Significant Decrease Research Articles

Metabolomics Reveal the Chemical Characteristic of Cigar Tobacco Leaves During Air-Curing Process

Air-curing is a critical process in the production of cigar tobacco leaves. This process involves the vital degradation and transformation of macromolecular substances into micromolecular chemical compounds. In this study, three different varieties of tobacco leaves harvested from the Wuzhishan and Danzhou areas of Hainan, China were used as materials. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was employed to investigate the chemical changes before and after air-curing in the metabolites. Metabolic analysis revealed significant stepwise alterations in the tobacco leaf metabolome during the air-curing process. A total of 172 differential metabolites were identified as significant contributors in the biosynthesis pathways of flavonoids, flavone, flavonol, and other secondary metabolites, among the total analyzed 1841 metabolites obtained from the tobacco leaves. Notably, the contents of flavonoid metabolites, including kaempferol, rutin, chlorogenic acid, and quercetin, exhibited a significant decrease throughout the air-curing period. Correlation analysis indicated a strong association between the biosynthesis of flavonoids and the contents of chlorogenic acid and kaempferol, suggesting their role in regulation the formation of yellow and brown colors in tobacco leaves. These findings provide valuable insights for future investigations into the quality, commercial value, and chemical properties of cigar tobacco.

Time-Restricted Feeding (16/8)

This study aimed to investigate the effects of 8-hour time-restricted feeding (TRF) on body weight, biochemical parameters, diet quality, and eating behavior in overweight females. In the TRF group, there was a statistically significant decrease in body weight, body mass index, and waist and hip circumference (P < .05). Furthermore, there was a statistically significant greater decrease in blood glucose, insulin, cholesterol, and low-density lipoprotein cholesterol in the TRF group (P < .05). TRF did not affect eating behavior or diet quality (P > .05), but it led to a decrease in fiber intake (P < .05). These findings suggest that consuming food within an 8-hour window may facilitate weight loss in individuals with obesity. Longitudinal studies with larger samples are needed to confirm this.

The Development of International Tourists During The Pandemic: The Perception of Local Tourists

The Covid-19 pandemic has hampered various kinds of activities, especially in the world of tourism. Based on data on international tourist visits to Indonesia in August, it experienced a significant decrease of 89.22%. The Deputy for Destination and Infrastructure Development of the Ministry of Tourism and Creative Economy (Kemenparekraf) predicts that international tourist visits to Indonesia only occupy the number 4 million people, which before the pandemic occupied the figure of 18 million visitors. The purpose of this study is to find out the perception of local tourists towards the development of international tourists during the pandemic, the method used is to conduct interviews with local tourists randomly in the Barru district. The analysis method used is descriptive qualitative to explain the research results obtained. The result of this study is that the decline in tourism visitors has a significant impact on people's income, especially in Barru district, but this, it can reduce the spread of the Covid-19 virus that is sweeping the world.

Metabolic interplay between Proteus mirabilis and Enterococcus faecalis facilitates polymicrobial biofilm formation and invasive disease.

Polymicrobial biofilms play an important role in the development and pathogenesis of CAUTI. Proteus mirabilis and Enterococcus faecalis are common CAUTI pathogens that persistently co-colonize the catheterized urinary tract and form biofilms with increased biomass and antibiotic resistance. In this study, we uncover the metabolic interplay that drives biofilm enhancement and examine the contribution to CAUTI severity. Through compositional and proteomic biofilm analyses, we determined that the increase in biofilm biomass stems from an increase in the protein fraction of the polymicrobial biofilm matrix. We further observed an enrichment in proteins associated with ornithine and arginine metabolism in polymicrobial biofilms compared to single-species biofilms. We show that L-ornithine secretion by E. faecalis promotes arginine biosynthesis in P. mirabilis, and that disruption of this metabolic interplay abrogates the biofilm enhancement we see in vitro and leads to significant decreases in infection severity and dissemination in a murine CAUTI model.

Use of Mesenchymal Stem Cells in Experimental Ovarian Damage.

Bisphenol-A (BPA) has a well-proven deleterious effect on the hypothalamicpituitary- gonadal axis. The current study investigated the therapeutic potentials of mesenchymal stem cells (MSCs) in a murine model of BPA-induced ovarian damage. Fifty adult female rats were divided into: Group 1; control group, Group IIa, IIb: rats were given oral gavage of BPA (25 and 50 mg/Kg body weight respectively) on a daily basis for 15 days, and Group IIIa, IIIb; rats were intravenously treated with of MSCs (106 cells) after receiving the last dose of BPA as in group II. Plasma and ovarian tissue levels of Malondialdehyde (MDA) and gonadal axis hormones were assessed. Apoptosis was evaluated by TUNNEL assay and by apoptosis markers (FAS, FASL, Caspase 3, SLTM). A histological examination of ovarian tissue was also conducted. BPA resulted in a significant elevation in plasma levels of LH, FSH, and ovarian tissue levels of MDA and a significant decrease in estradiol and progesterone. All genetic and protein markers of apoptosis were elevated in BPA treated group with decreased oestrogen receptor expression in the ovarian tissue. Increased apoptotic cells were confirmed by TUNEL assay. A high dose of BPA was able to increase the number of atretic follicles in the ovarian tissue whereas the numbers of primordial, primary, secondary and Graafian follicles were decreased. All the laboratory and histological abnormalities were ameliorated by treatment with MSCs. The antioxidant and anti-apoptotic effects of MSCs could possibly explain the ability of this therapeutic modality to ameliorate BPA-induced-ovarian damage.

Changes in systemic cancer therapy in Australia during the Delta and Omicron waves of the COVID-19 pandemic (2021-2022): a controlled interrupted time series analysis.

Australian lockdowns in response to the initial coronavirus disease 2019 (COVID-19) outbreak in 2020 were associated with small and transient changes in the use of systemic cancer therapy. We aimed to investigate the impacts of the longer and more restrictive lockdowns in the Australian states of New South Wales (NSW) and Victoria during both the Delta subvariant lockdowns in mid-2021 and the Omicron subvariant outbreak in late 2021/early 2022. Population-based, controlled interrupted time series analysis. We conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between July 2018 and July 2022. We used controlled interrupted time series analysis to investigate changes in the dispensing, initiation and discontinuation of all cancer medicines dispensed to residents of NSW and Victoria, using the rest of Australia as a control series. We used quasi-Poisson regression to model weekly counts and estimate incidence rate ratios (IRRs) for the effect of (each) the Delta phase lockdown and the Omicron outbreak on our systemic cancer therapy outcomes. Between July 2018 and July 2022, cancer medicines were dispensed 592 141 times to 33 198 people in NSW and Victoria. Overall, there were no changes to the rates of dispensing, initiation or discontinuation of antineoplastics during the Delta phase lockdowns. In both states during the Omicron outbreak, there were significant decreases in the dispensing of antineoplastics (NSW IRR 0.89; 95% confidence interval [CI] 0.84, 0.93. Victoria IRR 0.92; 95% CI 0.88, 0.96) and in the initiation of endocrine therapy (NSW IRR 0.85; 95% CI 0.74, 0.99. Victoria IRR 0.78; 95% CI 0.65, 0.94), and no changes in the discontinuation of any systemic cancer therapy. The 2021 lockdowns and 2021/2022 Omicron outbreaks in NSW and Victoria had significant impacts on the dispensing, initiation and discontinuation of systemic cancer therapies, however, the overall effects were minimal. The impacts of lockdowns were less significant than the Omicron outbreaks, suggesting COVID-19 infection, health system capacity, and patient and community concerns were important factors for treatment changes.

Super-Resolution Ultrasound Imaging for Monitoring the Therapeutic Efficacy of a Vascular Disrupting Agent in an Animal Model of Breast Cancer.

Evaluate the use of super-resolution ultrasound (SRUS) imaging for the early detection of tumor response to treatment using a vascular-disrupting agent (VDA). A population of 28 female nude athymic mice (Charles River Laboratories) were implanted with human breast cancer cells (MDA-MB-231, ATCC) in the mammary fat pad and allowed to grow. Ultrasound imaging was performed using a Vevo 3100 scanner (FUJIFILM VisualSonics Inc) equipped with the MX250 linear array transducer immediately before and after receiving bolus injections of a microbubble (MB) contrast agent (Definity, Lantheus Medical Imaging) via the tail vein. Following baseline ultrasound imaging, VDA drug (combretastatin A4 phosphate, CA4P, Sigma Aldrich) or control saline was injected via the placed catheter. After 4 or 24 hours, repeat ultrasound imaging along the same tumor cross-section occurred. Direct intratumoral pressure measurements were obtained using a calibrated sensor. All raw ultrasound data were saved for offline processing and SRUS image reconstruction using custom MATLAB software (MathWorks Inc). From a region encompassing the tumor space and the entire postprocessed ultrasound image sequence, time MB count (TMC) curves were generated in addition to traditional SRUS maps reflecting MB enumeration at each pixel location. Peak enhancement (PE) and wash-in rate (WIR) were extracted from these TMC curves. At termination, intratumoral microvessel density (MVD) was quantified using tomato lectin labeling of patent blood vessels. SRUS images exhibited a clear difference between control and treated tumors. While there was no difference in any group parameters at baseline (0 hour, P > .09), both SRUS-derived PE and WIR measurements in tumors treated with VDA exhibited significant decreases by 4 (P = .03 and P = .05, respectively) and 24 hours (P = .02 and P = .01, respectively), but not in control group tumors (P > .22). Similarly, SRUS derived microvascular maps were not different at baseline (P = .81), but measures of vessel density were lower in treated tumors at both 4 and 24 hours (P < .04). An inverse relationship between intratumoral pressure and both PE and WIR parameters were found in control tumors (R2 > .09, P < .03). SRUS imaging is a new modality for assessing tumor response to treatment using a VDA.

Phytol and α-Bisabolol Synergy Induces Autophagy and Apoptosis in A549 Cells and Additional Molecular Insights through Comprehensive Proteome Analysis via Nano LC-MS/MS.

Non-Small Cell Lung Cancer (NSCLC) is a malignancy with a significant prevalence and aggressive nature, posing a considerable challenge in terms of therapeutic interventions. Autophagy and apoptosis, two intricate cellular processes, are integral to NSCLC pathophysiology, each affecting the other through shared signaling pathways. Phytol (Phy) and α-bisabolol (Bis) have shown promise as potential anticancer agents individually, but their combined effects in NSCLC have not been extensively investigated. The present study was to examine the synergistic impact of Phy and Bis on NSCLC cells, particularly in the context of autophagy modulation, and to elucidate the resulting differential protein expression using LCMS/ MS analysis. The A549 cell lines were subjected to the patented effective concentration of Phy and Bis, and subsequently, the viability of the cells was evaluated utilizing the MTT assay. The present study utilized real-time PCR analysis to assess the expression levels of crucial apoptotic genes, specifically Bcl-2, Bax, and Caspase-9, as well as autophagy-related genes, including Beclin-1, SQSTM1, Ulk1, and LC3B. The confirmation of autophagy marker expression (Beclin-1, LC3B) and the autophagy-regulating protein SQSTM1 was achieved through the utilization of Western blot analysis. Differentially expressed proteins were found using LC-MS/MS analysis. The combination of Phy and Bis demonstrated significant inhibition of NSCLC cell growth, indicating their synergistic effect. Real-time PCR analysis revealed a shift towards apoptosis, with downregulation of Bcl-2 and upregulation of Bax and Caspase-9, suggesting a shift towards apoptosis. Genes associated with autophagy regulation, including Beclin-1, SQSTM1 (p62), Ulk1, and LC3B, showed significant upregulation, indicating potential induction of autophagy. Western blot analysis confirmed increased expression of autophagy markers, such as Beclin-1 and LC3B, while the autophagy-regulating protein SQSTM1 exhibited a significant decrease. LC-MS/MS analysis revealed differential expression of 861 proteins, reflecting the modulation of cellular processes. Protein-protein interaction network analysis highlighted key proteins involved in apoptotic and autophagic pathways, including STOML2, YWHAB, POX2, B2M, CDA, CAPN2, TXN, ECHS1, PEBP1, PFN1, CDC42, TUBB1, HSPB1, PXN, FGF2, and BAG3, emphasizing their crucial roles. Additionally, PANTHER pathway analysis uncovered enriched pathways associated with the differentially expressed proteins, revealing their involvement in a diverse range of biological processes, encompassing cell signaling, metabolism, and cellular stress responses. The combined treatment of Phy and Bis exerts a synergistic inhibitory effect on NSCLC cell growth, mediated through the interplay of apoptosis and autophagy. The differential protein expression observed, along with the identified proteins and enriched pathways, provides valuable insights into the underlying molecular mechanisms. These findings offer a foundation for further exploration of the therapeutic potential of Phy and Bis in the management of NSCLC.

Evaluation of Neuroprotective effect of Cassia occidentalis L. against Colchicine Induced Memory Impairment in Wistar Rats

Background: Alzheimer’s disease (AD) is a progressive neurological disorder that develops with aging. Objective: In this research, we have examined the anti - Alzheimer’s effect of ethanolic extract from roots of Cassia occidentalis L. on colchicine-induced Alzheimer’s in Wistar rats Methods: Ethanolic extract was obtained and spectroscopic, chromatography analysis was performed. Acute toxicity studies using Organization of Economic Co-operation and Development (OECD) Guidelines 423 were performed to examine and make sure that there were no signs of toxic effects. The induction of AD was done using colchicine which leads to symptoms like neurotoxicity, neuroinflammation, and neurodegeneration. In this experiment, a thorough analysis of body weight, behavioral parameters, locomotor activity, and biochemical evaluation was performed to estimate the medicinal properties of Cassia occidentalis L in treating Alzheimer’s disease. Results: Pharmacognostic analysis showed the presence of vascular bundles, starch grains, fibers, calcium oxalate crystals, elongated parenchyma, and collenchyma mucilage as shown in the supplementary files. Locomotor activity, Escape latency time, Conditioned avoidance response, and Transfer latency were improved with treatment. Interleukin- 6 (IL - 6) levels were reduced significantly in the Colchicine + 200 Cassia mg/kg group (739.2 ± 0.37 pg/ml) than in the Colchicine Group (850.6±0.40 pg/ml). Tumor necrosis factor (TNF-α) was decreased in the Colchicine + 200 Cassia mg/kg Group (1030.93±0.51 pg/ml) than in the Colchicine Group (1455.06±1.25 pg/ml). A significant decrease in total protein level was observed in the Colchicine Group (2.52±0.10 mg/ml), (3.33±0.90 mg/ml) as compared to Colchicine + 200 Cassia mg/kg Group (5.27±0.09 mg/ml, (5.01±0.10 mg/ml) respectively, in the Hippocampus and Entorhinal cortex. The levels of antioxidant enzymes such as Catalase (CAT), Serum superoxide dismutase (SOD), Reduced glutathione (GSH) and Malondialdehyde (MDA) were measured. When compared to the Colchicine Group (7.33±0.16 nM/ mg, the MDA level was lower in the Colchicine + 100 Cassia mg/kg Group (3.20±0.01 nM/ mg). The level of CAT in Colchicine + 200 Cassia mg/kg Group (7.01±0.03 μmoles of H2O2/mg of protein) was seen to be increased when compared to Colchicine Group (3.32 ± 0.17 μmoles of H2O2/mg of protein). The level of SOD in Colchicine + 200 Cassia mg/kg Group (7.43±0.02 U mg -1 of protein) was seen to be increased when compared with Colchicine Group (4.55±0.03 U mg -1 of protein). The level of GSH in Colchicine + 200 Cassia mg/kg Group (10.07±0.19 nM/mg -1 of protein) was increased when compared with the Colchicine Group (5.82±0.11nM/mg -1 of protein). Histopathology of the Hippocampus and Entorhinal cortex showed diminished amyloid plaques, and neurodegeneration in the treatment groups Conclusion: The present study showed that ethanolic extract from the roots of Cassia occidentalis L. At 100 and 200 mg/kg doses in Wistar rats improved memory damage, by reducing oxidative stress. Levels of the antioxidant enzymes as CAT, and SOD, GSH were increased and MDA was decreased. The cytokine levels in the serum of Wistar rats of IL-6 level and TNF-α level were reduced significantly. Estimation of total protein level was found to be increased. It restored neuronal degeneration in the Hippocampus, and Entorhinal cortex and reduced oxidative stress. This suggests that the ethanolic extract of Cassia occidentalis L. could be an effective therapeutic treatment for neurodegenerative diseases like AD.

INDEPENDENT EFFECT OF SGLT2I ON DIASTOLIC FUNCTION IN HFREF POPULATION

Abstract Background Scientific literature reinforces the role of diastolic dysfunction in patients with heart failure with reduced ejection fraction (HFrEF) as an independent prognostic indicator of all–cause mortality. In this context, E/e’ ratio plays a central role in diastolic dysfunction assessments and diagnosis. Despite the introduction of several novel medical therapies for HFrEF that led to improvement in mortality and HF hospitalization, the effect of the combined treatment with Sacubitril/Valsartan (SV) and Sodium Glucose Transporter 2 inhibitors (SGLT2i) on E/e’ ratio has not been addressed yet. Aim We aimed to evaluate the effect of SV alone vs SV+SGLT2i on E/e’ ratio in a real–life population of HFrEF outpatients. Methods This is an observational monocentric study including patients treated with either SV alone or with SV+SGLT2i from 2018 to 2023. E/e’ ratio was measured at baseline, at 6 and 12 months. Results 178 HFrEF patients (mean age 69 years±11, left ventricular ejection fraction (LVEF) 31±6%) in optimal medical therapy were enrolled. 121 of them received SV and 58 received SV+SGLT2i. Baseline E/e’ ratio was similar in the two groups (median value 11,2 [IQR 8;16] in SV group and 10,9 [IQR 8;16] in SV+SGLT2i group, p=0.45). At follow up, only SV+SGLT2i group showed a significative decrease in E/e’ ratio after therapy initiation while SV group showed a E/e’ ratio similar to baseline (E/e’ ratio median value 8,5 [IQR 7;12] vs 11,8 [IQR 8;15] respectively, p=0.035). Moreover, after 12 months most patients receiving SV+SGLT2i didn‘t required diuretic administration compared to those treated with only SV (43% vs 16% respectively; p=0,0002). Conclusions Among patients with HFrEF, treatment with SGLT2i+SV was associated with a significative reduction of E/e’ ratio and of diuretic administration. This result might suggest a favorable independent effect of SGLT2i on diastolic function and myocytes relaxation and might provide new evidence on the positive results observed on hard endpoints.

A Reduction in the Number of Hospitalized Cases of Acute Meningitis during the COVID-19 Pandemic in Japan.

Objective The changes in the prevalence of acute meningitis during the coronavirus disease 2019 (COVID-19) pandemic remain unclear. This study aimed to compare the prevalence of acute meningitis before and during the COVID-19 pandemic in Japan. Methods We retrospectively reviewed the Japanese nationwide administrative medical payment system database, Diagnosis Procedure Combination (DPC), from 2016 to 2022. A total of 547 hospitals consistently and seamlessly offered DPC data during this period. The study period was divided into the following three periods: April 2016 to March 2018 (fiscal years 2016-2017), April 2018-March 2020 (2018-2019), and April 2020-March 2022 (2020-2021). Results Among the 28,161,806 patients hospitalized during the study period, 28,399 were hospitalized for acute meningitis: 16,678 for viral/aseptic type, 6,189 for bacterial type, 655 for fungal type, 429 for tuberculous, 2,310 for carcinomatous type, and 2,138 for other or unknown types of meningitis. A significant decrease during the pandemic was confirmed in viral (n=7,032, n=5,775, and n=3,871 in each period; p<0.0001) and bacterial meningitis (n=2,291, n=2,239, and n=1,659; p<0.0001) cases. Meanwhile, no decrease was observed in fungal meningitis (n=212, n=246, and n=197; p=0.056) or carcinomatous meningitis (n=781, n=795, and n=734; p=0.27). The decrease in the number of tuberculous meningitis cases was equivocal (n=166, n=146, and n=117; p=0.014). The decrease during the pandemic was more remarkable in younger populations aged <50 years than in older populations, both for viral and bacterial meningitis. Conclusion The number of hospitalized cases of acute meningitis clearly decreased during the COVID-19 pandemic, especially for viral and bacterial meningitis in younger populations aged <50 years.

A Detailed Examination of Türkiye's Projected Precipitation and Growth Season Trends under Climate Change Condition

This study presents a comprehensive analysis of Türkiye's changing precipitation patterns and growing season dynamics in the context of global warming, utilizing the Coupled Model Intercomparison Project Phase 5 (CMIP5) and various Representative Concentration Pathway (RCP) scenarios. In light of global warming, this study provides a thorough analysis of Türkiye's evolving precipitation patterns and growing season dynamics using multiple RCP scenarios and CMIP5. The research aims to fill a crucial gap in climate research by combining historical data and future projections to assess Türkiye's precipitation path under different greenhouse gas emission scenarios. The study employs linear regression for trend analysis and uses data from the Climate Change Knowledge Portal (CCKP), with a focus on precipitation data from 1986 to 2100. According to various RCP scenarios, this study’s findings show a considerable variation in precipitation trends over the 21st century. The RCP 8.5 scenario predicts a significant decrease in precipitation, which would present difficulties for the management of water resources and agricultural productivity. In contrast, the least severe RCP 2.6 pathway shows a fairly stable pattern of precipitation. Complex seasonal hydrological responses to climate change are revealed by monthly precipitation analysis; RCP8.5 predicts an increase in the frequency of periods of drought and heavy precipitation events. The impact of these changes in precipitation on Türkiye's agricultural growing seasons was further investigated in this study. In high-emission scenarios, there was an initial tendency towards longer growing seasons, which were subsequently followed by shorter ones. This suggests that although global warming might initially result in an extended growing season, it might ultimately cause a reduction in it, particularly in situations where mitigation efforts are minimal. The need for adaptable strategies that can respond to long-term climate trends as well as seasonal variability was highlighted by this research. It draws attention to the fact that to mitigate the effects of climate variability, informed policy decisions and integrated resource management are essential. The results highlight the need for quick action to lower the risks associated with water and highlight the potential advantages of intensive mitigation efforts in stabilizing and extending growing seasons.

MiniMed 780GTM in children with type 1 diabetes under seven years of age: Prospective open-label, single-arm, double-center, follow-up study.

Given the steadily rising incidence of type 1 diabetes (T1D), particularly among the youngest preschool children, coupled with well-documented challenges of achieving and maintaining optimal metabolic control in this age group, there is a growing need for advanced technological devices. To evaluate glycaemic control in children below the age of seven with type 1 diabetes (T1D) and assess the safety of the advanced hybrid closed loop (AHCL) system in comparison to the previous treatment method, a sensor-augmented pump with predictive low-glucose suspend (SAP-PLGS). Data from 10 children (aged 2.60-6.98 years) with T1D who transitioned to the AHCL system from SAP-PLGS were analysed. SAP-PLGS records from two weeks prior to the initiation of AHCL were compared with records from the initial four weeks post-switch (excluding the training period). These data were examined at two 2-week intervals and compared with records from two weeks post six-month usage of the AHCL. A significant decrease in the average nighttime glucose concentration was observed compared to pre-AHCL values (p= 0.001, concordance W = 0.53). The Glucose Management Indicator (GMI) value significantly decreased from 6.88 ± 0.37% to 6.52 ± 0.32% (p= 0.018, rbc = 0.93) immediately following the device switch and stabilized at 6.50 ± 0.28% (p= 0.001, W = 0.53) and 6.55 ± 0.41% (p= 0.001, W = 0.53) at subsequent stages of the study. An improvement was also observed in mean glucose values for time spent < 54 mg/dl, while the proportion of time within this range was maintained, both during the day (p< 0.001, W = 0.58) and at night (p= 0.002, W = 0.83). The AHCL MiniMed 780GTM system improved glycaemic control in the studied group of children under seven years of age with T1D compared to previous SAP-PLGS therapy. It proved to be safe for delivering insulin in this age group.

Trends of mortality from external causes in the Umbria region of Italy: 1994-2004

The aim of the present paper is to analyse the mortality from external causes in the Umbria region, from 1994 to 2004, in order to have an indication of the effectiveness of primary prevention interventions. Sex and cause-specific AADR (the age-adjusted death rates) and YPLL rates (the age-adjusted rates of years of potential life lost up to 74 yrs) time trends were analysed by means of joinpoint regression utilising SEER software. The expected annual percent change and its significance were also calculated. The cause groups examined were: all external causes, transport accidents, falls, accidental poisoning and exposure to noxious substances, intentional self-harm and assault. The age-adjusted death rates from the selected external causes showed, in both sexes, a decreasing trend. The joinpoint regression of AADR indicated that all statistically significant variations are declining. For the AADR cause group significant decreases were found in all external combined and poisoning causes for both sexes, transport accidents and falls for females. Among males the age-adjusted YPLL rates showed significant decreases for all external causes combined (EACP = -2.8%). This analysis provides a useful tool to evaluate the effectiveness of interventions performed in the last decade and indicates that further assessment and monitoring are needed.

Integrated Time Nanosecond Pulse Irreversible Electroporation (INSPIRE): Assessment of Dose, Temperature, and Voltage on Experimental and Clinical Treatment Outcomes.

This study sought to investigate a novel strategy using temperature-controlled delivery of nanosecond pulsed electric fields as an alternative to the 50-100 microsecond pulses used for irreversible electroporation. INSPIRE treatments were carried out at two temperatures in 3D tumor models using doses between 0.001 s and 0.1 s. The resulting treatment zones were quantified using viability staining and lethal electric field intensities were determined numerically. Computational modeling was then used to determine parameters necessary for INSPIRE treatments to achieve equivalent treatment zones to clinical electroporation treatments and evaluate the potential for these treatments to induce deleterious thermal damage. Lethal thresholds between 1109 and 709 V/cm were found for nominal 0.01 s treatments with pulses between 350 ns and 2000 ns at physiological temperatures. Further increases in dose resulted in significant decreases in lethal thresholds. Given these experimental results, treatment zones comparable to clinical electroporation are possible by increasing the dose and voltage used with nanosecond duration pulses. Temperature-controlled simulations indicate minimal thermal cell death while achieving equivalent treatment volumes to clinical electroporation. Nanosecond electrical pulses can achieve comparable outcomes to traditional electroporation provided sufficient electrical doses or voltages are applied. The use of temperature-controlled delivery may minimize thermal damage during treatment. Intense muscle stimulation and the need for cardiac gating have limited irreversible electroporation. Nanosecond pulses can alleviate these challenges, but traditionally have produced significantly smaller treatment zones. This study suggests that larger ablation volumes may be possible with the INSPIRE approach and that future in vivo studies are warranted.

Dapagliflozin Alleviates Myocardial Ischaemia Reperfusion Injury by Activating Mitophagy via the AMPK-PINK1/Parkin Signalling Pathway.

Myocardial ischaemia reperfusion injury (MIRI) determines infarct size and long-term outcomes after acute myocardial infarction (AMI). Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, alleviates MIRI in animal models. We investigated the potential mechanisms underlying the cardioprotective effect of dapagliflozin against MIRI, focusing on mitochondrial injury and mitophagy. MIRI mouse and H9C2 cell models were established. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed a significant alleviation of MIRI after pre-treatment of dapagliflozin compared to the model group (14.91±1.76 vs. 40.47±3.69%). Data from the pre-treatment dapagliflozin group showed a significant decrease in left ventricular ejection fraction (LVEF) (44.8±2.7 vs. 28.5±5.3%, P<0.01), left ventricular end-diastolic volume (LVEDV) (70.6±9.5 vs. 93.5±13.8 ul, P<0.05), and left ventricular end-systolic volume (LVESV) (39.0± 8.3 vs. 67.9±13.7 ul, P<0.05) compared to the model group. Dapagliflozin also reduced the levels of reactive oxygen species (ROS) and fragmented mitochondrial DNA, reversed the decrease in mitochondrial membrane potential, and suppressed apoptosis. Further study showed that dapagliflozin could protect against mitochondrial injury by rapidly clearing damaged mitochondria via mitophagy in a phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)/parkindependent manner. Dapagliflozin regulated mitophagy in cardiomyocytes by suppressing the adenosine 5'monophosphate-activated protein kinase (AMPK)-PINK1/parkin signalling pathway, resulting in attenuated MIRI. Dapagliflozin alleviated MIRI by activating mitophagy via the AMPK-PINK1/parkin signalling pathway.

Crash modification factors for high friction surface treatment on horizontal curves of two-lane highways: A combined propensity scores matching and empirical Bayes before-after approach

Horizontal curves are locations that, as a result of the changing alignment, may be a contributing factor in roadway departure crashes. One low-cost countermeasure to mitigate crashes at these locations is the installation of the high friction surface treatment (HFST), which increases roadway friction and is intended to help keep drivers on the roadway when traversing a horizontal curve. This treatment has been implemented at numerous curves in Pennsylvania, but the overall safety effectiveness is not known. The purpose of this study is to estimate a suite of Crash Modification Factors (CMFs) for HFST applied to curve sections of undivided two-lane roadways. A novel combination of the empirical Bayes observational before-after study design and propensity score matching was used to estimate CMFs for multiple crash types, crash severities, and roadway settings (urban and rural). Propensity score matching was implemented to identify the most appropriate reference group to use within the empirical Bayes methodology. The results indicate that the installation of HFST is associated with a statistically significant decrease in all crash types and severities considered.

The effect of a short breathing intervention on postural control and heart rate variability

AbstractPurposeThe objective of this study was to determine the immediate effect of a short breathing intervention on postural control and heart rate variability in healthy individuals.Materials/MethodsThe study involved 28 participants. Heart rate variability and heart rate were measured using a Polar (H10) sensor, and the sway path during posturography was recorded using the NeuroCom system, with participants standing on a firm then a foam surface in the eyes open and eyes closed conditions. All measurements were performed before and after the breathing intervention to provide baseline and post-intervention data. A short breathing intervention was performed between testing to stimulate the autonomic nervous system. In the Wilcoxon matched pairs comparison using Statistica software, P &lt; 0.05 was considered statistically significant.ResultsThe breathing intervention caused a significant decrease in heart rate variability and an increase in heart rate. In the eyes closed condition, on a firm surface, the breathing intervention significantly reduced the sway path.ConclusionsThe breathing intervention reduced the sway path in conditions without visual information but appeared to have no effect on balance in conditions with visual information, suggesting that the postural function of the diaphragm becomes more prominent in nonvisual conditions. We obtained evidence of the relationship between the autonomic nervous system and postural control. The stimulation of the sympathetic tone by means of the breathing intervention had a significant effect on postural control on firm and foam surfaces without visual information and decreased postural sway.

Résultats fonctionnels à court terme de la cystectomie avec dérivation urinaire non continente par laparoscopie robot assistée dans le cadre de troubles du bas appareil urinaire : une étude rétrospective monocentrique

ObjectiveTo assess the short-term functional outcomes and morbidity of robotic-assisted cystectomy (RAC) and intracorporeal urinary diversion (ICUD) in patients with lower urinary tract dysfunction (LUTD). MethodsAll consecutive patients who underwent RAC+ICUD for LUTD in a tertiary hospital center, between July 2018 and May 2021 were retrospectively included. Medical records were systematically reviewed and patient, perioperative and postoperative data were collected. A good short-term functional outcome was defined by the combination of a satisfying urostomy equipment (absence of urine leakage and easy appliance of the urostomy bag), the absence of pelvicaliceal system dilatation on sonography, and the absence of renal function decrease at the 2months post-operative consultation. Intraoperative parameters and post-operative complications were collected to assess morbidity. ResultsThirty-five patients were included. Eight (22.8%) patients needed intraoperative conversion to laparotomy. Twenty-five patients (92,5%) met criteria for a good functional outcome 2months post-operatively. The median operative time was 346min (86.5–407.5). The median blood loss was 100mL (100–290) and 5 patients (18.5%) required blood transfusion. The median times to return of bowel function was 3 days (2–4) and the median length of hospital stay was 10 days (10–18). Peri-operative complications were reported in 16 patients (59.2%): 6 (22.2%) minor complications Clavien ≤ II and 10 (37%) major complications Clavien ≥ III. There was no significative decrease of the renal function (mean preoperative creatininemia of 61.2μmol/L (50.5–74.5) vs 64.5μmol/L (47–85.25) postoperatively) ConclusionRAC+ICUD in LUTD can provide good short-term functional outcomes while limiting blood transfusion, time to return of bowel function and the length of hospital stay. These results should be confirmed by larger prospective study. Level of evidence4

Correlation between cerebroplacental doppler ratio and neonatal respiratory disorders: A reference marker of fetal lung maturation.

The aim of this study was to investigate the role of cerebroplacental ratio (CPR) in the final prenatal care for neonatal respiratory diseases and to analyze the risk of relevant factors associated with neonatal respiratory disorders. A prospective cohort study of 795 singleton pregnancies was conducted. The pulsatility indices (PI) of the umbilical artery (UA) and the middle cerebral artery (MCA) were measured, and the MCA to UA ratio (CPR) was determined. The severity of the case is determined by whether or not the newborn has respiratory problems. Compare the CPR correlation between the two groups and examine the illness prediction factors through a binary logistic regression method. Of the 795 participants, 124 had neonatal respiratory disorders. The mean values of CPR between neonatal respiratory diseases group and control group were 1.78±0.6, 1.97±0.9, respectively (P < 0.001). Maternal age, abortion history, cesarean section history, placental thickness, placental maturity, and amniotic fluid index (AFI) were determined to have no significant link between the two groups after comparison analysis (P > 0.05). It could be found that compared with the control group, CPR MoM indicators of neonatal respiratory distress syndrome, neonatal pneumonia and wet lung disease all show significant decreases. In binary logistic regression analysis, among the variables included in the model, CPR (OR:2.90, P = 0.015), fetal heart monitoring (OR:5.26, P < 0.001), delivery mode (OR:2.86, P < 0.001) and gestational age of delivery (OR:0.92, P < 0.001) were statistically significant in both groups. The findings of this study showed that infant respiratory problems were substantially related to CPR value. The correlation indicates that CPR was a powerful reference marker for respiratory disorders.