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Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%–2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications. We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high‐throughput sequencing. We found no consistent group‐specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products. [ABSTRACT FROM AUTHOR]

Despite the considerable progress of in vivo neural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high dimensional functional connectivity measures to mechanistic models of network activity. We address this issue by investigating spike-field coupling (SFC) measurements, which quantify the synchronization between, on the one hand, the action potentials produced by neurons, and on the other hand mesoscopic "field" signals, reflecting subthreshold activities at possibly multiple recording sites. As the number of recording sites gets large, the amount of pairwise SFC measurements becomes overwhelmingly challenging to interpret. We develop Generalized Phase Locking Analysis (GPLA) as an interpretable dimensionality reduction of this multivariate SFC. GPLA describes the dominant coupling between field activity and neural ensembles across space and frequencies. We show that GPLA features are biophysically interpretable when used in conjunction with appropriate network models, such that we can identify the influence of underlying circuit properties on these features. We demonstrate the statistical benefits and interpretability of this approach in various computational models and Utah array recordings. The results suggest that GPLA, used jointly with biophysical modeling, can help uncover the contribution of recurrent microcircuits to the spatio-temporal dynamics observed in multi-channel experimental recordings. Author summary: Modern neural recording techniques give access to increasingly highly multivariate spike data, together with spatio-temporal activities of local field potentials reflecting integrative processes. We introduce GPLA as a generalized coupling measure between these point-process and continuous-time activities to help neuroscientists uncover the distributed organization of neural networks. We develop statistical analysis and modeling methodologies for this measure and demonstrate its interpretability in simulated and experimental multi-electrode recordings. [ABSTRACT FROM AUTHOR]

Since Middle East respiratory syndrome (MERS) was described in September 2012, over 90 cases have been reported worldwide, 70 from Saudi Arabia. The incidence of infection with the causative agent, [...]

Aim: Herpes simplex CNS infection is a rare but important cause of neurological disability. Long term outcomes after HSV CNS infection in Australia have not yet been fully described. We sought to provide a comprehensive review of HSV CNS infection in children using a retrospective 13‐year evaluation of statewide laboratory and clinical records and a parent survey conducted at least one year after the initial infection. Methods: All positive PCR HSV 1 and 2 results from cerebrospinal fluid (CSF) or brain tissue were obtained from Queensland pathology providers for children aged 0–16 years between 1 January 2005 and 31 December 2017. Clinical data were obtained from patient records and longer‐term outcomes via parent survey at least 1 year after initial infection. Results: Forty‐three children were identified over the 13‐year period, 17 (39.5%) neonates and 26 (60.4%) non‐neonates. The annual incidence for HSV CNS infection in Queensland children aged ≤16 years was 0.3/100 000 (95% confidence intervals (CIs): 0.2–0.4) with neonates at highest risk (incidence 2.5/100 000 live births, 95% CI: 1.5–3.9). HSV 1 was the predominant serotype in both neonates and non‐neonates (9/17, 52.9% neonates and 19/26, 73.1% non‐neonates). Seven (16.3%) children died, five (5/17, 29.4% neonates), directly attributable to HSV CNS infection (all neonates). Twenty‐five (58.1%) had neurological morbidity at discharge (9/17 neonates (52.9%) vs. 16/26 (61.5%) non‐neonates) and 20/27 (74.1%) reported long‐term neurological morbidity at follow‐up (5/9 neonates (55.6%) vs. 15/18 non‐neonates (83.3%)). Seven children (two neonates and four non‐neonates) with long‐term neurological sequelae had no neurological morbidity identified at discharge. Conclusion: Significant long‐term neurologic sequelae were seen in children with HSV CNS infection even in children with no neurological disability identified at discharge from hospital. Careful neurodevelopmental follow‐up of all children is recommended. [ABSTRACT FROM AUTHOR]

Children's vision screening children commonly uses optotype-based visual acuity or instrument-based methods measuring amblyogenic risk factors (ARFs). To compare the performance of the Spot Vision Screener (SVS) (PediaVision, Welch Allyn, NY) and a nurse-administered visual acuity screen (NVAS) in identifying ARFs and decreased visual acuity. A prospective, cross-sectional population-based study of preschool children in South-East Queensland, Australia. Eligible participants had both forms of screening by trained community nurses. All children with an abnormal result by either method as well as a cohort of randomly selected children who passed both assessments were assessed at a tertiary paediatric ophthalmology clinic. Over a 10 month period, 2237 children (mean age; 64.4 ± 4.0 months) were screened from 38 schools. 6.4% of children failed SVS and 8.3% failed NVAS (with 3.8% overlap, failing both). The positive predictive value (PPV) in identifying either ARFs and/or reduced VA for the SVS and NVAS was 70.4% (95% Confidence Interval (CI): 61.6%–78.2%) and 60.5% (95% CI: 52.6%–67.9%) respectively. Highest PPV to detect either ARFs and/or reduced VA was achieved by a 'hybrid' method by combining failed NVAS and failed SVS: 91.0% (95% CI: 82.4 to 96.3) but this would risk children with sight impairment being missed in the community. To our knowledge, this is the first population-based study providing detailed comparative measures of diagnostic accuracy for NVAS and SVS in preschool children. One in ten preschool children failed one or both screens. A number of children who required ophthalmic intervention were missed if only one screening method was utilized. [ABSTRACT FROM AUTHOR]

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) accounts for a high proportion of paediatric outpatient visits in Australia. Shared care by general practitioners (GPs) would deliver more timely care, closer to home, however GPs indicated the need for interprofessional training support. This study describes the use of Project ECHO®, a guided practice model, to support GPs with ADHD management, by connecting them virtually with an interprofessional team of paediatric specialists using a structured methodology. Methods: A retrospective pre/post-knowledge and self-efficacy survey across twentyseven aspects of ADHD management was administered, using a seven-point Likert scale. Results: Significant improvement (p < 0.001) in provider self-efficacy was demonstrated across all tested domains. Discussion: Use of the ECHO model™ by an interprofessional team of paediatric specialists achieved an increase in GP knowledge and self-efficacy in the local management of children and young people with complex healthcare needs. Learnings indicate viability to expand the application of the ECHO model™ to address fragmentation for other priority populations across the Australian healthcare and human service sector landscape. Conclusion: Use of the ECHO model™ to support and train GPs was successful. Integration of care was achieved through strengthened partnerships between content and context experts, and the ECHO model™'s case-based learning methodology. [ABSTRACT FROM AUTHOR]

Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these [...]

Viral hemorrhagic fevers are associated with high rates of illness and death. Although therapeutic options are limited, early differential diagnosis has implications for containment and may aid in clinical management. [...]

Naturally emerging and deliberately released pathogens demand new detection strategies to allow early recognition and containment. We describe a diagnostic system for rapid, sensitive, multiplex discrimination of microbial gene sequences [...]

Assay sensitivity can be a limiting factor in the use of PCR as a tool for the detection of tick-borne pathogens in blood. We evaluated the performance of Tick-borne disease Capture Sequencing Assay (TBDCapSeq), a capture sequencing assay targeting tick-borne agents, to test 158 whole blood specimens obtained from the Lyme Disease Biobank. These included samples from 98 individuals with signs and symptoms of acute Lyme disease, 25 healthy individuals residing in Lyme disease endemic areas, and 35 samples collected from patients admitted to the Massachusetts General Hospital or referred to the infectious disease clinic. Compared to PCR, TBDCapSeq had better sensitivity and could identify infections with a wider range of tick-borne agents. TBDCapSeq identified a higher rate of samples positive for Borrelia burgdorferi (8 vs. 1 by PCR) and Babesia microti (26 vs. 15 by PCR). TBDCapSeq also identified previously unknown infections with Borrelia miyamotoi , Ehrlichia , and Rickettsia species. Overall, TBDCapSeq identified a pathogen in 43 samples vs. 23 using PCR, with four co-infections detected versus zero by PCR. We conclude that capture sequencing enables superior detection of tick-borne agents relative to PCR. [ABSTRACT FROM AUTHOR]

Background: Obstetricians and gynaecologists (O&Gs) are at a risk of work‐related musculoskeletal injuries (WRMI) on a daily basis. Aims: To describe the prevalence of WRMI among O&Gs in Australia and New Zealand, explore risk factors for such injuries, and evaluate their impact. Methods: An online survey of Fellows of Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted in July 2016. It comprised questions on personal attributes, type of work, site and cause of WRMI, if any and treatment required. Results: We received responses from 765 O&Gs giving a response rate of 38.3% (765/1997). Four hundred and ten specialists (53.6%) reported suffering a WRMI at some point, including 252 (32.9%) who reported multiple injuries. In multivariable analysis, females had increased risk of WRMI (odds ratio (OR): 2.12; 95% CI: 1.54–2.91) and among generalists and subspecialists, gynaecological oncologists had highest risk for WRMI (OR: 3.13; 95% CI: 1.21–8.14). Commonest sites of injury were back (218/633, 34.4%) and shoulder (131/633, 20.7%). Laparoscopic surgery (117/633, 18.5%) was the commonest cause of injury. Treatment was required for 88.6% of injuries (561/633) including 8.4% (53/633) of cases which required surgery. Ongoing symptoms post‐injury were reported for 52.1% of injuries (330/633) and in 25.8% (163/633) of instances the practitioner needed to modify their scope of work. Conclusion: This survey among a large cohort of O&Gs shows a high prevalence of WRMI with a profound negative impact on the practitioner and profession. There is a pressing need to advocate for improved ergonomics in their workplaces. [ABSTRACT FROM AUTHOR]

Abstract Background We performed a longitudinal study of viral etiology in samples collected in New York City during May 2009 to May 2010 from outpatients with fever or respiratory disease symptoms in the context of a pilot respiratory virus surveillance system. Methods Samples were assessed for the presence of 13 viruses, including influenza A virus, by MassTag PCR. Results At least one virus was detected in 52% of 940 samples analyzed, with 3% showing co-infections. The most frequently detected agents were rhinoviruses and influenza A, all representing the 2009 pandemic H1N1 strain. The incidence of influenza H1N1-positive samples was highest in late spring 2009, followed by a decline in summer and early fall, when rhinovirus infections became predominant before H1N1 reemerged in winter. Our study also identified a focal outbreak of enterovirus 68 in the early fall of 2009. Conclusion MassTag multiplex PCR affords opportunities to track the epidemiology of infectious diseases and may guide clinicians and public health practitioners in influenza-like illness and outbreak management. Nonetheless, a substantial proportion of influenza-like illness remains unexplained underscoring the need for additional platforms.

The objective of this research is to explore the feasibility of factorial design in designing a novel ethosomal carrier based on Phosphatidyl choline and ethanol for skin application of curcumin in antifungal treatment. In dermal application the curcumin has many applications such as, anticancer, antioxidant, antiviral, antitumoral, and antimicrobial activities. When taken orally curcumin suffers from various problems such as its low bioavailability and less solubility in different mediums. so our research focuses on finding an alternative approach for the better therapeutic response of curcumin. We have decided to formulate ethanol based vesicular systems like ethosome for effectual skin delivery. During the formualation various variables effects the formulation of vesicles. Therefore a 32 factorial design was utilized for selecting the variable levels and for obtaining the desired responses from the experimental trial. During optimization two factors were characterized each at three different levels (low, medium and high) and experimental runs were performed on designed nine combinations using the Design-Expert® software (Version 12.0.0, Stat-Ease Inc., Minneapolis, USA). Cold method is used for preparation of ethosomes and charterized through vesicle size analysis, percent drug entrapment efficiency and zeta potential by experimental design. After optimization formulation of ethosome was carried by using 2 % w/v Phospatidylcholine and 47.97 % Ethanol. The planned drug loaded ethosomes demonstrate a vesicle size of 148.278 nm and entrappment capability of 94.36% Experimental results suggests that the ethosomes could be an competent system for skin delivery of curcumin in the treatment of fungal infections. [ABSTRACT FROM AUTHOR]

Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. The aim of the present study was to investigate the potential of transfersomal gel formulations for transdermal delivery of amphotericin B and to evaluate the effect of lipid concentration, ethanol concentration, drug concentration and stirrer time. Characterization of transfersomes was performed by vesicle size, surface charge, entrapment efficiency and stability study. Characterization of transfersomes containing gel performed by the measurement of viscosity, pH measurements, drug content, extrudability study, spreadability and in vitro drug diffusion study. It was found that viscosity of prepared gel TG-12 was 3350cps, % assay was 99.45±0.45, extrudability was 147g and spreadibility (g.cm/sec) was found that 13.25(g.cm/sec) respectively. In vitro drug release from transfersomes gel was carried out using Franz diffusion cell method and found 92.23% in 12 hr. In first 30 min it was 23.36 % drug release which slightly high. It was due to the release of free drug present in bag after leaching from transfersomes. Drug release from transferosomal gel formulation was found in very sustained and controlled manner. The prepared gel containing amphotericin B-loaded transfersomal formulation was optimized and can be use for topical preparation for its antifungal affect. The results were obtained which showed that transfersomal gel was a promising candidate for transdermal delivery with targeted and prolonged release of a drug. It also enhances skin permeation of many drugs. [ABSTRACT FROM AUTHOR]

In this issue of Neuron , Watakabe et al. 1 utilize serial two-photon tomography to reveal that the intra- and inter-regional prefrontal cortex projections in the marmoset brain terminate with two characteristic patterns, columnar and diffused, both of which display a topographically organized gradient. In this issue of Neuron , Watakabe et al. utilize serial two-photon tomography to reveal that the intra- and inter-regional prefrontal cortex projections in the marmoset brain terminate with two characteristic patterns, columnar and diffused, both of which display a topographically organized gradient. [ABSTRACT FROM AUTHOR]

Fast dissolving dosage forms are gaining popularity in recent time, as this dosage forms requires no water for administration. Oral films dissolve rapidly along with drug in mouth and majority of the drug is absorbed through buccal/oral mucosa in to systemic circulation avoiding first pass metabolism. Trazodone Hydrochloride (TRZ), an serotonin reuptake inhibitor antidepressant. TRZ undergoes first pass metabolism on oral administration resulting in reduced bioavailability (60%). Thus the objective of the present study was to formulate and evaluate fast dissolving oral films of TRZ to overcome the limitation of bioavailability and increase patient’s compliance. In the present study oral films were prepared by solvent casting method using HPMC K15 as a film formers and PEG 400, glycerine as plasticizers and evaluated for mechanical properties, disintegration and in vitro dissolution. All formulations showed good mechanical properties and in vitro drug release. The optimized (F5) Formulation (HPMC K15, CCS and PEG 400) Exhibited drug release of 92.12% in 15 minutes which was significantly high when compared to other formulation. [ABSTRACT FROM AUTHOR]

Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but rather suppress gastric acid secretion by specific inhibition of the (H+,K+)-ATPase enzyme system at the secretary surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the parietal cell, lansoprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus. The aim of the present study was to develop lansoprazole loaded thiolated chitosan microspheres were prepared by emulsifying method using liquid paraffin light and heavy in ratio of 50:50 as a dispersing medium and glutaraldehyde used as a cross-linking agent. The prepared microspheres were evaluated for mean particle size and particle size distribution, drug content, mucoadhesion measurement and in-vitro drug release. FT-IR spectroscopic analysis was performed to ascertain drug polymer interaction. The release profiles showed first order release behavior up to 12 hours where the highest drug release was 88.89 % of the lansoprazole loaded in the thiolated chitosan microspheres, indicating a strong crosslinking between chitosan and glutaraldehyde. From the results of the present investigation it may be concluded that drug loaded chitosan microspheres can be prepared by a simple technique which avoids the use of complex apparatus and special precautions. [ABSTRACT FROM AUTHOR]

Microemulsions (MEs) are clear, thermodynamically stable systems. They were used to solubilise drugs and to improve topical drug availability. Salicylic acid (SA) is a keratolytic agent used in topical products with antimicrobial actions. This study aimed to formulate an optimized SA micro emulsion gel for the slow, variable and incomplete oral drug absorption in patient suffering from psoriasis infection. The dispersion solubility of SA was studied in various oils, surfactants and co-surfactants and by constructing pseudo phase ternary diagram, micro emulsion area was identified. The optimized formulations of micro emulsion were subjected to thermodynamic stability tests. After stability study, stable formulation was characterized for droplet size, pH determination, centrifugation, % drug content in micro emulsion, zeta Potential and vesicle size measurement and then micro emulsion gel were prepared and characterized for spreadability, measurement of viscosity, drug content, In-vitro diffusion, in-vitro release data. Labrasol was selected as surfactant, plurol oleique as co surfactant and neem oil as oil component based on solubility study. The optimized formulation contained SA 0.05 (%w/w), labrasol (24%), plurol oleique (8 %) and neem oil (8%). The in vitro drug release from SA micro emulsion gel was found to be considerably higher in comparison to that of the pure drug. The in-vitro diffusion of micro emulsion gel was significantly good. Based on this study, it can be concluded the solubility and permeability of SA can be increased by formulating into micro emulsion gel. [ABSTRACT FROM AUTHOR]

Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae. [ABSTRACT FROM AUTHOR]

Access of sensory information to consciousness has been linked to the ignition of content-specific representations in association cortices. How does ignition interact with intrinsic cortical state fluctuations to give rise to conscious perception? We addressed this question in the prefrontal cortex (PFC) by combining multi-electrode recordings with a binocular rivalry (BR) paradigm inducing spontaneously driven changes in the content of consciousness, inferred from the reflexive optokinetic nystagmus (OKN) pattern. We find that fluctuations between low-frequency (LF, 1–9 Hz) and beta (∼20–40 Hz) local field potentials (LFPs) reflect competition between spontaneous updates and stability of conscious contents, respectively. Both LF and beta events were locally modulated. The phase of the former locked differentially to the competing populations just before a spontaneous transition while the latter synchronized the neuronal ensemble coding the consciously perceived content. These results suggest that prefrontal state fluctuations gate conscious perception by mediating internal states that facilitate perceptual update and stability. • vlPFC recordings during visual rivalry reveal frontal dynamics of conscious access • Update and stability of conscious content in a tug of war between distinct LFP bands • Changes in the encoding of conscious contents follow an increase in 1–9 Hz activity • Content-agnostic prefrontal fluctuations gate sensory access to consciousness Mesoscale ensemble recordings in the vlPFC during no-report binocular rivalry show that stochastic prefrontal state fluctuations are associated with spontaneous changes in the content of consciousness. Transitions from beta band to low-frequency field activity precede both spontaneous changes in perception and encoding of the contents of consciousness by competing neuronal ensembles. Temporal dynamics of prefrontal state fluctuations during awake resting state mimic the temporal dynamics of binocular rivalry, suggesting a causal role in perceptual multistability. [ABSTRACT FROM AUTHOR]

Today, there is lots of information available over the Internet but it's very difficult to filter out the required information from this overload of information. Thus a solution to this problem, came as "Recommender Systems", they can predict outcomes according to user's interests. Although Recommender Systems are very effective and useful for users but the mostly used type of Recommender System i.e. Collaborative Filtering Recommender System suffers from shilling/profile injection attacks in which fake profiles are inserted into the database in order to bias its output. This paper is aimed at discussing various attacks that can affect Recommender Systems and the attributes that are used for the detection of these attacks. [ABSTRACT FROM AUTHOR]

The Mapputta group comprises antigenically related viruses indigenous to Australia and Papua New Guinea that are included in the family Bunyaviridae but not currently assigned to a specific genus. We determined and analyzed the genome sequences of five Australian viruses isolated from mosquitoes collected during routine arbovirus surveillance in Western Australia (K10441, SW27571, K13190, and K42904) and New South Wales (12005). Based on matching sequences of all three genome segments to prototype MRM3630 of Trubanaman virus (TRUV), NB6057 of Gan Gan virus (GGV), and MK7532 of Maprik virus (MPKV), isolates K13190 and SW27571 were identified as TRUV, 12005 as GGV, and K42904 as a Mapputta group virus from Western Australia linking GGV and MPKV. The results confirmed serum neutralization data that had linked SW27571 to TRUV. The fifth virus, K10441 from Willare, was most closely related to Batai orthobunyavirus, presumably representing an Australian variant of the virus. Phylogenetic analysis also confirmed the close relationship of our TRUV and GGV isolates to two other recently described Australian viruses, Murrumbidgee virus and Salt Ash virus, respectively. Our findings indicate that TRUV has a wide circulation throughout the Australian continent, demonstrating for the first time its presence in Western Australia. Similarly, the presence of a virus related to GGV, which had been linked to human disease and previously known only from the Australian southeast, was demonstrated in Western Australia. Finally, a Batai virus isolate was identified in Western Australia. The expanding availability of genomic sequence for novel Australian bunyavirus variants supports the identification of suitably conserved or diverse primer-binding target regions to establish group-wide as well as virus-specific nucleic acid tests in support of specific diagnostic and surveillance efforts throughout Australasia. [ABSTRACT FROM AUTHOR]