The adeno-associated virus (AAV) is a small, nonpathogenic parvovirus, which depends on helper factors to replicate. Those helper factors can be provided by coinfecting helper viruses such as ...adenoviruses, herpesviruses, or papillomaviruses. We review the basic biology of AAV and its most-studied helper viruses, adenovirus type 5 (AdV5) and herpes simplex virus type 1 (HSV-1). We further outline the direct and indirect interactions of AAV with those and additional helper viruses.
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM), but incomplete restoration of healthy growth remains a major problem. The relationships between ...the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S ribosomal RNA data sets generated from monthly faecal samples obtained from birth onwards in a cohort of children living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a 'relative microbiota maturity index' and 'microbiota-for-age Z-score' that compare postnatal assembly (defined here as maturation) of a child's faecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors, including diarrhoea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children ...with moderate acute malnutrition have perturbed development of their gut microbiota.
In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference values at baseline and every 2 weeks during the intervention period and at 4 months. We compared the rate of change of these related phenotypes between baseline and 3 months and between baseline and 4 months. We also measured levels of 4977 proteins in plasma and 209 bacterial taxa in fecal samples.
A total of 118 children (59 in each study group) completed the intervention. The rates of change in the weight-for-length and weight-for-age z scores are consistent with a benefit of MDCF-2 on growth over the course of the study, including the 1-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 plasma proteins and of 21 associated bacterial taxa that were positively correlated with the weight-for-length z score (P<0.001 for comparisons of both protein and bacterial taxa). These proteins included mediators of bone growth and neurodevelopment.
These findings provide support for MDCF-2 as a dietary supplement for young children with moderate acute malnutrition and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the National Institutes of Health; ClinicalTrials.gov number, NCT04015999.).
Background
The increasing production of nanoplastics and the fragmentation of microplastics into smaller particles suggest a plausible yet unclear hazard in the natural environment, such as soil. We ...investigated the short-term effects (28 days) of polystyrene nanoparticles (PS-NPs) on the activity and biomass of soil microbiota, and the functional diversity of soil enzymes at environmental relevant low levels in an incubation experiment.
Results
Our results showed a significant decrease in microbial biomass in treatments of 100 and 1000 ng PS-NP g
−1
DM throughout the incubation period. Dehydrogenase activity and activities of enzymes involved in
N
-(leucine-aminopeptidase),
P
-(alkaline-phosphatase), and C-(β-glucosidase and cellobiohydrolase) cycles in the soil were significantly reduced at day 28 suggesting a broad and detrimental impact of PS-NPs on soil microbiota and enzymes. Leucine-aminopeptidase and alkaline-phosphatase activities tended to decrease consistently, while β-glucosidase and cellobiohydrolase activities increased at high concentrations (e.g., PS-NP-1000) in the beginning of the incubation period, e.g., at day 1. On the other hand, basal respiration and metabolic quotient increased with increasing PS-NP application rate throughout the incubation period possibly due to increased cell death that caused substrate-induced respiration (cryptic growth).
Conclusions
We herewith demonstrated for the first time the potential antimicrobial activity of PS-NPs in soil, and this may serve as an important resource in environmental risk assessment of PS-NPs in the soil environment.
Rheumatoid arthritis (RA) is the most common autoimmune articular disorder. It is characterized by chronic inflammation and progressive joint destruction. As research traditionally focused on immune ...cells and cytokines, the role of stromal cells was addressed only to a limited extent. However, cell-cell interactions within the rheumatoid synovium alter the phenotype of synovial fibroblasts (SFs), which are nowadays considered as active and aggressive drivers in the destructive process of RA. SFs actively attach to and invade articular cartilage, thereby expressing increased amounts of adhesion molecules and proinflammatory and matrix-degrading mediators. Furthermore, RASFs stimulate synovial vascularization through the release of proangiogenic factors. As a result, angiogenesis supports the influx of immune cells into affected joints, thereby perpetuating inflammatory processes, and facilitates access of RASFs to the bloodstream, thus boosting dissemination of RA. Despite intensive research, early pathophysiological processes still remain largely unknown. In this respect, a prearthritic phase of RA is discussed. Early and intensive therapy is considered to be very effective and beneficial for long-term outcome. However, although innovative therapy and improved treatment strategies are applied to achieve clinical remission, failure of or only partial response to therapy remains common. Given that none of the currently approved therapies target RASFs, intensive research into new strategies is warranted. In this review, novel findings leading to the altered fibroblast phenotype in RA are discussed in terms of progressive inflammation and destruction. Potential novel therapeutic concepts are also addressed.
The recently discovered three-dimensional or bulk topological insulators are expected to exhibit exotic quantum phenomena. It is believed that a trivial insulator can be twisted into a topological ...state by modulating the spin-orbit interaction or the crystal lattice, driving the system through a topological quantum phase transition. By directly measuring the topological quantum numbers and invariants, we report the observation of a phase transition in a tunable spin-orbit system, BiTl(S₁— δ Se δ )₂, in which the topological state formation is visualized. In the topological state, vortex-like polarization states are observed to exhibit three-dimensional vectorial textures, which collectively feature a chirality transition as the spin momentum—locked electrons on the surface go through the zero carrier density point. Such phase transition and texture inversion can be the physical basis for observing fractional charge (±e/2) and other fractional topological phenomena.
Medical treatment of advanced cutaneous squamous‐cell carcinoma Gellrich, F.F.; Hüning, S.; Beissert, S. ...
Journal of the European Academy of Dermatology and Venereology,
December 2019, 2019-Dec, 2019-12-00, 20191201, Letnik:
33, Številka:
S8
Journal Article
Recenzirano
Odprti dostop
Considering the rising incidence, cutaneous squamous‐cell carcinoma (cSCC) has a high clinical relevance. In patients with localized cSCC, complete surgical resection is indicated. Radiotherapy ...should be performed in patients with non‐resectable tumours or in patients who are not suitable for surgery. Systemic therapy is reserved for cSCC that are neither surgically nor radiotherapeutically curable due to their extensive local spread and/or local or distant metastasis. In the absence of prospective randomized phase 3 trials to evaluate and compare the efficacy and safety of chemotherapeutics, epidermal growth factor receptor (EGFR) inhibitors and anti‐PD‐1 antibodies, no final recommendation for systemic therapy can be given for patients with locally advanced or metastatic cSCC. Anti‐PD‐1 antibodies currently show promising results with response rates of up to 50% in both locally advanced and metastatic cSCC. Anti‐PD‐1 antibodies appear to achieve higher response rates compared with EGFR inhibitors, and the duration of response appears to be superior to both chemotherapy and EGFR inhibitors. Compared with chemotherapy, the side effect profile of anti‐PD‐1 antibodies appears to be favourable. Altogether, PD‐1 inhibitors are expected to become the new standard of care for patients with locally advanced and metastatic cSCC. Currently, placebo‐controlled clinical trials are investigating the adjuvant use of cemiplimab and pembrolizumab in patients undergoing resection and radiotherapy of high‐risk cSCC. Patients not eligible for anti‐PD‐1 treatment, e.g. in organ transplant recipients, or in patients refractory to anti‐PD‐1 may be offered EGFR inhibitors and/or chemotherapies. Chemotherapies appear to be superior to EGFR inhibitors in terms of response rates, whereas EGFR inhibitors have a more favourable toxicity profile. EGFR inhibitors are therefore more suitable for multimorbid and/or frail elderly patients. By combining EGFR inhibitors with local therapy such as surgery or radiotherapy, response rates and duration of response may be improved.
Helical Dirac fermions-charge carriers that behave as massless relativistic particles with an intrinsic angular momentum (spin) locked to its translational momentum-are proposed to be the key to ...realizing fundamentally new phenomena in condensed matter physics. Prominent examples include the anomalous quantization of magneto-electric coupling, half-fermion states that are their own antiparticle, and charge fractionalization in a Bose-Einstein condensate, all of which are not possible with conventional Dirac fermions of the graphene variety. Helical Dirac fermions have so far remained elusive owing to the lack of necessary spin-sensitive measurements and because such fermions are forbidden to exist in conventional materials harbouring relativistic electrons, such as graphene or bismuth. It has recently been proposed that helical Dirac fermions may exist at the edges of certain types of topologically ordered insulators-materials with a bulk insulating gap of spin-orbit origin and surface states protected against scattering by time-reversal symmetry-and that their peculiar properties may be accessed provided the insulator is tuned into the so-called topological transport regime. However, helical Dirac fermions have not been observed in existing topological insulators. Here we report the realization and characterization of a tunable topological insulator in a bismuth-based class of material by combining spin-imaging and momentum-resolved spectroscopies, bulk charge compensation, Hall transport measurements and surface quantum control. Our results reveal a spin-momentum locked Dirac cone carrying a non-trivial Berry's phase that is nearly 100 per cent spin-polarized, which exhibits a tunable topological fermion density in the vicinity of the Kramers point and can be driven to the long-sought topological spin transport regime. The observed topological nodal state is shown to be protected even up to 300 K. Our demonstration of room-temperature topological order and non-trivial spin-texture in stoichiometric Bi2Se3.Mx (Mx indicates surface doping or gating control) paves the way for future graphene-like studies of topological insulators, and applications of the observed spin-polarized edge channels in spintronic and computing technologies possibly at room temperature.
Summary
Background
The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk–benefit ratio of the ...programme remain unclear.
Objectives
To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not.
Methods
A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010–2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality.
Results
We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 95% confidence interval (CI) 0·30–0·46. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48–0·80).
Conclusions
Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.
What is already known about this topic?
There is limited evidence of the effectiveness of the German skin cancer screening programme and its associated risks more than 10 years after its initiation.
The reduction in mortality as a result of early diagnoses that was hoped for has so far not been demonstrated.
What does this study add?
A reduction in mortality is shown, but there is a high potential for bias.
Secondary data alone cannot explain the facts of the matter.
Linked Comment: T. Eigentler. Br J Dermatol 2022; 186:8–9.
Plain language summary available online
This study evaluated the relative validity of different consumer and research activity monitors during semistructured periods of sedentary activity, aerobic exercise, and resistance exercise.
...Fifty-two (28 male and 24 female) participants age 18-65 yr performed 20 min of self-selected sedentary activity, 25 min of aerobic exercise, and 25 min of resistance exercise, with 5 min of rest between each activity. Each participant wore five wrist-worn consumer monitors Fitbit Flex, Jawbone Up24, Misfit Shine (MS), Nike+ Fuelband SE (NFS), and Polar Loop and two research monitors ActiGraph GT3X+ on the waist and BodyMedia Core (BMC) on the arm while being concurrently monitored with Oxycon Mobile (OM), a portable metabolic measuring system. Energy expenditure (EE) on different activity sessions was measured by OM and estimated by all monitors.
Mean absolute percent error (MAPE) values for the full 80-min protocol ranged from 15.3% (BMC) to 30.4% (MS). EE estimates from ActiGraph GT3X+ were found to be equivalent to those from OM (± 10% equivalence zone, 285.1-348.5). Correlations between OM and the various monitors were generally high (ranged between 0.71 and 0.90). Three monitors had MAPE values lower than 20% for sedentary activity: BMC (15.7%), MS (18.2%), and NFS (20.0%). Two monitors had MAPE values lower than 20% for aerobic exercise: BMC (17.2%) and NFS (18.5%). None of the monitors had MAPE values lower than 25% for resistance exercise.
Overall, the research monitors and Fitbit Flex, Jawbone Up24, and NFS provided reasonably accurate total EE estimates at the individual level. However, larger error was evident for individual activities, especially resistance exercise. Further research is needed to examine these monitors across various activities and intensities as well as under real-world conditions.
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