Recent Advancement in Bioactive Chalcone Hybrids as Potential Antimicrobial Agents in Medicinal Chemistry.

Chalcones are flavonoid-related aromatic ketones and enones generated from plants. The chalcones have a wide range of biological activities, such as anti-tumor, calming, and antimicrobial activities. In the present review, we have focused on the recently published original research articles on chalcones as a unique antibacterial framework in medicinal chemistry. Chalcones are structurally diverse moieties and can be split into simple and hybrid chalcones, with both having core pharmacophore 1,3-diaryl-2-propen-1-one. Chalcones are isolated from natural sources and also synthesized by using various methods. Their structure-activity relationship, mechanisms, and list of patents are also summarized in this paper. This review article outlines the currently published antimicrobial chalcone hybrids and suggests that chalcone derivatives may be potential antimicrobial agents in the future.

Role of colour Doppler in predicting foetal outcome in maternal anaemia.

Context: Anaemia is the most common nutritional deficiency in Indian pregnant females. It ensues foetal hypoxia resulting in different compensatory mechanisms in the foetus which may result in adverse perinatal outcomes. Colour Doppler can be used to measure these hemodynamic changes of the foetus ahead of the clinical manifestations, guiding the obstetrician for the appropriate management and circumventing any dire complication. Aims: The aim of this study is to detect foetal haemodynamic changes associated with maternal anaemia and assess the parameters which predict these changes accurately. Settings and Design: Prospective cohort study. Materials and Methods: Two hundred and forty pregnant females in the third trimester, divided into four groups based on their haemoglobin levels in the non-anaemic, mild, moderate and severe anaemic groups, were included in the study. These patients were followed up for foetal outcome in terms of effective foetal weight, APGAR score and neonatal intensive care unit admission. Statistical Analysis Used: Analysis of Variance Appearance, Pulse, Grimace, Activity and Respiration (ANOVA) test was used to compare the quantitative variables. SPSS software was used. Results: The middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR) values were increasing while umbilical Doppler indices were decreasing with the increasing severity of anaemia. CPR was found to be the most sensitive predictor for foetal outcome. Conclusions: Maternal anaemia results in foetal hypoxia which can be measured in terms of foetal Doppler indices. CPR was found to be more sensitive than the umbilical or MCA in predicting foetal hypoxia and in turn the perinatal outcome of foetuses of anaemic pregnant females. The foetuses with low CPR values will require urgent intervention to improve the outcomes.

Securing healthcare information system through fuzzy based decision-making methodology.

The purpose of the healthcare Information System (HIS) is to replace the conventional method of data gathering and organization in hospitals into a modern method of systematic data collection, maintenance and dissemination. There has been an unprecedented rise in the malware and cyber-attacks on HIS recently. Cyber-attacks have become a major crisis for the healthcare industry. To address this scenario, the present paper conducts a study on the security factors integral to the healthcare information system and conducts the performance analysis of these factors. For this intent, the study has employed the Fuzzy Analytic Hierarchy Process (F.AHP) integrated with Technique Order Preference by Similarity to Ideal Solution (TOPSIS) integrated framework for evaluating the performance of each factor. Thereafter, the factors that play a vital role in healthcare data security breaches have been prioritized as per their security weights. Furthermore, the validity of the results obtained by the stated methodology has been established by conducting the sensitivity analysis and comparison of results with the other methods by using the same data set. Based on results thus obtained, the access control and software security have been identified as the most promising security factors.

Personality and achievement: A follow-up study.

Background: The health and well-being of medical students along with their successful progression is an important concern for society. Studies across the world demonstrated a high prevalence of psychiatric morbidity and low self-esteem among medical students requires immediate attention and effective management. Aim: To compare the symptoms of depression, anxiety, and stress between the groups who have cleared all papers in the first attempt with those who have got supplementary at least in one paper during their MBBS course. Materials and Methods: Raven's Progressive Matrices Scale, Eysenck personality Questionnaire, Sinha's Anxiety Scale, Stress Reaction Check (SRC) List, and 16-Personality Factors questionnaires were used along with performance score was recorded for the objective of the study. Results: Nonparametric tests, Mann-Whitney and Wilcoxon are used and found that RSPM scores and EPQ Lie-scale scores are statistically different as the P < 0.05. Overall performance and psychological problems association are found out using Spearman's correlation test and it is found that Factor C and Tough poise under 16 PF are significantly correlated. Conclusions: The study concluded that there is a significant difference between the abstract reasoning between the two groups of students measured by RSPM. When the students are compared by taking gender as grouping variable the study concluded psychosis, lie scale value is significantly different in the two groups and the mean value is higher in the female group. It is also concluded that the stress level measured by SRC is significantly different and the mean value is higher in the female group. Furthermore, the global factors Tough poise and independence are found to be significantly different in two groups with 16 PF questionnaire.

Evaluation of Hemodynamic Changes in Retrobulbar Blood Vessels Using Color Doppler Imaging in Diabetic Patients.

Background­Diabetic retinopathy is a common complication of long-standing hyperglycemia. Microangiopathy-induced retinal changes are well-visualized on ophthalmoscopic examination. However, certain hemodynamic alterations have also been documented in the diabetic population, which have not been completely understood. Aim­To study the hemodynamic changes in retrobulbar circulation in diabetic patients with and without retinopathy, and to compare these changes with non-diabetic controls. Materials and Methods­This hospital-based prospective study included 50 diabetic and 50 non-diabetic patients. The diabetic groups consisted of 25 patients without retinopathy and 25 patients with retinopathy, and were labeled as Groups I and II, respectively. All subjects underwent orbital color Doppler ultrasonography using a linear high-frequency probe. The color Doppler parameters (peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI)) were measured and recorded using the spectral waveform of the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCA). Comparison of obtained values was carried out using appropriate tests of significance. Results­The resistive indices of the ophthalmic, central retinal, and short posterior ciliary arteries were significantly higher in diabetic patients compared to controls (p < 0.001). The difference was also significant between Group I and Group II. Comparison of PSV and EDV of CRA and SPCAs among three groups using one-way ANOVA revealed a significant difference, with the highest blood flow velocities in the control group and the lowest in diabetics with retinopathy. The ophthalmic artery showed no significant change in blood flow velocity. Analysis using the Pearson correlation coefficient provided a positive correlation between the RI values of OA, CRA, and SPCA and the presence of diabetic retinopathy (OA = r 0.417, p < 0.001; CRA = r 0.466, p < 0.001; SPCA = r 0.438; p < 0.001). Conclusions­The resistive index of OA, CRA, and SPCA is a reliable indicator to assess diabetic-associated hemodynamic changes. The use of orbital color Doppler ultrasonography in diabetic patients can help in the identification of patients who are at risk of developing retinopathy.

Ensuring data integrity of healthcare information in the era of digital health.

Data integrity continues to be a persistent problem in the current healthcare sector. It ensures that the data is correct and has not even in any manner been improperly changed. Incorrect data might become significant health threats for patients and a big responsibility for clinicians, resulting in problems such as scam, misconduct, inadequate treatment and data theft. This sort of endangering scenario causes tremendous difficulty in handling healthcare data. This research intends to describe the threat plot of data integrity in healthcare through numerous attack statistics from around the world and Saudi Arabia and identify the criticality in Saudi Arabia in particular. A literature review by descriptive analysis, unit analysis and rating analysis to achieve the planned systematic literature review goal is outlined. The outcome of ranking analysis using a fuzzy analytical hierarchy process methodology offers a route for Saudi Arabian researchers to promote medical records or data security in Arabic healthcare. It is suggested that blockchain is the most prioritized method for regular use and adaptation across Saudi Arabia in all data integrity management techniques. To address the challenges of data integrity and future path, the authors critically examine the challenges posed by data integrity in the healthcare sector.

A fuzzy TOPSIS based analysis toward selection of effective security requirements engineering approach for trustworthy healthcare software development.

BACKGROUND: Today's healthcare organizations want to implement secure and quality healthcare software as cyber-security is a significant risk factor for healthcare data. Considering security requirements during trustworthy healthcare software development process is an essential part of the quality software development. There are several Security Requirements Engineering (SRE) methodologies, framework, process, standards available today. Unfortunately, there is still a necessity to improve these security requirements engineering approaches. Determining the most suitable security requirements engineering method for trustworthy healthcare software development is a challenging process. This study is aimed to present security experts' perspective on the relative importance of the criteria for selecting effective SRE method by utilizing the multi-criteria decision making methods. METHODS: The study was planned and conducted to identify the most appropriate SRE approach for quality and trustworthy software development based on the security expert's knowledge and experience. The hierarchical model was evaluated by using fuzzy TOPSIS model. Effective SRE selection criteria were compared in pairs. 25 security experts were asked to response the pairwise criteria comparison form. RESULTS: The impact of the recognized selection criteria for effective security requirements engineering approaches has been evaluated quantitatively. For each of the 25 participants, comparison matrixes were formed based on the scores of their responses in the form. The consistency ratios (CR) were found to be smaller than 10% (CR = 9.1% < 10%). According to pairwise comparisons result; with a 0.842 closeness coefficient (Ci), STORE methodology is the most effective security requirements engineering approach for trustworthy healthcare software development. CONCLUSIONS: The findings of this research study demonstrate various factors in the decision-making process for the selection of a reliable method for security requirements engineering. This is a significant study that uses multi-criteria decision-making tools, specifically fuzzy TOPSIS, which used to evaluate different SRE methods for secure and trustworthy healthcare application development.

Healthcare Data Breaches: Insights and Implications.

The Internet of Medical Things, Smart Devices, Information Systems, and Cloud Services have led to a digital transformation of the healthcare industry. Digital healthcare services have paved the way for easier and more accessible treatment, thus making our lives far more comfortable. However, the present day healthcare industry has also become the main victim of external as well as internal attacks. Data breaches are not just a concern and complication for security experts; they also affect clients, stakeholders, organizations, and businesses. Though the data breaches are of different types, their impact is almost always the same. This study provides insights into the various categories of data breaches faced by different organizations. The main objective is to do an in-depth analysis of healthcare data breaches and draw inferences from them, thereby using the findings to improve healthcare data confidentiality. The study found that hacking/IT incidents are the most prevalent forms of attack behind healthcare data breaches, followed by unauthorized internal disclosures. The frequency of healthcare data breaches, magnitude of exposed records, and financial losses due to breached records are increasing rapidly. Data from the healthcare industry is regarded as being highly valuable. This has become a major lure for the misappropriation and pilferage of healthcare data. Addressing this anomaly, the present study employs the simple moving average method and the simple exponential soothing method of time series analysis to examine the trend of healthcare data breaches and their cost. Of the two methods, the simple moving average method provided more reliable forecasting results.

Security Risk Assessment of Healthcare Web Application Through Adaptive Neuro-Fuzzy Inference System: A Design Perspective.

INTRODUCTION: The imperative need for ensuring optimal security of healthcare web applications cannot be overstated. Security practitioners are consistently working at improvising on techniques to maximise security along with the longevity of healthcare web applications. In this league, it has been observed that assessment of security risks through soft computing techniques during the development of web application can enhance the security of healthcare web applications to a great extent. METHODS: This study proposes the identification of security risks and their assessment during the development of the web application through adaptive neuro-fuzzy inference system (ANFIS). In this article, firstly, the security risk factors involved during healthcare web application development have been identified. Thereafter, these security risks have been evaluated by using the ANFIS technique. This research also proposes a fuzzy regression model. RESULTS: The results have been compared with those of ANFIS, and the ANFIS model is found to be more acceptable for the estimation of security risks during the healthcare web application development. CONCLUSION: The proposed approach can be applied by the healthcare web application developers and experts to avoid the security risk factors during healthcare web application development for enhancing the healthcare data security.

Attribute based honey encryption algorithm for securing big data: Hadoop distributed file system perspective.

Hadoop has become a promising platform to reliably process and store big data. It provides flexible and low cost services to huge data through Hadoop Distributed File System (HDFS) storage. Unfortunately, absence of any inherent security mechanism in Hadoop increases the possibility of malicious attacks on the data processed or stored through Hadoop. In this scenario, securing the data stored in HDFS becomes a challenging task. Hence, researchers and practitioners have intensified their efforts in working on mechanisms that would protect user's information collated in HDFS. This has led to the development of numerous encryption-decryption algorithms but their performance decreases as the file size increases. In the present study, the authors have enlisted a methodology to solve the issue of data security in Hadoop storage. The authors have integrated Attribute Based Encryption with the honey encryption on Hadoop, i.e., Attribute Based Honey Encryption (ABHE). This approach works on files that are encoded inside the HDFS and decoded inside the Mapper. In addition, the authors have evaluated the proposed ABHE algorithm by performing encryption-decryption on different sizes of files and have compared the same with existing ones including AES and AES with OTP algorithms. The ABHE algorithm shows considerable improvement in performance during the encryption-decryption of files.

Fusion to Tetrahymena thermophila granule lattice protein 1 confers solubility to sexual stage malaria antigens in Escherichia coli.

A transmission-blocking vaccine targeting the sexual stages of Plasmodium species could play a key role in eradicating malaria. Multiple studies have identified the P. falciparum proteins Pfs25 and Pfs48/45 as prime targets for transmission-blocking vaccines. Although significant advances have been made in recombinant expression of these antigens, they remain difficult to produce at large scale and lack strong immunogenicity as subunit antigens. We linked a self-assembling protein, granule lattice protein 1 (Grl1p), from the ciliated protozoan, Tetrahymena thermophila, to regions of the ectodomains of either Pfs25 or Pfs48/45. We found that resulting protein chimera could be produced in E. coli as nanoparticles that could be readily purified in soluble form. When produced in the E. coli SHuffle strain, fusion to Grl1p dramatically increased solubility of target antigens while at the same time directing the formation of particles with diameters centering on 38 and 25 nm depending on the antigen. In a number of instances, co-expression with chaperone proteins and induction at a lower temperature further increased expression and solubility. Based on Western blotting and ELISA analysis, Pfs25 and Pfs48/45 retained their transmission-blocking epitopes within E. coli-derived particles, and the particles themselves elicited strong antibody responses in rabbits when given with an aluminum-based adjuvant. Antibodies against Pfs25-containing nanoparticles blocked parasite transmission in standard membrane-feeding assays. In conclusion, fusion to Grl1p can act as a solubility enhancer for proteins with limited solubility while retaining correct folding, which may be useful for applications such as the production of vaccines and other biologics.

Security durability assessment through fuzzy analytic hierarchy process.

BACKGROUND: Security is an integral aspect of the development of quality software. Furthermore, security durability is even more imperative and in persistent demand due to high investment in recent years. To achieve the desired target of efficacious and viable durability of security services, there needs to be nodal focus on durability along with security. Unfortunately, the highly secure design of software becomes worthless because the durability of security services is not as it should be. METHODS: Security durability attributes have their own impact while integrating security with durability and assessment of security durability plays a crucial role during software development. Within this context, this paper estimates the security durability of the two alternatives versions of a locally developed software called version 1 and version 2. To assess the security durability, authors are using the hybrid fuzzy analytic hierarchy process decision analysis approach. RESULTS: The impact of the security durability on other attributes has been evaluated quantitatively. The result obtained contains the assessment of security durability. The study posits conclusions which are based on this result and are useful for practitioners to assess and improve the security life span of software services.

A multiplatform strategy for the discovery of conventional monoclonal antibodies that inhibit the voltage-gated potassium channel Kv1.3.

Identifying monoclonal antibodies that block human voltage-gated ion channels (VGICs) is a challenging endeavor exacerbated by difficulties in producing recombinant ion channel proteins in amounts that support drug discovery programs. We have developed a general strategy to address this challenge by combining high-level expression of recombinant VGICs in Tetrahymena thermophila with immunization of phylogenetically diverse species and unique screening tools that allow deep-mining for antibodies that could potentially bind functionally important regions of the protein. Using this approach, we targeted human Kv1.3, a voltage-gated potassium channel widely recognized as a therapeutic target for the treatment of a variety of T-cell mediated autoimmune diseases. Recombinant Kv1.3 was used to generate and recover 69 full-length anti-Kv1.3 mAbs from immunized chickens and llamas, of which 10 were able to inhibit Kv1.3 current. Select antibodies were shown to be potent (IC50<10 nM) and specific for Kv1.3 over related Kv1 family members, hERG and hNav1.5.

Breast screening revisited.

Breast screening is the medical screening of asymptomatic, apparently healthy women for breast lump in an attempt to achieve an earlier diagnosis. The assumption is that the early detection will improve outcomes. In western countries, breast screening programs have led to a significant reduction in mortality and improved prognosis of patients with breast cancer. However in India, although the number of breast cancer are on the rise there is no such organized program. This article emphasizes on the importance of breast screening and protocol to be followed in our country where it can have significant impact on the prognosis.

Role of ultrasound with color Doppler in acute scrotum management.

BACKGROUND AND OBJECTIVE: An acute scrotum is defined as acute pain with or without scrotal swelling, may be accompanied by local signs or general symptoms. Acute scrotal pain is a medical emergency. Depending on cause, the management is entirely different. Torsion of testis and strangulated hernia are surgical emergency; whereas, epididymo-orchitis is treated by medicines. Testicular trauma and obstructed hernia can be differentiated by taking history from patient. Physical examination adds only a little information. Color Doppler ultrasound (US) is the modality of choice to differentiate testicular torsion from inflammatory conditions and can thus help in avoiding unnecessary surgical explorations. SUBJECTS AND METHODS: A study on 50 patients was conducted who were referred with history of acute scrotal pain to our department between January 2013 and January 2014. Trauma and scrotal mass were excluded from the study. The clinical presentation, outcome, and US results were analyzed. RESULTS: Color Doppler sonography yielded a positive and negative predictive value (PPV and NPV) of 100% each for torsion, whereas, 93.9 and 70.6% for epididymo-orchitis, respectively; a sensitivity and specificity of 100% for torsion, whereas, for epididymo-orchitis it was found to be 86.1 and 85.7%, respectively. In cases of incomplete or early torsion, some residual perfusion may be detected leading to false-negative results. CONCLUSION: We therefore conclude that color Doppler sonography can reliably rule out testicular torsion and can thus help in avoiding unnecessary surgical explorations. Hence, it can significantly improve outcome and decrease morbidity of patient. It is an accurate, rapid, nonexpensive, nonionizing, important adjunct to clinical assessment of scrotum.

Mycobacterium tuberculosis DNA gyrase ATPase domain structures suggest a dissociative mechanism that explains how ATP hydrolysis is coupled to domain motion.

DNA gyrase, a type II topoisomerase, regulates DNA topology by creating a double-stranded break in one DNA duplex and transporting another DNA duplex [T-DNA (transported DNA)] through this break. The ATPase domains dimerize, in the presence of ATP, to trap the T-DNA segment. Hydrolysis of only one of the two ATPs, and release of the resulting Pi, is rate-limiting in DNA strand passage. A long unresolved puzzle is how the non-hydrolysable ATP analogue AMP-PNP (adenosine 5'-[ß,γ-imido]triphosphate) can catalyse one round of DNA strand passage without Pi release. In the present paper we discuss two crystal structures of the Mycobacterium tuberculosis DNA gyrase ATPase domain: one complexed with AMP-PCP (adenosine 5'-[ß,γ-methylene]triphosphate) was unexpectedly monomeric, the other, an AMP-PNP complex, crystallized as a dimer. In the AMP-PNP structure, the unprotonated nitrogen (P-N=P imino) accepts hydrogen bonds from a well-ordered 'ATP lid', which is known to be required for dimerization. The equivalent CH2 group, in AMP-PCP, cannot accept hydrogen bonds, leaving the 'ATP lid' region disordered. Further analysis suggested that AMP-PNP can be converted from the imino (P-N=P) form into the imido form (P-NH-P) during the catalytic cycle. A main-chain NH is proposed to move to either protonate AMP-P-N=P to AMP-P-NH-P, or to protonate ATP to initiate ATP hydrolysis. This suggests a novel dissociative mechanism for ATP hydrolysis that could be applicable not only to GHKL phosphotransferases, but also to unrelated ATPases and GTPases such as Ras. On the basis of the domain orientation in our AMP-PCP structure we propose a mechanochemical scheme to explain how ATP hydrolysis is coupled to domain motion.

Purification, crystallization and preliminary X-ray crystallographic studies of the Mycobacterium tuberculosis DNA gyrase ATPase domain.

Mycobacterium tuberculosis DNA gyrase, a nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and hence is the sole target of fluoroquinolones in the treatment of tuberculosis. The ATPase domain provides the energy required for catalysis by ATP hydrolysis. Two constructs corresponding to this 43 kDa domain, Mtb-GyrB47(C1) and Mtb-GyrB47(C2), have been overproduced, purified and crystallized. Diffraction data were collected from three crystal forms. The crystals belonged to space groups P1 and P21 and diffracted to resolutions of 2.9 and 3.3 Å, respectively.

Cerebrotendinous xanthomatosis--the spectrum of imaging findings.

Cerebrotendinous xanthomatosis (CTX), also known as Van Bogaert-Scherer-Epstein disease is a rare autosomal recessive genetic disorder of the lipid metabolism. To date, there are less than 300 cases reported worldwide. We present a case of a 30 year old male who presented with mental retardation and swelling of ankles, with the a spectrum of CTX imaging findings. Imaging studies were performed which included plain X-ray, Ultrasound(US) and Magnetic Resonance Imaging(MRI) of both the brain and ankles. These pointed towards the diagnosis of CTX with the entire spectrum of findings which was confirmed with biopsy and laboratory findings. CTX is a potentially treatable condition with replacement therapy, and hence early diagnosis before neurological deterioration is important. This is aided by the imaging findings which are conclusive forte diagnosis of CTX.

Domain swapping in allosteric modulation of DNA specificity.

SgrAI is a type IIF restriction endonuclease that cuts an unusually long recognition sequence and exhibits allosteric self-modulation of cleavage activity and sequence specificity. Previous studies have shown that DNA bound dimers of SgrAI oligomerize into an activated form with higher DNA cleavage rates, although previously determined crystal structures of SgrAI bound to DNA show only the DNA bound dimer. A new crystal structure of the type II restriction endonuclease SgrAI bound to DNA and Ca(2+) is now presented, which shows the close association of two DNA bound SgrAI dimers. This tetrameric form is unlike those of the homologous enzymes Cfr10I and NgoMIV and is formed by the swapping of the amino-terminal 24 amino acid residues. Two mutations predicted to destabilize the swapped form of SgrAI, P27W and P27G, have been made and shown to eliminate both the oligomerization of the DNA bound SgrAI dimers as well as the allosteric stimulation of DNA cleavage by SgrAI. A mechanism involving domain swapping is proposed to explain the unusual allosteric properties of SgrAI via association of the domain swapped tetramer of SgrAI bound to DNA into higher order oligomers.