Spatiotemporal Trends of Colorectal Cancer Mortality Due to Low Physical Activity and High Body Mass Index From 1990 to 2019: A Global, Regional and National Analysis

Background: Understanding the spatiotemporal trends of colorectal cancer (CRC) deaths caused by low physical activity (LPA) and high body mass index (BMI) is essential for the prevention and control of CRC. We assessed patterns of LPA and high BMI-induced CRC deaths from 1990 to 2019 at global, regional, and national levels.Methods: Data on CRC deaths due to LPA and high BMI was downloaded from the Global Burden of Disease 2019 Study. We calculated estimated annual percentage change (EAPC) to quantify spatiotemporal trends in the CRC age-standardized mortality rate (ASMR) due to LPA and high BMI.Results: In 2019, CRC deaths due to LPA and high BMI were estimated as 58.66 thousand and 85.88 thousand, and the corresponding ASMRs were 0.77/100,000 and 1.07/100,000, with EAPCs of−0.39 [95% confidence interval (CI):−0.49,−0.29] and 0.64[95% CI: 0.57, 0.71] from 1990 to 2019 respectively. Since 1990, the ASMR of CRC attributable to LPA and high BMI has been on the rise in many geographic regions, especially in low middle and middle sociodemographic index (SDI) regions. Thirteen countries had a significant downward trend in CRC ASMR attributed to LPA, with EAPCs < −1. And, only 4 countries had a significant downward trend in CRC ASMR attributable to high BMI, with EAPCs < −1. Countries with a higher baseline burden in 1990 and a higher SDI in 2019 had a faster decline in ASMR due to high BMI and LPA.Conclusions: The burden of CRC caused by LPA and high BMI is on the rise in many countries. Countries should adopt a series of measures to control the local prevalence of obesity and LPA in order to reduce disease burden, including CRC.

Longitudinal Bowel Behavior Assessed by Bowel Ultrasound to Predict Early Response to Anti-TNF Therapy in Patients with Crohn's Disease: A Pilot Study

Background Early changes in bowel behavior during anti-TNF induction therapy in Crohn’s disease (CD) are relatively unknown. We determined (a) onset of changes in bowel behavior in CD patients receiving anti-TNF therapy by ultrasound; and (b) the feasibility of shear wave elastography (SWE) in predicting early response to anti-TNF therapy. Methods Consecutive ileal/ileocolonic CD patients programmed to initiate anti-TNF therapy were enrolled. Bowel ultrasound was performed at baseline, and at weeks 2, 6, and 14. Changes in bowel wall thickness, Doppler signals of the bowel wall (Limberg score), and SWE values were compared using a linear mixed model. Early response to anti-TNF therapy was based on a composite strategy of clinical and colonoscopy assessment at week 14. Results Of the 30 patients enrolled in this study, 20 patients achieved a response to anti-TNF therapy at week 14. The bowel wall thickness and SWE value of the response group showed a significant downward trend compared with the non-response group (P=0.003, P=0.011). Bowel wall thickness, the Limberg score, and SWE values were significantly reduced as early as week 2 compared with baseline (P<0.001, P<0.001, P=0.003) in the response group. Baseline SWE values (21.3±8.7 vs. 15.3±4.7 kPa, P=0.022) and bowel wall thickness (8.5±2.3 vs. 6.9±1.5 mm, P=0.027) in the non-response group were significantly higher than in the response group. Conclusions This pilot study suggested that changes in bowel ultrasound behavior could be assessed as early as week 2 after starting anti-TNF therapy. Bowel ultrasound together with elasticity imaging could predict early response to anti-TNF therapy.

Negative histology in cervical specimens obtained with the "see and treat" method among women at a referral center in Rio de Janeiro, Brazil: a cross-sectional study

Background According to the Brazilian Guidelines on Cervical Cancer Screening, women with cytopathologic diagnosis of high-grade intraepithelial lesion, abnormal colposcopic findings, fully visible squamocolumnar junction and age 25 years or older should be treated at the first visit (“see and treat—S&T”). The main limitation to this approach is the risk of overtreatment, identified by histology without preinvasive lesion. The objectives of this study were to identify the overtreatment rate in women undergoing S&T in cervical cancer prevention at a referral center with extensive experience with the method and to detect possible factors associated with this rate. Methods This was a cross-sectional study that analyzed records from a database with 616 women submitted to S&T from 1996 to 2017. Negative histology was defined as the following histopathologic results: human papillomavirus without cervical intraepithelial neoplasia (CIN), inflammatory, low-grade squamous intraepithelial lesion, and CIN 1. Results Of the 616 women, there were 52 (8.44%, 95%CI 6.25–10.64%) with a histopathologic report without preinvasive cervical lesion. No statistical association was found between this outcome and age or a significant downward trend over time. Conclusion The overtreatment rate in this study can be considered low and consistent with the acceptable rates reported in the literature, reinforcing the prevailing Brazilian guideline, in which the benefits of immediate treatment outweigh the risk of losses following biopsy.

DDT in Crimea coastal waters and blubber of Black Sea cetaceans

This research is based on the multi-year data on the distribution of organochlorine pesticides of the DDT group in the water of the coastal Black Sea areas of Crimea, obtained in expeditions of the “Professor Vodyanitsky” research vessel from 1999 to 2020. Study of content of DDT and its metabolites (DDTs) in the blubber of three species of Black Sea cetaceans that were astrand on the Black Sea coast from the 1980s to the 2020s was grounded on own and literature data. While there was an overall significant variability in ∑DDT content during the study period, there was a significant downward trend in their concentrations in the water of coastal areas of Crimea. Despite the significantly decreased DDTs pollution of the habitat of the Black Sea marine mammals over the last 10 years, high concentrations of DDTs were accumulated in their blubber, the maximum value of the sum of DDTs concentrations reached (163 µg/g of lipids) in the blubber of adult depleted bottlenose dolphin. The minimum concentrations were determined in the blubber of a newborn harbour porpoise female. In blubber samples up to 70% was of DDE, DDD - from 21 to 24%, and the concentration of the initial DDT varied from 6 to 14%. Based on the analysis of own and literature data, it is assumed that in the modern period, as compared to the 1990s, there is a downward trend in the content of the DDTs in the blubber of Black Sea cetaceans.

Probing Gut-Brain Links in Alzheimer's Disease with Rifaximin

Gut-microbiome-inflammation interactions have been linked to neurodegeneration in Alzheimers disease (AD) and other disorders. We hypothesized that treatment with rifaximin, a minimally absorbed gut-specific antibiotic, may modify the neurodegenerative process by changing gut flora and reducing neurotoxic microbial drivers of inflammation. In a pilot, open-label trial, we treated 10 subjects with mild to moderate probable AD dementia (MMSE = 17 + 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (p <0.004) and a significant increase in fecal phylum Firmicutes microbiota. Serum pTau181 and GFAP levels were reduced (effect sizes of -0.41 and -0.48 respectively) but did not reach significance. There was also a non-significant downward trend in serum cytokine IL-6 and IL-13 levels. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau 181 and serum GFAP. Insights from this pilot trial are being used to design a larger placebo-controlled clinical trial to determine if specific microbial flora/products underlie neurodegeneration, and whether rifaximin is clinically efficacious as a therapeutic.

Neither COVID-19, Nor Cryopreservation, Prevented Allogeneic Product Infusion: A Report from the National Marrow Donor Program

The COVID-19 pandemic posed numerous logistical challenges in the way that the National Marrow Donor Program (NMDP) delivered allogeneic products to patients undergoing hematopoietic cell transplant (HCT). Prior to COVID-19, fresh bone marrow (BM) and peripheral blood stem cell (PBSC) grafts were infused into patients at the time of transplant in more than 90% of cases. Due to the pandemic, graft products could no longer be reliably delivered fresh and required cryopreservation given patient safety issues as well as logistical issues in ensuring timely delivery of a fresh product. Given these challenges, the NMDP as well as other donor registries pivoted to providing cryopreserved products. We sought to evaluate the effect of cryopreservation on the infusion of allogeneic products, analyzing all allogeneic products collected from March 17, 2020 through June 30, 2021. A total of 9294 products were collected from both related donors (RDs) and unrelated donors (URDs). Of these, a total of 8702 products were infused both domestically and internationally: 476 were RDs and 8226 were URDs. One main difference between fresh and cryopreserved products is that transplant centers (TCs) can wait to infuse the product depending on the status of the patient, patient's preference of when to receive HCT, and other factors. Moreover, TCs also can assess the product quality both at the time of product receipt and after cryopreservation thaw, thereby allowing the TC to determine if they will infuse a patient based on product quality. Due to this nuance for cryopreservation, 370 products are pending infusion. Over the last 18 months, only 222 products were not infused for a variety of reasons including patient death, patient choice, poor product quality (low cell counts, clumps in the product, viability or a positive culture) or unknown reasons. The number of products collected and infused on average per month was 544, while the number of products that were not infused each month averaged 14. Figure 1 shows the number of products infused, pending and not infused each month. We hypothesized that as TCs and apheresis centers became more adept at cryopreservation and infusing cryopreserved products, fewer products not infused would decrease. To determine if there was a difference in the number of products that were not infused in the first half of the pandemic compared to the latter half of the pandemic, we compared the first 5 months (March-July 2020) to the last 5 months (March-July 2021) using the Kruskal-Wallis test to compare the two timeframes. As shown in Figure 2, a significant downward trend (p&lt;0.04) was noted in non-infused products by domestic TCs (p&lt;0.02), but not international TCs, most likely reflecting low volume from the international TCs. In the study cohort, we were also able to analyze the effect of COVID-19 on product infusion. Since March 2020, a total of 34 COVID-19 positive cases were noted with 33 being PCR positive and one being antibody positive. In the PCR positive cases, 16 had a donor that tested positive for COVID-19 post-donation: 12 products were infused and 4 were not infused based on the TC's preference. Thirteen (13) had a donor with COVID-19 concerns that caused the collection to be stopped and 4 were uncharacterized. In the patients that had products infused, there were no known infections of COVID-19 or deleterious effects on engraftment. Taken together this analysis demonstrates that despite cryopreservation, a surprisingly low number of products were not infused. Moreover, patients that received products from a COVID-19 positive donor did not become infected with COVID-19 nor suffered deleterious effects. This preliminary data may help inform donors to aid them in making choices about donation as well as guide TCs and donor centers in future crises or instances when a donor's allogeneic products need to be cryopreserved Figure 1 Figure 1. Disclosures Stefanski: Novartis: Honoraria. Devine: Magenta Therapeutics: Current Employment, Research Funding; Tmunity: Current Employment, Research Funding; Sanofi: Consultancy, Research Funding; Johnsonand Johnson: Consultancy, Research Funding; Orca Bio: Consultancy, Research Funding; Be the Match: Current Employment; Vor Bio: Research Funding; Kiadis: Consultancy, Research Funding.

Recent decrease in summer precipitation over the Iberian Peninsula closely links to reduction of local moisture recycling

The inherently dry summer climate of the Iberian Peninsula (IP) is undergoing drought exacerbated by more intense warming and reduced precipitation. Although many studies have studied changes in summer climate factors, it is still unclear how the changes in moisture contribution from the source lead to the decrease in summer precipitation. This study investigates the differences in the IP precipitationshed between 1980–1997 and 1998–2019 using the Water Accounting Model-2layers with ERA5 data, and assesses the role of local recycling and external moisture in reducing summer precipitation. Our findings indicate that the moisture contributions from the local IP, and from the west and the east of the precipitationshed contributed 1.7, 3.6 and 1.1 mm mon−1 less precipitation after 1997 than before 1997, accounting for 26 %, 57 % and 17 % of the main source supply reduction, respectively. The significant downward trend of the IP local recycling closely links to the disappearance of the wet years after 1997 as well as the decrease of local contribution in the dry years. Moreover, the feedback between the weakened local moisture recycling and the drier land surface can exacerbate the local moisture scarcity and summer drought.

Impacts of Climate and Anthropogenic Activities on Streamflow Regimes in the Beiluo River, China

Quantitatively assessing the characteristics of river streamflow variation and conducting research on attribution identification are the basis for formulating climate-change response strategies and rational use of water resources. Based on the daily streamflow data of the Zhuangtou Hydrological Station in 1970–2018, this paper analyzes the streamflow changes in the Beiluo River Basin and studies the impact of climate change and anthropogenic activities on the streamflow in this basin. A non-parametric Mann–Kendall test and Pettitt’s test were used to determine the trend and detect abrupt changes of streamflow and baseflow. The method based on precipitation and potential evapotranspiration, as well as the double-mass curve of precipitation–streamflow, was established to evaluate the impact of climate change and non-climate factors on annual streamflow. The results reveal a statistically significant downward trend (p = 0.01) in both annual streamflow and baseflow, with the abrupt point year in 1994 and 1988, respectively. When comparing to a modest declining trend in annual average precipitation, we see that the temperature showed a significant upward trend (p = 0.01), whose abrupt point year was 1996. Under the policy of returning farmland to forest, land-use analysis shows that the area of farmland had decreased by 222.4 km2, of which 31.4% was mainly converted into the forestland. By the end of 2015, the area of forestland had increased by 123.4 km2, which has largely caused streamflow decrease. For the method based on precipitation and potential evapotranspiration, climate change contributed 43.7% of the annual streamflow change, and human activities (mainly refers to LUCC) contributed 56.3%. For the DMC of precipitation–streamflow, the precipitation contributed 9.4%, and non-precipitation factors (mainly refers to human activities) contributed 90.6%, and human activities played a more vital part in driving streamflow reduction in different decades, with a contribution rate of more than 70%. This study is of great practical significance to the planning, management, development and utilization of water resources in basins.

Ovariectomy on Ultrastructure of Meibomian Gland Epithelial Cells in Rats

Dry eye mainly occurs in perimenopausal women, perimenopausal women with ovarian atrophy, estrogen and androgen levels showed a significant downward trend, and androgen related Estrogen Progesterone and prolactin receptors are widely distributed in lacrimal gland, meibomian gland, cornea and other tissues. The purpose of this study was to investigate the effect of ovariectomy on the ultrastructure of meibomian gland epithelial cells in rats. At the same time, we used the laboratory experiment method to select the non ovariectomized rats and ovariectomized rats were divided into two groups. After ovariectomy, we studied the effect of ovariectomy on the ultrastructure of meibomian gland epithelial cells in rats, objective to investigate the curative effect of palpebral margin in the treatment of moderate and severe meibomian gland dysfunction.The results showed that the ultrastructure of meibomian gland epithelial cells had obvious pathological changes after ovariectomy. It can improve 90% of female patients’ subjective symptoms and severity, increase tear secretion and reduce corneal fluorescein staining, reduce tear film damage, enhance the stability of tear film, and restore meibomian gland function. The treatment effect is significant. It can lay the foundation for the future clinical treatment of meibomian gland dysfunction and other related dry eyes, and it can also become an effective new treatment for postmenopausal women.

Changes in and Modelling of Hydrological Process for a Semi-Arid Catchment in the Context of Human Disturbance

Hydrological modelling is of critical importance to flood control. However, flood forecasting in semi-arid region is a great challenge to hydrologists, particularly in a changing environment. Taking the Zhulong River catchment located in north China as a case, the performance of GR4J model for hydrological modelling was investigated based on the analysis for changes in hydrological process of three periods defined as natural period (1967–1979), moderate human impact period (1980–1996) and intensive human impact period (1997–2015). Results show that 1) the annual precipitation and temperature of the catchment both presented upward trends, while the annual observed runoff exhibited a significant downward trend in the time span from 1967 to 2015; 2) the correlations between runoff and precipitation were comparatively higher on both monthly and annual scales in natural period than those in human disturbed periods; 3) both annual runoff and daily peak discharge in human disturbed periods decreased relative to those in natural period due to the environmental changes; 4) the GR4J model performed well for runoff simulations in natural period but gradually lost its applicability with the intensification of human activities. It is essential to improve the accuracy of hydrological modelling under a changing environment in further studies.