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We appreciate Ahmed Sami Aljabali and his colleagues for their interest and comments [...]

A low-cost quantitative structured office measurement of movements in the extremities of people with Parkinson's disease [1,2] was performed on people with Parkinson's disease, multiple system atrophy, and age-matched healthy volunteers. Participants underwent twelve videotaped procedures rated by a trained examiner while connected to four accelerometers [1,2] generating a trace of the three location dimensions expressed as spreadsheets [3,4]. The signals of the five repetitive motion items [1,2] underwent processing to fast Fourier [5] and continuous wavelet transforms [6]. The dataset [7] includes the coding form with scores of the live ratings [1,2], the raw files [3], the converted spreadsheets [4], and the fast Fourier [5] and continuous wavelet transforms [6]. All files are unfiltered.The data also provide findings suitable to compare and contrast with data obtained by investigators applying the same procedure to other populations. Since this is an inexpensive procedure to quantitatively measure motions in Parkinson's disease and other movement disorders, this will be a valuable resource to colleagues, particularly in underdeveloped regions with limited budgets. The dataset will serve as a template for other investigations to develop novel techniques to facilitate the diagnosis, monitoring, and treatment of Parkinson's disease, other movement disorders, and other nervous and mental conditions. The procedure will provide the basis to obtain objective quantitative measurements of participants in clinical trials of new agents.

Harvest index (HI) is the ratio of grain to total shoot dry matter and is as a measure of reproductive efficiency. HI is determined by interactions between genotypes (G), environment (E), and crop management (M). Historic genetic yield gains due to breeding in wheat have largely been achieved by increasing HI. Environmental factors are important for HI and include seasonal pattern of water supply and extreme temperatures during crop reproductive development. Wheat production in Australia has been dominated by fast-developing spring cultivars that when sown in late-autumn will flower at an optimal time in early spring. Water limited potential yield can be increased by sowing slower developing wheats with a vernalization requirement (winter wheat) earlier than currently practiced such that their development is matched to environment and they flower at the optimal time. This means a longer vegetative phase which increases rooting depth, proportion of water-use transpired, and transpiration efficiency by allowing more growth during winter when vapour pressure deficit is low. All these factors can increase biomass accumulation, grain number and thus grain yield potential. However higher yields are not always realized due to a lower HI of early sown slow developing wheats compared to fast developing wheats sown later. Here, we evaluate genotype × management practices to improve HI and yield in early sown slow developing wheat crops using 6 field experiments conducted across south eastern Australia from 2014 to 2018 in yield environments ranging from ~1 to ~4.7 t/ha. Practices included low plant densities (30–50 plants/m²), mechanical defoliation, and deferred application of nitrogen fertilizer. Lower plant densities had similar yield and HI to higher plant densities. Defoliation tended to increase HI but reduce yield except when there was severe stem frost damage. Deferring nitrogen had a variable effect depending on starting soil N and in crop rainfall. All management strategies evaluated gave variable HI and yield responses with small effect sizes, and we conclude that none of them can reliably increase HI in early sown wheat. We propose that genetic improvement is the most promising avenue for increasing HI and yield in early sown wheat, and postulate that this could be achieved more rapidly through early generation screening for HI in slow developing genotypes than by crop management.

The assessment of Parkinson’s disease currently relies on the history of the present illness, the clinical interview, the physical examination, and structured instruments. Drawbacks to the use of clinical ratings include the reliance on real-time human vision to quantify small differences in motion and significant inter-rater variability due to inherent subjectivity in scoring the procedures. Rating tools are semi-quantitative by design, however, in addition to significant inter-rater variability, there is inherent subjectivity in administering these tools, which are not blinded in clinical settings. Sophisticated systems to quantify movements are too costly to be used by some providers with limited resources. A simple procedure is described to obtain continuous quantitative measurements of movements of people with Parkinson’s disease for objective analysis and correlation with visual observation of the movements. • Inexpensive accelerometers are attached to the upper and lower extremities of patients with Parkinson’s disease and related conditions to generate a continuous, three-dimensional recorded representation of movements occurring while performing tasks to characterize the deficits of Parkinson’s disease. • Movements of the procedure are rated by trained examiners live in real-time and later by videotapes. • The output of the instrumentation can be conveyed to experts for interpretation for diagnostic and therapeutic purposes. Method name: Quantitative continuous movement measurement space, Keywords: Accelerometer, Instrumentation, Signal processing

Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by marked deficits in social communication and interaction, including limited and repetitive patterns of behavior. We selected key nuclear neurotransmitter molecular imaging reports of ASD by combining “autism” AND “positron” AND “dopamine” OR “serotonin” OR “glutamate” OR “GABA” utilizing databases as follows: PubMed, Scopus, Web of Science, Science Direct, and Google Scholar. This review reports important findings in ASD utilizing positron emission tomography (PET) and single-photon emission computed tomography (SPECT). We studied major neurotransmitter systems, dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). Dopamine neurotransmission was decreased in the anterior medial prefrontal cortex in children with autism. Dopamine transporter was increased in the orbital frontal cortex of adults with ASD and decreased in the striatum of children with ASD. Decreased tryptophan metabolism, an estimate of serotonin synthesis, (A) in left frontal cortex correlated with severe language impairment and (B) in the right frontal cortex correlated with left and mixed handedness. Although not confirmed by some investigators, serotonin transporter was decreased in the cingulate, the medial frontal cortex, the midbrain, and the temporal lobes. Serotonin receptors were decreased in the thalamus in individuals with ASD and in the cortices of parents of children with ASD. Metabotropic glutamate receptor subtype 5 (mGluR 5 ) was increased in the post-central gyrus and the cerebellum of men with autism. PET studies for GABA did not differentiate people with ASD from controls. The increasing incidence of ASD and the inconsistent findings of different nuclear molecular imaging studies are evidence for the urgent need for further investigations utilizing nuclear molecular imaging to identify the key neurophysiological mechanisms underlying the pathophysiology of ASD.

Among green tea catechins, epigallocatechin gallate (EGCG) is the most abundant and has the highest biological activities. This study aims to develop and statistically optimise an EGCG-loaded niosomal system to overcome the cutaneous barriers and provide an antioxidant effect. EGCG-niosomes were prepared by thin film hydration method and statistically optimised. The niosomes were characterised for size, zeta potential, morphology and entrapment efficiency. Ex vivo permeation and deposition studies were conducted using full-thickness human skin. Cell viability, lipid peroxidation, antioxidant enzyme activities after UVA-irradiation and cellular uptake were determined. The optimised niosomes were spherical and had a relatively uniform size of 235.4 ± 15.64 nm, with a zeta potential of −45.2 ± 0.03 mV and an EE of 53.05 ± 4.46%. The niosomes effectively prolonged drug release and demonstrated much greater skin penetration and deposition than free EGCG. They also increased cell survival after UVA-irradiation, reduced lipid peroxidation, and increased the antioxidant enzymes’ activities in human dermal fibroblasts (Fbs) compared to free EGCG. Finally, the uptake of niosomes was via energy-dependent endocytosis. The optimised niosomes have the potential to be used as a dermal carrier for antioxidants and other therapeutic compounds in the pharmaceutical and cosmetic industries.

Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.

Multiple lines of evidence suggest that a deficiency of Fragile X Mental Retardation Protein (FMRP) mediates dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) in the pathogenesis of fragile X syndrome (FXS), the most commonly known single-gene cause of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Nevertheless, animal and human studies regarding the link between FMRP and mGluR5 expression provide inconsistent or conflicting findings about the nature of those relationships. Since multiple clinical trials of glutamatergic agents in humans with FXS did not demonstrate the amelioration of the behavioral phenotype observed in animal models of FXS, we sought measure if mGluR5 expression is increased in men with FXS to form the basis for improved clinical trials. Unexpectedly marked reductions in mGluR5 expression were observed in cortical and subcortical regions in men with FXS. Reduced mGluR5 expression throughout the living brains of men with FXS provides a clue to examine FMRP and mGluR5 expression in FXS. In order to develop the findings of our previous study and to strengthen the objective tools for future clinical trials of glutamatergic agents in FXS, we sought to assess the possible value of measuring both FMRP levels and mGluR5 expression in men with FXS. We aimed to show the value of measurement of FMRP levels and mGluR5 expression for the diagnosis and treatment of individuals with FXS and related conditions. We administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a specific mGluR5 radioligand for quantitative measurements of the density and the distribution of mGluR5s, to six men with the full mutation (FM) of FXS and to one man with allele size mosaicism for FXS (FXS-M). Utilizing the seven cortical and subcortical regions affected in neurodegenerative disorders as indicator variables, adjusted linear regression of mGluR5 expression and FMRP showed that mGluR5 expression was significantly reduced in the occipital cortex and the thalamus relative to baseline (anterior cingulate cortex) if FMRP levels are held constant (F(7,47) = 6.84, p < 0.001).These findings indicate the usefulness of cerebral mGluR5 expression measured by PET with [18F]FPEB and FMRP values in men with FXS and related conditions for assessments in community facilities within a hundred-mile radius of a production center with a cyclotron. These initial results of this pilot study advance our previous study regarding the measurement of mGluR5 expression by combining both FMRP levels and mGluR5 expression as tools for meaningful clinical trials of glutamatergic agents for men with FXS. We confirm the feasibility of this protocol as a valuable tool to measure FMRP levels and mGluR5 expression in clinical trials of individuals with FXS and related conditions and to provide the foundations to apply precision medicine to tailor treatment plans to the specific needs of individuals with FXS and related conditions.

Although tempting to envisage the emerging violence in conservation as either against nature or in defence of it, this paper argues that such violence is increasingly between 'the included' and ‘rogues’ in ways that transcend the nature : society binary. The paper traces how the emergence of these battle lines is associated with the digital information revolution that is producing discourses and practices of ‘inclusion’ that embrace social and natural worlds, whilst recasting a hitherto knowable and governable ‘excluded’ as more unknowable and threatening ‘rogues’. Accordingly, the paper then illustrates how the battle against the 'invisible enemy' of Ebola was fought not just against rogue viruses but against rogue bats, rogue deforesters and rogue patients, transcending any nature: human binary, and similarly that sustainable solutions are being sought in rearranging landscapes within an inclusive 'One Health' approach.

In this study, supercritical carbon dioxide (scCO2) extractions of cannabinoids were conducted at four different densities (231, 590, 818, and 911 kg/m3) using ethanol (5% w/v) as a co-solvent. The chemical profiles of these cannabinoids were analysed via reverse-phase high-performance liquid chromatography (RP-HPLC). It was determined that scCO2, at low density (231 kg/m3), produced an extract yield of 6.1% w/v. At high scCO2 density (~818 kg/m3), the yield was 16.1% w/v. More specifically, the amounts of tetrahydrocannabinol (THC) and cannabidiol (CBD) in the scCO2 extract at 818 kg/m3 were 10.8 and 15.6% w/v, respectively. It was also found that the use of 5% w/v ethanol increased scCO2 extract yields at both low and high densities (7.6% w/v and 18.2% w/v, respectively). Additionally, the use of co-solvent increased this yield further under both low- and high-density conditions, to 13.7 and 19.1% w/v, respectively. Interestingly, higher scCO2 density (911 kg/m3) with and without ethanol did not improve the scCO2 extract yield or the amount of cannabinoids. Although this study provides new insights into the correlation between scCO2 density and ethanol co-extraction of CBD and THC, more studies are needed to determine how different scCO2 densities and co-solvents influence the extraction of cannabinoids.

ObjectiveObesity is a risk factor for colorectal cancer (CRC), accounting for more than 14% of CRC incidence. Microbial dysbiosis and chronic inflammation are common characteristics in both obesity and CRC. Human and murine studies, together, demonstrate the significant impact of the microbiome in governing energy metabolism and CRC development; yet, little is understood about the contribution of the microbiome to development of obesity-associated CRC as compared to individuals who are not obese.DesignIn this study, we conducted a meta-analysis using five publicly available stool and tissue-based 16S rRNA and whole genome sequencing (WGS) data sets of CRC microbiome studies. High-resolution analysis was employed for 16S rRNA data, which allowed us to achieve species-level information to compare with WGS. ResultsCharacterisation of the confounders between studies, 16S rRNA variable region and sequencing method did not reveal any significant effect on alpha diversity in CRC prediction. Both 16S rRNA and WGS were equally variable in their ability to predict CRC. Results from diversity analysis confirmed lower diversity in obese individuals without CRC; however, no universal differences were found in diversity between obese and non-obese individuals with CRC. When examining taxonomic differences, the probability of being classified as CRC did not change significantly in obese individuals for all taxa tested. However, random forest classification was able to distinguish CRC and non-CRC stool when body mass index was added to the model.ConclusionOverall, microbial dysbiosis was not a significant factor in explaining the higher risk of colon cancer among individuals with obesity.

Introduction Emergency medical services (EMS) agencies transport a significant majority of patients with low acuity and non-emergent conditions to local emergency departments (ED), affecting the entire emergency care system’s capacity and performance. Opportunities exist for alternative models that integrate technology, telehealth, and more appropriately aligned patient navigation. While a limited number of programs have evolved recently, no empirical evidence exists for their efficacy. This research describes the development and comparative effectiveness of one large urban program. Methods The Houston Fire Department initiated the Emergency Telehealth and Navigation (ETHAN) program in 2014. ETHAN combines telehealth, social services, and alternative transportation to navigate primary care-related patients away from the ED where possible. Using a case-control study design, we describe the program and compare differences in effectiveness measures relative to the control group. Results During the first 12 months, 5,570 patients participated in the telehealth-enabled program, which were compared against the same size control group. We found a 56% absolute reduction in ambulance transports to the ED with the intervention compared to the control group (18% vs. 74%, P

The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia.

Quasi steady‐state enzyme kinetic models are increasingly used in systems modelling. The Michaelis Menten model is popular due to its reduced parameter dimensionality, but its low‐enzyme and irreversibility assumption may not always be valid in thein vivo context. Whilst the total quasi‐steady state assumption (tQSSA) model eliminates the reactant stationary assumptions, its mathematical complexity is increased. Here, we propose the differential quasi‐steady state approximation (dQSSA) kinetic model, which expresses the differential equations as a linear algebraic equation. It eliminates the reactant stationary assumptions of the Michaelis Menten model without increasing model dimensionality. The dQSSA was found to be easily adaptable for reversible enzyme kinetic systems with complex topologies and to predict behaviour consistent with mass action kineticsin silico. Additionally, the dQSSA was able to predict coenzyme inhibition in the reversible lactate dehydrogenase enzyme, which the Michaelis Menten model failed to do. Whilst the dQSSA does not account for the physical and thermodynamic interactions of all intermediate enzyme‐substrate complex states, it is proposed to be suitable for modelling complex enzyme mediated biochemical systems. This is due to its simpler application, reduced parameter dimensionality and improved accuracy.

Religious notions have long played a role in epistemology. Theological thought experiments, in particular, have been effective in a wide range of situations in the sciences. Some of these are merely picturesque, others have been heuristically important, and still others, as I will argue, have played a role that could be called essential. I will illustrate the difference between heuristic and essential with two examples. One of these stems from the Newton−Leibniz debate over the nature of space and time; the other is a thought experiment of my own constructed with the aim of making a case for a more liberal view of evidence in mathematics.