is essential for optimizing both local control and survival. However, the absolute quantitative width of the negative margin does not significantly influence outcome, and so attempts at wide margins of resection appear to be unnecessary. Importantly, the conclusions drawn from this study must not be applied to those patients undergoing surgery alone as the local treatment of their STS, in which case wider margins of resection may be necessary.

IMPLICATIONS FOR PRACTICE
In patients undergoing radiation therapy and limb-sparing surgery for soft tissue sarcoma, the quantitative width of the negative margin does not influence outcome, and so attempts at wide margins of resection appear to be unnecessary, especially when such attempts compromise the functional outcome. Importantly, the conclusions drawn from this study must not be applied to those patients undergoing surgery alone as the local treatment of their soft tissue sarcoma, in which case wider margins of resection may be necessary.

Ahmad|Rima|R|
Jacobson|Alex|A|
Hornicek|Francis|F|
Haynes|Alex B|AB|
Choy|Edwin|E|
Cote|Gregory|G|
Nielsen|G Petur|GP|
Chen|Yen-Lin|YL|
DeLaney|Thomas F|TF|
Mullen|John T|JT|

Outcome
Extremity
Soft tissue sarcoma
Margin width
Radiation therapy


Macroinvertebrate communities from the shallow soft-bottoms of Deception Island (Southern Ocean): A paradise for opportunists.

Abstract: Deception Island (South Shetland Islands) is an atypical spot in its Antarctic context, being a still active volcano with a submerged caldera. Although the sea-floor of its enclosed bay, Port Foster, has been extensively studied from 40 m down, little is known about the macrozoobenthic composition of its shallower areas. The aim of this study was to characterize the so far unexplored soft-bottom marine macroinvertebrate communities living within the first few meters depth in Port Foster. Eight sampling stations were selected, and three replicates per station and depth (5 and 15 m) were collected by SCUBA diving using 0.008 m-2 corers. Six clusters of samples were distinguished, showing a high variability in the composition of the shallow-water macrofauna. This heterogeneity did not appear to be related to the proximity of the sites to the open sea (entrance of the caldera) or depth, nor to the sediment type or the organic matter content. Overall, the assemblages within each cluster were generally dominated by highly abundant opportunistic species, including the annelids Capitella perarmata, Mesospio moorei, Leitoscoloplos kerguelensis, Apistobranchus glacierae, and Tharyx cincinnata, the amphipod Cheirimedon femoratus, and the bivalve Aequiyoldia eightsii. The remarkably high densities reported in several stations, suggest that the shallow-water environment of Port Foster is highly productive. In light of these results, we propose a general trophic web for the shallow waters of Port Foster linking the unusually high densities of macroinvertebrates with the also high occurrence of megafaunal echinoderms present in this area.

Angulo-Preckler|Carlos|C| Leiva|Carlos|C| Avila|Conxita|C| Taboada|Sergi|S|

Organic matter
Opportunistic species
Antarctic invertebrates
Benthic communities
Polychaeta


Unmet Needs in the Treatment of Gastroesophageal Reflux Disease.

Abstract: Gastroesophageal reflux disease (GERD) is a highly prevalent gastrointestinal disorder. Proton pump inhibitors have profoundly revolutionized the treatment of GERD. However, several areas of unmet need persist despite marked improvements in the ther-apeutic management of GERD. These include the advanced grades of erosive esophagitis, nonerosive reflux disease, main-tenance treatment of erosive esophagitis, refractory GERD, postprandial heartburn, atypical and extraesophageal manifestations of GERD, Barrett's esophagus, chronic protein pump inhibitor treatment, and post-bariatric surgery GERD. Consequently, any fu-ture development of novel therapeutic modalities for GERD (medical, endoscopic, or surgical), would likely focus on the afore-mentioned areas of unmet need.

Gastroesophageal Reflux
Proton Pump Inhibitors
Heartburn


A Heterogeneously Expressed Gene Family Modulates the Biofilm Architecture and Hypoxic Growth of Aspergillus fumigatus.

Abstract: The genus Aspergillus encompasses human pathogens such as Aspergillus fumigatus and industrial powerhouses such as Aspergillus niger In both cases, Aspergillus biofilms have consequences for infection outcomes and yields of economically important products. However, the molecular components influencing filamentous fungal biofilm development, structure, and function remain ill defined. Macroscopic colony morphology is an indicator of underlying biofilm architecture and fungal physiology. A hypoxia-locked colony morphotype of A. fumigatus has abundant colony furrows that coincide with a reduction in vertically oriented hyphae within biofilms and increased low oxygen growth and virulence. Investigation of this morphotype has led to the identification of the causative gene, biofilm architecture factor A (bafA), a small cryptic open reading frame within a subtelomeric gene cluster. BafA is sufficient to induce the hypoxia-locked colony morphology and biofilm architecture in A. fumigatus Analysis across a large population of A. fumigatus isolates identified a larger family of baf genes, all of which have the capacity to modulate hyphal architecture, biofilm development, and hypoxic growth. Furthermore, introduction of A. fumigatus bafA into A. niger is sufficient to generate the hypoxia-locked colony morphology, biofilm architecture, and increased hypoxic growth. Together, these data indicate the potential broad impacts of this previously uncharacterized family of small genes to modulate biofilm architecture and function in clinical and industrial settings.IMPORTANCE The manipulation of microbial biofilms in industrial and clinical applications remains a difficult task. The problem is particularly acute with regard to filamentous fungal biofilms for which molecular mechanisms of biofilm formation, maintenance, and function are only just being elucidated. Here, we describe a family of small genes heterogeneously expressed across Aspergillus fumigatus strains that are capable of modifying colony biofilm morphology and microscopic hyphal architecture. Specifically, these genes are implicated in the formation of a hypoxia-locked colony morphotype that is associated with increased virulence of A. fumigatus Synthetic introduction of these gene family members, here referred to as biofilm architecture factors, in both A. fumigatus and A. niger additionally modulates low oxygen growth and surface adherence. Thus, these genes are candidates for genetic manipulation of biofilm development in aspergilli.

Kowalski|Caitlin H|CH|
Morelli|Kaesi A|KA|
Stajich|Jason E|JE|0000-0002-7591-0020
Nadell|Carey D|CD|0000-0003-1751-4895
Cramer|Robert A|RA|0000-0001-5503-5006

biofilm
Aspergillus fumigatus
morphology
genetics
cryptic gene
hypoxia


Cross- species communication in bacterial world.

Abstract: Biofilms are the compact association of micro organisms and the communication processes in these biofilms are always a wonder. Electrical and chemical signaling mechanism are the key to understand the bacterial communication network. Quorum sensing so far has been able to explain the coordinated motion of bacteria through its chemical signaling mechanism. Bacteria residing within biofilm communities are trivial to communicate. But the recent observation in 2017 by Humphries et al. has revealed that the ion channels enabled electrical signaling mechanism can be as powerful as to attract the distant cells i.e., this signaling mechanism are capable of holding a long range behavior. As a result long range cross species communication in the bacterial world have been possible. This substantial outcome has brought this field into a new paradigm to investigate the complex co-existence of biofilm communities and distant cells with a possible scope of application in synthetic biology. In this present article, we briefly describe this new signaling mechanism and how it gives rise to a long range communication ability in bacterial communities.

Biofilms
Quorum sensing
Bacteria
Ion channels
Electrical signaling


Alterations in cellular RNA decapping dynamics affect tomato spotted wilt virus cap snatching and infection in Arabidopsis.

Abstract: RNA processing and decay pathways have important impacts on RNA viruses, particularly animal-infecting bunyaviruses, which utilize a cap-snatching mechanism to translate their mRNAs. However, their effects on plant-infecting bunyaviruses have not been investigated. The roles of mRNA degradation and non-sense-mediated decay components, including DECAPPING 2 (DCP2), EXORIBONUCLEASE 4 (XRN4), ASYMMETRIC LEAVES2 (AS2) and UP-FRAMESHIFT 1 (UPF1) were investigated in infection of Arabidopsis thaliana by several RNA viruses, including the bunyavirus, tomato spotted wilt virus (TSWV). TSWV infection on mutants with decreased or increased RNA decapping ability resulted in increased and decreased susceptibility, respectively. By contrast, these mutations had the opposite, or no, effect on RNA viruses that use different mRNA capping strategies. Consistent with this, the RNA capping efficiency of TSWV mRNA was higher in a dcp2 mutant. Furthermore, the TSWV N protein partially colocalized with RNA processing body (PB) components and altering decapping activity by heat shock or coinfection with another virus resulted in corresponding changes in TSWV accumulation. The present results indicate that TSWV infection in plants depends on its ability to snatch caps from mRNAs destined for decapping in PBs and that genetic or environmental alteration of RNA processing dynamics can affect infection outcomes.

D015967:Gene Expression Regulation, Viral


Real-Time Quantitative Assessment of Accuracy and Precision of Blood Volume Derived from DCE-MRI in Individual Patients During a Clinical Trial.

Abstract: Accuracy and precision of quantitative imaging (QI) metrics should be assessed in real time in each patient during a clinical trial to support QI-based decision-making. We developed a framework for real-time quantitative assessment of QI metrics and evaluated accuracy and precision of dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI)-derived blood volume (BV) in a clinical trial for head and neck cancers. Patients underwent DCE-MRI before and after 2 weeks of radiation therapy (2wkRT). A mean as a reference value and a repeatability coefficient (RC) of BV values established from n patients in cerebellum volumes of interest (VOIs), which were normal and affected little by therapy, served as accuracy and precision measurements. The BV maps of a new patient were called accurate and precise if the values in cerebellum VOIs and the difference between the 2 scans agreed with the respective mean and RC with 95% confidence. The new data could be used to update reference values. Otherwise, the data were flagged for further evaluation before use in the trial. BV maps from 62 patients enrolled on the trial were evaluated. Mean BV values were 2.21 (±0.14) mL/100 g pre-RT and 2.22 (±0.17) mL/100 g at 2wkRT; relative RC was 15.9%. The BV maps from 3 patients were identified to be inaccurate and imprecise before use in the clinical trial. Our framework of real-time quantitative assessment of QI metrics during a clinical trial can be translated to different QI metrics and organ-sites for supporting QI-based decision-making that warrants success of a clinical trial.

Aryal|Madhava P|MP|
Lee|Choonik|C|
Hawkins|Peter G|PG|
Chapman|Christina|C|
Eisbruch|Avraham|A|
Mierzwa|Michelle|M|
Cao|Yue|Y|

blood volume
quantitative imaging
head and neck cancer
repeatability
dynamic contrast enhanced MRI
real-time assessment


Trogossitidae: A review of the beetle family, with a catalogue and keys.

Abstract: Cleroidea) is reviewed to species level. Keys to its genera, tribes and subfamilies are presented for the first time. All known species and subspecies are listed, together with complete taxonomic references back to 1910, the date of issue of the last catalogue of Trogossitidae. Higher taxa reviews are accompanied by remarks on phylogeny, distribution and biology as well as a brief description of adults and larvae. All known fossil records of Trogossitidae are reviewed and discussed. The work includes maps of distribution, colour photographs of generic representatives, morphological illustrations, SEM photographs and phylogenetic trees.

Trogossitidae catalogue key Cleroidea Coleoptera


Integrated Analysis of the Altered lncRNAs and mRNAs Expression in 293T Cells after Ionizing Radiation Exposure.

Abstract: Tissue and cell damage caused by ionizing radiation is often highly genotoxic. The swift repair of DNA damage is crucial for the maintenance of genomic stability and normal cell fitness. Long noncoding RNAs (lncRNAs) have been reported to play an important role in many physiological and pathological processes in cells. However, the exact function of lncRNAs in radiation-induced DNA damage has yet to be elucidated. Therefore, this study aimed to analyze the potential role of lncRNAs in radiation-induced DNA damage. We examined the expression profiles of lncRNAs and mRNAs in 293T cells with or without 8 Gy irradiation using high-throughput RNA sequencing. We then performed comprehensive transcriptomic and bioinformatic analyses of these sequencing results. A total of 18,990 lncRNAs and 16,080 mRNAs were detected in all samples. At 24 h post irradiation, 49 lncRNAs and 323 mRNAs were differentially expressed between the irradiation group and the control group. qRT-PCR was used to verify the altered expression of six lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the predicted genes were mainly involved in the histone mRNA metabolic process and Wnt signaling pathways. This study may provide novel insights for the study of lncRNAs in radiation-induced DNA damage.

Yang|Mengmeng|M| Sun|Yuxiao|Y| Xiao|Changyan|C| Ji|Kaihua|K| Zhang|Manman|M| He|Ningning|N| Wang|Jinhan|J| Wang|Qin|Q| Sun|Zhijuan|Z| Wang|Yan|Y| Du|Liqing|L| Liu|Yang|Y| Xu|Chang|C| Liu|Qiang|Q|0000-0002-7668-6868

D019295:Computational Biology
D004249:DNA Damage
D020869:Gene Expression Profiling
D005786:Gene Expression Regulation
D053263:Gene Regulatory Networks
D057809:HEK293 Cells
D006801:Humans
D035683:MicroRNAs
D034622:RNA Interference
D062085:RNA, Long Noncoding
D012333:RNA, Messenger
D011839:Radiation, Ionizing
D015203:Reproducibility of Results
D059467:Transcriptome

lncRNA
mRNA
ionizing radiation
DNA damage


Tyrosine 284 phosphorylation is required for ClC-3 chloride channel activation in vascular smooth muscle cells.

Abstract:
AIMS
The ClC-3 chloride channel (and current, ICl,ClC-3) plays an important role in cell volume regulation, proliferation, and apoptosis in vascular smooth muscle cells, and is a potential target for prevention of vascular remodelling and stroke. However, modulation of ICl,ClC-3 by intercellular signalling is not fully understood. Although it has been suggested that tyrosine phosphorylation is required for ICl,ClC-3 activation, the potential tyrosine residues in the ClC-3 protein are not clear. In the present study, the critical tyrosine residues in ClC-3 protein were investigated.

METHODS AND RESULTS
Site-specific mutagenesis, immunoprecipitation, patch clamp, and Cl(-) transport imaging techniques were employed. We found that activation of ICl,ClC-3 was associated with tyrosine phosphorylation of the ClC-3 protein. Three potential tyrosine residues, Y284, Y572, and Y631, were mutated to phenylalanine, and only mutation, at Y284 within a consensus Src-phosphorylation site, completely blocked ICl,ClC-3. Phosphomimetic mutation Y284D increased the Cl(-) current and Cl(-) efflux mediated by ClC-3. The Y284F mutation completely abolished the protective effect of ClC-3 on apoptosis, whereas the Y284D mutation potentiated it. There was an interaction between Src kinase and ClC-3 protein, and the Y284D mutation abrogated the inhibitory effect of SU6656, a Src family kinase inhibitor, on ClC-3 Cl(-) current.

CONCLUSION
Tyrosine 284 phosphorylation in the ClC-3 channel targeted by Src kinase is an important molecular mechanism for ClC-3 channel activation.

Wang|Xiao-Guang|XG| Tao|Jing|J| Ma|Ming-Ming|MM| Tang|Yong-Bo|YB| Zhou|Jia-Guo|JG| Guan|Yong-Yuan|YY|

Tyrosine
Phosphorylation
ClC-3 chloride channel
Vascular smooth muscle cell
Apoptosis


A predictive model of outcomes during cerebral aneurysm coiling.

Abstract:
BACKGROUND
Benchmarking of complications is necessary in the context of the developing path to accountable care. We attempted to create a predictive model of negative outcomes in patients undergoing cerebral aneurysm coiling (CACo).

METHODS
We performed a retrospective cohort study involving patients who underwent CACo from 2005 to 2009 and who were registered in the Nationwide Inpatient Sample database. A model for outcome prediction based on individual patient characteristics was developed.

RESULTS
Of the 10 607 patients undergoing CACo, 6056 presented with unruptured aneurysms (57.1%) and 4551 with subarachnoid hemorrhage (42.9%). The respective inpatient postoperative risks were 0.3%, 5.7%, 1.8%, 0.8%, 0.5%, 0.2%, 1.9%, and 0.1% for unruptured aneurysms, and 13.8%, 52.8%, 4.9%, 36.7%, 1%, 2.9%, 2.3%, and 0.8% for ruptured aneurysms for death, unfavorable discharge, stroke, treated hydrocephalus, cardiac complications, deep vein thrombosis, pulmonary embolism, and acute renal failure. Multivariate analysis identified risk factors independently associated with the above outcomes. A validated model for outcome prediction based on individual patient characteristics was developed. The accuracy of the model was estimated by the area under the receiver operating characteristic curve, and it was found to have good discrimination.

CONCLUSIONS
The presented model can aid in the prediction of the incidence of postoperative complications, and can be used as an adjunct in tailoring the treatment of cerebral aneurysms.

Bekelis|Kimon|K|
Missios|Symeon|S|
Mackenzie|Todd A|TA|
Fischer|Adina|A|
Labropoulos|Nicos|N|
Eskey|Clifford|C|


miR-141 as potential suppressor of β-catenin in breast cancer.

Abstract: Triple negative breast cancer (TNBC) is well known for its heterogeneous features and lack of targeted therapy. A variety of cell signaling pathways have been linked to the initiation and progression of these tumors where canonical Wnt signaling is one of the main candidate pathways. Considering past literatures on this matter and negative reports regarding mutations in β-catenin gene (CTNNB1), we focus our attention to another level of gene expression control level, microRNAs (miRNAs). For proper miRNA target detection, we utilized bioinformatics as a relatively new and reliable tool for miRNA: mRNA prediction. MDA-MB-231 (invasive breast cancer) and MCF-10A (normal breast) cell lines were chosen as models. We used different bioinformatic tools such as TargetScan, miRanda, etc. For miRNA targeting CTNNB1-3´UTR confirmation, luciferase assay was carried out. miRNA expression was induced in cell lines through viral constructs expressing desired miRNA. Quantitative real-time PCR was performed for the measurement of expression levels of selected miRNA and target gene. miR-141 was selected via expanded search among various bioinformatic tools. miR-141 expression level was downregulated in MDA-MB-231 cell line, and CTNNB1 gene expression was upregulated. After transduction with viral construct, miR-141 expression was elevated in both cell lines, and gene expression was notably decreased. β-Catenin can be considered as one of the main players in these tumors' pathogenesis. Also, it is the potential target of miR-141, in which its downregulation was detected in cell lines, and can be considered as a promising new targeted approach toward TNBC.

Abedi|Nairi|N| Mohammadi-Yeganeh|Samira|S| Koochaki|Ameneh|A| Karami|Fariba|F| Paryan|Mahdi|M|

D015972:Gene Expression Regulation, Neoplastic

D064726:Triple Negative Breast Neoplasms

Triple negative breast cancer
Wnt signaling
miRNA
Luciferase assay
CTNNB1 gene


Brain perfusion SPECT in patients with Behçet's disease.

Abstract: The aim of this study was to detect brain functional deficits in patients with Behçet's disease (BD) and signs or symptoms of central nervous system (CNS) involvement at different times in their clinical history. A total of 24 patients aged 20 to 53years (median age 39years; 20 women, four men) with Behçet's syndrome fulfilling the diagnosis as defined by the syndrome classification were enrolled in this study. Single-photon emission computed tomography (SPECT) with (99m)Technetium (Tc)-hexamethylpropyleneamine oxime (HMPAO) as the perfusion tracer was performed to detect brain lesions. The results of (99m)Tc-HMPAO brain SPECT scans showed impaired perfusion in all cases with neurological complaints (24 out of 24, 100%). Temporal lobes and basal ganglia were the most common areas with such lesions. In contrast, brain MRI and CT images were normal or non-specific in all cases. In conclusion, (99m)Tc-HMPAO brain SPECT imaging is a powerful and sensitive tool for disclosing brain involvement in numerous clinical situations, even including patients with subtle neurological symptoms/signs such as headaches and dizziness. It is also a useful modality for evaluating the effects of treatment and disease monitoring to prevent CNS damage.

Chuang|Ya-Wen|YW| Hsu|Chien-Chin|CC| Huang|Ying-Fong|YF| Lin|Hsiu-Fen|HF| Chang|Chin-Chuan|CC| Lin|Chia-Yang|CY| Tyan|Yu-Chang|YC|

Behçet's disease
Behçet's syndrome
(99m)Tc-HMPAO
Brain SPECT scan
Neuro-Behçet's syndrome


Host-Range Shift Between Emerging P[8]-4 Rotavirus and Common P[8] and P[4] Strains.

Abstract: In Tunisia, we observed that rotavirus P[8]-3 and P[4] strains in young children with gastroenteritis associate with secretor histo-blood group phenotype. In contrast, the emerging P[8]-4 strain, representing 10% of cases, was exclusively found in nonsecretor patients. Unlike VP8* from P[8]-3 and P[4] strains, the P[8]-4 VP8* protein attached to glycans from saliva samples regardless of the donor's secretor status. Interestingly, a high frequency of FUT2 enzyme deficiency (nonsecretor phenotype) was observed in the population. This may allow cocirculation of P[8]-3 and P[8]-4 strains in secretor and nonsecretor children, respectively.

Khachou|Amira|A|
Le Moullac-Vaidye|Béatrice|B|
Peltier|Cécile|C|
Breiman|Adrien|A|
Imbert-Marcille|Berthe-Marie|BM|
Ruvoen-Clouet|Nathalie|N|
Aouni|Mahjoub|M|
Mastouri|Maha|M|
Chouchane|Slaheddine|S|
Le Pendu|Jacques|J|

rotavirus
FUT2
fucosyltransferase
genetic susceptibility
histo-blood group antigen
host range
secretor/nonsecretor phenotypes


Usefulness of surgical pleth index-guided analgesia during general anesthesia: a systematic review and meta-analysis of randomized controlled trials.

Abstract:
OBJECTIVE
Previous studies comparing surgical pleth index (SPI)-guided and conventional analgesia have shown differing results. Therefore, we compared the intraoperative opioid requirement, extubation time, postoperative pain scores, and perioperative adverse events between these two modalities.

METHODS
A comprehensive literature search was conducted to identify randomized controlled trials comparing the intraoperative opioid requirement and other outcomes between the two modalities. The mean difference (MD) or the pooled risk ratio and corresponding 95% confidence interval (CI) were used for analysis. A heterogeneity (I2) assessment was performed.

RESULTS
Six randomized controlled trials comparing 463 patients were included. Intraoperative opioid consumption was significantly lower in the SPI-guided than conventional analgesia group (standardized MD, -0.41; 95% CI, -0.70 to -0.11; I2 = 53%). No significant intergroup difference was observed in the pain score on the first postoperative day or the incidence of perioperative adverse events. The extubation time was considerably shorter in the SPI-guided than conventional analgesia group (MD, -1.91; 95% CI, -3.33 to -0.49; I2 = 67%).

CONCLUSIONS
Compared with conventional analgesia, SPI-guided analgesia can reduce intraoperative opioid consumption and facilitate extubation. Moreover, no intergroup difference was observed in the degree of postoperative pain or incidence of perioperative adverse events.

D016032:Randomized Controlled Trials as Topic

Analgesia general anesthesia opioid analgesics hemodynamics photoplethysmography


Prognostic performance of pre-treatment NLR and PLR in patients suffering from osteosarcoma.

Abstract:
BACKGROUND
Inflammatory response markers have been proposed to predict the clinical outcomes in various cancers. The aim of this study was to explore the influence of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of osteosarcoma.

METHODS
Three hundred fifty-nine patients who underwent curative surgery for osteosarcoma were enrolled from 2005 to 2010. NLR and PLR were calculated from peripheral blood cell counts taken at pre-treatment. Optimal cutoff values of NLR and PLR were determined on the basis of receiver operating characteristic curve analysis. A predictive model was established to predict the clinical outcome for overall survival, and the predictive accuracy of this model was determined by concordance index (c-index).

RESULTS
Our results showed that advanced stage and metastasis at diagnosis were significantly associated with the high NLR and PLR groups. NLR was an independent prognostic indicator for overall survival (HR = 1.80, 95% CI = 1.35-2.41, P < 0.001) and progression-free survival (HR = 1.65, 95% CI = 1.26-2.15, P < 0.001), except for PLR. The nomogram could perform well in the prediction of overall survival in patients with osteosarcoma (c-index 0.829).

CONCLUSIONS
Our results suggest that both NLR and PLR can reflect clinical prognosis. NLR is more predictive of overall survival and progression-free survival than PLR.

Xia|Wen-Kai|WK| Liu|Zhi-Li|ZL| Shen|Dong|D| Lin|Qing-Feng|QF| Su|Jun|J| Mao|Wei-Dong|WD|


Targeting B Cell Signaling in Chronic Lymphocytic Leukemia.

Abstract: In recent years, a revolution in the management of chronic lymphocytic leukemia (CLL) has centered on the targeting of the B cell receptor (BCR) signaling pathway. Our improved understanding of the biology of cell signaling in CLL and the development of oral kinase inhibitors directed at the BCR pathway has led to the approval of two new agents and has the potential to radically change the treatment of CLL in both the relapsed/refractory and upfront settings. In this review, we will describe the underlying biology of the BCR signaling pathway. We will discuss the landmark clinical trials resulting in the approval of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib and the PI3Kδ inhibitor idelalisib. We will highlight ongoing trials that are evaluating the use of combinations of these agents with standard chemotherapy. We will evaluate some of the emerging data regarding toxicity, potential off-target effects, and mechanisms of resistance to BCR signaling pathway blockade. Finally, we will highlight some of the next-generation BCR pathway inhibitors currently in development.

D015451:Leukemia, Lymphocytic, Chronic, B-Cell

B cell receptor
Ibrutinib
Idelalisib
Chronic lymphocytic lymphoma


Lipocalin 2 deficiency-induced gut microbiota dysbiosis evokes metabolic syndrome in aged mice.

Abstract: Lipocalin 2 (Lcn2) is a multifunctional innate immune protein that limits microbial overgrowth. Our previous study demonstrated that the gut microbiota directly induces intestinal Lcn2 production, and Lcn2-deficient (Lcn2-/-) mice exhibit gut dysbiosis. Coincidentally, gut dysbiosis is associated with metabolic syndrome pathogenesis, and elevated Lcn2 levels has been considered a potential clinical biomarker of metabolic syndrome. Yet whether Lcn2 mitigates or exacerbates metabolic syndrome remains inconclusive. Our objective was to determine whether Lcn2 deficiency-induced compositional changes in gut microbiota contribute to gain in adiposity in aged mice. Utilizing Lcn2-/- mice and their wild-type (WT) littermates, we measured metabolic markers, including fasting blood glucose, serum lipids, fat pad weight, and insulin resistance at ages 3, 6, and 9 mo old. Relative to WT mice, aged Lcn2-/- mice exhibited a gain in adiposity associated with numerous features of metabolic syndrome, including insulin resistance and dyslipidemia. Surprisingly, supplementation with a high-fat diet did not further aggravate metabolic syndrome that spontaneously occurs in Lcn2-/- mice by 6 mo of age. Interestingly, chow-fed Lcn2-/- mice displayed marked differences in the bacterial abundance and metabolomic profile of the gut microbiota compared with WT mice. Overall, our results demonstrate that Lcn2 is essential to maintain metabolic and gut microbiotal homeostasis, where deficiency induces spontaneous delayed onset of metabolic syndrome.

Singh|Vishal|V|
Galla|Sarah|S|
Golonka|Rachel M|RM|
Patterson|Andrew D|AD|
Chassaing|Benoit|B|0000-0002-4285-769X
Joe|Bina|B|
Vijay-Kumar|Matam|M|0000-0002-8732-0167

insulin resistance
dyslipidemias
microbial-host interactions
obesity


Purified isolation of vacuoles from Sedum alfredii leaf-derived protoplasts.

Abstract: This study aims to develop a method for isolating and purifying protoplasts/vacuoles from fresh leaves of the Cd hyperaccumulator plant species, Sedum alfredii. The results revealed that preheating cellulase and macerozyme at 50 °C for 5 min significantly accelerated the cell wall degradation. For the most optimal conditions for mesophyll protoplast isolation, the mixture of fresh leaves and cell lysates was followed by a 2-h-long vibration. The protoplast lysate for vacuole isolation was diluted, and 0.675 mmol/L was identified as the most appropriate 3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonic acid (CHAPS) level, in which S. alfredii large vacuoles are characterized by a high metal and malic acid content. For the best vacuole purification results, we established that 0.8 mol/L was the most optimal mannitol level in the vacuole buffer in terms of vacuole protection during centrifugation, whereas a Ficoll concentration of 0.10 g/ml was adopted in the density-gradient centrifugation.

Gao|Xiao-Yu|XY| Liao|Xing-Cheng|XC| Wu|Ruo-Lai|RL| Liu|Ting|T| Wang|Hai-Xing|HX| Lu|Ling-Li|LL|

Purified isolation
Vacuole
Sedum alfredii
Protoplast
Hyperaccumulator plant


Combinatorial control of gene function with wavelength-selective caged morpholinos.

Abstract: Caged morpholino oligonucleotides (cMOs) are useful research tools in developmental biology because they allow spatiotemporal control of gene expression in whole organisms. While cMOs are usually triggered by light of a single wavelength, the introduction of spectrally distinct chromophores can enable combinatorial regulation of multiple genes. This chapter describes the general principles and methods of wavelength-selective cMO design and synthesis from commercially available reagents. Synthetic protocols for the linkers and the two-step cMO assembly are described in detail, as well as the microinjection and photoactivation techniques. Following these protocols, spectrally separated cyclic cMOs for multiple genes of interest can be prepared, enabling their inhibition in zebrafish embryos and other animal models.

Pattanayak|Sankha|S|
Vázquez-Maldonado|Luis Angel|LA|
Deiters|Alexander|A|
Chen|James K|JK|

Caged morpholinos
Developmental biology
Zebrafish
Antisense oligonucleotides
Gene silencing
Photolabile linkers
Wavelength-selective activation


A deregulated expression of estrogen-target genes is associated with an altered response to estradiol in aged rats perinatally exposed to bisphenol A.

Abstract: Here we assessed the effects of perinatal exposure to bisphenol A (BPA) on the uterine response to 17β-estradiol (E2) in aged rats. Pregnant rats were orally exposed to 0.5 or 50 μg BPA/kg/day from gestational day 9 until weaning. On postnatal day (PND) 360, the rats were ovariectomized and treated with E2 for three months. The uterine tissue of BPA50 and BPA0.5 rats showed increased density of glands with squamous metaplasia (GSM) and glands with daughter glands respectively. Wnt7a expression was lower in GSM of BPA50 rats than in controls. The expression of estrogen receptor 1 (ESR1) and its 5'- untranslated exons ESR1-O and ESR1-OT was lower in BPA50 rats. Both doses of BPA modified the expression of coactivator proteins and epigenetic regulatory enzymes. Thus, perinatal BPA-exposed rats showed different glandular abnormalities associated with deregulated expression of E2-target genes. Different mechanisms would be involved depending on the BPA dose administered.

Vigezzi|Lucía|L|
Ramos|Jorge G|JG|
Kass|Laura|L|
Tschopp|María V|MV|
Muñoz-de-Toro|Mónica|M|
Luque|Enrique H|EH|
Bosquiazzo|Verónica L|VL|

D011297:Prenatal Exposure Delayed Effects

Rat
Bisphenol A
ESR1
Uterine glands
Uterus
Wnt


Advance care planning in patients with incurable cancer: study protocol for a randomised controlled trial.

Abstract:
INTRODUCTION
There is limited evidence documenting the effectiveness of Advance Care Planning (ACP) in cancer care. The present randomised trial is designed to evaluate whether the administration of formal ACP improves compliance with patients' end-of-life (EOL) wishes and patient and family satisfaction with care.

METHODS AND ANALYSIS
A randomised control trial in eight oncology centres across New South Wales and Victoria, Australia, is designed to assess the efficacy of a formal ACP intervention for patients with cancer. Patients with incurable cancer and an expected survival of 3-12 months, plus a nominated family member or friend will be randomised to receive either standard care or standard care plus a formal ACP intervention. The project sample size is 210 patient-family/friend dyads. The primary outcome measure is family/friend-reported: (1) discussion with the patient about their EOL wishes and (2) perception that the patient's EOL wishes were met. Secondary outcome measures include: documentation of and compliance with patient preferences for medical intervention at the EOL; the family/friend's perception of the quality of the patient's EOL care; the impact of death on surviving family; patient-family and patient-healthcare provider communication about EOL care; patient and family/friend satisfaction with care; quality of life of patient and family/friend subsequent to trial entry, the patient's strength of preferences for quality of life and length of life; the costs of care subsequent to trial entry and place of death.

ETHICS AND DISSEMINATION
Ethical approval was received from the Sydney Local Health District (RPA Zone) Human Research Ethical Committee, Australia (Protocol number X13-0064). Study results will be submitted for publication in peer-reviewed journals and presented at national and international conferences.

TRIAL REGISTRATION NUMBER
Pre-results; ACTRN12613001288718.

Johnson|Stephanie|S|0000-0002-6777-8816
Clayton|Josephine|J|
Butow|Phyllis N|PN|
Silvester|William|W|
Detering|Karen|K|
Hall|Jane|J|
Kiely|Belinda E|BE|
Cebon|Jonathon|J|
Clarke|Stephen|S|
Bell|Melanie L|ML|
Stockler|Martin|M|
Beale|Phillip|P|
Tattersall|Martin H N|MH|

D032722:Advance Care Planning
D003142:Communication
D003643:Death
D005190:Family
D006801:Humans
D009369:Neoplasms
D010358:Patient Participation
D057240:Patient Preference
D057184:Practice Patterns, Nurses'
D011368:Professional-Family Relations
D011369:Professional-Patient Relations
D011787:Quality of Health Care
D011788:Quality of Life
D012107:Research Design
D013727:Terminal Care

Advance care planning
Randomised controlled trial
Advance Directive
End of Life


Transversely isotropic material characterization of the human anterior longitudinal ligament.

Abstract: The present work represents the first study to report transversely isotropic material parameters for the human anterior longitudinal ligament (ALL) in the thoraco-lumbar spine. Force-deformation data from multi-axial testing was collected from 30 cadaveric spine test specimens using an anisotropic quarter punch test technique. The experimental data was fit to a commonly used anisotropic soft tissue material model using an FEA system identification technique. The material model correlated well with the experimental response (R(2)≥0.98). The constitutive parameter values, as well as the nonlinear anisotropic stress-strain response of the ALL specimens are reported to facilitate application to biomechanical models (including finite element models) of the spine.

Hortin|Mitchell|M| Graham|Sarah|S| Boatwright|Kara|K| Hyoung|Peter|P| Bowden|Anton|A|

Anterior longitudinal ligament
Biomechanics
Anisotropic punch test
Finite element analysis
Spinal ligaments


Validity of computed tomography in diagnosing midfacial fractures.

Abstract: The aim of this study was to evaluate the sensitivity, accuracy, and reliability of two-dimensional computed tomography (2D-CT) scans (axial, coronal, sagittal planes) and three-dimensional computed tomography (3D-CT) reconstructions in diagnosing midfacial fractures in relation to actual fractures identified clinically and during surgery (gold standard). The imaging diagnosis was performed by a radiologist and an oral and maxillofacial surgeon. Sixty-two patients with a total of 429 midfacial fractures were included. Frontal sinus and nose fractures were easily diagnosed. For the three CT planes, there was a statistically significant difference between the CT examination and the gold standard for five to seven of the nine bones evaluated, while for 3D-CT, a difference was observed only for fractures of the orbital floor. The inter-observer agreement between the oral and maxillofacial surgeon and the radiologist was 75.5%. In conclusion, in this study 3D-CT reconstructions showed significantly the best sensitivity, accuracy, and reliability for the diagnosis of midfacial fractures. The sagittal reconstructions were the least diagnostic of the 2D-CT images. For areas where the parameters studied showed less agreement and hence a more difficult diagnosis, we recommend a combination of 3D and 2D-CT images to improve diagnostic accuracy.

de Carvalho|M F|MF|
Vieira|J N M|JNM|
Figueiredo|R|R|
Reher|P|P|
Chrcanovic|B R|BR|
Chaves|M G A M|MGAM|

D005147:Facial Bones
D005626:Frontal Sinus
D006801:Humans
D021621:Imaging, Three-Dimensional
D009917:Orbital Fractures
D015203:Reproducibility of Results
D012887:Skull Fractures
D014057:Tomography, X-Ray Computed

Computed tomography
Midfacial fractures
Diagnosis
Facial trauma


Neurological autoimmune diseases following vaccinations against SARS-CoV-2: a case series.

Abstract:
BACKGROUND AND PURPOSE
Population-based studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may trigger immune-mediated thrombotic thrombocytopenia (VITT) raising concerns for other autoimmune responses. The aim was to characterize neurological autoimmunity after SARS-CoV-2 vaccinations.

METHODS
In this single-centre prospective case study patients with neurological autoimmunity in temporal association (≤6 weeks) with SARS-CoV-2 vaccinations and without other triggers are reported. Clinical, laboratory and imaging data were collected with a median follow-up of 49 days.

RESULTS
In the study period 232,603 inhabitants from the main catchment area of our hospital (Rhein-Neckar-Kreis, county) received SARS-CoV-2 vaccinations. Twenty-one cases (new onset n = 17, flares n = 4) diagnosed a median of 11 days (range 3-23) following SARS-CoV-2 vaccinations (BNT162b2 n = 12, ChAdOx1 n = 8, mRNA-1273 n = 1) were identified. Cases included VITT with cerebral venous sinus thrombosis (n = 3), central nervous system demyelinating diseases (n = 8), inflammatory peripheral neuropathies (n = 4), myositis (n = 3), myasthenia (n = 1), limbic encephalitis (n = 1) and giant cell arteritis (n = 1). Patients were predominantly female (ratio 3.2:1) and the median age at diagnosis was 50 years (range 22-86). Therapy included administration of steroids (n = 15), intravenous immunoglobulins in patients with Guillain-Barré syndrome or VITT (n = 4), plasma exchange in cases unresponsive to steroids (n = 3) and anticoagulation in VITT. Outcomes were favourable with partial and complete remissions achieved in 71% and 24%, respectively. Two patients received their second vaccination without further aggravation of autoimmune symptoms under low-dose immunosuppressants.

CONCLUSIONS
In this study various neurological autoimmune disorders encountered following SARS-CoV-2 vaccinations are characterized. Given the assumed low incidence and mostly favourable outcome of autoimmune responses, the benefits of vaccinations outweigh the comparatively small risks.

autoimmune
cerebral venous sinus thrombosis
myositis
Guillain-Barré syndrome
COVID-19
multiple sclerosis
myelitis


Triterpenoids from Gutenbergia nigritana(Benth). Oliv and Hiern.

Abstract: Gutenbergia nigritana (Benth). Oliv and Hein (Asteraceae) is a Nigerian ethnomedicinal plant which has long being used medicinally in traditional systems of medicine. The plant has diverse ethnomedicinal uses which include: The Plant is used in the Ijaw area of Niger Delta region of Nigeria to treat Malaria, convulsion, diarrhea and as a remedy for skin infection. The antibacterial study on dichloromethane extract and chromatographic fractions:dichloromethane soluble part(DC1), ethyl acetate soluble part(E1) and N-butanol soluble portions of methanolic extract were investigated using agar diffusion assay method by measuring the zone of inhibition against clinical isolates: Bacillus subtillis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. Extensive Chromatographic separation and preparative TLC were employed in the isolation steps. Column chromatograpy of the dichloromethane extract, gel filteration on sephadex and preparative TLC led to the isolation of two triterpenoids: Lupenol(1) and Lupenol acetate(2). The structures were elucidated by NMR spectroscopy and compared with literature. The dichloromethane extract exhibited antibacterial activity against all the test microorganisms with zones of inhibition ranging between 12-26mm. The chromatographic fraction (Fr-6) exhibited activity against E. coli, Ps. aeruginosa and S. aureus but in-active against B. subtilis, while the methanol soluble portions: dichloromethane and ethyl acetate showed weak activity while the n-butanol portion was in active. Dichloromethane extract of Gutenbergia nigritana leaves exhibited anti-bacterial activity, though the compounds isolated did not show activity, it is likely that the activity might reside in other components present in the dichloromethane extract.

Ahmadu|Augustine A|AA|
Tarimaledei|Pondei|P|
Onanuga|A|A|

D000900:Anti-Bacterial Agents
D019659:Asteraceae
D001407:Bacillus
D004926:Escherichia coli
D015394:Molecular Structure
D010936:Plant Extracts
D011550:Pseudomonas aeruginosa
D013211:Staphylococcus aureus
D014315:Triterpenes

Lupenol
Lupenol acetate
ntibacterial activity


Associations between practice-reported medical homeness and health care utilization among publicly insured children.

Abstract:
BACKGROUND
The patient-centered medical home (PCMH) is widely promoted as a model to improve the quality of primary care and lead to more efficient use of health care services. Few studies have examined the relationship between PCMH implementation at the practice level and health care utilization by children. Existing studies show mixed results.

METHODS
Using practice-reported PCMH assessments and Medicaid claims from child-serving practices in 3 states participating in the Children's Health Insurance Program Reauthorization Act of 2009 Quality Demonstration Grant Program, this study estimates the association between medical homeness (tertiles) and receipt of well-child care and nonurgent, preventable, or avoidable emergency department (ED) use. Multilevel logistic regression models are estimated on data from 32 practices in Illinois (IL) completing the National Committee for Quality Assurance's (NCQA) medical home self-assessment and 32 practices in North Carolina (NC) and South Carolina (SC) completing the Medical Home Index (MHI) or Medical Home Index-Revised Short Form (MHI-RSF).

RESULTS
Medical homeness was not associated with receipt of age-appropriate well-child visits in either sample. Associations between nonurgent, preventable, or avoidable ED visits and medical homeness varied. No association was seen among practices in NC and SC that completed the MHI/MHI-RSF. Children in practices in IL with the highest tertile NCQA self-assessment scores were less likely to have a nonurgent, preventable, or avoidable ED visit than children in practices with low (odds ratio 0.65; 95% confidence interval 0.47-0.92; P < .05) and marginally less likely to have such a visit compared with children in practices with medium tertile scores (odds ratio 0.72, 95% confidence interval 0.52-1.01; P = .06).

CONCLUSIONS
Higher levels of medical homeness may be associated with lower nonurgent, preventable, or avoidable ED use by publicly insured children. Robust longitudinal studies using multiple measures of medical homeness are needed to confirm this observation.

Christensen|Anna L|AL|
Zickafoose|Joseph S|JS|
Natzke|Brenda|B|
McMorrow|Stacey|S|
Ireys|Henry T|HT|

D065326:Children's Health Insurance Program

D010342:Patient Acceptance of Health Care

health care quality, access, and evaluation


Fragment-Based Discovery of Non-bisphosphonate Binders of Trypanosoma brucei Farnesyl Pyrophosphate Synthase.

Abstract: Trypanosoma brucei is the causative agent of human African trypanosomiasis (HAT). Nitrogen-containing bisphosphonates, a current treatment for bone diseases, have been shown to block the growth of the T. brucei parasites by inhibiting farnesyl pyrophosphate synthase (FPPS); however, due to their poor pharmacokinetic properties, they are not well suited for antiparasitic therapy. Recently, an allosteric binding pocket was discovered on human FPPS, but its existence on trypanosomal FPPS was unclear. We applied NMR and X-ray fragment screening to T. brucei FPPS and report herein on four fragments bound to this previously unknown allosteric site. Surprisingly, non-bisphosphonate active-site binders were also identified. Moreover, fragment screening revealed a number of additional binding sites. In an early structure-activity relationship (SAR) study, an analogue of an active-site binder was unexpectedly shown to bind to the allosteric site. Overlaying identified fragment binders of a parallel T. cruzi FPPS fragment screen with the T. brucei FPPS structure, and medicinal chemistry optimisation based on two binders revealed another example of fragment "pocket hopping". The discovery of binders with new chemotypes sets the framework for developing advanced compounds with pharmacokinetic properties suitable for the treatment of parasitic infections by inhibition of FPPS in T. brucei parasites.

D001665:Binding Sites
D055808:Drug Discovery
D004791:Enzyme Inhibitors
D051228:Geranyltranstransferase
D008958:Models, Molecular
D015394:Molecular Structure
D013329:Structure-Activity Relationship
D014346:Trypanosoma brucei brucei

Trypanosoma brucei
farnesyl pyrophosphate synthase
fragment screening
drug discovery
structural biology


The Construction and Application of Three-Dimensional Biomaterials.

Abstract: Biomaterials have been widely explored and applied in many areas, especially in the field of tissue engineering. The interface of biomaterials and cells has been deeply investigated. However, it has been demonstrated that conventional 2D biomaterials fail to maintain the 3D structures and phenotypes of cells, which is the result of their limited ability to mimic the latter's complex extracellular matrix. To overcome this challenge, cell cultivation dependent on 3D biomaterials has emerged as an alternative strategy to make the recovery of 3D structures and functions of cells possible. Thus, with the thriving development of 3D cell culture in tissue engineering, a holistic review of the construction and application of 3D biomaterials is desired. Here, recent developments in 3D biomaterials for tissue engineering are reviewed. An overview of various approaches to construct 3D biomaterials, such as electro-jetting/-spinning, micro-molding, microfluidics, and 3D bio-printing, is first presented. Their typical applications in constructing cell sheets, vascular structures, cell spheroids, and macroscopic cellular constructs are described as well. Following these two sections, the current status and challenges are analyzed, as well as the future outlook of 3D biomaterials for tissue engineering.

Wang|Jie|J| Yu|Yunru|Y| Guo|Jiahui|J| Lu|Wei|W| Wei|Qiong|Q| Zhao|Yuanjin|Y|0000-0001-9242-4000

biomaterials
tissue engineering
3D cell culture


Marine Algae as a Potential Source for Anti-diabetic Compounds - A Brief Review.

Abstract:
BACKGROUND
Diabetes Mellitus (DM) is a major chronic metabolic disorder characterized by hyperglycemia that leads to several complications such as retinopathy, atherosclerosis, nephropathy, etc. In 2019, it was estimated that about 463 million people had diabetes, and it may increase up to 700 million in 2045. Marine macroalgae are the rich source of bioactive compounds for the treatment of diabetes mellitus.

OBJECTIVE
This review summarizes the recent epidemiology and possible use of marine macroalgae-derived bioactive compounds for the protection against chronic metabolic disease, diabetes mellitus and marine macroalgae as a nutraceutical supplement.

CONCLUSION
The present therapies available for diabetes treatment are oral medicines and insulin injections. But continuous use of synthetic medicines provides low therapeutic with many side effects. In continuing search of anti-diabetic drugs, marine macroalgae remain as a promising source with potent bioactivity. Among existing marine algae, red and brown algae are reported to show anti-diabetic activity. Hence, the present review focuses on the epidemiology, diabetes biomarkers and different secondary bioactive compounds present in marine macroalgae to treat diabetes mellitus.

Diabetes mellitus
metabolic disorder
hyperglycemia
anti-diabetic drugs
brown marine algae
red marine algae


Downregulated PITX1 Modulated by MiR-19a-3p Promotes Cell Malignancy and Predicts a Poor Prognosis of Gastric Cancer by Affecting Transcriptionally Activated PDCD5.

Abstract:
BACKGROUND/AIMS
PITX1 has been identified as a potential tumor-suppressor gene in several malignant tumors. The molecular mechanism underlying PITX1, particularly its function as a transcription factor regulating gene expression during tumorigenesis, is still poorly understood.

METHODS
The expression level and location of PITX1 were determined by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemical staining in gastric cancer (GC). The effect of PITX1 on the GC cell proliferation and tumorigenesis was analyzed in vitro and in vivo. To explore how PITX1 suppresses cell proliferation, we used PITX1-ChIP-sequencing to measure genome-wide binding sites of PITX1 and assessed global function associations based on its putative target genes. ChIP-PCR, electrophoretic mobility shift assay, and promoter reporter assays examined whether PITX1 bound to PDCD5 and regulated its expression. The function of PDCD5 in GC cell apoptosis was further examined in vitro and in vivo. The relationship between the PITX1 protein level and GC patient prognosis was evaluated by the Kaplan-Meier estimator. Meanwhile, the expression level of miR-19a-3p, which is related to PITX1, was also detected by luciferase reporter assay, qRT-PCR, and western blotting.

RESULTS
The expression level of PITX1 was decreased in GC tissues and cell lines. Elevated PITX1 expression significantly suppressed the cell proliferation of GC cells and tumorigenesis in vitro and in vivo. PITX1 knockdown blocked its inhibition of GC cell proliferation. PITX1 bound to whole genome-wide sites, with these targets enriched on genes with functions mainly related to cell growth and apoptosis. PITX1 bound to PDCD5, an apoptosis-related gene, during tumorigenesis, and cis-regulated PDCD5 expression. Increased PDCD5 expression in GC cells not only induced GC cell apoptosis, but also suppressed GC cell growth in vitro and in vivo. Moreover, PITX1 expression was regulated by miR-19a-3p. More importantly, a decreased level of PITX1 protein was correlated with poor GC patient prognosis.

CONCLUSION
Decreased expression of PITX1 predicts shorter overall survival in GC patients. As a transcriptional activator, PITX1 regulates apoptosis-related genes, including PDCD5, during gastric carcinogenesis. These data indicate PDCD5 to be a novel and feasible therapeutic target for GC.

Qiao|Fengchang|F| Gong|Pihai|P| Song|Yunwei|Y| Shen|Xiaohui|X| Su|Xianwei|X| Li|Yiping|Y| Wu|Huazhang|H| Zhao|Zhujiang|Z| Fan|Hong|H|

D051761:Paired Box Transcription Factors


Analyses of the photosynthetic characteristics, chloroplast ultrastructure, and transcriptome of apple (Malus domestica) grown under red and blue lights.

Abstract:
BACKGROUND
Light quality significantly affects plant growth and development, photosynthesis, and carbon and nitrogen metabolism. Apple (Malus domestica Borkh.) is a widely cultivated and economically important fruit crop worldwide. However, there are still few studies on the effects of different light qualities on the growth and development of apple seedlings.

RESULTS
In this study, we explored the effects of blue and red light treatments on the growth and development, photosynthetic characteristics, leaf chloroplast ultrastructure, and carbon and nitrogen metabolism of apple seedlings. Blue light significantly inhibited apple plant growth and leaf extension, but it promoted the development of leaf tissue structures and chloroplasts and positively affected leaf stomatal conductance, the transpiration rate, and photosynthetic efficiency. The red light treatment promoted apple plant growth and root development, but it resulted in loosely organized leaf palisade tissues and low chlorophyll contents. The blue and red light treatments enhanced the accumulation of ammonium nitrogen in apple seedlings. Moreover, the blue light treatment significantly promoted nitrogen metabolism. Additionally, an RNA-seq analysis revealed that both blue light and red light can significantly up-regulate the expression of genes related to carbon and nitrogen metabolism. Blue light can also promote amino acid synthesis and flavonoid metabolism, whereas red light can induce plant hormone signal transduction. The expression of a gene encoding a bHLH transcription factor (MYC2-like) was significantly up-regulated in response to blue light, implying it may be important for blue light-mediated plant development.

CONCLUSIONS
Considered together, blue and red light have important effects on apple growth, carbon and nitrogen metabolism. These findings may be useful for determining the ideal light conditions for apple cultivation to maximize fruit yield and quality.

Li|Zhiqiang|Z| Chen|Qiaojing|Q| Xin|Youyan|Y| Mei|Zhuoxin|Z| Gao|Aiyun|A| Liu|Wenjun|W| Yu|Lei|L| Chen|Xuesen|X| Chen|Zijing|Z| Wang|Nan|N|

Apple
Red and blue light
Growth and development
Carbon and nitrogen metabolism


Activated Graphene Oxide-Calcium Alginate Beads for Adsorption of Methylene Blue and Pharmaceuticals.

Abstract: The remarkable adsorption capacity of graphene-derived materials has prompted their examination in composite materials suitable for deployment in treatment of contaminated waters. In this study, crosslinked calcium alginate-graphene oxide beads were prepared and activated by exposure to pH 4 by using 0.1M HCl. The activated beads were investigated as novel adsorbents for the removal of organic pollutants (methylene blue dye and the pharmaceuticals famotidine and diclofenac) with a range of physicochemical properties. The effects of initial pollutant concentration, temperature, pH, and adsorbent dose were investigated, and kinetic models were examined for fit to the data. The maximum adsorption capacities qmax obtained were 1334, 35.50 and 36.35 mg g-1 for the uptake of methylene blue, famotidine and diclofenac, respectively. The equilibrium adsorption had an alignment with Langmuir isotherms, while the kinetics were most accurately modelled using pseudo- first-order and second order models according to the regression analysis. Thermodynamic parameters such as ΔG°, ΔH° and ΔS° were calculated and the adsorption process was determined to be exothermic and spontaneous.

adsorption
methylene blue
pharmaceuticals
kinetics
graphene oxide
isotherms and thermodynamics


Identification of potential crucial genes associated with the pathogenesis and prognosis of prostate cancer.

Abstract: Aim: Prostate cancer (PCa) is the sixth leading cause of cancer-related deaths in men throughout the world. This study aimed to investigate genes associated with the pathogenesis and prognosis of PCa. Materials & methods: Data of PCa cases were obtained from public datasets and were analyzed using an integrated bioinformatics strategy. Results: A total of 969 differential expression genes were identified. Moreover, GSE16560 and The Cancer Genome Atlas (TCGA) data showed a prognostic prompt function of the nine-gene signature, as well as in PCa with Gleason 7. Finally, majority of the nine hub genes were associated with drug sensitivity, mutational landscape, immune infiltrates and clinical characteristics of PCa. Conclusion: The nine-gene signature was correlated with drug sensitivity, mutational landscape, immune infiltrates, clinical characteristics and survival from PCa.

Mu|Hai-Qi|HQ| Liang|Zhi-Qiang|ZQ| Xie|Qi-Peng|QP| Han|Wei|W| Yang|Sen|S| Wang|Shuai-Bin|SB| Zhao|Cheng|C| Cao|Ye-Min|YM| He|You-Hua|YH| Chen|Jian|J|0000-0001-5230-7141

prognosis
prostate cancer
immune infiltrates
gene signature
protein–protein interaction


Distinguished properties of cells isolated from the dentin-pulp interface.

Abstract:
BACKGROUND
Dental odontoblasts produce dentin mineralized matrix, trigger immune responses and act as sensory cells. The understanding of the mechanisms of these functions has been particularly restricted due to the lack of odontoblasts being cultivable in vitro. Because of the lack of specific markers to identify cells of the odontoblastic lineage, properties of the cells isolated from the dentin-pulp interface were compared to dental pulp cells, periodontal ligament cells, osteoblasts, skin fibroblasts, epithelial cells (A549) and HeLa in the present study.

METHODS
After surgical procedures, the pulp tissue was removed from the tooth crown, and cells were scrapped off the dentin-pulp interface. Explants from teeth of three patients were routinely cultivated, and cells were harvested after several weeks. Cell morphology and ultrastructure was studied by light microscopy (LM), scanning (SEM) or transmission electron microscopy (TEM). Expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), TRPV4, and S100 calcium binding protein A4 (S100A4) were analyzed at the protein level by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting using specific antibodies. The differential expression of S100A4 in the various cell lines was further investigated at the gene level by semiquantitative real-time PCR. Mineralization in the various cell types was observed after alizarin red staining after a 28 days incubation period. The immunophenotype of the cells was examined by flow cytometry using monoclonal anti-human antibodies CD90-FITC, CD73-PE, CD105-PE, CD29-PE, CD140a-FITC, CD144-PE, CD45-FITC or CD34-FITC. Differences between median values were statistically analyzed (Mann-Whitney U-test).

RESULTS
Cells from the dentin-pulp interface retain the polarity of odontoblast morphology in culture with an elongated, rounded cell body, and an extended cellular process. Ultrastructural analysis of the cells indicates high secretory activity including the extracellular deposition of fibrillar collagen. An extended rough endoplasmic reticulum is lined by a large number of ribosomes, and a vast number of secretory granules merges with the cell membrane. Protein expression of DSPP, DMP1, and TRPV4 as a transient receptor potential cation was detected in all cell lines. S100A4 was found differentially expressed in cultures of cells from tooth tissues. High expression of S100A4 was observed at the protein and gene level in two fractions of cells isolated from the dentin-pulp interface, but was absent or only weakly expressed in pulp cells. S100A4 expression in cells from the dentin-pulp interface and pulp cells is consistent with the intensity of the formation of mineralized nodules detected by alizarin red staining. Immunophenotyping revealed that a high percentage of CD73 (ecto-5-nucleotidase), an enzyme active on the surface of immune-competent cells, was expressed in cells of the dentin-pulp interface. While 72%-78% of positive cells were detected in dentin-pulp interface fractions, only 28-64% of the cells in pulp cell cultures were stained.

CONCLUSIONS
The present findings obtained with a variety of cells of different origin provide experimental evidence that cells isolated from the dentin-pulp interface express unique properties different from dental pulp cells in particular. The differential expression of S100A4 is a relevant marker candidate for differentiating between dental pulp cells and cells of the odontoblast lineage.

Gallorini|Marialucia|M| Krifka|Stephanie|S| Widbiller|Matthias|M| Schröder|Agnes|A| Brochhausen|Christoph|C| Cataldi|Amelia|A| Hiller|Karl-Anton|KA| Buchalla|Wolfgang|W| Schweikl|Helmut|H|


Rational Design of Effective Binders for LiFePO4 Cathodes.

Abstract: Polymer binders are critical auxiliary additives to Li-ion batteries that provide adhesion and cohesion for electrodes to maintain conductive networks upon charge/discharge processes. Therefore, polymer binders become interconnected electrode structures affecting electrochemical performances, especially in LiFePO4 cathodes with one-dimensional Li+ channels. In this paper, recent improvements in the polymer binders used in the LiFePO4 cathodes of Li-ion batteries are reviewed in terms of structural design, synthetic methods, and working mechanisms. The polymer binders were classified into three types depending on their effects on the performances of LiFePO4 cathodes. The first consisted of PVDF and related composites, and the second relied on waterborne and conductive binders. Profound insights into the ability of binder structures to enhance cathode performance were discovered. Overcoming the bottleneck shortage originating from olivine structure LiFePO4 using efficient polymer structures is discussed. We forecast design principles for the polymer binders used in the high-performance LiFePO4 cathodes of Li-ion batteries. Finally, perspectives on the application of future binder designs for electrodes with poor conductivity are presented to provide possible design directions for chemical structures.

Huang|Shu|S|0000-0002-1695-0006 Huang|Xiaoting|X| Huang|Youyuan|Y| He|Xueqin|X| Zhuo|Haitao|H| Chen|Shaojun|S|0000-0001-8892-5136

LiFePO4 cathode
polymer binder
Li-ion batteries
electrochemical performance
structure design


Role and mechanism of PTEN in Burkitt's lymphoma.

Abstract: The aim of the present study was to explore the possible mechanisms of phosphatase and tensin homolog (PTEN) in the pathogenesis of Burkitt's lymphoma, and provide novel information that can be used in the targeted treatment of this disease. PTEN lentiviral overexpression vector and short‑hairpin PTEN silencing vectors were constructed. The effect of PTEN on the growth and proliferation of CA46 and RAJI cells was analyzed using a Cell Counting Kit‑8 assay. Apoptosis was detected by Hoechst 33342 and propidium iodide double staining. Flow cytometry was used to analyze the cell cycle. A Transwell chamber was used to detect cell migration and invasion abilities. Western blot analysis was used to detect related protein changes. The mechanism of the effect of PTEN on the biological characteristics of Burkitt's lymphoma cells was subsequently analyzed. The results revealed that PTEN inhibited the proliferation of CA46 and RAJI cells by downregulating the expression of p‑AKT, It was indicated that the upregulation of proapoptotic proteins (including Bad and Bax) induced apoptosis, regulated cyclin (including P53, P21, CDK4, CDK6, cyclin D3 and cyclin H) to inhibit cell cycle progression, and mediated epithelial‑mesenchymal transition‑like cell markers (including E‑cadherin, N‑cadherin, β‑catenin, TCF‑8, vimentin, Slug and Snail) to inhibit cell migration and invasion. In conclusion, the tumor‑suppressor gene PTEN inhibited the phosphoinositide 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway and inhibited the proliferation and migration of Burkitt's lymphoma cells, induced apoptosis and cell cycle arrest, thus playing a crucial role in the pathogenesis of Burkitt's lymphoma.

Li|Chuntuan|C| Xu|Yahong|Y| Xin|Pengliang|P| Zheng|Yan|Y| Zhu|Xiongpeng|X|

PTEN
Burkitt's lymphoma
cell cycle
invasion
cell proliferation


Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging.

Abstract: Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle-to-skin signaling occurs. We demonstrate that endurance exercise attenuates age-associated changes to skin in humans and mice and identify exercise-induced IL-15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL-15 expression in part through skeletal muscle AMP-activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL-15 therapy mimics some of the anti-aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low-dose IL-15 therapy may prove to be a beneficial strategy to attenuate skin aging.

Crane|Justin D|JD|
MacNeil|Lauren G|LG|
Lally|James S|JS|
Ford|Rebecca J|RJ|
Bujak|Adam L|AL|
Brar|Ikdip K|IK|
Kemp|Bruce E|BE|
Raha|Sandeep|S|
Steinberg|Gregory R|GR|
Tarnopolsky|Mark A|MA|

D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha

skin metabolism aging exercise muscle mitochondria