Search

Onchocerciasis and lymphatic filariasis are targeted for elimination, primarily using mass drug administration at the country and community levels. Elimination of transmission is the onchocerciasis target and global elimination as a public health problem is the end point for lymphatic filariasis. Where program duration, treatment coverage, and compliance are sufficiently high, elimination is achievable for both parasites within defined geographic areas. However, transmission has re-emerged after apparent elimination in some areas, and in others has continued despite years of mass drug treatment. A critical question is whether this re-emergence and/or persistence of transmission is due to persistence of local parasites—i.e., the result of insufficient duration or drug coverage, poor parasite response to the drugs, or inadequate methods of assessment and/or criteria for determining when to stop treatment—or due to re-introduction of parasites via human or vector movement from another endemic area. We review recent genetics-based research exploring these questions in Onchocerca volvulus, the filarial nematode that causes onchocerciasis, and Wuchereria bancrofti, the major pathogen for lymphatic filariasis. We focus in particular on the combination of genomic epidemiology and genome-wide associations to delineate transmission zones and distinguish between local and introduced parasites as the source of resurgence or continuing transmission, and to identify genetic markers associated with parasite response to chemotherapy. Our ultimate goal is to assist elimination efforts by developing easy-to-use tools that incorporate genetic information about transmission and drug response for more effective mass drug distribution, surveillance strategies, and decisions on when to stop interventions to improve sustainability of elimination.

Study Design Systematic review and meta-analysis Objectives The present review aimed to summarize the evidence regarding differences in proprioception between children with and without adolescent idiopathic scoliosis (AIS). Methods Seven electronic databases were searched from their inception to April 10, 2021. Articles were included if they involved: (1) AIS patients aged between 10 and 18 years, (2) measurements of proprioceptive abilities, and (3) comparisons with non-AIS controls. Animal studies, case reports, commentaries, conference proceedings, research protocols, and reviews were excluded. Two reviewers independently conducted literature screening, data extraction, risks of bias assessments, and quality of evidence evaluations. Relevant information was pooled for meta-analyses. Results From 432 identified citations, 11 case-control studies comprising 1121 participants were included. The meta-analyses showed that AIS participants displayed proprioceptive deficits as compared to non-AIS controls. Moderate evidence supported that AIS participants showed significantly larger repositioning errors than healthy controls (pooled mean difference = 1.27 degrees, P < .01). Low evidence substantiated that AIS participants had significantly greater motion detection threshold (pooled mean difference = 1.60 degrees, P < .01) and abnormal somatosensory evoked potentials (pooled mean difference = .36 milliseconds, P = .01) than non-AIS counterparts. Conclusions Consistent findings revealed that proprioceptive deficits occurred in AIS patients. Further investigations on the causal relationship between AIS and proprioception, and the identification of the subgroup of AIS patients with proprioceptive deficit are needed.

To investigate the relation between subjectively and objectively assessed cognitive and physical functioning among community-dwelling stroke survivors, and to examine the association of stroke severity with subjectively and objectively assessed cognitive and physical impairments.Secondary data analysis was conducted with 127 community-dwelling stroke survivors. For cognitive functioning, objective measures included the NIH Toolbox Cognition Battery and the Executive Function Performance Test; subjective measures included the Quality of Life in Neurological Disorders Applied Cognition. Objective and subjective physical functioning was measured by the NIH Toolbox 2-Minute Walk Test and the Patient-Reported Outcomes Measurement Information System Physical Function, respectively.A positive correlation was observed between subjective and objective physical functioning, whereas the correlation between subjective and objective cognitive functioning was nonsignificant. Stroke severity was associated with objective cognitive impairment and objective and subjective physical impairment, but not subjective cognitive impairment.The lack of association between objective and subjective cognitive functioning challenges the conventional assumption that perceived functioning reflects actual performance. We recommend using both objective and subjective measures to accurately identify cognitive and physical impairment following stroke.Implications for RehabilitationSubjective cognitive functioning is not associated with objective cognitive functioning, suggesting that solely relying on stroke patients' reports is inadequate and may inaccurately estimate patients' actual deficits.Both objective and subjective measures should be used to accurately identify cognitive and physical impairment following stroke.Practitioners should be cognizant of stroke patients' behavioral signs associated with underlying cognitive problems that warrant further evaluation.

Background Currently, there is limited data on long-term persistence of antibodies and boostability of intradermal (ID) rabies pre-exposure prophylaxis (PrEP) schedules. This study investigated travellers who received a primary ID PrEP schedule at least 5 years previously to determine the persistence of antibodies and subsequent antibody response after one 0.1-ml ID booster dose. Methods Adults (age ≥ 18 years) who had previously received ID PrEP at a specialist travel medicine clinic in Brisbane, Australia were included. At Day 0, blood was collected for serology and one dose of 0.1-ml ID rabies vaccine (Verorab®) was administered. At Day 7, serology was repeated. At Day 14, participants were given results and enquired if they experienced adverse events following immunization (AEFIs). Antibodies were measured using Platelia Rabies II ELISA; levels ≥0.5 EU/mL were considered antibody-positive. Results 158 participants were included [64.6% female, median age at enrolment 56.4 years, interquartile range (IQR) 42.4–65.2 years], and median time since the primary ID PrEP was 8.5 years (IQR 6.9–11.7 years). The majority of participants (82.3%) were antibody-positive at Day 0. The proportion of participants who were antibody-positive at Day 0 was higher among those who were younger at primary vaccination (87.0% if aged Conclusions Rabies antibodies persist for many years after ID PrEP and can be rapidly boosted with a single ID dose. Future studies are needed to confirm that ID PrEP primes the immune system sufficiently so that boosters are not routinely needed, and only given in the event of a rabies-prone exposure.

Squamous metaplasia is not uncommonly observed in salivary gland neoplasms, including pleomorphic adenomas (PAs). It poses as a diagnostic pitfall with cytomorphologic features overlapping with low-grade epithelial malignances and carcinoma ex-PA. We report series of aspirates of PAs with squamous metaplasia and review the literature for the clinicopathological and cytologic features of this diagnostically challenging entity.Three cases including index aspiration cytology, post-aspiration specimen cytology, cell block immunohistochemistry (IHC), histologic correlation, and clinical data were reviewed. Literature search was performed for cases of PAs with squamous metaplasia, yielding 22 case reports including 11 with aspiration cytology performed.Metaplastic squamous components were seen in all index aspirations, but foreign body reaction and cystic changes were observed only after aspiration or in irritated lesions. PLAG1 IHC demonstrated reliable immunoreactivity in cell block preparations. Summarizing cases in this series and in the literature, cytologic features reported were variable and no consistent diagnostic feature was identified. Most reported cases were initially diagnosed as suspicious or malignant, but all ran a benign clinical course. Significant morbidity was reported only in one case due extensive surgery based on a malignant diagnosis.Squamous metaplasia in PAs is not associated with adverse outcomes, but may induce reactive changes upon aspiration/irritation, resulting in worrisome cytologic features. PLAG1 IHC is a useful adjunct when characteristic cytologic features for PAs are absent or obscured. Prudent use of the diagnostic category salivary gland neoplasm of uncertain malignant potential (SUMP) in the Milan system can avoid overtreatment.

Background The COVID-19 pandemic has forced rapid digital transformation of many health systems. These innovations are now entering the literature, but there is little focus on the resulting disruption. Objective We describe the implementation of digital innovations during the COVID-19 response of Australia's largest health service, Metro North (in Brisbane, Queensland), the challenges of the subsequent digital disruption, how these were managed, and lessons learned. Methods Prior to the COVID-19 pandemic, the Australian state of Queensland created the Queensland Digital Clinical Charter, which provides guidance for the development of digital health programs. The guidelines utilize three horizons: digitizing workflows, leveraging digital data to transform clinical care, and reimagining new and innovative models of care. The technical response to COVID-19 in Metro North is described across these horizons. The rapid digital response caused significant disruption to health care delivery; management of the disruption and the outcomes are detailed. This is a participatory action research project, with members of the research team assisting with leading the implementation project informing the case report content. Results Several digital innovations were introduced across Metro North during the COVID-19 response. This resulted in significant disruption creating digital hypervigilance, digital deceleration, data discordance, and postdigital “depression.” Successful management of the digital disruption minimized the negative effects of rapid digital transformation, and contributed to the effective management of the pandemic in Queensland. Conclusion The rapid digital transformation in Metro North during COVID-19 was successful in several aspects; however, ongoing challenges remain. These include the need to improve data sharing and increase interoperability. Importantly, the innovations need to be evaluated to ensure that Metro North can capitalize on these changes and incorporate them into long-term routine practice. Moving forward, it will be essential to manage not only the pandemic, but increasingly, the resultant digital disruption.

Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted 7 rounds of mass drug administration (MDA) between 2000 and 2006. The territory passed transmission assessment surveys (TASs) in 2011 (TAS-1) and 2015 (TAS-2). In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Abs) may have provided a timelier indication of LF resurgence in American Samoa.We examined school-level antigen (Ag) and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, and Bm33 Ags at each TAS. Pearson chi-square test and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3.Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% confidence interval [CI] 1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33, or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5).Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in surveillance after MDA and decision making should be further investigated in other settings.

Sex steroid hormones have been implicated as disease modifiers in the neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Androgens, signalling

Light pollution in recent years has drawn surging public concerns in Hong Kong. The improper management of the light sources causes pollution, particularly light trespass on the community level, which obstructs the residents. Yet more studies are expected to quantitatively and systematically assess the severity of the artificial light trespass problem, and to offer practical solutions for mitigation and urban management. This study was conducted on a typical high-density, mixed-use neighbourhood in Tsim Sha Tsui district. The study consists of on-site measurement and model simulation. Three illuminance measurements were conducted to evaluate the impact of light pollution on the streets and light trespass on the nearby buildings. It was found that the impacts on the buildings (mean illuminance of 3 lx) are less significant than on the streets (mean illuminance of 188 lx) for the target study area. Indoor measurement at various height levels showed a mean illuminance level of 0.6 lx, which is much lower than the international limit of 25 lx. Meanwhile, the modelling work, consisting of correlation, verification and regression analysis, was carried to bridge luminous flux from light sources and illuminance received at the target. A three-dimensional (3D) model was developed to mimic the actual situation and was used to identify the primary light sources causing impacts. While a growing number of research is found on measuring and modelling the intricate light pollution in such a micro scale that elevates explicitly the importance of extrapolating the light pollution effect vertically from street level to building level, direct simulation is still lacking. This study also refined and summarised the research methodology to serve as a feasible and organised protocol for setting up the measurement and modelling work. This can be adapted in future assessments on light trespass issues under similar circumstances elsewhere, like scientific research, urban planning, or property development projects.

Stabilising piles have been proven as an effective slope stabilization approach. This study aims to investigate the optimal location of stabilising pile for an embankment slope with a surcharge loading at crest. A series of finite element analyses were performed to determine the optimal location of the pile with considerations of varying slope gradients. An additional analysis was performed to compare the factor of safety computed from the present 2D analysis with the previous 3D analysis. The results showed that the introduction of the stabilising pile could effectively minimise the deformed soil mass and slip surface, with the greatest improvement recorded for the embankment of 1.5V:1H gradient. The optimal pile location was found to be at the middle of the slope. The pile influence zone (Wpile ) obtained from the present numerical study showed reasonably good agreement with previous results of centrifuge experiments. Based on the comparison of factor of safety computed from the present 2D analysis with a previous 3D analysis, the 2D analysis generally yielded a more conservative FOS (about 20% lower) than the more rigorous 3D analysis because of the absence of soil arching effect. As conclusions, it is recommended to install piles at the middle of slope to yield the most favourable slope stabilization effect. A simple 2D analysis can be used to analyse the problem of pile stabilised embankment with a slightly more conservative FOS was expected than the rigorous 3D analysis.

Lymphatic filariasis (LF) is a major public health problem globally and in the Pacific Region. The Global Programme to Eliminate LF has made great progress but LF is persistent and resurgent in some Pacific countries and territories. Samoa remains endemic for LF despite elimination efforts through multiple two-drug mass drug administrations (MDA) since 1965, including renewed elimination efforts started in 1999 under the Pacific Programme for Elimination of LF (PacELF). Despite eight rounds of national and two rounds of subnational MDA under PacELF, Samoa failed transmission assessment surveys (TAS) in all three evaluation units in 2017. In 2018, Samoa was the first to distribute countrywide triple-drug MDA using ivermectin, diethylcarbamazine (DEC), and albendazole. This paper provides a review of MDAs and historical survey results from 1998 to 2017 in Samoa and highlights lessons learnt from LF elimination efforts, including challenges and potential ways to overcome them to successfully achieve elimination.

Background: Adolescent idiopathic scoliosis (AIS) patients have lower physical activity levels than normal adolescents, and there is an association with poorer bone and muscle health. This study evaluated the effects of a home-based exercise intervention (E-Fit) on bone mineral density (BMD), muscle function, and quality of life (QoL) in AIS-affected girls. Methods: A total of 40 AIS females aged 11 to 14 years were randomly assigned to the E-Fit or control group. The E-Fit group performed modified 7-min high-intensity interval training (HIIT) 5 days per week for 6 months. Outcome measures including BMD using dual-energy X-ray absorptiometry (DXA), muscle strength and endurance tests, physical activity levels, and QoL using self-reported questionnaires were assessed at baseline and at 6-month and 12-month follow-up. Results: In total, 14 patients in the E-Fit and 16 in the control group completed the study. The E-Fit group showed a marginally significant interaction effect in the whole body areal BMD at the 6- (p = 0.096) and 12-month follow-ups (p = 0.085). The left arm lean mass in the E-Fit group showed a statistically significant interaction effect between the 6- and 12-month follow-ups (p = 0.046). The E-Fit group showed improvements in physical activity participation, as measured by the Modified Baecke Questionnaire (MBQ), with a significant interaction effect in work index (p = 0.043), sport index (p = 0.050), and total score (p = 0.016) from baseline to the 12-month follow-up. Improvement on self-image were noted in E-Fit group across time. Conclusions: The present results provided some evidence to support the positive benefits of E-Fit for bone health and muscle function in AIS girls.

Global movement of people plays a key role in the spread of antimicrobial resistant (AMR) organisms. We found that 58% of Australian travellers returning from Asia were asymptomatic carriers of AMR Escherichia coli, including resistance to critically important antibiotics. Future studies are needed to identify interventions for travellers to reduce their risk of AMR acquisition.

IntroductionThe increase in international travel brought about by globalisation has enabled the rapid spread of emerging pathogens with epidemic and pandemic potential. While travel connectivity-based assessments may help understand patterns of travel network-mediated epidemics, such approaches are rarely carried out in sufficient detail for Oceania where air travel is the dominant method of transportation between countries.DesignTravel data from the Australian Bureau of Statistics, Stats NZ and the United Nations World Tourism Organization websites were used to calculate travel volumes in 2018 within Oceania and between Oceania and the rest of the world. The Infectious Disease Vulnerability Index (IDVI) was incorporated into the analysis as an indicator of each country’s capacity to contain an outbreak. Travel networks were developed to assess the spread of infectious diseases (1) into and from Oceania, (2) within Oceania and (3) between each of the Pacific Island Countries and Territories (PICTs) and their most connected countries.ResultsOceania was highly connected to countries in Asia, Europe and North America. Australia, New Zealand and several PICTs were highly connected to the USA and the UK (least vulnerable countries for outbreaks based on the IDVI), and to China (intermediate low vulnerable country). High variability was also observed between the PICTs in the geographical distribution of their international connections. The PICTs with the highest number of international connections were Fiji, French Polynesia, Guam and Papua New Guinea.ConclusionTravel connectivity assessments may help to accurately stratify the risk of infectious disease importation and outbreaks in countries depending on disease transmission in other parts of the world. This information is essential to track future requirements for scaling up and targeting outbreak surveillance and control strategies in Oceania.

Various phenomena of life are typically explained by the physical sciences. Although the biological structures of a living being are subject to physical laws, we suggest that life, information, and...

The coded aperture snapshot spectral imager (CASSI) is a computational imaging system that acquires a three dimensional (3D) spectral data cube by a single or a few two dimensional (2D) measurements. The 3D data cube is reconstructed computationally. Binary on-off random coded apertures with square pixels are primarily implemented in CASSI systems to modulate the spectral images in the image plane. The design and optimization of coded apertures have been shown to improve the imaging performance of these systems significantly. This work proposes a different approach to code design. Instead of traditional squared tiled coded elements, hexagonal tiled elements are used. The dislocation between the binary hexagonal coded apertures and the squared detector pixels is shown to introduce an equivalent grey-scale spatial modulation that increases the degrees of freedom in the sensing matrix, thus further improving the spectral imaging performance. Based on the restricted isometry property (RIP) of compressive sensing theory, this article derives optimal coded aperture patterns under a hexagonal lattice which obey blue noise spatial characteristics, where “on” elements are placed as far from each other as possible. In addition, optimal coded apertures used in different snapshots are complementary to each other. The superiority of hexagonal blue noise coded apertures over the traditional coded apertures with squared tiled elements is shown.

The current study investigated the cognitive and neural substrates that underpin writing ability. We explored similarities and differences in writing numbers and words and compared these to language and manual actions in a large group of sub-acute, stroke patients (n = 740). The behavioral data showed association and dissociation in the ability to write words and numbers. Comorbidities of writing deficits with both language and motor impairments were prevalent, with less than a handful showing deficits restricted to the writing tasks. A second analysis with a subset of patients (n = 267) explored the neural networks that mediate writing abilities. Lesion to right temporal contributed to writing words, while lesions to left postcentral contributed to writing numbers. Overlapping neural mechanisms included the bilateral prefrontal cortex, right inferior parietal, left middle occipital and the right cerebellum. With the former regions associated with error pattern typical to writing based on prior knowledge (the lexical route), while lesion to left MOG was associated with errors to the phonological (non-lexical) route. Using principle components extracted from the behavioral data, we showed that right prefrontal and right parietal contributed to the ability to use pen, while lesion to bilateral prefrontal, inferior temporal and cerebellum supported unique use of pen for writing. The behavioral and imaging data suggested that writing numbers and words primarily relied on overlapping cognitive and neural functions. Incidents of pure writing deficits, in the absence of motor or language deficits were rare. Nevertheless, the PCA and neural data suggested that writing abilities were associated with some unique neuro-cognitive functions, specifically dedicated to the use of pen and the ability to transform meaning to motor command.

In this work, the effective electro-elastic properties of piezoelectric composites are computed using the Maxwell homogenization method (MHM). The composites are made by several families of spheroidal inhomogeneities embedded in a homogeneous infinite medium (matrix). Each family of spheroidal inhomogeneities is made of the same material, and all the inhomogeneities have identical size and shape and are randomly oriented. The inhomogeneities and matrix materials exhibit piezoelectric transversely isotropic symmetry. It is shown that the shape of the “effective inclusion” substantially affects the effective piezoelectric properties. A new and simple form to calculate the aspect ratio of effective inclusion is presented. The effect on the overall piezoelectric properties due to the orientation of the inhomogeneities and different families of piezoelectric inhomogeneities is discussed. The MHM approach is applied in two examples, material with inhomogeneities having scatter orientation and composites with two different families of spheroidal inhomogeneities.

Objectives Our aim was to investigate the emergence and spread of ciprofloxacin resistance in clinical Neisseria gonorrhoeae isolates in New South Wales, Australia, from the first reported case in 1991 until ciprofloxacin resistance was sustained at or above the WHO threshold for treatment change of 5% (1999), to inform future strategies for controlling gonococcal antimicrobial resistance. Methods The index isolate and all subsequent clinical isolates of ciprofloxacin-resistant N. gonorrhoeae in New South Wales from 1991 to 1999 were genotyped using a previously described method on the Agena MassARRAY iPLEX platform. Region of acquisition data, where available, were used to determine whether cases were travel associated. Results In New South Wales, of the 325 ciprofloxacin-resistant N. gonorrhoeae isolates reported from 1991 to 1999, 98% (320/325) were able to be recovered and 100% (320/320) were genotyped. There were 66 different genotypes, comprising 1–99 isolates each. Notably no single clone was found to account for ciprofloxacin resistance being sustained in the population, with considerable variability in genotype prevalence observed throughout the study period. A total of 65% (209/320) of genotyped isolates had information regarding the likely place of acquisition; of these, 44% (93/209) were associated with overseas travel or sexual contact with an overseas visitor. The first ciprofloxacin-resistant N. gonorrhoeae in New South Wales was associated with travel to Thailand. Index cases of each resistant genotype were significantly more likely to have been acquired overseas (51.5%), predominantly in Asia (45%, 30/66). Conclusions The continued importation of multiple genotypes, rather than the expansion of a single genotype, led to ciprofloxacin-resistant N. gonorrhoeae being established in New South Wales.

Significance Huntington’s disease (HD) is a devastating neurodegenerative disorder caused by expansion of a polyglutamine repeat within the huntingtin (HTT) protein. A normal function of HTT is that of a scaffold for selective autophagy, a mechanism of protein and organelle degradation by the lysosome required for neuronal health. Here, we show that the inflammatory IκB kinase (IKK) kinase subunit IKKβ may function in vivo to regulate autophagy through direct phosphorylation of HTT at serine 13 and through the activation of autophagy gene expression. IKKβ is required to slow HD behavioral progression and to suppress neurodegeneration and microglial activation in HD transgenic mice. Our work suggests that the early activation of IKK may be protective to activate autophagy, thereby slowing HD progression., Neuroinflammation is an important contributor to neuronal pathology and death in neurodegenerative diseases and neuronal injury. Therapeutic interventions blocking the activity of the inflammatory kinase IKKβ, a key regulator of neuroinflammatory pathways, is protective in several animal models of neurodegenerative disease and neuronal injury. In Huntington’s disease (HD), however, significant questions exist as to the impact of blocking or diminishing the activity of IKKβ on HD pathology given its potential role in Huntingtin (HTT) degradation. In cell culture, IKKβ phosphorylates HTT serine (S) 13 and activates HTT degradation, a process that becomes impaired with polyQ expansion. To investigate the in vivo relationship of IKKβ to HTT S13 phosphorylation and HD progression, we crossed conditional tamoxifen-inducible IKKβ knockout mice with R6/1 HD mice. Behavioral assays in these mice showed a significant worsening of HD pathological phenotypes. The increased behavioral pathology correlated with reduced levels of endogenous mouse full-length phospho-S13 HTT, supporting the importance of IKKβ in the phosphorylation of HTT S13 in vivo. Notably, many striatal autophagy genes were up-regulated in HD vs. control mice; however, IKKβ knockout partially reduced this up-regulation in HD, increased striatal neurodegeneration, and enhanced an activated microglial response. We propose that IKKβ is protective in striatal neurons early in HD progression via phosphorylation of HTT S13. As IKKβ is also required for up-regulation of some autophagy genes and HTT is a scaffold for selective autophagy, IKKβ may influence autophagy through multiple mechanisms to maintain healthy striatal function, thereby reducing neuronal degeneration to slow HD onset.

International audience; A unique outbreak of Ross River virus (RRV) infection was reported in Fiji in 1979. In 2013, RRV seroprevalence among residents was 46.5% (362/778). Of the residents who were seronegative in 2013 and retested in 2015, 10.9% (21/192) had seroconverted to RRV, suggesting ongoing endemic circulation of RRV in Fiji.

Background Work-related neck and shoulder pain (WRNSP) is highly prevalent among patients who seek physiotherapy treatment. Clinicians may tend to focus on teaching home exercises and provide general advice about workplace improvement. The present study investigates the short- and long-term impact of an intervention approach that emphasizes on integrating the motor control re-education with ergonomic advice. Methods Participants diagnosed with WRNSP (n = 101) were randomly assigned into two groups in this randomized controlled trial. The Ergo-motor Group (EM, n = 51) received an integrated intervention with ergonomic advice/modifications and motor control training individualized for each participant based on their specific work demands. Control Group (CO, n = 50) received treatment for pain relief and general exercises of their necks at a designated physiotherapy clinic. Neck pain intensity and functional outcome measures were assessed before, immediately and 1-year after the 12-week intervention programmes. Global Rating of Change Score was used to evaluate the perceived recovery at 1-year follow-up. Results Both groups reported significant reductions in pain and functional disability scores at post-intervention (EM, n = 44; CO, n = 42) and 1-year follow-up (EM, n = 40; CO, n = 38); however, no significant between-group differences were found (p > 0.05). Significantly higher rating in global recovery score was reported in EM group at 1-year follow-up (p Conclusions Intervention integrating ergonomic advice/modification with motor control exercise was found to be equally effective as pain relief and general exercise for pain and functional recovery. However, at 1-year follow-up, such integrated approach resulted in significantly better global recovery perceived by people with WRNSP. Significance Integrating ergonomic intervention and motor control training achieved similar reduction in pain and functional outcomes compared to conventional physiotherapy at post-intervention and at 1-year follow-up, for patients with moderate level of work-related neck-shoulder pain and mild degree of functional disability. The Ergo-motor Group reported significantly better perceived overall recovery at 1-year follow-up.

New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation., Graphical abstract Image 1, Highlights • P. knowlesi >6-fold less susceptible to several ATP4 inhibitors than P. falciparum. • P. knowlesi equally susceptible to artemisinins and synthetic endoperoxides. • Isobolograms show similar drug interactions for P. knowlesi and P. falciparum. • New P. knowlesi isolate (UM01) similarly susceptible to antimalarials as A1-H.1

Summary: Transmission of many infectious diseases depends on interactions between humans, animals, and the environment. Incorporating these complex processes in transmission dynamic models can help inform policy and disease control interventions. We identified 20 diseases involving environmentally persistent pathogens (ie, pathogens that survive for more than 48 h in the environment and can cause subsequent human infections), of which indirect transmission can occur from animals to humans via the environment. Using a systematic approach, we critically appraised dynamic transmission models for environmentally persistent zoonotic diseases to quantify traits of models across diseases. 210 transmission modelling studies were identified and most studies considered diseases of domestic animals or high-income settings, or both. We found that less than half of studies validated their models to real-world data, and environmental data on pathogen persistence was rarely incorporated. Model structures varied, with few studies considering the animal–human–environment interface of transmission in the context of a One Health framework. This Review highlights the need for more data-driven modelling of these diseases and a holistic One Health approach to model these pathogens to inform disease prevention and control strategies.

Background Although multiple studies have investigated risk factors for symptomatic adjacent segment disease (ASD) after lumbar fusion, their findings were diverse and inconsistent. This review aimed to summarize risk factors for ASD in order to guide the management of ASD and future research. Methods Six electronic databases were systematically searched from inception to December 2019. Two reviewers independently screened titles, abstracts, and full-text articles to identify studies investigating risk factors for ASD after lumbar fusion in humans. The methodological quality of the included studies and the strength of evidence regarding risk factors were evaluated. Results Sixteen studies involving 3,553 patients were included. Meta-analyses revealed that high body mass index, facet joint violation, anterior shift of the preoperative and postoperative lumbosacral sagittal plumb line, decreased preoperative and postoperative lumbar lordosis, preoperative adjacent disc degeneration, decreased preoperative adjacent disc height, increased postoperative lumbopelvic mismatch, postoperative pelvic incidence, and postoperative pelvic tilt were significantly related to ASD. Conclusions This meta-analysis addressed the limitations of prior reviews and summarized evidence with regard to risk factors for ASD following lumbar fusion. Future prospective studies should investigate whether modification of these risk factors can reduce the ASD development. Level of evidence Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

In 1911 and 1917, the first commercial plantings of African oil palm (

Chronic cellular stress associated with neurodegenerative disease can result in the persistence of stress granule (SG) structures, membraneless organelles that form in response to cellular stress. In Huntington's disease (HD), chronic expression of mutant huntingtin generates various forms of cellular stress, including activation of the unfolded protein response and oxidative stress. However, it has yet to be determined whether SGs are a feature of HD neuropathology. We examined the miRNA composition of extracellular vesicles (EVs) present in the cerebrospinal fluid (CSF) of patients with HD and show that a subset of their target mRNAs were differentially expressed in the prefrontal cortex. Of these targets, SG components were enriched, including the SG-nucleating Ras GTPase-activating protein-binding protein 1 (G3BP1). We investigated localization and levels of G3BP1 and found a significant increase in the density of G3BP1-positive granules in the cortex and hippocampus of R6/2 transgenic mice and in the superior frontal cortex of the brains of patients with HD. Intriguingly, we also observed that the SG-associated TAR DNA-binding protein 43 (TDP43), a nuclear RNA/DNA binding protein, was mislocalized to the cytoplasm of G3BP1 granule-positive HD cortical neurons. These findings suggest that G3BP1 SG dynamics may play a role in the pathophysiology of HD.

BackgroundCholesteatoma often presents with persistent otorrhoea, conductive hearing loss or vestibular dysfunction. Rarely, cholesteatoma can cause dysgeusia if the lesion invades into the chorda tympani nerve. This paper presents an individual with cholesteatoma whose dysgeusia resolved following a mastoidectomy in which the chorda tympani was sacrificed. The current literature was reviewed for explanations behind this phenomenon.Case reportA previously fit 57-year-old man presented with a 3-month history of persistent otorrhoea and the complaint of a metallic taste in the mouth, and was diagnosed with cholesteatoma. The patient underwent radical mastoidectomy and the chorda tympani nerve was sacrificed. On post-operative review, he reported complete resolution of dysgeusia.ConclusionThe sense of taste is mediated by a complex neural network. It is possible that once the diseased chorda tympani is transected, compensation arises from other parts of the network. Sectioning of the chorda tympani could lead to a beneficial outcome in selected patients.

Background Chemoprophylaxis with weekly doses of tafenoquine (200 mg/day for 3 days before departure [loading dose], 200 mg/week during travel and 1-week post-travel [maintenance doses]) is effective in preventing malaria. Effectiveness of malaria chemoprophylaxis drugs in travellers is often compromised by poor compliance. Shorter schedules that can be completed before travel, allowing ‘drug-free holidays’, could increase compliance and thus reduce travel-related malaria. In this meta-analysis, we examined if a loading dose of tafenoquine alone is effective in preventing malaria in short-term travellers. Methods Four databases were searched in November 2020 for randomized controlled trials (RCTs) that assessed efficacy and/or safety of tafenoquine for chemoprophylaxis. Network meta-analysis using the generalized pair-wise modelling framework was utilized to estimate the odds ratio (OR) of malaria infection in long-term (>28 days) and short-term (≤28 days) travellers, as well as adverse events (AEs) associated with receiving loading dose of tafenoquine alone, loading dose of tafenoquine followed by maintenance doses, loading dose of mefloquine followed by maintenance doses, or placebo. Results Nine RCTs (1714 participants) were included. In long-term travellers, compared to mefloquine, tafenoquine with maintenance doses (OR = 1.05; 95% confidence interval [CI]: 0.44–2.46) was equally effective in preventing malaria, while there was an increased risk of infection with the loading dose of tafenoquine alone (OR = 2.89; 95% CI: 0.78–10.68) and placebo (OR = 62.91; 95% CI: 8.53–463.88). In short-term travellers, loading dose of tafenoquine alone (OR = 0.98; 95% CI: 0.04–22.42) and tafenoquine with maintenance doses (OR = 1.00; 95% CI: 0.06–16.10) were as effective as mefloquine. The risk of AEs with tafenoquine with maintenance doses (OR = 1.03; 95% CI: 0.67–1.60) was similar to mefloquine, while loading dose of tafenoquine alone (OR = 0.58; 95% CI: 0.20–1.66) was associated with lower risk of AEs, although the difference was not statistically significant. Conclusions For short-term travellers, loading dose of tafenoquine alone was equally effective, had possibly lower rate of AEs, and likely better compliance than standard tafenoquine or mefloquine chemoprophylaxis schedules with maintenance doses. Studies are needed to confirm if short-term travellers remain free of infection after long-term follow-up. Registration The meta-analysis was registered in PROSPERO (CRD42021223756). Highlight Tafenoquine is the latest approved drug for malaria chemoprophylaxis. A loading dose of tafenoquine (200 mg/day for 3 days before departure) is as effective in preventing malaria in short-term (≤28 days) travellers as chemoprophylaxis schedules of tafenoquine or mefloquine with maintenance doses, allowing travellers to have a ‘drug-free holiday’.