Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii.

Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug resistance. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new antibacterial molecules. Here we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii. Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii. Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE. Moreover, abaucin could control an A. baumannii infection in a mouse wound model. This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen.

Impact of pancreas transplantation alone on kidney function: A multicenter clinical cohort study.

Pancreas transplantation alone (PTA) is a ß cell replacement option for selected patients with type 1 diabetes mellitus; concerns have been raised regarding deterioration in kidney function (KF) after PTA. This retrospective multicenter study assessed actual impact of transplantation and immunosuppression on KF in PTA recipients at three Transplant Centers. The primary composite endpoint 10 years after PTA was >50% eGFR decline, eGFR < 30 mL/min/1.73 m2 , and/or receiving a kidney transplant (KT). Overall, 822 PTA recipients met eligibility. Median baseline and 10-year eGFR (mL/min/1.73 m2 ) were 76.3 (58.1-100.8) and 51.3 (35.3-65.9), respectively. Primary composite endpoint occurred in 98 patients (53.5%) with 45 experiencing a >50% decrease in eGFR by 10 years post-transplant, 38 eGFR < 30 mL/min/1.73 m2 and 49 requiring KT. KF declined most significantly within 6 months post-PTA, more often in females and patients with better preserved GFR up to 5 years with 11.6% kidney failure at 10 years. Patient survival and death-censored graft survival were both 68% at 10 years with overall graft thrombosis rate 8%. KF declined initially after PTA but stabilized with further slow progression. In conclusion, prospective intervention studies are needed to test renal sparing interventions while gathering more granular data.

The potential of nano graphene oxide and chlorhexidine composite membranes for use as a surface layer in functionally graded membranes for periodontal lesions.

Membranes have been used for treating periodontal defects and play a crucial role in guided bone regeneration applications. Nano graphene oxide have been exploited in tissue engineering due to its biomechanical properties. Its composite formulations with hydroxyapatite and chitosan with controlled degradation could aid in becoming part of a surface layer in a functionally graded membrane. The aim of the study was to synthesize chitosan and composite formulations of nano graphene oxide, hydroxyapatite and chlorhexidine digluconate using solvent casting technique and to characterize the physiochemical, mechanical, water vapor transmission rate (barrier), degradation and antimicrobial potential of the membranes. Altogether four different membranes were prepared (CH, CCG, 3511 and 3322). Results revealed the chemical interactions of hydroxyapatite, chitosan and nanographene oxide due to inter and intra molecular hydrogen bonding. The tensile strength of 3322 (33.72 ± 6.3 MPa) and 3511 (32.06 ± 5.4 MPa) was higher than CH (27.46 ± 9.6 MPa). CCG showed the lowest water vapor transmission rate (0.23 ± 0.01 g/h.m2) but the highest weight loss at day 14 (76.6 %). 3511 showed a higher drug release after 72 h (55.6 %) Significant biofilm growth inhibition was observed for all membranes. 3511 showed complete inhibition against A. actinomycetemcomitans. Detailed characterization of the synthesized membranes revealed that 3511 composite membrane proved to be a promising candidate for use as a surface layer of membranes for guided bone regeneration of periodontal lesions.

Towards Automatic License Plate Detection.

Automatic License Plate Detection (ALPD) is an integral component of using computer vision approaches in Intelligent Transportation Systems (ITS). An accurate detection of vehicles' license plates in images is a critical step that has a substantial impact on any ALPD system's recognition rate. In this paper, we develop an efficient license plate detecting technique through the intelligent combination of Faster R-CNN along with digital image processing techniques. The proposed algorithm initially detects vehicle(s) in the input image through Faster R-CNN. Later, the located vehicle is analyzed by a robust License Plate Localization Module (LPLM). The LPLM module primarily uses color segmentation and processes the HSV image to detect the license plate in the input image. Moreover, the LPLM module employs morphological filtering and dimension analysis to find the license plate. Detailed trials on challenging PKU datasets demonstrate that the proposed method outperforms few recently developed methods by producing high license plates detection accuracy in much less execution time. The proposed work demonstrates a great feasibility for security and target detection applications.

SpecSeg Network for Specular Highlight Detection and Segmentation in Real-World Images.

Specular highlights detection and removal in images is a fundamental yet non-trivial problem of interest. Most modern techniques proposed are inadequate at dealing with real-world images taken under uncontrolled conditions with the presence of complex textures, multiple objects, and bright colours, resulting in reduced accuracy and false positives. To detect specular pixels in a wide variety of real-world images independent of the number, colour, or type of illuminating source, we propose an efficient Specular Segmentation (SpecSeg) network based on the U-net architecture that is expeditious to train on nominal-sized datasets. The proposed network can detect pixels strongly affected by specular highlights with a high degree of precision, as shown by comparison with the state-of-the-art methods. The technique proposed is trained on publicly available datasets and tested using a large selection of real-world images with highly encouraging results.

Availability, coverage, and scope of health information systems for kidney care across world countries and regions.

BACKGROUND: Health information systems (HIS) are fundamental tools for the surveillance of health services, estimation of disease burden and prioritization of health resources. Several gaps in the availability of HIS for kidney disease were highlighted by the first iteration of the Global Kidney Health Atlas. METHODS: As part of its second iteration, the International Society of Nephrology conducted a cross-sectional global survey between July and October 2018 to explore the coverage and scope of HIS for kidney disease, with a focus on kidney replacement therapy (KRT). RESULTS: Out of a total of 182 invited countries, 154 countries responded to questions on HIS (85% response rate). KRT registries were available in almost all high-income countries, but few low-income countries, while registries for non-dialysis chronic kidney disease (CKD) or acute kidney injury (AKI) were rare. Registries in high-income countries tended to be national, in contrast to registries in low-income countries, which often operated at local or regional levels. Although cause of end-stage kidney disease, modality of KRT and source of kidney transplant donors were frequently reported, few countries collected data on patient-reported outcome measures and only half of low-income countries recorded process-based measures. Almost no countries had programs to detect AKI and practices to identify CKD-targeted individuals with diabetes, hypertension and cardiovascular disease, rather than members of high-risk ethnic groups. CONCLUSIONS: These findings confirm significant heterogeneity in the global availability of HIS for kidney disease and highlight important gaps in their coverage and scope, especially in low-income countries and across the domains of AKI, non-dialysis CKD, patient-reported outcomes, process-based measures and quality indicators for KRT service delivery.

TLR2 Plays a Pivotal Role in Mediating Mucosal Serotonin Production in the Gut.

Serotonin (5-hydroxytryptamine [5-HT]) is a key enteric signaling molecule that mediates various physiological processes in the gut. Enterochromaffin (EC) cells in the mucosal layer of the gut are the main source of 5-HT in the body and are situated in close proximity to the gut microbiota. In this study, we identify a pivotal role of TLR2 in 5-HT production in the gut. Antibiotic treatment reduces EC cell numbers and 5-HT levels in naive C57BL/6 mice, which is associated with downregulation of TLR2 expression but not TLR1 or TLR4. TLR2-deficient (Tlr2 -/-) and Myd88 -/- mice express lower EC cell numbers and 5-HT levels, whereas treatment with TLR2/1 agonist upregulates 5-HT production in irradiated C57BL/6 mice, which are reconstituted with Tlr2 -/- bone marrow cells, and in germ-free mice. Human EC cell line (BON-1 cells) release higher 5-HT upon TLR2/1 agonist via NF-κB pathway. Tlr2 -/- mice and anti-TLR2 Ab-treated mice infected with enteric parasite, Trichuris muris, exhibited attenuated 5-HT production, compared with infected wild-type mice. Moreover, excretory-secretory products from T. muris induce higher 5-HT production in BON-1 cells via TLR2 in a dose-dependent manner, whereby the effect of excretory-secretory products is abrogated by TLR2 antagonist. These findings not only suggest an important role of TLR2 in mucosal 5-HT production in the gut by resident microbiota as well as by a nematode parasite but also provide, to our knowledge, novel information on the potential benefits of targeting TLR2 in various gut disorders that exhibit aberrant 5-HT signaling.

Agro-morphological and genetic diversity studies in Rice (Oryza sativa L.) germplasm using microsatellite markers.

BACKGROUND: Knowledge of the genetic diversity and population structure of germplasm collections is an important foundation for crop improvement. Rice production across a broad range of rice-growing environments results in a diverse array of local rice varieties. Many rice varieties have been lost as a result of biodiversity loss and are now grown in Pakistan. METHODS AND RESULTS: To protect the biodiversity of rice varieties, an experiment was carried out to check the genetic and morphological variations between 8 exotic and 7 local rice genotypes, using 5 different SSR markers, i.e., RM3, RM259, RM341, RM520, and RM11943. The analysis of morphological and quality traits of rice observed significant variation across genotypes. The results revealed that genotype Irri-Pak attained the highest plant height and primary branch plant-1, while genotype Mushkan produced a higher number of productive tillers and obtained a higher fertility factor (%). Similarly, the highest value for panicle length was observed for genotype Faker-e-Malakand, 1000-grains weight in genotype Calmochi, and maximum days to maturity was noticed in genotype Swati-2014. Moreover, the genotype Brio attained the highest value of stem diameter, while maximum seed length was noted in the genotype Sug Dasi. The highest number of primary branches plant-1 in genotype Ibge-I and secondary branches plant-1 in genotype Calmochi were noticed. A higher concentration of sodium and potassium was observed for the genotype Marte, while the genotype Muskan attained the maximum content of copper. Moreover, the highest concentration of iron in genotype Originario, zinc in genotype JP-5, and cadmium content were noticed in genotype Ibge. Similarly, the dendrogram analysis for quantitative parameters showed three clusters at 74.13% similarities. Whereas all the genotypes of European origin formed a separate cluster. A set of 5 simple sequence repeat primers, covering four chromosomes, amplified a total of 14 alleles and showed 100% polymorphism with an average PIC value ranging from 0.39 to 0.91. The UPGMA cluster analysis separated the 15 rice genotypes into 3 main groups based on 32.5% similarities and the highest genetic distance (45.1%) was observed between two genotypes (Fakher-e-malakand and Musa), having different geographical origins. There was no genetic distance between the genotypes Marte and Brio, irrespective of having the same origin. CONCLUSIONS: The maximum genetic distances were noted for genotype, Fakhre-e-Malakand and Musa having a different origin, while the minimum genetic distance was shown by genotypes, Marte and Onice, from the same origin.

Workplace Mental State Monitoring during VR-Based Training for Offshore Environment.

Adults are constantly exposed to stressful conditions at their workplace, and this can lead to decreased job performance followed by detrimental clinical health problems. Advancement of sensor technologies has allowed the electroencephalography (EEG) devices to be portable and used in real-time to monitor mental health. However, real-time monitoring is not often practical in workplace environments with complex operations such as kindergarten, firefighting and offshore facilities. Integrating the EEG with virtual reality (VR) that emulates workplace conditions can be a tool to assess and monitor mental health of adults within their working environment. This paper evaluates the mental states induced when performing a stressful task in a VR-based offshore environment. The theta, alpha and beta frequency bands are analysed to assess changes in mental states due to physical discomfort, stress and concentration. During the VR trials, mental states of discomfort and disorientation are observed with the drop of theta activity, whilst the stress induced from the conditional tasks is reflected in the changes of low-alpha and high-beta activities. The deflection of frontal alpha asymmetry from negative to positive direction reflects the learning effects from emotion-focus to problem-solving strategies adopted to accomplish the VR task. This study highlights the need for an integrated VR-EEG system in workplace settings as a tool to monitor and assess mental health of working adults.

Novel Mannich base 3FB3FA8H induces apoptosis by upregulating P53 pathway in neuroblastoma cells.

P53 plays an important role in maintaining genetic stability and development of resistance against tumors. Dysregulation of P53 gene is one of the key factors contributing to the etiology of neuroblastoma which causes cells to evade apoptosis. Activating P53 pathway can be a therapeutic alternative to the currently available medicinal strategies. Mannich bases have been known to possess various biological activities including the anticancer activity. In this study, we have targeted the P53 pathway by novel Mannich base (3FB3FA8H) which can be a future prospect to cure neuroblastoma. 3FB3FA8H has shown modulation of P53 pathway leading to apoptosis of neuroblastoma cells. Mitochondrial membrane permeability is also increased by 3FB3FA8H which may be a consequence of P53 pathway modulation. 3FB3FA8H increases the mRNA levels of P53 leading to activation of BAX. Inclining BAX/BCL2 ratio towards apoptotic BAX leads to cleavage of caspase 3, ultimately, causing apoptosis. Series of experiments provide the evidence that Mannich base 3FB3FA8H leads to P53-mediated apoptosis. Inducing apoptosis by this mechanism could be of central importance in reducing tumor burden which can be a good prospect for neuroblastoma patients.

Clinical efficacy of photodynamic therapy and laser irradiation as an adjunct to open flap debridement in the treatment of chronic periodontitis: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review and meta-analyses was to assess the quality of evidence and efficacy of antimicrobial photodynamic therapy (aPDT) and laser irradiation (LI) as an adjunct to open flap debridement (OFD) in the treatment of chronic periodontitis. METHODS: Electronic searches were conducted in databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) up to March 2019. Randomized clinical trials (RCTs) comparing clinical efficacy of either aPDT and/or LI, placebo, or no treatment were included. Primary outcomes included clinical attachment level (CAL), while secondary outcomes were reduction in probing depth (PD) and gingival recession (GR) depth. The weighted mean differences (WMD) of outcomes and 95% confidence intervals (CI) for each variable were calculated using random effect model. RESULTS: Six RCTs were included. For aPDT studies, the overall mean difference for CAL gain (WMD = -0.61, 95% CI = -1.22 to -0.016, P = .044) and PD reduction (WMD = -1.79, 95% CI = -3.44 to -0.14, P = .034) was significant between aPDT and OFD groups at follow-up. No significant overall mean difference was observed for GR depth (WMD = 0.02, 95% CI = -0.75 to 0.79, P = .95). For LI studies, none of the clinical periodontal parameters including CAL gain (WMD = 0.23, 95% CI = -0.09 to 0.55, P = .159, Figure 3A), PD reduction (WMD = 0.31, 95% CI = -0.67 to 1.31, P = .52, Figure 3B) and GR depth (WMD = -0.34, 95% CI = -2.47 to 1.78, P = .74, Figure 3C) were found to be significant between LI and OFD groups at follow-up. CONCLUSION: With the limited data available, only aPDT as an adjunct to OFD showed superior results for clinical periodontal parameters compared to OFD alone in the treatment of chronic periodontitis. Further RCTs are warranted in order to obtain robust conclusions with regard to laser therapy.

Evaluation of Deep Neural Networks for Semantic Segmentation of Prostate in T2W MRI.

In this paper, we present an evaluation of four encoder-decoder CNNs in the segmentation of the prostate gland in T2W magnetic resonance imaging (MRI) image. The four selected CNNs are FCN, SegNet, U-Net, and DeepLabV3+, which was originally proposed for the segmentation of road scene, biomedical, and natural images. Segmentation of prostate in T2W MRI images is an important step in the automatic diagnosis of prostate cancer to enable better lesion detection and staging of prostate cancer. Therefore, many research efforts have been conducted to improve the segmentation of the prostate gland in MRI images. The main challenges of prostate gland segmentation are blurry prostate boundary and variability in prostate anatomical structure. In this work, we investigated the performance of encoder-decoder CNNs for segmentation of prostate gland in T2W MRI. Image pre-processing techniques including image resizing, center-cropping and intensity normalization are applied to address the issues of inter-patient and inter-scanner variability as well as the issue of dominating background pixels over prostate pixels. In addition, to enrich the network with more data, to increase data variation, and to improve its accuracy, patch extraction and data augmentation are applied prior to training the networks. Furthermore, class weight balancing is used to avoid having biased networks since the number of background pixels is much higher than the prostate pixels. The class imbalance problem is solved by utilizing weighted cross-entropy loss function during the training of the CNN model. The performance of the CNNs is evaluated in terms of the Dice similarity coefficient (DSC) and our experimental results show that patch-wise DeepLabV3+ gives the best performance with DSC equal to 92 . 8 % . This value is the highest DSC score compared to the FCN, SegNet, and U-Net that also competed the recently published state-of-the-art method of prostate segmentation.

Real-Time Stress Assessment Using Sliding Window Based Convolutional Neural Network.

Mental stress has been identified as a significant cause of several bodily disorders, such as depression, hypertension, neural and cardiovascular abnormalities. Conventional stress assessment methods are highly subjective and tedious and tend to lack accuracy. Machine-learning (ML)-based computer-aided diagnosis systems can be used to assess the mental state with reasonable accuracy, but they require offline processing and feature extraction, rendering them unsuitable for real-time applications. This paper presents a real-time mental stress assessment approach based on convolutional neural networks (CNNs). The CNN-based approach afforded real-time mental stress assessment with an accuracy as high as 96%, the sensitivity of 95%, and specificity of 97%. The proposed approach is compared with state-of-the-art ML techniques in terms of accuracy, time utilisation, and quality of features.

An Evidence-Based Update on the Molecular Mechanisms Underlying Periodontal Diseases.

Several investigators have reported about the intricate molecular mechanism underlying periodontal diseases (PD). Nevertheless, the role of specific genes, cells, or cellular mechanisms involved in the pathogenesis of periodontitis are still unclear. Although periodontitis is one of the most prevalent oral diseases globally, there are no pre-diagnostic markers or therapeutic targets available for such inflammatory lesions. A pivotal role is played by pro- and anti-inflammatory markers in modulating pathophysiological and physiological processes in repairing damaged tissues. In addition, effects on osteoimmunology is ever evolving due to the ongoing research in understanding the molecular mechanism lying beneath periodontal diseases. The aim of the current review is to deliver an evidence-based update on the molecular mechanism of periodontitis with a particular focus on recent developments. Reports regarding the molecular mechanism of these diseases have revealed unforeseen results indicative of the fact that significant advances have been made to the periodontal medicine over the past decade. There is integrated hypothesis-driven research going on. Although a wide picture of association of periodontal diseases with immune response has been further clarified with present ongoing research, small parts of the puzzle remain a mystery and require further investigations.

Correction to: the Effect of Cross-Linking Efficiency of Drug-Loaded Novel Freeze Gelated Chitosan Templates for Periodontal Tissue Regeneration.

The correct spelling of the second author's name is Liebert Parreiras Nogueira.

The Effect of Cross-linking Efficiency of Drug-Loaded Novel Freeze Gelated Chitosan Templates for Periodontal Tissue Regeneration.

Innovative strategies for periodontal regeneration have been the focus of research clusters across the globe for decades. In order to overcome the drawbacks of currently available options, investigators have suggested a novel concept of functionally graded membrane (FGM) templates with different structural and morphological gradients. Chitosan (CH) has been used in the past for similar purpose. However, the composite formulation of composite and tetracycline when cross-linked with glutaraldehyde have received little attention. Therefore, the purpose of the study was to investigate the drug loading and release characteristics of novel freeze gelated chitosan templates at different percentages of glutaraldehyde. These were cross-linked with 0.1 and 1% glutaraldehyde and loaded with doxycycline hyclate. The electron micrographs depicted porous morphology of neat templates. After cross-linking, these templates showed compressed ultrastructures. Computerized tomography analysis showed that the templates had 88 to 92% porosity with average pore diameter decreased from 78 to 44.9 µm with increasing concentration. Fourier transform infrared spectroscopy showed alterations in the glycosidic segment of chitosan fingerprint region which after drug loading showed a dominant doxycycline spectral composite profile. Interestingly, swelling profile was not affected by cross-linking either at 0.1 and 1% glutaraldehyde and template showed a swelling ratio of 80%, which gained equilibrium after 15 min. The drug release pattern also showed a 40 µg/mL of release after 24 h. These doxycycline-loaded templates show their tendency to be used in a functionally graded membrane facing the defect site.

Open-Healing Socket Preservation with a Novel Dense Polytetrafluoroethylene (dPTFE) Membrane: A Retrospective Clinical Study.

Background and objectives: Non-resorbable dense polytetrafluoroethylene (dPTFE) membranes are widely used for regeneration procedures, alone or in combination with particulate materials. The aim of this work was to examine the efficacy of a newly developed dPTFE membrane in the management of extraction socket healing. Materials and Methods: The extraction premolar sockets of 44 patients (20 men and 24 women) were preserved. One group received prosthetic rehabilitation with a fixed partial denture (FPD) (PROS group, N = 19) and a second group received immediate implant placement (IMPL group, N = 25). The PROS group sockets were augmented with a bovine derived xenograft and covered with a newly developed dPTFE membrane prior to FPD rehabilitation. Results: In the IMPL group, socket preservation was combined with immediate implant placement. Before (T0) and 6 months after surgery (T1), horizontal and vertical dimensions were measured with customized stents. No significant differences in alveolar bone loss from T0 to T1 were observed between the PROS and IMPL groups in the horizontal dimension for any tooth type. There was a significant difference in alveolar bone loss from T0 to T1 between the two groups for only single-rooted maxillary premolars in the vertical dimension. Conclusions: The use of the examined new dPTFE membrane consistently led to the preservation of hard tissue in the extraction sites.

N-(2-hydroxyphenyl)acetamide and its gold nanoparticle conjugation prevent glycerol-induced acute kidney injury by attenuating inflammation and oxidative injury in mice.

The protective activity of N-(2-hydroxyphenyl)acetamide (NA-2) and NA-2-coated gold nanoparticles (NA-2-AuNPs) in glycerol-treated model of acute kidney injury (AKI) in mice was investigated. NA-2 (50 mg/kg) and NA-2-AuNPs (30 mg/kg) were given to the animals for four days followed by 24-h water deprivation and injection of 50% glycerol (10 ml/kg im). The animals were sacrificed on the next day. Blood and kidneys were collected for biochemical investigations (urea and creatinine), histological studies (hematoxylin and eosin; and periodic acid-Schiff staining), immunohistochemistry (actin and cyclooxygenase-2, Cox-2), and real-time RT-PCR (inducible nitric oxide synthase, iNOS; nuclear factor-κB p50, NFκB; hemeoxygenase-1, HO-1; and kidney injury molecule-1, Kim-1). NA-2 protected renal tubular necrosis and inflammation, though the result of NA-2-AuNPs was better than compound alone and it also exhibited the activity at far less dose. The test compound and its gold nano-formulation decreased the levels of serum urea and creatinine level in the treated animals. Both NA-2 and NA-2-AuNPs also conserved actin cytoskeleton, and lowered COX-2 protein expression. Moreover, the mRNA expressions of iNOS and NFkB p50 were down-regulated, and HO-1 and Kim-1 genes were up-regulated. We conclude that NA-2 and NA-2-AuNPs ameliorates kidney inflammation and injury in glycerol-induced AKI animal model via anti-oxidant and anti-inflammatory mechanisms which make it a suitable candidate for further studies. We believe that these findings will contribute in the understanding of the mechanism of action of paracetamol-like drugs and can be considered for clinical research for the prevention of AKI.

First spot urine sodium after initial diuretic identifies patients at high risk for adverse outcome after heart failure hospitalization.

BACKGROUND: Relief of congestion is the primary goal of initial therapy for acute decompensated heart failure (ADHF). Early measurement of urine sodium concentration (UNa) may be useful to identify patients with diminished response to diuretics. The aim of this study was to determine if the first spot UNa after diuretic initiation could select patients likely to require more intensive therapy during hospitalization. METHODS: At the time of admission, 103 patients with ADHF were identified prospectively, and UNa was measured after the first dose of intravenous diuretic. Clinical outcomes were compared for patients with UNa >60 mmol/L and UNa of ≤60 mmol/L, with the primary outcome of a composite of death at 90 days, mechanical circulatory support during admission, and requirement of inotropic support at discharge. RESULTS: Patients with UNa ≤60 had lower admission blood pressure, had less chronic neurohormonal antagonist prior to admission, and were more than twice as likely to experience the primary end point (hazard ratio 2.40, 95% CI 1.02-5.66, P = .045), which was marginally significant after adjusting for renal function and baseline home loop diuretic. Worsening renal function was significantly more common in patients with UNa <60 (23.6% vs 6.5%, P = .05). Although the initial assessment of congestion was similar at admission, patients with low early UNa had a longer length of stay (11 vs 6 days, P < .006) than patients with UNa >60. CONCLUSIONS: Assessment of spot UNa after initial intravenous loop diuretic administration may facilitate identification and triage of a population of HF patients at increased risk for adverse events and prolonged hospitalization.

A novel, semi-synthetic diterpenoid 16(R and S)-phenylamino-cleroda-3,13(14), Z-dien-15,16 olide (PGEA-AN) inhibits the growth and cell survival of human neuroblastoma cell line SH-SY5Y by modulating P53 pathway.

Neuroblastoma being the most common extracranial pediatric solid tumor accounts for 15% of overall cancer-related childhood mortalities. Resistance to chemotherapeutic drugs is one of the limiting factors for positive prognosis for neuroblastoma. Therefore, there is always a need for developing new therapeutic moieties which can become a future prospect of neuroblastoma therapy. Terpenoids being the largest natural compounds have demonstrated many biological activities including anticancer activity. Keeping in mind the role of terpenoids in biological system, we aimed to identify novel semi-synthetic terpenoid derived from cleroda diterpene, 16-oxo-cleroda-3,13(14)E-diene-15-oic acid (1) as a potential anticancer moiety against neuroblastoma. We choose γ-amino γ-lactone (PGEA-AN, 2) of 1 to study further because it exhibited the most potent cytotoxic activity in preliminary screening. In comparison to cisplatin, PGEA-AN significantly decreased the nuclear area factor which suggest the potential apoptosis as cause of cell death. PGEA-AN demonstrated a significant increase in the percent of late apoptosis and necrotic cell death at 48-h treatment with IC50 dose. PGEA-AN significantly increased expression of P53 and BAX with no or little effect on BCL2 shifting BAX/BCL2 towards BAX promoting apoptosis. Increment in mitochondrial permeability supports P53 pathway involvement. Despite similarity in actions with cisplatin, PGEA-AN has found to have no effect on renal system. Based on these observations, we suggest that PGEA-AN modulates P53 system which further leads to the death of the neuroblastoma cells with no effect on renal system in vivo owing it to be a future prospect for development of anticancer moiety against neuroblastoma.