New horizons in translational medicine最新文献

The advantages of antibiotics have been most clearly seen in those acute bacterial infections which had a high mortality before the introduction of antibiotics. The reality of the potential harmful effects of antibiotics, both short term in individual patients and long term in favoring emergent resistance and opportunistic pathogens are discussed. Bacterial resistance makes the standard treatments ineffective, and increases the risk of infection spreading. The shortage of novel antibiotics has strengthened the efforts of genome sequencing to control bacterial resistance. The future would include novel approaches, based on a re-conceptualization of the nature of resistance, disease and prevention.

Background

Lung transplantation is the choice of therapy in severe cases of idiopathic pulmonary fibrosis (IPF) but is compounded with post-transplant complications. The paucity of deceased organ donations underlines the need for alternate approaches that improves the quality of life. Herein, we attempted to develop an autologous adult bone marrow derived mesenchymal stromal cell (BMSC) therapy via central line access, and evaluated the safety of a single dose (~13 × 10⁶ cells/mL), in treating “no option” IPF.

Method

The study included severe IPF subjects (n = 6) both male and female, aged 40–70 years of age with a forced vital capacity <50%, diffusing capacity of lung for carbon monoxide (DLco) <35% of predicted, and/or oxygen (SpO₂) saturation <88% on 6 min walk distance (6 MWD). BMSCs at passage 2 were suspended in 30.0 mL normal saline and dispensed through the central line route in a respiratory intensive care unit of Gleneagles Global Hospitals. The subjects were monitored for the first 24 h for serious adverse events and hemodynamic parameters. They were followed up periodically at intervals of 1, 4, and 9 months for safety and monitoring of adverse events, including secondary objectives of changes in pulmonary function test, DLco, 6 MWD, and quality of life as per the study protocol.

Results

It was observed that central line infusions were well tolerated by all subjects. Furthermore, there was an improved quality of life.

Conclusions

BMSC central line infusion in “no option” IPF cases provided an insight into the strategies in improving the quality of life for patient and thereby increasing the therapeutic window period for lung transplantation.

Large numbers of machine learning approaches have been developed for analysis of medical data in recent years. These approaches have also proved their significance through accurate and earlier diagnosis of diseases. The objective of this work is to develop a diagnostic model for earlier diagnosis of dengue disease. Dengue fever is spread through the bite of the female mosquito (Aedes aegypti). The symptoms of this fever are similar to other fever such as that of Viral influenza, Chikungunya, Zika fever, and so on. However, in this fever, human life can be at risk due to severe depletion of blood platelets. Therefore, early diagnosis of dengue disease can help in protecting human lives by making a preventive move before it turns into an infectious disease. In this work, an effort is made to develop a PSO-ANN based diagnostic model for earlier diagnosis of dengue fever. In the proposed model, PSO technique is applied to optimize the weight and bias parameters of ANN method. Further, PSO optimized ANN approach is used to detect dengue patients. The effectiveness of the proposed model is evaluated based on accuracy, sensitivity, specificity, error rate and AUC parameters. The results of the proposed model have been compared with other existing approaches like ANN, DT, NB, and PSO. It is observed that the proposed diagnostic model is a proficient and powerful model for more accurate and earlier detection of dengue fever.

Knowledge extraction is an important part of e-Health system. However, datasets in health domain are highly imbalanced, voluminous, conflicting and complex in nature, and these can lead to erroneous diagnosis of diseases. So, designing accurate and robust clinical diagnosis models for such datasets is a challenging task in data mining. In literature, numerous standard intelligent models have been proposed for this purpose but they usually suffer from several drawbacks like lack of understandability, incapability of operating rare cases, inefficiency in making quick and correct decision, etc. In fact, specific health application using standard intelligent methods may not satisfy multiple criteria. However, recent research indicates that hybrid intelligent methods (integrating several standard ones, can achieve better performance for health applications. Addressing the limitations of the existing approaches, the present research introduces a new hybrid predictive model (integrating C4.5 and PRISM learners) for diagnosing effectively the diseases (instead of any specific disease) in comprehensible way by the practitioners with better prediction results in comparison to the traditional approaches. The empirical results (in terms of accuracy, sensitivity and false positive rate) obtained over fourteen benchmark datasets demonstrate that the model outperforms the base learners in almost all cases. The performance of the model also claims that it can be good alternative to the specialized learners (each designed for specific disease) published in the literature. After all, the presented intelligent system is effective in undertaking medical data classification task.

6-nitrobenzofuran-2-carbohydrazide Schiff base derivatives have been synthesized and their structure has been confirmed via H¹NMR, Mass spectrometry and elemental (CHN/S) analysis. These synthesized analogs showed significant cytotoxic and antioxidant activity. Doxorubicin (IC₅₀ = 0.94 ± 0.20 μM) and n-propyl gallate (IC₅₀ = 30.30 ± 0.40 μM) were used as standard in cytotoxic and antioxidant activities, respectively. Compound 1 (IC₅₀ = 3.30 ± 0.90 μM), 2 (IC₅₀ = 2.70 ± 0.25 μM), 3 (IC₅₀ = 2.70 ± 0.25 μM), 10 (IC₅₀ = 2.70 ± 1.10 μM), 11 (IC₅₀ = 1.00 ± 1.20 μM), and 17 (IC₅₀ = 3.75 ± 0.90 μM) showed excellent while 21 (IC₅₀ = 7.50 ± 0.60 μM) and 28 (IC₅₀ = 7.50 ± 0.66 μM) showed moderate anti cancer activity. Furthermore, compound 10 (IC₅₀ = 17.50 ± 0.85 μM), 11 (IC₅₀ = 24.20 ± 0.55 μM), 12 (IC₅₀ = 21.10 ± 1.58 μM), 13 (IC₅₀ = 14.60 ± 0.32 μM), 14 (IC₅₀ = 29.20 ± 0.75 μM) and 15 (IC₅₀ = 9.26 ± 0.15 μM) showed better antioxidant activity than the standard n-propyl gallate. This study will be useful to develop potential lead molecules with cytotoxic and antioxidant potential.

Background

The Bone Morphogenetic Protein 4 (BMP4) is identified to play a significant role in cardiac remodelling; gene polymorphism and its resulting associations with Left Ventricular Hypertrophy (LVH) in diabetic Chronic Kidney Disease (CKD) patients of this protein are yet to be established.

Aim

To analyse the association between BMP4 gene polymorphism and LVH in diabetic CKD patients.

Materials and methods

Isolation of DNA from whole blood samples of 50 patients each; patients diagnosed LVH with diabetic CKD and also from LVH patients without diabetic CKD, diabetic CKD without LVH and also normal patients as control were extracted. The gene of interest (BMP4 gene) purified from various samples digested using zero-cutter restriction endonucleases (Hind III and Bam HI) by employing the Restriction Fragment Length Polymorphism (RFLP) technique. The restriction has been analysed using 1% agarose gel Electrophoresis.

Results

The gene from patient having LVH without diabetic CKD when digested with Hind III showed fragmentation, more specifically, it presented three/four fragments which were at a comparable distance corresponding with the following size reference markers at 2000 bp(few cases), 1500 bp, between 700–600 bp and the last one near 100 bp. This fragmentation pattern was repeated identically for the gene from blood sample of patient having LVH with diabetic CKD which was also digested with Hind III. A similar fragmentation was not visualized for sample from patient having diabetic CKD without LVH when digested with Hind III. But no such fragments were noted for the samples from the same patients when digested with Bam HI.

Conclusion

BMP4 gene polymorphism has been confirmed in patients having LVH regardless of the presence or absence of diabetic CKD along with it.

Focal points

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  Benchside:

Left ventricular (LV) hypertrophy is a strong autonomous predictor of increased cardiovascular morbidity and mortality in clinical and population-based samples. Thus understanding the correlation of LVH with BMP4 gene is necessitated to provide alternate therapeutics strategy at genome level. Eventually, genetic investigations provide high assurance for future prevention, early intervention and treatment of this major public health issue.

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  Bedside:

Determination of BMP4 Polymorphism would raise a new drug development target using single nucleotide polymorphism. They also serve as molecular marker for next generation therapeutics of personalized medicine at genome level.