Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring ...system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and 'quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.
Interactions between plants and insect herbivores are important determinants of plant productivity in managed and natural vegetation. In response to attack, plants have evolved a range of defenses to ...reduce the threat of injury and loss of productivity. Crop losses from damage caused by arthropod pests can exceed 15% annually. Crop domestication and selection for improved yield and quality can alter the defensive capability of the crop, increasing reliance on artificial crop protection. Sustainable agriculture, however, depends on reduced chemical inputs. There is an urgent need, therefore, to identify plant defensive traits for crop improvement. Plant defense can be divided into resistance and tolerance strategies. Plant traits that confer herbivore resistance typically prevent or reduce herbivore damage through expression of traits that deter pests from settling, attaching to surfaces, feeding and reproducing, or that reduce palatability. Plant tolerance of herbivory involves expression of traits that limit the negative impact of herbivore damage on productivity and yield. Identifying the defensive traits expressed by plants to deter herbivores or limit herbivore damage, and understanding the underlying defense mechanisms, is crucial for crop scientists to exploit plant defensive traits in crop breeding. In this review, we assess the traits and mechanisms underpinning herbivore resistance and tolerance, and conclude that physical defense traits, plant vigor and herbivore-induced plant volatiles show considerable utility in pest control, along with mixed species crops. We highlight emerging approaches for accelerating the identification of plant defensive traits and facilitating their deployment to improve the future sustainability of crop protection.
To report the long-term results of a randomized radiotherapy dose escalation trial for prostate cancer.
From 1993 to 1998, a total of 301 patients with stage T1b to T3 prostate cancer were accrued to ...a randomized external beam dose escalation trial using 70 Gy versus 78 Gy. The median follow-up is now 8.7 years. Kaplan-Meier analysis was used to compute rates of prostate-specific antigen (PSA) failure (nadir + 2), clinical failure, distant metastasis, disease-specific, and overall survival as well as complication rates at 8 years post-treatment.
For all patients, freedom from biochemical or clinical failure (FFF) was superior for the 78-Gy arm, 78%, as compared with 59% for the 70-Gy arm (p = 0.004, and an even greater benefit was seen in patients with initial PSA >10 ng/ml (78% vs. 39%, p = 0.001). The clinical failure rate was significantly reduced in the 78-Gy arm as well (7% vs. 15%, p = 0.014). Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm. Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients (26% vs. 13%), although genitourinary toxicity of grade 2 or greater was less (13% vs. 8%) and not statistically significantly different. Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum.
Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA >10 ng/ml.
The majority of patients who report chemotherapy‐related cognitive deficits are women. Many chemotherapeutic agents suppress ovarian function, decreasing circulating estrogen. Because estrogen ...regulates high affinity choline uptake (HACU) and HACU is the rate‐limiting step for acetylcholine (ACh) synthesis, chemotherapeutic agents may indirectly impair cholinergic mediated cognitive processes. ACh suppresses cytokine synthesis, inhibits inflammation and prevents tissue damage and cell death by activating α7 nicotinic ACh receptors (nAChRs), thus impaired HACU and ACh synthesis following chemotherapy may exacerbate the adverse effects of neuroinflammation caused by tumors and chemotherapeutic agents. Since increasing available choline can maintain cholinergic function when demand for the precursor is high, and because choline is a full agonist at α7 nAChRs, increasing dietary choline may protect ACh systems from degeneration by attenuating pro‐inflammatory processes.
We have demonstrated that one administration of cyclophosphamide (CYP) and doxorubicin (DOX) impairs HACU in the striatum (STR) and hippocampus (HCC) of non tumor‐bearing (M‐) and tumor‐bearing MMTV‐PyVT (M+) female mice. Further, we have shown that the effect of one administration of CYP+DOX on HACU is prevented by placing mice on a 2% choline diet, and a 2% choline diet slows tumor growth in female M+ mice.
The present study sought to determine whether a 2% choline diet could: 1) prevent the manifestation of spatial memory deficits resulting from repeated exposure to CYP (66.7mg/kg i.v.; ≍200mg/m2/wk) and DOX (6.7mg/kg i.v.; ≍20mg/m2/wk); 2) maintain HACU in the frontal cortex (CTX), STR and HCC of mice following 4 weekly administrations of CYP+DOX; 3) prevent reductions in circulating E2 consequent to repeated CYP+DOX exposure; 4) attenuate elevations of circulating cytokines induced by repeated CYP+DOX exposure and/or the presence of tumors; and 5) suppress tumor growth and enhance the antineoplastic effects of CYP+DOX treatment in female M+ mice.
Results indicate that M‐ and M+ mice exposed to CYP+DOX exhibit deficits in spatial memory 10‐12 days following 4 weekly injections of CYP+DOX and 5 weeks following the final administration. HACU was reduced in the STR and HCC following a single exposure to CYP+DOX and this effect persisted in the STR. However, reduced HACU in the HCC was transient. Supplementation with a 2% choline diet prevented the manifestation of spatial memory deficits in M‐ and M+ mice and HACU in these mice did not differ from controls, suggesting that impaired HACU mediated the deficit in spatial memory. Although we did not observe an anticipated reduction in circulating estradiol due to CYP+DOX exposure, the regular appearance of proestrous was disrupted in groups exposed to either CYP+DOX or 2% choline diet, suggestive of amenorrhea. Circulating concentrations of cytokines, including G‐CSF, IL6, IP10, MCP1 and RANTES, were altered by the presence of tumors as well as the administration of CYP+DOX. 2% choline significantly reduced circulating concentrations of IL‐5, a cytokine associated with poor prognosis and metastasis, and total tumor volume was lower in mice placed on 2% choline diet when compared to tumor bearing mice on standard diet.
In the Antarctic ozone hole, ozone mixing ratios have been decreasing to extremely low values of 0.01–0.1 ppm in nearly all spring seasons since the late 1980s, corresponding to 95–99% local chemical ...loss. In contrast, Arctic ozone loss has been much more limited and mixing ratios have never before fallen below 0.5 ppm. In Arctic spring 2020, however, ozonesonde measurements in the most depleted parts of the polar vortex show a highly depleted layer, with ozone loss averaged over sondes peaking at 93% at 18 km. Typical minimum mixing ratios of 0.2 ppm were observed, with individual profiles showing values as low as 0.13 ppm (96% loss). The reason for the unprecedented chemical loss was an unusually strong, long‐lasting, and cold polar vortex, showing that for individual winters the effect of the slow decline of ozone‐depleting substances on ozone depletion may be counteracted by low temperatures.
Plain Language Summary
The severe stratospheric chemical ozone loss in the Antarctic ozone hole and its impact on human health and climate have generated widespread public, political, and scientific interest. In contrast, Arctic stratospheric ozone reduction has been much more limited because of higher temperatures and higher transport variability in the Northern Hemisphere (lower temperatures lead to more chemical loss, and more transport can increase ozone values). In the Arctic spring 2020, however, observations of balloon sondes and satellites show that locally, absolute values of ozone (measured in mixing ratios, i.e., molecules of ozone per molecules of air) are significantly lower than in any previous year and are comparable to typical local values in the Antarctic ozone hole, albeit over a much narrower vertical layer. Locally, the chemical loss of ozone peaked at 93% in the Arctic spring of 2020, compared to values of 95–99% in the Antarctic in most winters since the late 1980s. The reason for the unprecedented loss was unusually cold and stable conditions in the Arctic stratosphere.
Key Points
Local minimum ozone mixing ratios of 0.1–0.2 ppm observed by sondes in Arctic spring 2020 are significantly lower than in any previous year
Local ozone loss (93%) and low mixing ratios are comparable to typical values in the Antarctic ozone hole (95–99%, 0.01–0.1 ppm)
The reason for the unprecedented chemical loss was an unusually strong, long‐lasting, and record cold polar vortex
The ubiquitous presence of TiO
2
nanoparticles (nTiO
2
) and microplastics (MPs) in marine ecosystems has raised serious concerns about their combined impact on marine biota. This study investigated ...the combined toxic effect of nTiO
2
(1 mg/L) and NH
2
and COOH surface functionalized polystyrene MPs (PSMPs) (2.5 and 10 mg/L) on
Chlorella
sp. All the experiments were carried out under both visible light and UV-A radiation conditions to elucidate the impact of light on the combined toxicity of these pollutants. Growth inhibition results indicated that pristine nTiO
2
exhibited a more toxic effect (38%) under UV-A radiation when compared to visible light conditions (27%). However, no significant change in the growth inhibitory effects of pristine PSMPs was observed between visible light and UVA radiation conditions. The combined pollutants (nTiO
2
+ 10 mg/L PSMPs) under UV-A radiation exhibited more growth inhibition (nTiO
2
+ NH
2
PSMPs 66%; nTiO
2
+ COOH PSMPs 50%) than under visible light conditions (nTiO
2
+ NH
2
PSMPs 55%; TiO
2
+ COOH PSMPs 44%). Independent action modeling indicated that the mixture of nTiO
2
with PSMPs (10 mg/L) exhibited an additive effect on the algal growth inhibition under both the light conditions. The photoactive nTiO
2
promoted increased production of reactive oxygen species under UV-A exposure, resulting in cellular damage, lipid peroxidation, and impaired photosynthesis. The effects were more pronounced in case of the mixtures where PSMPs added to the oxidative stress. The toxic effects of the binary mixtures of nTiO
2
and PSMPs were further confirmed through the field emission electron microscopy, revealing specific morphological abnormalities. This study provides valuable insights into the potential risks associated with the combination of nTiO
2
and MPs in marine environments, considering the influence of environmentally relevant light conditions and the test medium.
To report long-term failure patterns and survival in a randomized radiotherapy dose escalation trial for prostate cancer.
A total of 301 patients with Stage T1b-T3 prostate cancer treated to 70 Gy ...versus 78 Gy now have a median follow-up of 9 years. Failure patterns and survival were compared between dose levels. The cumulative incidence of death from prostate cancer versus other causes was examined and regression analysis was used to establish predictive factors.
Patients with pretreatment prostate-specific antigen (PSA) >10 ng/mL or high-risk disease had higher biochemical and clinical failures rates when treated to 70 Gy. These patients also had a significantly higher risk of dying of prostate cancer. Patients <70 years old at treatment died of prostate cancer nearly three times more frequently than of other causes when they were radiated to 70 Gy, whereas those treated to 78 Gy died of other causes more frequently. Patients age 70 or older treated to 70 Gy died of prostate cancer as often as other causes, and those receiving 78 Gy never died of prostate cancer within 10 years of follow-up. In regression analysis, factors predicting for death from prostate cancer were pretreatment PSA >10.5 ng/mL, Gleason score 9 and 10, recurrence within 2.6 years of radiation, and doubling time of <3.6 months at the time of recurrence.
Moderate dose escalation (78 Gy) decreases biochemical and clinical failure as well as prostate cancer death in patients with pretreatment PSA >10 ng/mL or high-risk disease.
The unsustainable manufacturing, utilization and inadequate handling of plastics have led to a surge in global plastic pollution. In recent times, there has been increasing concern about the ...plausible hazards associated with exposure to micro/nanoplastics (M/NPs). As aquatic systems are considered to be the likely sink for M/NPs, it is crucial to comprehend their environmental behavior. The bioavailability, toxicity and fate of M/NPs in the environment are predominantly dictated by their surface characteristics. In the aquatic environment, M/NPs are prone to be internalized by aquatic organisms. This may facilitate their interaction with a diverse array of biomolecules within the organism, resulting in the formation of a biocorona (BC). The development of BC causes modifications in the physicochemical attributes of the M/NPs including changes to their size, stability, surface charge and other properties. This review details the concept of BC formation and its underlying mechanism. It provides insight on the analytical techniques employed for characterizing BC formation and addresses the associated challenges. Further, the eco-toxicological implications of M/NPs and the role of BC in modifying their potential toxicity on aquatic organisms is specified. The impact of BC formation on the fate and transport of M/NPs is discussed. A concise outlook on the future perspectives is also presented.
Biocorona formation on M/NPs potentially impacts the eco-toxicity and fate and transport of M/NPs in the aquatic environment.
The increasing production and utilization of nano-based commercial products have resulted in a significant release of engineered nanoparticles (ENPs) in the environment. Upon their release into the ...aquatic systems, ENPs interact with a wide range of natural constituents and undergo a multitude of diverse transformation processes. The majority of these transformations entail physical, chemical, and biological transformations. This review provides a comprehensive evaluation of the investigations that have scrutinized the fate and transformation behavior of ENPs such as TiO
2
, ZnO, CuO, Ag, Fe
3
O
4
, NiO, SiO
2
, CeO
2
, quantum dots, and carbon nanotubes. The physicochemical properties of ENPs and the prevailing environmental conditions constitute the pivotal parameters governing the environmental fate and transformation of ENPs. These transformations are intertwined with a range of environmental aspects which includes aggregation, agglomeration, sedimentation, dissolution, reduction, oxidation, sulfidation, and adsorption. Thus, the insights gleaned from these studies may help to comprehend the behavior of transformed ENPs, including their environmental fate, bioavailability, and mechanisms of toxicity. Overall, forthcoming nanomanufacturing processes should thoroughly prioritize the considerations of health, safety, and environmental consequences, all while ensuring that the functionality of consumer products remains uncompromised.
•Female mice exhibit deficits in spatial memory when exposed to doxorubicin and cyclophosphamide.•The spatial memory of male mice is not affected by exposure to doxorubicin and ...cyclophosphamide.•Spatial memory deficits in females persist following exposure to chemotherapeutic agents.
Self-reports of chemotherapy-related cognitive deficits (CRCDs) are more prevalent among women than men, suggesting that women may be more vulnerable to the cognitive-impairing effects of chemotherapy. However, there have been no direct comparisons of females and males using objective measures of cognitive function either during or following exposure to the same chemotherapeutic regimen. The present study used an animal model, and a prospective longitudinal design, to assess sex differences in the manifestation and persistence of spatial memory deficits resulting from exposure to doxorubicin (DOX) and cyclophosphamide (CYP), commonly used anticancer drugs. The spatial memory of female and male BALB/C mice was assessed using the Morris water maze prior to, during and following 4 weekly intravenous injections of DOX (2.5mg/kg) and CYP (25mg/kg) or vehicle. Females receiving DOX+CYP experienced significant deficits in spatial memory during and following injections when compared to baseline or females receiving vehicle. These deficits persisted for at least 34 days following the final injection. In contrast, males receiving DOX+CYP injections did not exhibit alterations in spatial memory relative to baseline or males receiving vehicle. These findings indicate that females may be more vulnerable than males to the cognitive-impairing effects of DOX+CYP and demonstrate that deficits in females persist for at least several weeks following drug exposure. Preclinical studies of CRCDs should parallel clinical work by including females and examine sex specific factors as potential mechanisms.
PDF
