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Influenza viruses cause approximately half a million deaths every year worldwide. Vaccines are available but partially effective, and the number of antiviral medications is limited. Thus, it is crucial to develop therapeutic strategies to counteract this major pathogen. Influenza viruses enter the host cell via their hemagglutinin (HA) proteins. The HA subtypes of influenza A virus are phylogenetically classified into groups 1 and 2. Here, we identified an inhibitor of the HA protein, a tertiary aryl sulfonamide, that prevents influenza virus entry and replication. This compound shows potent antiviral activity against diverse H1N1, H5N1, and H3N2 influenza viruses encoding HA proteins from both groups 1 and 2. Synthesis of derivatives of this aryl sulfonamide identified moieties important for antiviral activity. This compound may be considered as a lead for drug development with the intent to be used alone or in combination with other influenza A virus antivirals to enhance pan-subtype efficacy.

"A collection of cognitive, social, and interpersonal abilities that assist people to make informed decisions, solve problems, think critically, intellectually to develop good relationships, and manage their lives in a productive way," is how life skills are defined. In order to work alongside with the community, an engineer must have interpersonal skills, communication skills, and self-awareness. The proposed tool, E-skills Evaluator, helps to test students for these important life skills. The tool facilitates the mentor to schedule the test and access the detailed report of the test. The report captures the current skill level of the student. Accordingly, mentor can plan the training sessions. Additionally, the tool provides an automated chat-bot that assists users if they encounter any issues during the assessment. The application implements the Firebase store which provides the online cloud storage with security for user data. It ensures data accuracy, reduces paper work, makes information flow efficient, paves the way for easy report generation and uses time efficiently. The proposed system indicates to students the areas of improvement., {"references":["\"Importance of Soft Skills for Education and Career Success\",Shaheen Majid, Zhang Liming, Shen Tong, Siti Raihana,Nanyang Technological University, Singapore.","\"Significance Of Life Skills Education\",Ravindra Prajapati, Ph.D., Fiji National University, Fiji,Bosky Sharma, Fiji National University, Fiji, Dharmendra Sharma, Ph.D., Fiji National University, Fiji.","\"ASSESSMENT OF COLLABORATIVE SKILLS\",Baranovichi State University, the Republic of Belarus, Parkovaya street, 62, Baranovichi, 225406, Brest region.","\"Critical Thinking and it's Importance in Education\",I. Lenin Assistant Professor, AUCE Karaikudi.","\"Methodology for training engineers teamwork skills\", Rubén DoradoVicente,Department of Mechanical and Mining Engineering,University of Jaén,Jaén, Spain, Rocío BolañosJiménez Department of Mechanical and Mining Engineering, University of Jaén Jaén, Spain Eloisa Torres-Jiménez, Department of Mechanical and Mining Engineering, University of Jaén Jaén, Spain, Cándido Gutiérrez-Montes, Department of Mechanical and Mining Engineering, University of Jaén, Jaén, Spain.","\"Critical Thinking in the Classroom...and Beyond\", Linda M. Murawski, EdD, Adjunct Professor, Department of Human Resources Development Graduate & Professional Studies Tusculum College Knoxville, Tennessee.","\"Reflection of Critical Thinking on the Sustainable Educational Development\" A Case Study of the Middle East and North Africa, Dana Bakry, Maoloud Dabab, Rafaa Khalifa Dept. of Engineering and Technology Management, Portland State University, Portland, OR – USA."]}

Fusobacterium is a gram negative obligate anaerobic bacilli, a normal inhabitant of gastrointestinal tract, oropharynx and female genital tract. Here we report a case of Fourniers gangrene from which Fusobacterium varium has been isolated along with certain other pathogens. There are only a few reported cases of Fusobacterium varium in literature and it has never been reported from Fournier's gangrene. Through this report we intend to shed some light on the pathogenic potential of anaerobes which are considered as normal flora.

BACKGROUND: Rapid turnaround time of blood culture reports should be the main motive for a clinical microbiologist for optimal patient care. Categorical agreement (CA) between direct disk diffusion (dDD) and reference disk diffusion (rDD) may vary between laboratories. AIMS AND OBJECTIVES: This study was designed to determine the CA and understand various types of errors associated with antibiotic organism combination, so that caution can be derived while interpreting and reporting dDD results in the earliest meaningful time frame. MATERIALS AND METHODS: In the present study, dDD results were compared to the rDD results from the positive blood culture bottles. CA and various types of errors were evaluated. RESULTS: A total of 965 pathogens and 7106 organism antibiotic combinations were evaluated in this study. Overall, there was a CA of 96% which was extremely satisfactory. The categorical disagreement was found only in 4% of organism antibiotic combinations; majority of which were major error (ME, 2.1%) followed by very ME (1%) and minor error (0.9%). The errors were marginally high for Enterobacteriaceae testing against β lactam- β lactamase inhibitor combinations, for Pseudomonas species; against aminoglycosides and ciprofloxacin and Staphylococcus species against cefoxitin, one should be vigilant while reporting dDD result of these antibiotic organism combinations. CONCLUSION: dDD is of paramount importance for early institution of targeted therapy and is considered as one of the key stewardship intervention. Our study gives an insight that every laboratory must perform dDD for positively flagged blood culture specimens; the result of which should be confirmed later by performing rDD. One should be vigilant while reporting dDD result of BL BLI for Enterobacteriaceae; aminoglycosides and CF for Pseudomonas species; cefoxitin for Staphylococcus species and HLG for Enterococcus species. Supplementary tests such as MRSA latex should be included when necessary.

Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here we show that infection of human lung epithelial cells with Influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. While these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, specific inhibition of the IAV-induced splicing in several cases also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein that required for efficient splicing of the IAV M transcript in nuclear speckles. Notably, we find that hnRNP K accumulates in nuclear speckles upon IAV infection, which is likely to alter the accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication.

Background Healthcare-associated infections (HAIs) are a major threat to patient safety worldwide. HAIs are mainly transmitted via the hands of healthcare workers (HCWs), and HCW compliance with hand hygiene (HH) practices is reportedly low. Therefore, multimodal interventions are needed to develop effective HH improvement strategies. In this study, we assessed the effect of multimodal interventions on improvement of HH compliance. Methods This study was conducted in 2 intensive care units from August 2016 to October 2016. It encompassed 3 phases: pre-intervention (20 days), intervention (1 month), and post-intervention (20 days). A total of 53 HCWs, including physicians, nurses, and housekeeping staff, were included in the HH audit. The audit was analyzed by direct observation and by a completed knowledge, attitude, and practice (KAP) questionnaire. Results A total of 6350 HH opportunities were recorded; the results were 34.7%, 35%, and 69.7% for hand hygiene complete adherence rate (HHCAR), hand hygiene partial adherence rate (HHPAR), and hand hygiene adherence rate (HHAR), respectively. The HHCAR in the pre-intervention and post-intervention phases were 3% and 70.1%, respectively. HHCAR was highest among nurses (3.6% in the pre-intervention phase and 80.7% in the post-intervention phase). Other findings were that senior physicians had better HH compliance than junior physicians; in the pre-intervention phase, the HHCAR was better in the evening (4.8%); in the post-intervention phase, the HHCAR was better in the morning (72.1%); women had a higher HHCAR than men; and in the pre-intervention phase, good compliance was seen with Moments 2 and 3 of the World Health Organization's (WHO) Five Moments for Hand Hygiene, whereas in the post-intervention phase, good compliance was seen with Moments 3, 4, and 5. Questionnaire-based data were also analyzed to assess KAP of HH. We found that only 55%-82% of HCWs were aware of the WHO's Five Moments for Hand Hygiene. In the post-intervention phase, we observed a significant improvement in KAP of the study group. Conclusion Significant improvement in HH compliance can be achieved through a systematic, multidimensional intervention involving all types of HCWs.

Nuclear pore complexes (NPCs) are important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing and mRNA export. The multi-faceted nature of NPCs and the slow turnover of their components has made it difficult to understand the role of basket nucleoporins (Nup153, Nup50 and Tpr) in these diverse processes. To address this question, we used anAuxin-InducedDegron (AID) system to distinguish roles of basket nucleoporins: Loss of individual nucleoporins caused distinct alteration in patterns of nucleocytoplasmic trafficking and gene expression. Importantly, Tpr elimination caused rapid and pronounced changes in transcriptomic profiles within two hours of auxin addition. These changes were dissimilar to shifts observed after loss of Nup153 or Nup50, but closely related to changes after depletion of mRNA export receptor NXF1 or the GANP subunit of the TRanscription-EXport-2 (TREX-2) mRNA export complex. Moreover, GANP association to NPCs was specifically disrupted upon TPR depletion. Together, our findings demonstrate a unique and pivotal role of Tpr in regulating gene expression through GANP- and/or NXF1-dependent mRNA nuclear export.

Vibrio vulnificus is a halophilic Vibrio found globally. They are thought to be normal microbiome in the estuaries along the coasts associated with seawater and seashells. Infection usually results from consumption of raw oysters or shellfish or exposure of broken skin or open wounds to contaminated salt or brackish water. Clinical manifestations range from gastroenteritis to skin and subcutaneous infection and primary sepsis. Pathogen has the ability to cause infections with significant mortality in high-risk populations, including patients with chronic liver disease, immunodeficiency, diabetes mellitus and iron storage disorders. There is often a lack of clinical suspicion in cases due to Vibrio vulnificus leading to delay in treatment and subsequent mortality. Herein we report a case of necrotising fasciitis in a diabetic patient with alcoholic liver disease caused by Vibrio vulnificus which ended fatally.

Three of the eight RNA segments encoded by the influenza A virus (IAV) undergo alternative splicing to generate distinct proteins. Previously, we found that host proteins hnRNP K and NS1-BP regulate IAV M segment splicing, but the mechanistic details were unknown. Here we show NS1-BP and hnRNP K bind M mRNA downstream of the M2 5′ splice site (5′ss). NS1-BP binds most proximal to the 5′ss, partially overlapping the U1 snRNP binding site, while hnRNP K binds further downstream and promotes U1 snRNP recruitment. Mutation of either or both the hnRNP K and NS1-BP-binding sites results in M segment mis-splicing and attenuated IAV replication. Additionally, we show that hnRNP K and NS1-BP regulate host splicing events and that viral infection causes mis-splicing of some of these transcripts. Therefore, our proposed mechanism of hnRNP K/NS1-BP mediated IAV M splicing provides potential targets of antiviral intervention and reveals novel host functions for these proteins.

With an increase in the number of warehouses, cold storage units and factories in today's industrialized and automated world, the need for monitoring various attributes in such factories has become a thing of great necessity. With advances in technology, and in particular, the various sensors to measure different parameters such as temperature, gases, humidity etc. have become more viable and affordable. Upcoming IoT architectures and wireless sensor networks allow real time remote monitoring and analysis of a system as well as the possibility to take immediate remedial actions if necessary. In order to incorporate all these features and understand the feasibility of the system, in our present work, we have developed a prototype consisting of a sensor network to measure and analyze temperature, humidity and carbon-monoxide gas levels. This work provides an overview of the development of an IoT based cold storage monitoring system.

Hand hygiene (HH) practice is considered the most simple, cost-effective, and efficient way to prevent device-associated infections. Continuous auditing plays a vital role in the conversion of HH knowledge into practice.An HH audit was carried out October 2015-September 2016 in 18 locations for a total of 1,080 observation periods and 64,800 minutes of observation. HH complete adherence rate (HHCAR) and HH partial adherence rate were analyzed.The HHCAR, HH partial adherence rate, and nonadherence rate were 45.5%, 21.17%, and 33.3%, respectively. There was gradual statistically significant increase in monthly HHCAR during the study period from 37.5%-51.7% (P = .001). HHCAR was found to be highest among nurses (58.9%) followed by other staff (46.7%) and doctors (46.6%). World Health Organization Moments 3 and 4 had statistically significant compliance (78.5% and 71.8%, respectively; P.001) compared with Moments 1, 2, and 5. As the HHCAR increases there is statistically significant decrease in device-associated infection rate from 10.6-3.9 per 1,000 device days (P = .042).HH audit has a significant influence on HH compliance. More emphasis needs to be given on compliance with HH practice by doctors and with the World Health Organization "before" Moments, especially. HH audits should be a part of the infection control manual of every hospital.

Vibrio vulnificusis a halophilicVibriofound globally. They are thought to be normal microbiome in the estuaries along the coasts associated with seawater and seashells. Infection usually results from consumption of raw oysters or shellfish or exposure of broken skin or open wounds to contaminated salt or brackish water. Clinical manifestations range from gastroenteritis to skin and subcutaneous infection and primary sepsis. Pathogen has the ability to cause infections with significant mortality in high-risk populations, including patients with chronic liver disease, immunodeficiency, diabetes mellitus and iron storage disorders. There is often a lack of clinical suspicion in cases due toVibrio vulnificusleading to delay in treatment and subsequent mortality. Herein we report a case of necrotising fasciitis in a diabetic patient with alcoholic liver disease caused byVibrio vulnificuswhich ended fatally.

INTRODUCTION: Blood stream infections (BSIs) are responsible for significant morbidity and mortality. Numerous studies have pointed to the importance of early and prompt institution of empirical antimicrobial therapy in reducing morbidity and mortality in BSI. The antibiotic spectrum must be narrowed as soon as possible, considering the clinical condition of the patient, the pathogens identified in cultures and the sensitivity profile obtained from the antibiogram. When no evidence of bacterial infection is present, antibiotic therapy must be suspended. However, it is often observed that the clinician does not adhere to the guideline and continues with the same empirical treatment. MATERIALS AND METHODS: The study was conducted at Department of Microbiology, in a tertiary care hospital from April 2017 to September 2017. Two hundred patients with microbiologically documented BSIs were included in the study. They were followed up to find the appropriateness of change in empirical treatment carried out according to culture sensitivity report, and antimicrobial consumption was also calculated. RESULTS: We observed that there was an increased use of antipseudomonal penicillins plus beta-lactamase inhibitors, amikacin and carbapenems which was due to higher prevalence of multidrug-resistant Gram-negative bacilli among blood culture isolated. We also found that in most of the patients, the empirical treatment was inappropriately modified at day four after availability of culture reports, i.e., inappropriately escalated or de-escalated or continued while there was no indication to do so. CONCLUSION: Treatment inappropriate group was associated with higher treatment failure as compared to treatment appropriate group. Studies of the other factors associated with inappropriate treatment such as changes in resistance patterns, antimicrobial-related adverse effect and of the long-term clinical outcomes are warranted.

Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15-20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy. (C) 2015 Elsevier Ltd. All rights reserved.

Translation initiation in Hepatitis C Virus (HCV) is mediated by Internal Ribosome Entry Site (IRES), which is independent of cap-structure and uses a limited number of canonical initiation factors. During translation initiation IRES-40S complex formation depends on high affinity interaction of IRES with ribosomal proteins. Earlier, it has been shown that ribosomal protein S5 (RPS5) interacts with HCV IRES. Here, we have extensively characterized the HCV IRES-RPS5 interaction and demonstrated its role in IRES function. Computational modelling and RNA-protein interaction studies demonstrated that the beta hairpin structure within RPS5 is critically required for the binding with domains II and IV. Mutations disrupting IRES-RPS5 interaction drastically reduced the 80S complex formation and the corresponding IRES activity. Computational analysis and UV cross-linking experiments using various IRES-mutants revealed interplay between domains II and IV mediated by RPS5. In addition, present study demonstrated that RPS5 interaction is unique to HCV IRES and is not involved in 40S-3 ` UTR interaction. Further, partial silencing of RPS5 resulted in preferential inhibition of HCV RNA translation. However, global translation was marginally affected by partial silencing of RPS5. Taken together, results provide novel molecular insights into IRES-RPS5 interaction and unravel its functional significance in mediating internal initiation of translation.

In this study, we combine available high resolution structural information on eukaryotic ribosomes with low resolution cryo-EM data on the Hepatitis C Viral RNA (IRES) human ribosome complex. Aided further by the prediction of RNA-protein interactions and restrained docking studies, we gain insights on their interaction at the residue level. We identified the components involved at the major and minor contact regions, and propose that there are energetically favorable local interactions between 40S ribosomal proteins and IRES domains. Domain II of the IRES interacts with ribosomal proteins S5 and S25 while the pseudoknot and the downstream domain IV region bind to ribosomal proteins S26, S28 and S5. We also provide support using UV cross-linking studies to validate our proposition of interaction between the S5 and IRES domains II and IV. We found that domain IIIe makes contact with the ribosomal protein S3a (S1e). Our model also suggests that the ribosomal protein S27 interacts with domain IIIc while S7 has a weak contact with a single base RNA bulge between junction IIIabc and IIId. The interacting residues are highly conserved among mammalian homologs while IRES RNA bases involved in contact do not show strict conservation. IRES RNA binding sites for S25 and S3a show the best conservation among related viral IRESs. The new contacts identified between ribosomal proteins and RNA are consistent with previous independent studies on RNA-binding properties of ribosomal proteins reported in literature, though information at the residue level is not available in previous studies.

Hepatitis C virus (HCV) and Classical swine fever virus (CSFV) mRNAs contain related (HCV-like) internal ribosome entry sites (IRESs) that promote 5’-end independent initiation of translation, requiring only a subset of the eukaryotic initiation factors (eIFs) needed for canonical initiation on cellular mRNAs1. Initiation on HCV-like IRESs relies on their specific interaction with the 40S subunit2–8, which places the initiation codon into the P site, where it directly base-pairs with eIF2-bound Met-tRNAiMet to form a 48S initiation complex. However, all HCV-like IRESs also specifically interact with eIF32,5–7,9–12, but the role of this interaction in IRES-mediated initiation has remained unknown. During canonical initiation, eIF3 binds to the 40S subunit as a component of the 43S pre-initiation complex, and comparison of the ribosomal positions of eIF313 and the HCV IRES8 revealed that they overlap, so that their rearrangement would be required for formation of ribosomal complexes containing both components13. Here, we present a cryo-electron microscopy reconstruction of a 40S ribosomal complex containing eIF3 and the CSFV IRES. Strikingly, although the position and interactions of the CSFV IRES with the 40S subunit in this complex are similar to those of the HCV IRES in the 40S/IRES binary complex8, eIF3 is completely displaced from its ribosomal position in the 43S complex, and instead interacts through its ribosome-binding surface exclusively with the apical region of domain III of the IRES. Our results suggest a role for the specific interaction of HCV-like IRESs with eIF3 in preventing ribosomal association of eIF3, which could serve two purposes: relieving the competition between the IRES and eIF3 for a common binding site on the 40S subunit, and reducing formation of 43S complexes, thereby favoring translation of viral mRNAs.

Background: Needlestick, sharp, and splash injuries (NSSSIs) are the major occupational hazards among the healthcare workers (HCWs) for blood-borne viruses (BBVs) such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). This study was designed to determine the impact of an established nodal center for NSSSI management and to analyze the epidemiological characteristics. Materials and Methods: Dedicated nodal center was established for NSSSI documentation. A standard operating protocol was set for NSSSI management and postexposure prophylaxis (PEP) for BBVs. The epidemiological characteristics of NSSSIs were collected using a structured pro forma. Results: Between December 2014 and November 2016, 452 NSSSIs were reported, which included 411 (90.9%) needlestick and other sharp injuries and 41 (9.1%) splash injuries. Doctors reported the maximum episodes (32.5%), followed by attenders (28.8%) and nurses (21.9%). Most injuries were contracted during device use (44.8%), followed by after withdrawal before disposing (28.5%) and recapping (14.8%). Increased reporting was observed among newly-joined junior doctors. 6.9% of source was positive for BBVs (1.8% HIV; 4.0% HBV; 1.1% HCV). PEP first dose was taken by 30.5% of HCWs. PEP continuation was indicated in 161 cases but could not be traced. 40.9% HCWs were completely vaccinated for HBV (of which 49.2% are protected), 7.1% were partially, and 52.0% were not vaccinated. Conclusion: Our findings endorse the essential role of an established nodal center for NSSSI documentation. Continuous education, engineering control, vaccination campaign, and other interventional strategies such as biomedical waste auditing are crucial measures which should be taken to tackle this issue.

Translation initiation of hepatitis C Virus (HCV) RNA is the initial obligatory step of the viral life cycle, mediated through the Internal Ribosome Entry Site (IRES) present in the 5′-untranslated region (UTR). Initiation on the HCV IRES is mediated by multiple structure-specific interactions between IRES RNA and host 40S ribosomal subunit. In the present study we demonstrate that the SLIIIef domain, in isolation from other structural elements of HCV IRES, retain the ability to interact with 40S ribosome subunit. A small RNA SLRef, mimicking the SLIIIef domain was found to interact specifically with human La protein and the ribosomal protein S5 and selectively inhibit HCV RNA translation. More importantly, SLRef RNA showed significant suppression of replication in HCV monocistronic replicon and decrease of negative strand synthesis in HCV cell culture system. Finally, using Sendai virus based virosome, the targeted delivery of SLRef RNA into mice liver succeeded in selectively inhibiting HCV IRES mediated translation in vivo.

Adeno-tonsillar hypertrophy, with signs of upper airway obstruction is a common presentation in ENT clinics. Recently it is identified as a major cause of sleep apnea syndrome. Several isolated case reports of pulmonary hypertension and corpulmonale appeared in the literature. The authors report two such children aged less than 2 years with cardio-pulmonary changes occurring secondary to chronic adeno-tonsillar hypertrophy that were successfully treated with the surgical removal.