• Meadows McIntyre opublikował 1 rok, 3 miesiące temu

    Our database did not include information on genome and the subtypes of psoriasis.

    Our study showed a decreased risk of psoriasis in the tonsillectomy group after adjustmentforbaseline characteristics, comorbidities, and medical confounders compared with the reference group.

    Our study showed a decreased risk of psoriasis in the tonsillectomy group after adjustment for baseline characteristics, comorbidities, and medical confounders compared with the reference group.Biological drugs, specifically proteins and peptides, are a privileged class of medicinal agents and are characterized with high specificity and high potency of therapeutic activity. However, biologics are fragile and require special care during storage, and are often modified to optimize their pharmacokinetics in terms of proteolytic stability and blood residence half-life. In this review, we showcase glycosylation as a method to optimize biologics for storage and application. Specifically, we focus on chemical glycosylation as an approach to modify biological drugs. We present case studies that illustrate the success of this methodology and specifically address the highly important question does connectivity within the glycoconjugate have to be native or not? We then present the innovative methods of chemical glycosylation of biologics and specifically highlight the emerging and established protecting group-free methodologies of glycosylation. We discuss thermodynamic origins of protein stabilization via glycosylation, and analyze in detail stabilization in terms of proteolytic stability, aggregation upon storage and/or heat treatment. Finally, we present a case study of protein modification using sialic acid-containing glycans to avoid hepatic clearance of biological drugs. This review aims to spur interest in chemical glycosylation as a facile, powerful tool to optimize proteins and peptides as medicinal agents.A novel heterotrophic nitrification and aerobic denitrification (HNAD) bacteria, identified as Bacillus thuringiensis strain WXN-23, was isolated from husk feed filtrate of a pig farm. It was the first report of Bacillus thuringiensis with the capability for HNAD and could adapt to the condition of low Carbon/Nitrogen (C/N) ratio. Nitrogen could be efficiently removed by the strain WXN-23 in simulated wastewater, be it in single or mixed form nitrogen sources. The nitrogen balance revealed that 63.5% of the initial nitrogen (5.32 mg) was lost in the form of N2. The conditions for maximum total nitrogen (TN) removal efficiency (95.996%) were shaking speed of 126.89 r/min, a carbon C/N ratio of 5.91, the temperature of 32.81 °C, and a pH value of 8.17. The nitrification-denitrification metabolic pathway (NH4+-N→NH2OH→NO2–N→NO3–N→NO2–N→NO→N2O→N2) under aerobic conditions was determined on the basic of characteristic of N removal, N balance analysis, enzyme assay and functional genes amplification results. Strain WXN-23 was effective at wastewater treatment, with TN, NH4+-N, NO3–N and NO2–N removal efficiencies of 82.12%, 86.74%, 90.74% and 100%, respectively.Wastewater treatment plants (WWTPs) in urban China generally face operational difficulties. To comprehensively analyze the current operation status and determine the factors that caused difficulties in urban domestic WWTPs, we conducted a questionnaire survey, and 18 operating conditions of scale-level WWTPs in seven regions in China were investigated. The research results showed that, of the 467-urban domestic WWTPs surveyed in China, approximately 63.17% of the WWTPs’ hydraulic loading rates (HLRs) are greater than 80%, 67.02% of the WWTPs have mixed liquor suspended solids (MLSS) concentrations greater than 4000 mg/L, and 95.93% of the WWTPs’ mixed liquor volatile suspended solids to mixed liquor suspended solids (MLVSS/MLSS) ratios are lower than 0.7. The WWTP energy consumption accounts for approximately 1% of the national electricity consumption, and approximately 100,000 tons of various chemicals are consumed every year. A high HLR, a high activated sludge concentration and low sludge activity, design value mismatches with actual values, high energy and material consumption, etc. have become the main operational difficulties of urban domestic WWTPs. In this study, the main barriers that hinder improving the operating efficiency of WWTPs were investigated, the causes of operational dilemmas were analyzed, and pathways were jointly explored to solve them. This study may provide valuable implications for industry practitioners with a comprehensive grasp of the industry’s current status and related policy formulation.This paper addresses the effects of atmospheric conditions on the spread of the SARS-CoV-2 coronavirus and its associated disease, COVID-19. For this purpose, we assess the limitations of bioclimatic correlative models to explain the geographic distribution of SARS-CoV-2 in the context of medical geography. Overall, there is a broad consensus that the global distribution of COVID-19 is not random but conditioned by environmental drivers. However, as the COVID-19 distribution becomes global, including tropical climates, the evidence reveals that atmospheric conditions explain, at most, only a limited amount of the space-time dynamics of SARS-CoV-2. Therefore, the usefulness of approaches based on bioclimatic envelopes is in question since the dominant route for the spread of COVID-19 seems to be the anthroposphere’s non-stationary environment. In this sense, there is a need to clarify further the role of different transmission routes at multiple scales and outdoor and indoor environments beyond bioclimatic envelopes. At this time, the possible influence of the weather in COVID-19 spread is not sufficient to be taken into account in public health policies. Hence, until reliable bioclimatic envelopes of SARS-CoV-2, if any, are found, caution should be exercised when reporting, as this could have unforeseen consequences.Neurogenesis plays a crucial role during neurodevelopment and its dysfunction can lead to neurodevelopmental disorders. A recent hypothesis stipulates that exogenous factors could corrupt this process and predispose to neurodegenerative disorders later in life. The presence of pesticide residues in the diet represents a threat of which we have recently become aware of. Indeed, they could corrupt neurogenesis, especially during gestation, potentially leading to impaired neuronal and synaptic functions. Since the effects of this low-noise contamination have not yet been evaluated on the neurodevelopment, we investigated the impact of fungicide residues on WT mice exposed throughout gestation. Thus, mice were exposed to fungicides, cyprodinil, mepanipyrim and pyrimethanil, alone at 0.1 μg/L during gestation until P3. Besides, another group was exposed to a cocktail of these three fungicides (0.1 μg/L each) for the same time. Exposure was performed through drinking water at the regulatory limit dose of the Europeelopment of neurological diseases later in life.

    Previous studies have focused on associations between individual built environment (BE) characteristics and mortality, and found the BE-mortality associations differed by socioeconomic status (SES). Different individual BE characteristics may have different impacts on health and thus could interact. Combinations of BE characteristics may be a better approach to explore the BE-mortality associations.

    This study aimed to investigate the associations of BE pattern with mortality in a prospective cohort of elderly Hong Kong Chinese (Mr. OS and Ms. OS Study), and assess whether the BE-mortality association differed by SES.

    Between 2001 and 2003, 3944 participants aged 65-98yearsat baseline were included in the present analysis. BE characteristics were assessed via Geographic Information System. Data on all-cause and cause-specific mortality were obtained from the Hong Kong Government Death Registry. Latent profile analysis was used to derive BE class, and the Cox proportional hazards model was used to estimaeffect on mortality risk for different SES groups.

    Our findings provide new evidence on the role of SES as an effect modifier of BE pattern and mortality. BE pattern has a varied effect on mortality risk for different SES groups.

    Previously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring.

    To identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD.

    We obtained stored mid-pregnancy serum from 214 mothers who lived in California’s Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman’s average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5μm) during the first trimester using the California Line Source Dispersion Model, version 4 (CALINE4). By utilizing liquid chromatography-high resolution mass spectrometry, we identified the metabolic profiles of maternal serum for 116 mon metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.

    Using high resolution metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.The current study aimed to investigate how selective reporting of study results indicating increased health effects will influence its receiver’s risk perception. Using the example of the Interphone Study from 2010 on mobile phone usage and cancer, an online experiment was conducted separating respondents into two groups. One group of subjects was informed selectively about a relationship between heavy mobile phone use and an elevated risk of glioma (brain cancer) only. The other group of subjects was informed about the full results of the analyses of glioma risk by cumulative call time, which suggests that other than for the heavy users, there were no statistically significant elevated risks related to mobile phone use. The results showed that selective reporting of risk information increased risk perception when compared to receiving the full information. Additionally, the selectively informed subjects revealed a stronger tendency towards overgeneralization of the 'elevated brain cancer risk’ to all mobile phone users, although this did not extend to an overgeneralization to other electromagnetic field sources or differences in the perception of a usage time dependency for possible health risks. These results indicate that reporting of full results is an important factor in effective risk communication.

    To evaluate and compare nurses’ depression, anxiety and stress symptoms at the beginning of the COVID-19 pandemic and after six months; to evaluate and compare the frequency of use of mental health promotion strategies during the same period; and to identify the relationship between the frequency of use of mental health promotion strategies, during the same period, with nurses’ depression, anxiety and stress symptoms.

    Data collection was carried out in two moments at baseline and after six months. An online questionnaire was applied to nurses to assess the frequency of use of some mental health promotion strategies and their depression, anxiety, and stress symptoms (through the Depression Anxiety Stress Scales – short version (DASS-21)).

    The anxiety and stress symptoms significantly decreased over time. The physical activity increased, and a decrease was observed in the remote social contacts after six months. The stress, anxiety and depression scores were significantly lower in nurses who frequently or always used all strategies compared to participants who never or rarely used them, except for one strategy (rejecting information about COVID-19 from unreliable sources).

    Mental health promotion strategies, such as physical activity, relaxation activity, recreational activity, healthy diet, adequate water intake, breaks between work shifts, maintenance of remote social contacts, and verbalization of feelings/emotions, are crucial to reduce nurses’ stress, anxiety and depression symptoms during the COVID-19 outbreak.

    Mental health promotion strategies, such as physical activity, relaxation activity, recreational activity, healthy diet, adequate water intake, breaks between work shifts, maintenance of remote social contacts, and verbalization of feelings/emotions, are crucial to reduce nurses’ stress, anxiety and depression symptoms during the COVID-19 outbreak.Livestock is a major producer of agricultural greenhouse gas emissions in South Africa. Cattle methane (CH4) from enteric fermentation is the main source of the emissions. However, due to shortage of information to guide agricultural mitigation plans in the country, the main objective of this study is to investigate causal factors of the emissions from cattle in all nine national provinces. This study calculates provincial CH4 emission factors and factors (i.e. nitrogen excretion rate and average annual nitrogen excretion per animal) required for nitrous oxide (N2O) emissions from cattle manure management. The study further uses these factors and other values obtained from the literature to calculate cattle CH4 emissions from enteric fermentation and manure management. It also provides similar N2O emissions from manure management as well as urine and dung deposited on the pasture, range and paddock. The emissions are calculated for each cattle type commercial dairy, commercial beef, subsistence and feedlot caoping national factors to avoid uncertainties in emissions. As a result of national landscape and environmental conditions, the eastern provinces of the country are major sources of cattle emissions in the country.

    Ambient temperature extremes due to heat exposure was an established risk factor for preterm birth (<37 gestational weeks). However, there is insufficient epidemiological evidence on the effects of temperature variation(TV), although TV is also associated with heat exposure and can influence human health risk. This study aimed to investigate the relationship between inter- and intraday TV and preterm birth (PTB).

    A total of 1,388,994 live singleton births were collected from January 2003 to December 2012, from the Shenzhen Birth registry system. Daily temperature range (DTR) was defined as the difference between the highest and lowest recorded daily temperature. Intraday TV was defined as the maximum daily diurnal temperature range in a given week (Max-DTR). Inter-day TV was defined as the maximum increase or decrease in daily mean temperature between days t and t-1in a given week; either an increase (Temp-inc) or a decrease (Temp-dec). We used Cox proportional hazards models to estimate TV-related PTBwomen and their fetuses against extreme temperatures.In the present paper, an association between the growth rate of PTB and the environmental impacting elements in the pearl river delta region and the closed industry related cities in China is studied. We summarized the characteristics of different industry characteristics in this region by three echelons of urban agglomerations conducted by K-means clustering model on the time series of their monthly AQI data. To determine the impact of environmental factors on the increase of PTB, the SMLR in GLM has been applied. We then measured the seasonal effect and suggest the spring to be the leading season which keep the highest possibility of the incidence of PTB. Besides giving the analysis by fixed meteorological factors, we presented a sensitive analysis with a variation of precipitation. The Genetic algorithms (GAs) is used to determine the „tolerant” interval and as the results, the width of „tolerant” almost keep a declining trend as the precipitation increasing except when the precipitation comes the interval [68,74]. In addition, with the precipitation increasing higher than 64 mm, the „tolerant” for the AQI values from the first and the second echelon both trend to decline, and a lenient environmental policy currently may easily cause a rapid development of PTB growth rate.At each stage of innate immune response, there are stimulatory and inhibitory signals that modulate the strength and character of the response. RIG-I-like receptor (RLR) signaling pathway plays pivotal roles in antiviral innate immune response. Recent studies have revealed the molecular mechanisms that viral infection leads to the activation of RLRs-mediated downstream signaling cascades and the production of type I interferons (IFNs). However, antiviral immune responses must be tightly regulated in order to prevent detrimental type I IFNs production. Previous reviews have highlighted negative regulation of RLR signaling pathway, which mainly target to directly regulate RIG-I, MDA5, MAVS and TBK1 function in mammals. In this review, we summarize recent advances in our understanding of negative regulators of RLR signaling pathway in teleost, with specific focus on piscine and viral regulatory mechanisms that directly or indirectly inhibit the function of RIG-I, MDA5, LGP2, MAVS, TRAF3, TBK1, IRF3 and IRF7 both in the steady state or upon viral infection. We also further discuss important directions for future studies, especially for non-coding RNAs and post-translational modifications via fish specific TRIM proteins. The knowledge of negative regulators of RLR signaling pathway in teleost will shed new light on the critical information for potential therapeutic purposes.Arecoline N-oxide (ANO), an oxidative metabolite of the areca nut, is a predictable initiator in carcinogenesis. The mechanisms of arecoline metabolites in human cancer specimens is still limited. This present study aims to estimate the oral squamous cell carcinoma (OSCC) inductive activity between arecoline metabolites in human cancer specimens/OSCC cells. We have collected 22 pairs (tumor and non-tumor part) of patient’s specimens and checked for clinical characteristics. The identification of arecoline and its metabolites levels by using LC-MS/MS. The NOD/SCID mice model was used to check the OSCC inductive activity. The tumor part of OSCC samples exhibited higher levels of arecoline and ANO. Besides, ANO treated mice accelerates the NOTCH1, IL-17a and IL-1β expressions compared to the control mice. ANO exhibited higher cytotoxicity, intracellular ROS levels and decline in antioxidant enzyme levels in OC-3 cells. The protein expression of NOTCH1 and proliferation marker levels are significantly lower in NOM treated cells. Overall, ANO induced initial stage carcinogenesis in the oral cavity via inflammation, ROS and depletion of antioxidant enzymes. Arecoline N-oxide mercapturic acid (NOM) attenuates the initiation of oral carcinogenesis.

    The aim of this study is to provide new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in spontaneously hypertensive rats.

    An untargeted lipidomics using ultrahigh performance liquid chromatography-mass spectrometry metabolomics was used to identify the differentially expressed lipid metabolites over 24h in Spontaneously hypertensive rats (SHR) with reference to Wistar-Kyoto rats (WKY). The expression of circadian clock genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2) and lipid metabolism related genes (Rev-erbα, Pparα and Sirt1) was analysed RT-qPCR.

    Ten lipid metabolites with significant differences in their levels in SHR compared to WKY were identified. The levels of MG (250), PA (363) and PE (382) were lower and the levels of LysoPCs (200 and 203) and TGs (545, 5912, 280, 6010 and 6013) were found to be higher in SHR. SHR showed obvious disorders in the expression of circadian genes and lipid metabolism associated genes. A strong association between the levels of lipid metabolites and circadian genes and lipid metabolism associated genes was found.

    Rhythm genes may further affect the 24-hour lipid metabolism level of spontaneously hypertensive rats by mediating lipid metabolism associated genes. This research provides new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in SHR.

    Rhythm genes may further affect the 24-hour lipid metabolism level of spontaneously hypertensive rats by mediating lipid metabolism associated genes. This research provides new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in SHR.Chronic ulceration of the colon is associated with the activation of TLR4/NF-κB and P2X7R/NLRP3 signaling pathways. We investigated the effect of individual or combined administration of BBG, a P2X7R blocker, and OLT1177, a selective NLRP3 inhibitor, in the dextran sodium sulfate-induced ulcerative colitis (UC) rat model. The ulcerative rats were treated orally with brilliant blue G (BBG) (50 mg/kg/day) or OLT1177 (200 mg/kg/day) or a combination of both. Myd88 and NF-κB levels were measured by ELISA, qRT-PCR, and immunohistochemical staining. Cytokines known to be associated with TLR4/NF-κB or P2X7R/NLRP3 signaling were measured by ELISA. P2X7R and NLRP3 expression were measured by ELISA and qRT-PCR. The administration of BBG or OLT1177 ameliorated the toxic effects of DSS on the colon as they restored normal colonic macroscopic and microscopic morphology. BBG administration, but not OLT1177, reduced the expression of Myd88, NF-κB, IL-6, and TNF-α in addition to lowering P2X7R and oxidative stress levels. Individual BBG or OLT1177 administration decreased NLRP3 inflammasome recruitment and subsequent activation of caspase-1, IL-1β, and IL-18. However, the combined administration of OLT1177 with BBG potentiated its inhibitory effect on the NLRP3, which was reflected by the additional suppressive effect on caspase-1, IL-1β, IL-18 levels. In conclusion, BBG/OLT1177 exhibited complementary effects and effectively ameliorated UC. This novel approach provides a basis for the clinical application of this combination for the treatment of IBDs and might also be promising for the pharmacological intervention of other NLRP3 inflammasome-dependent inflammatory conditions.Acute kidney injury (AKI) is a progressive renal complication which significantly affects the patient’s life with huge economic burden. Untreated acute kidney injury eventually progresses to a chronic form and end-stage renal disease. Although significant breakthroughs have been made in recent years, there are still no effective pharmacological therapies for the treatment of acute kidney injury. Toll-like receptor 4 (TLR4) is a well-characterized pattern recognition receptor, and increasing evidence has shown that TLR4 mediated inflammatory response plays a pivotal role in the pathogenesis of acute kidney injury. The expression of TLR4 has been seen in resident renal cells, including podocytes, mesangial cells, tubular epithelial cells and endothelial cells. Activation of TLR4 signaling regulates the transcription of numerous pro-inflammatory cytokines and chemokines, resulting in renal inflammation. Therefore, targeting TLR4 and its downstream effectors could serve as an effective therapeutic intervention to prevent renal inflammation and subsequent kidney damage. For the first time, this review summarizes the literature on acute kidney injury from the perspective of TLR4 from year 2010 to 2020. In the current review, the role of TLR4 signaling pathway in AKI with preclinical evidence is discussed. Furthermore, we have highlighted several compounds of natural and synthetic origin, which have the potential to avert the renal TLR4 signaling in preclinical AKI models and have shown protection against AKI. This scientific review provides new ideas for targeting TLR4 in the treatment of AKI and provides strategies for the drug development against AKI.Long non-coding RNAs (lncRNAs) were considered as accumulated genetic waste until they were found to be gene expression regulators by highly sensitive modern genomics platforms. It is a huge class of non-coding transcripts with an arbitrary length of >200 nucleotides, which has gained much attention in the past few years. Increasing evidence from several experimental studies unraveled the expression of lncRNA linked to immune response and disease progression. However, only a small number of lncRNAs have robust evidence of their function. Differential expression of lncRNAs in different immune cells is also evident. In this review, we focused on how lncRNAs expression assist in shaping immune cells (Macrophages, Dendritic cells, NK cells, T cells, B cells, eosinophils, neutrophils, and microglial cells) function and their response to the diseased conditions. Emerging evidence revealed lncRNAs may serve as key regulators in the innate and adaptive immune response system. So, the molecular mechanism insight into the function of lncRNAs in immune response may contribute to the development of potential therapeutic targets for various disease treatments. Therefore, it is imperative to explore the expression of lncRNAs and understand its relevance associated with the immune system.Pancreatic cancer is among the most lethal malignancies with poor prognosis and patients become chemoresistant to current therapies, supporting further investigations to identify new therapeutic regimens in the treatment of this condition. Preclinical and clinical studies now appear to support the role of the renin-angiotensin system (RAS) in the regulation of tumor growth, angiogenesis, and metastasis in different malignancies including pancreatic cancer. These studies suggest that RAS blockers; Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs); could have anti-carcinogenic effects and improve clinical outcomes in the management of pancreatic cancer. Here we provided an overview of ACE inhibitors and ARBs as a potential therapeutic option in the treatment of pancreatic cancer.

    Current understanding of the risk of neoplastic progression in patients with Barrett’s esophagus with indefinite dysplasia (BE-IND) stems from small retrospective and pathology registry studies. In this multicenter cohort study, we aimed to determine the incidence and prevalence of neoplasia in BE-IND.

    Patients with confirmed BE-IND from 2 academic centers were included if they had no previous evidence of dysplasia and underwent endoscopic follow-up (FU) of≥1 year. The rate of progression to neoplasia was calculated and categorized as prevalent (progressionwithin 1 year of FU) and incident (progressionafter 1 year of FU). Multivariable regression adjusted for relevant clinical features was performed to identify risk factors for progression.

    Four hundred sixty-five patients diagnosed with BE-IND were identified between 1997 and 2017, of which 223 (48.0%) were excluded. Of the remaining 242 patients, 184 (76.0%) had no evidence of dysplasia during FU. In 23 patients (9.5%), prevalent neoplasia occurred (2cular biomarkers for risk stratification are warranted.

    Colonic endoscopic submucosal dissection (ESD) is particularly challenging and limited to a few expert centers. We recently conducted a pilot study on improvement of colonic ESD with systematic use of a countertraction device (double-clip traction with rubber band [DCT-ESD]).

    A French prospective multicenter study was conducted between March 2017 and September 2019, including all consecutive cases of naive colonic ESD. Since the first case of DCT-ESD in March 2017, all cases of colonic ESD have been performed using the DCT-ESD strategy in the 3 centers involved in the study.

    Five hundred ninety-nine lesions with a mean size of 53mm were included in this study, resected by 5 operators in 3 centers. The en bloc, R0, and curative resection rates were 95.7%, 83.5%, and 81.1%, respectively. The adverse event rates were 4.9% for perforation and 4.2% for postprocedure bleeding. Between 2017 and 2019, the rates of R0 and curative resections increased significantly from 74.7% in 2017 to 88.4% in 2019 (P= .003) and from 72.6% in 2017 to 86.3% in 2019 (P= .004), respectively. Procedure duration and speed of resection were 62.4 minutes and 39.4mm

    /minute, respectively. No differences were noted between operators.

    DCT-ESD is a safe and reproducible technique, with results comparable with those of the large Japanese teams with speed of resection twice as high as previously reported studies. The DCT strategy is promising, cheap, and seems to be reproducible. Physicians performing colonic ESD should be aware of this promising tool to improve their results in ESD.

    DCT-ESD is a safe and reproducible technique, with results comparable with those of the large Japanese teams with speed of resection twice as high as previously reported studies. The DCT strategy is promising, cheap, and seems to be reproducible. Physicians performing colonic ESD should be aware of this promising tool to improve their results in ESD.Two non-aqueous titrimetric and one visible spectrophotometric methods were developed and validated for the determination of valganciclovir hydrochloride (VLGH) in pure drug and tablets. The titrimetric methods were carried out by titrating the VLGH solution in glacial acetic acid with acetous perchloric acid (HClO4) in the presence of mercuric acetate and the end point of this titration was being located either visually (method A) or potentiometrically (method B). The spectrophotometric method (method C) was based on the addition of p-dimethylaminobenzaldehyde (DMAB) solution to VLGH solution and the formed yellow condensation product was measured at 420nm. In titrimetric procedures, both the methods A and B were applicable over the range of 4-20mg VLGH, and the calculations were based on a 11 reaction stoichiometry (VLGHHClO4). In a spectrophotometric method, Beer’s law was valid in a concentration range of 5-50 μg/mL VLGH with the corresponding value of molar absorptivity of 4.43×103L/mol cm for method C. The limits of detection (LOD) and quantification (LOQ) for method C were 0.3 and 0.92μg/mL, respectively. The developed methods were successfully applied to the determination of VLGH in tablets, and the results were statistically compared with those of a reference method by applying Student’s t-test and F-test. Further, the validity of the developed methods was confirmed by recovery studies via standard addition technique.Due to the increasing prescription of oral anticancer therapies, the inpatient care pathway has shifted to an outpatient care pathway. This transformation requires an interdisciplinary coordination to provide a continuum of care and ensure therapeutic monitoring, as well as patient safety. To better support patients on oral anticancer therapies, a task group named „hospital-to-community pharmacist coordination” has been set up to create tools aiming at standardising the information exchanged between ambulatory and hospital pharmacists. A retrospective study examined the utilisation of the tools over a period of one year. The task group identified the expectations of all parties regarding the care pathways of patients undergoing oral chemotherapy, which lead to the creation of computerised exchange tools (integrated into the computerised patient’s medical file). Over the course of this study, the cancer centre’s pharmaceutical team contacted 425 ambulatory pharmacists regarding the prescription of oral chemotherapy to patients. Forty-two follow-ups from ambulatory pharmacists, gathering information on 34 patients, were submitted to the cancer centre pharmacists (7,7%). These first follow-ups allowed pharmaceutical responses regarding patient compliance, drug interaction and toxicities.

    RDT and self-tests are sold in pharmacies. These are medical biology procedures that are currently reserved for biologists. Nevertheless, their use is now being reinforced by the COVID-19pandemic. What role should the dispensing pharmacist have in relation to the patient? What role can the biologist have in this system?

    A survey was carried out in pharmacies in the Auvergne-Rhône-Alpes region, as well as in Cameroon during the summer of 2020, to evaluate the use of RDT and self-tests. The answers obtained to the 10questions were discussed after a simple statistical analysis.

    Two hundred and eighty-three pharmacies and 13Cameroonian pharmacies participated in our survey. Pharmacists want to develop the use of RDT and self-test, but agree that training is necessary. Some tests are dispensed despite their unproven clinical usefulness.

    The delivery of TRODs and self-tests is acquired in pharmacies despite the reluctance of biologists. Pharmacists should be trained by biologists to use these tests in a relevant and appropriate manner.

    The delivery of TRODs and self-tests is acquired in pharmacies despite the reluctance of biologists. Pharmacists should be trained by biologists to use these tests in a relevant and appropriate manner.

    Although recruiting highly qualified, diverse applicants into cardiothoracic surgery remains a national priority, their characteristics remain unknown. This study aims to describe current and future applicants in cardiothoracic surgery.

    Aspiring cardiothoracic surgeons (students interested in matriculating in a North American training program) were voluntarily enrolled in the study through Twitter and email outreach. A 33-question survey evaluated their backgrounds, research experiences, attitudes, and interests within cardiothoracic surgery. Standard descriptive statistics were used.

    There were 111 participants, 40 of whom were female (36.0%) and 27 of whom identified as an underrepresented minority (24.3%). Of the total, 63 belonged to an institution with a cardiothoracic surgery training program (56.8%). A total of 91 students envisioned having a mostly operative career (82.0%) and 75 envisioned pursuing educational roles (67.6%). The most popular surgical specialties were heart transplantation (50.5e warranted to find areas for improvement in recruitment, retention, and diversity.The brain is a critical target for the toxic action of organophosphorus (OP) inhibitors of acetylcholinesterase (AChE) such as the nerve agent sarin. However, the available oxime antidote 2-PAM only reactivates OP-inhibited AChE in peripheral tissues. Monoisonitrosoacetone (MINA), a tertiary oxime, reportedly reactivates AChE in the central nervous system (CNS). The current study investigated whether MINA would be beneficial as a supplemental oxime treatment in preventing lethality and reducing morbidity following lethal sarin exposure, MINA supplement would improve AChE recovery in the body, and MINA would be detectable in the CNS. Guinea pigs were exposed to sarin and treated with atropine sulfate and 2-PAM at one minute. Additional 2-PAM or MINA was administered at 3, 5, 15, or 30 min after sarin exposure. Survival and morbidity were assessed at 2 and 24 h. AChE activity in brain and peripheral tissues was evaluated one hour after MINA and 2-PAM treatment. An in vivo microdialysis technique was used to determine partitioning of MINA into the brain. A liquid chromatography-tandem mass spectrometry method was developed for the analysis of MINA in microdialysates. MINA-treated animals exhibited significantly higher survival and lower morbidity compared to 2-PAM-treated animals. 2-PAM was significantly more effective in reactivating AChE in peripheral tissues, but only MINA reactivated AChE in the CNS. MINA was found in guinea pig brain microdialysate samples beginning at ~10 min after administration in a dose-related manner. The data strongly suggest that a centrally penetrating oxime could provide significant benefit as an adjunct to atropine and 2-PAM therapy for OP intoxication.Cobalt protoporphyrin (CoPP) is a potent heme oxygenase-1 inductor that produces temporary hypophagia and chronic weight loss. A complete description of this effect and the underlying mechanisms are unknown. In this work, we challenged the ability of CoPP to produce changes in rat behavior and cellular alterations in the Nucleus Accumbens that would explain those effects. We subcutaneously administered 25 µmol/kgbody weight CoPP in female rats and determined body weight, food intake, hyperactivity, and anxiety-like behavior, as well as the number of neurons and glial cells in the Nucleus Accumbens. CoPP significantly reduced food intake, water consumption, and body weight. Behavioral tests showed that anxiety-like behaviors and locomotor activity were not modified five days after the administration of CoPP. We also found a reduced number of neurons in the Nucleus Accumbens Shell. The above results could be relevant to diseases like anorexia, so it is necessary to deepen the study about the molecular mechanisms involved in reducing the food intake and weight loss elicited by CoPP.The serotonin 6 receptor (5-HT6) is a more recently identified therapeutic target for several neuropsychiatric disorders. While the 5-HT6 receptor has gained interest as a target for novel therapeutics, determining the basic sex differences is lacking in the literature. To address this, the present study examined the effects of 5-HT6 receptor modulation on locomotor activity and open field measures of anxiety in C57BL/6J mice. Female and male mice were tested after acute treatment with either 5-HT6 receptor antagonist SB 271046 or 5-HT6 receptor agonist EMD 386088. Acute 5-HT6 receptor blockade with SB 271046 attenuated locomotor activity in C57BL6/J mice, irrespective of sex. When locomotor activity was analyzed for six 10 min time blocks, 0.1, 5, or 15 mg/kg of SB 271046 reduced locomotor activity for the initial 40 min of testing, but only 5 and 15 mg/kg SB 271046 exhibited a reduction in locomotor activity for at least 60 min. EMD 386088 only attenuated locomotor activity when mice were treated with the high dose of 15 mg/kg EMD 386088. This was true for all time blocks except for the 40-50 min time block. In addition, EMD 386088 at the 15 mg/kg dose reduced locomotor activity in female mice more than males during the 20-30 and 30-40 minute time blocks. Analysis of the anxiolytic properties of 5-HT6 receptor modulation via the open field, showed that SB 271046 did not demonstrate anxiogenic properties in either sex at the doses tested. Instead, 15 mg/kg EMD 386088 produced an anxiogenic effect in both female and male mice. Together these findings highlight the differing impact of specific 5-HT6 receptor modulation on locomotor activity in C57BL/6J mice.Ethanol is associated with oxidative stress. Exposure to ethanol during childhood may lead to neurological disorders. Congenital disorders induced by alcohol are mainly caused by an oxidative-inflammatory cascade due to extensive apoptotic neurodegeneration in the brain, particularly in the hippocampus. Simvastatin, which acts as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA), is widely used to manage cardiovascular diseases. Recently, the neuroprotective effects of simvastatin against nervous system disorders have been introduced. In this study, we examined the protective effects of simvastatin on ethanol-related neurotoxicity in the hippocampus of rat pups. Ethanol (5.27 g/kg) in a milk solution (27.8 mL/kg) was administered to male rat pups via intragastric intubation at 2-10 days after birth. Also, 10 and 20 mg/kg of simvastatin were injected to the animals. By using Morris water maze task, the hippocampus-dependent memory and spatial learning was evaluated 36 days after birth. An ELISA atatin in rat pups with ethanol exposure in the postnatal period.Rosmarinic acid (RA), a natural polyphenol, possesses potent antioxidant and anti-inflammatory activities. To evaluate the ability of RA to cure ischemic stroke and post-stroke depression (PSD), rats were treated with various doses of RA after cerebral ischemia. Neurological deficits and infarct volume of the brain were measured. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were examined at different time points. In addition, a forced swimming test and sucrose preference test were performed to detect the anti-depressive effects of RA. Our results revealed RA administration significantly alleviated neurological deficits and reduced infarct volumes. RA attenuated the decrease of SOD, CAT activities and GSH levels in the ischemic penumbra of the brain. Most importantly, RA treatment alleviated the depression behaviors. Increased expression of Nrf2 was also induced by RA, while down regulation Nrf2 by Nrf2-short-hairpin RNA sequences reversed the increasing activity of SOD and CAT induced by RA, as well as the protection against PSD. The present study indicates that RA exerts a potent neuroprotective effect against stroke and PSD, which could be a promising therapeutic intervention for stroke.Treatment of Alzheimer’s Disease (AD) remains an unsolved issue despite the pronounced global attention it has received from researchers over the last four decades. Determining the primary cause of the disease is challenging due to its long prodromal phase and multifactorial etiology. Regardless, academic disagreements amongst the scientific community have helped in making significant advancements in underpinning the molecular basis of disease pathogenesis. Substantial development in fluid and imaging biomarkers for AD led to a sharp turn in defining the disease as a molecular construct, dispensing its clinical definition. With conceptual progress, revisions in the diagnostic criteria of AD were made, culminating into the research framework proposed by National Institute on Aging and Alzheimer’s Association in 2018 which unified different stages of the disease continuum, giving a common language of AT(N)1 classification to researchers. With realization that dementia is the final stage of AD spectrum, its early diagnosis by means of cerebrospinal fluid biomarkers, Positron Emission Tomography and Magnetic Resonance Imaging of the brain holds crucial importance in discovering ways of halting the disease progression. This article maps the insights into the pathogenesis as well as the diagnostic criteria and tests for AD as these have evolved over time. A contextualized timeline of how the understanding of AD has matured with advancing knowledge allows future research to be directed and unexplored avenues to be prioritized.

    Immediate contraceptive initiation, including start of a method before abortion completion, is a convenient option for women seeking abortion care.

    To evaluate the effect of systemic hormonal contraception initiation on medical abortion effectiveness and the safety of hormonal contraceptive methods following abortion.

    PubMed, Popline, Cochrane Library, and Clinicaltrials.gov.

    Studies that assessed medical abortion effectiveness after systemic hormonal contraception initiation and the safety of hormonal contraception initiation after abortion.

    Pregnant persons undergoing or who had recently undergone an abortion.

    Initiation of systemic hormonal contraception post abortion or on the day of the first pill of the medical abortion.

    We assessed study quality using the US Preventive Services Task Force evidence grading system. We created narrative summaries and calculated pooled relative risks when appropriate.

    We identified 16 studies for inclusion, 7 randomized controlled trials, and 9 cohorts. Ninortion appeared minimal.

    Initiating a hormonal contraceptive method after an abortion and as early as the same day as the first pill of the medical abortion is an option if contraception is desired. The slight increase in ongoing pregnancy with immediate DMPA initiation highlights the importance of information provision during contraceptive counseling.

    Initiating a hormonal contraceptive method after an abortion and as early as the same day as the first pill of the medical abortion is an option if contraception is desired. The slight increase in ongoing pregnancy with immediate DMPA initiation highlights the importance of information provision during contraceptive counseling.This study aimed to evaluate the in vitro effects of syringic acid on human colorectal cancer cells (SW-480) and the effect of orally administered syringic acid on in vivo models of colorectal cancer induced in rats by administration of 1,2-dimethylhydrazine (DMH). In vitro effects of syringic acid treatment on human colorectal cancer SW-480 cell lines were assessed by performing cell proliferation assay (MTT and Trypan Blue staining), apoptosis assays (TUNEL assay, Annexin-V/PI flowcytometry and lactate dehydrogenase release assay), measuring reactive oxygen species (ROS), antioxidant enzymes and DNA damage, and evaluating protein levels of proliferative genes, and autophagy markers. In vitro anti-cancer roles of syringic acid were studied in rats with DMH-induced colorectal cancer cells. The effect of orally administered syringic acid (50 mg/kg) on tumor growth and incidence was studied in four groups (n = 6) of animals injected with DMH and treated for 15 weeks. Syringic acid treatment resulted in a significant dose-dependent inhibition of cellular proliferation, induction of apoptosis through increasing cellular ROS and DNA damage levels, as well as downregulating major proliferative genes. In vivo, treatment of rats with syringic acid demonstrated a statistically significant tumor volume and incidence reduction when compared to the control. This is the first study demonstrating an in vivo growth inhibitory effect of orally administered syringic acid on colorectal tumors in rats.Dark Leathery Surface of Geoduck Clams (LSGC) is an alteration that affects the periostracum of the mantle and siphon of Panopea generosa from the northwest coast of Canada and Mexico. This alteration affects commercialization and possibly the survival of the clams. The cause of LSGC is unknown but has been correlated with presence of fungi and protozoans. We detected a similar alteration in Panopea globosa from Baja California, Mexico and the histophagous ciliate Uronema marinum was isolated from affected siphon tissue. U. marinum was identified by its morphology and by genetic analysis of the gene 18S rRNA. This is the first record of LSGC in P. globosa and the first identification of a histophagous protozoan associated with it.

    To compare the use of the parent-report Pediatric Symptom Checklist (PSC-17P) and youth-report Patient Health Questionnaire-9 Modified for Teens (PHQ-9M) in compliance with recent quality standards for adolescent depression screening.

    Parents of 5411 pediatric outpatients (11.0-17.9years old) completed the PSC-17P, which contains scales that assign categorical risk for overall (PSC-17P-OVR), internalizing (PSC-17P-INT), externalizing (PSC-17P-EXT), and attention (PSC-17P-ATT) problems. Adolescents completed the PHQ-9M, which assesses depressive symptoms. Both forms were completed online within 24hours of each other before pediatric well-child visits.

    A total of 9.9% of patients (n=535) were at risk on the PSC-17P-OVR, 14.3% (n=775) were at risk on the PSC-17P-INT, and 17.0% (n=992) were at risk on either or both scales (PSC-17P-OVR and/or PSC-17P-INT). Using the PHQ-9M cut-off score of 10 (moderate-very severe depression), an additional 2.4% (n=131) were classified as at risk, with 66.8% (n=263) of all depression as well as overall screening in pediatrics. Primary care clinicians can add the PHQ-9M to identify additional adolescents who may self-report depressive symptoms.

    To compare the effects of 2 treatment options on neurodevelopmental and laboratory outcomes in young children with nonanemic iron deficiency.

    A blinded, placebo-controlled, randomized trial of children 1-3years with nonanemic iron deficiency (hemoglobin ≥110g/L, serum ferritin <14μg/L) was conducted in 8 primary care practices in Toronto, Canada. Interventions included ferrous sulfate or placebo for 4months; all parents received diet advice. The primary outcome was the Early Learning Composite (ELC) using the Mullen Scales of Early Learning (mean 100, SD 15). Secondary outcomes included serum ferritin. Measurements were obtained at baseline and 4 and 12months. Sample size was calculated to detect a between-group difference of 6-7 points in ELC.

    At enrollment (n=60), mean age was 24.2 (SD 7.4) months and mean serum ferritin was 10.0 (SD 2.4) μg/L. For ELC, the mean between-group difference at 4months was 1.1 (95% CI -4.2 to 6.5) and at 12months was 4.1 (95% CI -1.9 to 10.1). For serum ferritin, at 4months, the mean between-group difference was 16.9μg/L (95% CI 6.5 to 27.2), and no child randomized to ferrous sulfate had a serum ferritin <14μg/L (0% vs 31%, P=.003).

    For young children with nonanemic iron deficiency, treatment options include oral iron and/or diet advice. We remain uncertain about which option is superior with respect to cognitive outcomes; however, adding ferrous sulfate to diet advice resulted in superior serum ferritin outcomes after 4months. Shared decision-making between practitioners and parents may be considered when selecting either option.

    Clinicaltrials.gov NCT01481766.

    Clinicaltrials.gov NCT01481766.

    To examine whether adverse childhood experiences (ACEs) and physical punishment (ie, spanking) are unique risk factors for behavior problems in early childhood, and whether ACEs moderate the associations of spanking with child behavior problems.

    We conducted prospective, longitudinal analyses on 2380 families in the Fragile Families and Child Wellbeing Study. Mothers reported outcomes of externalizing and internalizing behavior problems at age 5 years; and the main predictors, ACEs and spanking, at age 3 years. ACEs included 9 items physical abuse, emotional abuse, physical neglect, emotional neglect, mother’s exposure to intimate partner violence, parental mental health problem, parental substance use, parental incarceration, and parental death. Multilevel models examined the associations between ACEs, spanking, and behavior problems, and the moderating effect of ACEs in the associations of spanking with behavior problems. Analyses were adjusted for preexisting behavior problems, demographics, and neighborhood conditions.

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