Biofilm formation, agr typing and antibiotic resistance pattern in methicillin-resistant Staphylococcus aureus isolated from hospital environments.

Biofilm development significantly enhances the virulence of methicillin-resistant Staphylococcus aureus (MRSA), leading to severe infections and decreased susceptibility to antibiotics, especially in strains associated with hospital environments. This study examined the occurrence of MRSA, their ability to form biofilms, agr typing, and the antibiotic resistance profiles of biofilm-forming MRSA strains isolated from environmental surfaces at Mymensingh Medical College Hospital (MMCH). From 120 swab samples, 86 (71.67%) tested positive for S. aureus. MRSA was identified in 86 isolates using the disk diffusion technique, and by polymerase chain reaction (PCR), 56 (65.1%) isolates were confirmed to carry the mecA gene. The Crystal Violet Microtiter Plate (CVMP) test revealed that 80.35% (45 isolates) were biofilm-forming and 19.6% (11 isolates) were non-biofilm-forming. Out of 45 biofilm producer isolates 37.5% and 42.9% isolates exhibited strong and intermediate biofilm-forming characteristics, respectively. Molecular analysis revealed that 17.78% of MRSA isolates carried at least one gene related to biofilm formation, specifically icaA, icaB, and icaD genes were discovered in 13.33%, 8.89%, 6.67% of the MRSA isolates, respectively. In agr typing, the most prevalent group was agr I (71.11%), followed by group III (17.78%) and group II (11.11%). Group IV was not detected. The distribution of agr gene groups showed a significant difference among biofilm-forming isolates (p < 0.05). In agr group I, 18.75% of isolates carried the icaA gene, 12.5% carried the icaB gene, and 9.37% carried the icaD gene. Biofilm-forming genes were not detected in any of the isolates from agr groups II or III. There are no statistically significant differences between agr groups and the presence of these genes (p > 0.05). Antibiotic resistance varied significantly among agr groups, with agr group I displaying the highest resistance, agr group II, and agr group III exhibiting the least resistance (p < 0.05). Seventy-three (73.3%) of the isolates were multi-drug resistant, with agr group I displaying nineteen MDR patterns. The occurrence of MRSA in hospital environments and their capacity to form biofilm raises concerns for public health. These findings support the importance of further research focused on agr quorum sensing systems as a basis for developing novel antibacterial agents.

Perceptions of vulnerable roadway users on autonomous vehicle regulations.

INTRODUCTION: Development and implementation of autonomous vehicle (AV) related regulations are necessary to ensure safe AV deployment and wide acceptance among all roadway users. Assessment of vulnerable roadway users' perceptions on AV regulations could inform policymakers the development of appropriate AV regulations that facilitate the safety of diverse users in a multimodal transportation system. METHOD: This research evaluated pedestrians' and bicyclists' perceptions on six AV regulations (i.e., capping AV speed limit, operating AV in manual mode in the sensitive areas, having both pilot and co-pilot while operating AVs, and three data-sharing regulations). In addition, pedestrians' and bicyclists' perceptions of testing AVs in public streets were evaluated. Statistical testing and modeling techniques were applied to accomplish the research objectives. RESULTS: Compared to the other AV regulations assessed in this research, strong support for AV-related data sharing regulations was identified. Older respondents showed higher approval of AV testing on public roadways and less support for regulating AVs. AV technology familiarity and safe road sharing perceptions with AVs resulted in lower support for AV regulations. CONCLUSIONS: Policymakers and AV technology developers could develop effective educational tools/resources to inform pedestrians and bicyclists about AV technology reliability and soften their stance, especially on AV regulations, which could delay technology development. PRACTICAL APPLICATIONS: The findings of this research could be used to develop informed AV regulations and develop policies that could improve pedestrians' and bicyclists' attitudes/perceptions on regulating AVs and promoting AV technology deployments.

Prevalence and Associated Factors of Liver Enzyme Abnormalities Among Bangladeshi Women: A Cross-Sectional Study.

Background Liver enzyme abnormalities can indicate underlying liver health issues and are influenced by various factors. This study aimed to investigate the prevalence of liver enzyme abnormalities and their associated factors among nonpregnant and nonlactating (NPNL) women in Bangladesh. Methodology A cross-sectional study was conducted among 251 NPNL Bangladeshi women. Data on demographic, socioeconomic, and health-related variables were collected. Logistic regression analysis was used to determine the association between liver enzyme abnormalities and associated factors. Results The prevalence of liver enzyme abnormalities among participants was determined, with associated factors such as age, body mass index (BMI), monthly income, and food security status examined. Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were observed in 54 (21.5%) and 47 (18.7%) of participants, respectively, with 116 (46.2%) exhibiting an AST/ALT ratio exceeding 1.00. Food insecurity was significantly associated with a higher prevalence of elevated ALT levels (24.4% vs. 8.7%, P = 0.02), as well as low monthly income (18.8%, 14.7% vs. 36.7%, P < 0.01) and higher BMI (11% vs. 27.7% and 25.6%, P = 0.02). Similar trends were observed for AST levels. Moreover, participants with a higher BMI exhibited significantly higher rates of at least one abnormal liver function enzyme (15.9% vs. 34.9%, P = 0.01). Logistic regression analysis revealed a significant association between abnormal liver enzyme levels and certain demographic and socioeconomic factors, specifically BMI and age. Conclusions This study provides insights into the prevalence of liver enzyme abnormalities and their associated factors among NPNL Bangladeshi women. The findings underscore the importance of addressing factors such as BMI and age in mitigating liver health issues in this population. Further research and targeted interventions are warranted to address these concerns effectively.

A systematic review of the real-world effectiveness and economic and humanistic outcomes of selected oral antipsychotics among patients with schizophrenia in the United States: Updating the evidence and gaps.

BACKGROUND: Schizophrenia is a chronic, relapsing, and burdensome psychiatric disorder affecting approximately 0.25%-0.6% of the US population. Oral antipsychotic treatment (OAT) remains the cornerstone for managing schizophrenia. However, nonadherence and high treatment failure lead to increased disease burden and medical spending. Cost-effective management of schizophrenia requires understanding the value of current therapies to facilitate better planning of management policies while addressing unmet needs. OBJECTIVE: To review existing evidence and gaps regarding real-world effectiveness and economic and humanistic outcomes of OATs, including asenapine, brexpiprazole, cariprazine, iloperidone, lumateperone, lurasidone, olanzapine/samidorphan, paliperidone, and quetiapine. METHODS: We conducted a literature search using PubMed, American Psychological Association PsycINFO (EBSCOhost), and the Cumulative Index of Nursing and Allied Health Literature from January 2010 to March 2022 as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language articles describing adults with schizophrenia receiving at least 1 of the selected OATs and reporting real-world effectiveness, direct or indirect costs, humanistic outcomes, behavioral outcomes, adherence/persistence patterns, or product switching were identified. RESULTS: We identified 25 studies from a total of 24,190 articles. Real-world effectiveness, cost, and adherence/persistence outcomes were reported for most OATs that were selected. Humanistic outcomes and product switching were reported only for lurasidone. Behavioral outcomes (eg, interpersonal relations and suicide ideation) were not reported for any OAT. The key economic outcomes across studies were incremental cost-effectiveness ratios, cost per quality-adjusted life-years, and health care costs. In studies that compared long-acting injectables (LAIs) with OATs, LAIs had a higher pharmacy and lower medical costs, while total health care cost was similar between LAIs and OATs. Indirect costs associated with presenteeism, absenteeism, or work productivity were not reported for any of the selected OATs. Overall, patients had poor adherence to OATs, ranging between 20% and 61% across studies. Product switching did not impact the all-cause health care costs before and after treatment. CONCLUSIONS: Our findings showed considerable gaps exist for evidence on behavioral outcomes, humanistic outcomes, medication switching, and adherence/persistence across OATs. Our findings also suggest an unmet need regarding treatment nonadherence and lack of persistence among patients receiving OATs. We identified a need for research addressing OATs' behavioral and humanistic outcomes and evaluating the impact of product switching in adults with schizophrenia in the United States, which could assist clinicians in promoting patient-centered care and help payers understand the total value of new antipsychotic drugs.

Commonly consumed processed packaged foods in Bangladesh are unhealthy and their nutrient contents are not in conformity with the label declaration.

The present study was undertaken to identify the major nutrient content in processed foods commonly consumed in Bangladesh, their label conformity healthiness, and percent daily nutrient contribution. Twenty-four nationally representative composite samples were analyzed using AOAC and other standard methods. Results were compared with label information using a restrictive approach and EU tolerance guidelines. The healthiness of the products was evaluated in terms of the Health Star Rating (HSR) scheme and the UK traffic light labeling system. Among the analyzed samples, fried pulse, chanachur, lozenge, and fried peas had the highest amount of protein, fat, carbohydrates, and dietary fiber, respectively. Biscuits and milk chocolate had high levels of trans fatty acids (TFA) and saturated fatty acids (SFA). It was observed that around half of the products lacked information about saturated fatty acid (46%), followed by total dietary fiber and trans-fat (38% each). Other information was missing in one-fifth of the products, namely protein (17%), total fat (17%), available carbohydrate (17%), energy (17%), sugar (21%), and salt (21%). Label compliance analysis according to the restrictive approach revealed that none of the products accurately reported the salt, sugar, saturated fat, and trans fat content on the label. According to the EU tolerance guideline, approximately half of the products had protein (58%), fat (54%), and carbohydrate (42%) levels that fell within the EU tolerance limit. However, only around one-third of the samples had sugar (21%), salt (38%), and saturated fat (33%) levels that met the EU tolerance limit. In terms of healthiness analysis, according to the HSR, the range of stars was between 0.5 and 2.5 of the foods where fried peas got the highest rating (2.5 stars), while in terms of the UK traffic light system, none of the samples got all green signals. The lozenge got green lights for fat, SFA, and salt contents. It was also found that consumption of 100 g of fried peas or pulse would exceed the acceptable daily limit of salt, sugar, and SFA compared to the daily maximum allowable intake for the 2000 kcal diet recommended by the WHO. However, according to the serving size, biscuits were major contributors of TFA, sugar, and SFA, whereas fried pulse was a key contributor of sodium/salt. Proper regulatory actions should be introduced to promote healthy processed foods with user-friendly front-of-the-pack labeling and monitor their quality to prevent non-communicable diseases (NCDs).

Draft genome sequence of multidrug-resistant Escherichia coli MAHK_SCM_BAU_30A strain isolated from a subclinical mastitis cow in Bangladesh.

This study announces the sequence of a multidrug-resistant Escherichia coli MAHK_SCM_BAU_30A strain isolated from bovine subclinical mastitis milk in 2022 in Bangladesh. Our assembled genome had a length of 4,884,948 bp, three plasmids, two CRISPR arrays, five prophages, 51 predicted antibiotic resistance, and 72 predicted virulence factor genes.

Understanding the convergence of social enterprise, digital health, and citizen engagement for co-producing integrated Person-Centred health services: A critical review and theoretical framework.

INTRODUCTION: To achieve Universal Health Coverage and the United Nations' (UN) Sustainable Development Goals (SDGs) agenda for 2030, the World Health Organisation (WHO) recommended the use of social enterprise, digital technology, and citizen engagement in the delivery of Integrated People-Centred Health Services (IPCHS) as part of its strategic vision for 21st century primary care. METHODS: We conducted a hermeneutic review of frameworks, models and theories on social enterprise, digital health, citizen engagement and IPCHS. This involved multiple iterative cycles of (i) searching and acquisition, followed by (ii) critical analysis and interpretation of literature to assemble arguments and evidence for conceptual relationships until information saturation was reached. This process identified a set of constructs which we synthesised into a testable framework. RESULTS: Several interdisciplinary frameworks, models and theories explain how social enterprises could use digital technology, and citizen engagement to enable the technical and social integration required to facilitate people-centred primary care. Innovative approaches can be used to maintain financial sustainability while delivering IPCHS at lower cost to vulnerable and marginalised populations in both developed and developing countries. CONCLUSION: This framework provides a theoretical grounding to guide empirical inquiry into how social enterprises use digital technology to engage citizens in co-producing IPCHS.

[Double to avoid trouble? An experience of double Memokath(tm) 044TW stents insertion for multiple anterior urethral stricture in hospital universiti sains Malaysia].

For the past two decades urethral stenting became more popular for treatment of urethral stricture. However, urethral stents still not widely used in view of good outcome from urethroplasty surgery. The MemokathTM stent is the most popular in this field. It is manufactured from a biocompatible alloy of nickel and titanium. Most of the studies have been limited to single stent insertion, and no studies done for double stents insertion. An 81-year-old man with history of multiple anterior urethral strictures since 2013. He underwent internal urethrotomy in the same year but failed and was on urinary catheter since then. The MemokathTM 044TW was the option due to patient has multiple comorbidities. The micturating cystourethrogram (MCUG) and ascending urethrogram showed multiple anterior urethral strictures. He underwent direct visual internal urethrotomy and two MemokathTM stents inserted in the whole length of urethral. However, one year after procedure, he had recurrent lower urinary tract symptoms and ultimately developed acute urinary retention (AUR). Patients stents were removed endoscopically. During endoscopic removal, he had encrustation of both stents that causing obstructive symptoms. He is under our follow-up with no recurrent urinary retention or urosepsis with satisfactory uroflowmetry. Stent encrustation is known to be a common late complication of urethral stents. Stent encrustation should be suspected if patient comes with obstructive symptoms. Endoscopic is shown to be the best method to detect the cause of obstructed stent.

Dietary vitamin A intake and its major food sources among rural pregnant women of South-West Bangladesh.

The study aimed to estimate the dietary intake of vitamin A and its major food sources among rural pregnant women from the southwest region of Bangladesh. A multi-stage random cluster sampling method was used to select the respondents (N = 1012). A semi-structured questionnaire was used to collect the data, and statistical analysis was conducted using IBM SPSS 20.0. The mean age of the respondents was 23.27 ± 5.23 years, and the majority were in their second (48%) and third trimester (49%). The mean dietary intake of vitamin A was 392 ± 566 µg Retinol Activity Equivalent (RAE)/day (51% of Recommended Dietary Allowance). The contribution of ß-carotene (plant source) and retinol (animal source) in vitamin A intake was about 60% and 40%, respectively. The major ß-carotene contributing food groups were vegetables (dark and light) and tubers, and food items were colocasia, potato, beans, brinjal, and ripe tomatoes. On the other hand, the major retinol-contributing food groups were fish, eggs, and milk, and food items were small fish, Rui (carp) fish, and cow's milk. It was also observed that the consumption of food items from ß-carotene and retinol-contributing food groups did not differ significantly among the three groups of respondents, but the variations in the amount of the different food items consumed were significant. Dietary vitamin A intake is low among pregnant women in the South-West region of Bangladesh. Hence, they are at a greater risk of adverse materno-fetal health outcomes associated with vitamin A deficiency.

Identification of high-risk roadway segments for wrong-way driving crash using rare event modeling and data augmentation techniques.

Wrong-Way Driving (WWD) crashes are relatively rare but more likely to produce fatalities and severe injuries than other crashes. WWD crash segment prediction task is challenging due to its rare nature, and very few roadway segments experience WWD events. WWD crashes involve complex interactions among roadway geometry, vehicle, environment, and drivers, and the effect of these complex interactions is not always observable and measurable. This study applied two advanced Machine Learning (ML) models to overcome the imbalanced dataset problem and identified local and global factors contributing to WWD crash segments. Five years (2015-2019) of WWD crash data from Florida state were used in this study for WWD model development. The first modeling approach applied four different hybrid data augmentation techniques to the training dataset before applying the XGBoost classification algorithm. In the second model, a rare event modeling approach using the Autoencoder-based anomaly detection method was applied to the original data to identify WWD roadway segments. A third model was applied based on the statistical method to compare the performance of ML models in predicting the WWD segments. The performance comparison of the adopted models showed that the XGBoost model with the Adaptive Synthetic Sampling (ADASYN) method performed best in terms of precision and recall values compared to the autoencoder-based anomaly detection method. The best-performing model was used for the feature analysis with an interpretable machine-learning technique. The SHapley Additive exPlanations (SHAP) values showed that high-intensity developed land use, length of roadway, log of Annual Average Daily traffic (AADT), and lane width were positively associated with WWD roadway segments. The results of this study can be used to deploy WWD countermeasures effectively.

Application of Bayesian Space-Time interaction models for Deer-Vehicle crash hotspot identification.

The objective of this research was to identify and prioritize deer-vehicle crash (DVC) hotspots using five years of crash data. This study applied Bayesian spatiotemporal models for the identification of the DVC hotspots. The Bayesian spatiotemporal model allows to observe area-specific trends in the DVC data and highlights specific locations where DVC occurrence is deteriorating or improving over time. Census Tracts (CTs) were used as the geographic units to aggregate DVC, land use, and transportation infrastructure related data of Minnesota (MN) for the year 2015 to 2019. Several tests were conducted to evaluate the performance of the hotspot identification methods. The result showed that Type-I spatiotemporal interaction model (Model-2) outperforms other four space-time models in terms of predicting DVC frequency in CTs and hotspot identification performance test measures. Results showed that forest area, vegetation, and wetland percentages were positively associated with DVC frequency, whereas the percentage of developed land use was negatively associated with DVC frequency. The findings of this study suggest that the deer population plays an important role in DVCs, which indicates that deer population management is necessary to minimize the DVC risks. Using the final Type-I spatiotemporal interaction model, 65 "High-High" CTs were identified, where both the posterior mean of the decision parameter (potential for safety improvement) and the area-specific trend were higher. The distribution of the identified hotspots showed that the risk of DVCs was more in suburban areas with mixed land use conditions. These CTs represent high-risk zones, which need immediate safety improvement measures to reduce the DVC risks. As DVC can occur at any roadway segment location, DVC hotspots information is important for safety engineers and policymakers to implement area specific countermeasures.

Community health alliances as social enterprises that digitally engage citizens and integrate services: A case study in Southwestern Sydney (protocol).

South Western Sydney (SWS) is one of the fastest growing regions in the state of New South Wales (Australia). Much of the population live in local government areas (LGAs) with levels of disadvantage higher than the state average, with a predominance of non-communicable and chronic diseases that are typically associated with age-related and behavioural factors. This necessitates the management of social determinants of health through the integrated provision of primary and social care. The SWS Local Health District and Primary Health Network is exploring the potential of community health alliances (CHAs) as an innovative approach to support the provision of integrated health services. CHAs are a population health approach for addressing health challenges faced by people who share a common area of residence, sociocultural characteristic or health need, and are characterised by a shared mission, shared resource needs and acquiring/developing necessary organisational knowledge and skills. We explore how CHAs operate as social enterprises that utilise digital health and citizen engagement to deliver integrated people-centred health services (IPCHS) by conducting two case studies of CHAs operating in SWS: in Wollondilly and Fairfield LGAs. Using this approach, we aim to unpack the conceptual convergence that enables social enterprises to utilise digital health interventions and citizen engagement strategies to co-produce IPCHS with a view to developing theory and a framework for engaging digital citizens in integrated primary health care via social enterprise.

Kinetic Spinodal Instabilities in the Mott Transition in V_{2}O_{3}: Evidence from Hysteresis Scaling and Dissipative Phase Ordering.

We present the first systematic observation of scaling of thermal hysteresis with the temperature scanning rate around an abrupt thermodynamic transition in correlated electron systems. We show that the depth of supercooling and superheating in vanadium sesquioxide (V_{2}O_{3}) shifts with the temperature quench rates. The dynamic scaling exponent is close to the mean field prediction of 2/3. These observations, combined with the purely dissipative continuous ordering seen in "quench-and-hold" experiments, indicate departures from classical nucleation theory toward a barrier-free phase ordering associated with critical dynamics. Observation of critical-like features and scaling in a thermally induced abrupt phase transition suggests that the presence of a spinodal-like instability is not just an artifact of the mean field theories but can also exist in the transformation kinetics of real systems, surviving fluctuations.

Development of a mobile groundwater desalination system for communities in rural India.

The consumption of saline groundwater has contributed to a growing incidence of renal diseases, particularly in coastal communities of India. Although reverse osmosis (RO) is routinely used to remove salt from groundwater, conventional RO systems (i.e. centralized systems using spiral wound RO elements) have limited utility in these communities due to high capital and maintenances costs, and lack of infrastructure to distribute the water. Consequently, there is a need to develop an appropriate solution for groundwater treatment based on small-scale, mobile and community-led systems. In this work, we designed a mobile desalination system to provide a simple platform for water treatment and delivery of goods to rural communities. The system employs tubular RO membranes packed in a single, low-profile vessel which fits below the cargo space. The low-profile enables minimal intrusion on the space available for the transportation of goods. Pressure is delivered by a belt driven clutch pump, powered by the engine. Water is treated locally by connecting the intake to the village well while the vehicle idles. A combined numerical and experimental approach was used to optimise the module/system design, resulting in ∼20% permeate flux enhancement. Experimental results revealed that the system can produce 16 L per square meter of membrane area per hour (LMH) at a salinity level of 80 ppm from a ∼2000 ppm groundwater when it is feed at 1 m3/h at 8 bars. This indicates that a vehicle equipped with 12 m2 of tubular RO membranes can deliver 1 m3 of drinkable water by using ∼0.9 L of diesel. Assuming eight such systems could be implemented in a community to fulfil the water demands for a village with 2000 residents, a social business study revealed that a payback time of 2.5 years is achievable, even if the sale price of the water is relatively low, USD 0.18 (Rs 12, which is half of the lowest market price) per 20 L, including providing a goods transportation service at price of USD 5.25 (Rs 350) per 100 km.

In silico Identification of the Indispensable Quorum Sensing Proteins of Multidrug Resistant Proteus mirabilis.

Catheter-associated urinary tract infections (CAUTI) is an alarming hospital based disease with the increase of multidrug resistance (MDR) strains of Proteus mirabilis. Cases of long term hospitalized patients with multiple episodes of antibiotic treatments along with urinary tract obstruction and/or undergoing catheterization have been reported to be associated with CAUTI. The cases are complicated due to the opportunist approach of the pathogen having robust swimming and swarming capability. The latter giving rise to biofilms and probably inducible through autoinducers make the scenario quite complex. High prevalence of long-term hospital based CAUTI for patients along with moderate percentage of morbidity, cropping from ignorance about drug usage and failure to cure due to MDR, necessitates an immediate intervention strategy effective enough to combat the deadly disease. Several reports and reviews focus on revealing the important genes and proteins, essential to tackle CAUTI caused by P. mirabilis. Despite longitudinal countrywide studies and methodical strategies to circumvent the issues, effective means of unearthing the most indispensable proteins to target for therapeutic uses have been meager. Here, we report a strategic approach for identifying the most indispensable proteins from the genome of P. mirabilis strain HI4320, besides comparing the interactomes comprising the autoinducer-2 (AI-2) biosynthetic pathway along with other proteins involved in biofilm formation and responsible for virulence. Essentially, we have adopted a theoretical network model based approach to construct a set of small protein interaction networks (SPINs) along with the whole genome (GPIN) to computationally identify the crucial proteins involved in the phenomenon of quorum sensing (QS) and biofilm formation and thus, could be therapeutically targeted to fight out the MDR threats to antibiotics of P. mirabilis. Our approach utilizes the functional modularity coupled with k-core analysis and centrality scores of eigenvector as a measure to address the pressing issues.

A side-effect free method for identifying cancer drug targets.

Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

The "handedness" of language: Directional symmetry breaking of sign usage in words.

Language, which allows complex ideas to be communicated through symbolic sequences, is a characteristic feature of our species and manifested in a multitude of forms. Using large written corpora for many different languages and scripts, we show that the occurrence probability distributions of signs at the left and right ends of words have a distinct heterogeneous nature. Characterizing this asymmetry using quantitative inequality measures, viz. information entropy and the Gini index, we show that the beginning of a word is less restrictive in sign usage than the end. This property is not simply attributable to the use of common affixes as it is seen even when only word roots are considered. We use the existence of this asymmetry to infer the direction of writing in undeciphered inscriptions that agrees with the archaeological evidence. Unlike traditional investigations of phonotactic constraints which focus on language-specific patterns, our study reveals a property valid across languages and writing systems. As both language and writing are unique aspects of our species, this universal signature may reflect an innate feature of the human cognitive phenomenon.

Synthetic transcription elongation factors license transcription across repressive chromatin.

The release of paused RNA polymerase II into productive elongation is highly regulated, especially at genes that affect human development and disease. To exert control over this rate-limiting step, we designed sequence-specific synthetic transcription elongation factors (Syn-TEFs). These molecules are composed of programmable DNA-binding ligands flexibly tethered to a small molecule that engages the transcription elongation machinery. By limiting activity to targeted loci, Syn-TEFs convert constituent modules from broad-spectrum inhibitors of transcription into gene-specific stimulators. Here we present Syn-TEF1, a molecule that actively enables transcription across repressive GAA repeats that silence frataxin expression in Friedreich's ataxia, a terminal neurodegenerative disease with no effective therapy. The modular design of Syn-TEF1 defines a general framework for developing a class of molecules that license transcription elongation at targeted genomic loci.

Diagnostic Approach to Viral Acute Encephalitis Syndrome (AES) in Paediatric Age Group: A Study from New Delhi.

INTRODUCTION: Acute Encephalitis Syndrome has heralded the emergence of multiple virulent pathogens, which may result in severe morbidity and mortality. In India, encephalitis is not notified and there has been a dearth of analysis for trends in encephalitis death rates and causation. A downward trend has been observed in encephalitis deaths, due to 'known' causes, which can be largely explained by improvement in diagnostic, treatment, and prevention methods. There is still a very high proportion of encephalitis deaths in developing countries, where the aetiological diagnosis of the pathogen is not established and thus, lies the importance of monitoring encephalitis morbidity and mortality with a view to improve pathogen diagnosis and identify emerging infectious diseases. AIM: To formulate a diagnostic approach to viral acute encephalitis syndrome in paediatric age group. MATERIALS AND METHODS: A cross-sectional study including 50 paediatric patients, clinically diagnosed with acute encephalitis syndrome using WHO criteria was conducted. The CSF of all the patients was evaluated to diagnose the aetiology for viral pathogens. ELISA was used for diagnosing Japanese encephalitis and dengue encephalitis; and multiplex real time PCR was used for detecting HSV-1, HSV-2, Varicella zoster virus, Mumps virus, Enterovirus and Parechovirus. RESULTS: Confirmed diagnosis was established in 11 (22%) of 50 cases. A confirmed or probable viral agent of encephalitis was found in 7 (14%), bacterial agent was found in 2 (4%), non-infectious aetiology was found in 2 (4%). Fatal outcome was independently associated with patient age. CONCLUSION: Despite extensive testing, the aetiologies of more than three fourth of the cases remains elusive. Nevertheless the result from the present study may be useful for future design of early diagnosis and treatment of the disease. New strategies for pathogen identification and continued analysis of clinical features and case histories should help us improve our ability to diagnose, treat and prevent encephalitis.

Global eHealth, Social Business and Citizen Engagement: A Natural Convergence?

This paper draws on the vision, mission and experience with the WHO Collaborating Centre on eHealth (WHOCC-eHealth) and Yunus Social Business Health Hub (YSBHH) based at UNSW Australia, and the Asia electronic Health Information Network (AeHIN). Global eHealth aims to provide equitable access to ICT and health care, particularly to the poor, vulnerable and disadvantaged. Social business aims to solve social and economic problem. Its best known product is microcredit financial services for the poor which are small loans that enable them to "produce something, sell something, earn something to develop self-reliance and a life of dignity". Citizen engagement and community participation is integral to both constructs within the context of global partnerships for Integrated People-Centred Health Services (IPCHS) and Sustainable Development Goals (SDGs). The eHealth dimension is consumer heath informatics, social media, mHealth and the Internet of Things. The convergence is multidimensional, mutually beneficial and requires good governance and leadership.