ResearchPad - Anatomy https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Bi-Level ventilation decreases pulmonary shunt and modulates neuroinflammation in a cardiopulmonary resuscitation model]]> https://www.researchpad.co/product?articleinfo=Nfc29e3d5-af29-453c-bdc8-d5378300b77b

Background

Optimal ventilation strategies during cardiopulmonary resuscitation are still heavily debated and poorly understood. So far, no convincing evidence could be presented in favour of outcome relevance and necessity of specific ventilation patterns. In recent years, alternative models to the guideline-based intermittent positive pressure ventilation (IPPV) have been proposed. In this randomized controlled trial, we evaluated a bi-level ventilation approach in a porcine model to assess possible physiological advantages for the pulmonary system as well as resulting changes in neuroinflammation compared to standard measures.

Methods

Sixteen male German landrace pigs were anesthetized and instrumented with arterial and venous catheters. Ventricular fibrillation was induced and the animals were left untreated and without ventilation for 4 minutes. After randomization, the animals were assigned to either the guideline-based group (IPPV, tidal volume 8–10 ml/kg, respiratory rate 10/min, FiO21.0) or the bi-level group (inspiratory pressure levels 15–17 cmH2O/5cmH2O, respiratory rate 10/min, FiO21.0). Mechanical chest compressions and interventional ventilation were initiated and after 5 minutes, blood samples, including ventilation/perfusion measurements via multiple inert gas elimination technique, were taken. After 8 minutes, advanced life support including adrenaline administration and defibrillations were started for up to 4 cycles. Animals achieving ROSC were monitored for 6 hours and lungs and brain tissue were harvested for further analyses.

Results

Five of the IPPV and four of the bi-level animals achieved ROSC. While there were no significant differences in gas exchange or hemodynamic values, bi-level treated animals showed less pulmonary shunt directly after ROSC and a tendency to lower inspiratory pressures during CPR. Additionally, cytokine expression of tumour necrosis factor alpha was significantly reduced in hippocampal tissue compared to IPPV animals.

Conclusion

Bi-level ventilation with a constant positive end expiratory pressure and pressure-controlled ventilation is not inferior in terms of oxygenation and decarboxylation when compared to guideline-based IPPV ventilation. Additionally, bi-level ventilation showed signs for a potentially ameliorated neurological outcome as well as less pulmonary shunt following experimental resuscitation. Given the restrictions of the animal model, these advantages should be further examined.

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<![CDATA[Acute ST-Elevation Myocardial Infarction Caused by Simultaneous Occlusion of Two Culprit Arteries]]> https://www.researchpad.co/product?articleinfo=N68f27915-4624-43c4-a572-fd5cbbd5812b

ST-elevation myocardial infarction (STEMI) is usually caused by acute thrombosis of a single culprit vessel, whereas STEMI caused by the simultaneous thrombosis of multiple coronary arteries is rare. A review of 711 STEMI cases undergoing percutaneous coronary intervention (PCI) revealed that only 2.5% of patients had acute coronary thrombosis of multiple arteries. We present a case of an 80-year-old female with a history of hypertension who presented with acute onset chest pain and underwent emergent angiography. Her angiography showed acute coronary thrombosis of both the distal left anterior descending artery (dLAD) and the distal obtuse marginal branch 3. She underwent PCI and had restoration of flow. Given the unique presentation of simultaneous multiple coronary thrombi, she underwent additional diagnostic workup before being discharged with guideline-directed medical therapy. While the American College of Cardiology and the European Society of Cardiology guidelines address culprit lesion only PCI versus complete revascularization of non-infarct related lesions, there are no guidelines or randomized controlled trials that have attempted to characterize the best management of STEMI caused by multiple culprit lesions. As a result, the best management of these cases is not standardized. Further case reports leading to prospective studies are needed to better predict outcomes and guide future management.

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<![CDATA[Size matters: micro-evolution in Polynesian rats highlights body size changes as initial stage in evolution]]> https://www.researchpad.co/product?articleinfo=N2dd55868-5849-4fff-8cf7-11bb065f2041

Microevolutionary patterns in populations of introduced rodent species have often been the focus of analytic studies for their potential relevance to understanding vertebrate evolution. The Polynesian rat (Rattus exulans) is an excellent proxy species because of its wide geographic and temporal distribution: its native and introduced combined range spans half the globe and it has been living for at least seven centuries wherever it was introduced. The objective of this study was to assess the effects of long-term isolation (insularity; up to 4,000 years) and geographic variables on skull shape variation using geometric morphometrics. A sample of 513 specimens from 103 islands and four mainland areas was analysed. This study, to my knowledge the first to extensively sample introduced rats, analysed 59 two-dimensional landmarks on the skull. Landmarks were obtained in three separate aspects (dorsal, lateral, ventral skull view). The coordinate data were then subjected to a multivariate ordination analysis (principal components analysis, or PCA), multivariate regressions, and a canonical variates analysis (CVA). Three measures of disparity were evaluated for each view. The results show that introduced Polynesian rats evolve skull shapes that conform to the general mammalian interspecific pattern of cranial evolutionary allometry (CREA), with proportionally longer snouts in larger specimens. In addition, larger skulls are more tubular in shape than the smaller skulls, which are more balloon-shaped with a rounder and wider braincase relative to those of large skulls. This difference is also observed between the sexes (sexual dimorphism), due to the slightly larger average male size. Large, tubular skulls with long snouts are typical for Polynesia and Remote Oceania, where no native mammals occur. The greater disparity of Polynesian rats on mammal species-poor islands (’exulans-only’ region) provides further insight into how diversity may affect diversification through ecological release from predators and competitors.

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<![CDATA[Effect of additional body weight on arch index and dynamic plantar pressure distribution during walking and gait termination]]> https://www.researchpad.co/product?articleinfo=Na3a41dc1-9743-460c-b4f0-1bde6646e983

The medial longitudinal arch is considered as an essential feature which distinguishes humans from other primates. The longitudinal arch plays a supporting and buffering role in human daily physical activities. However, bad movement patterns could lead to deformation of arch morphology, resulting in foot injuries. The authors aimed to investigate any alterations in static and dynamic arch index following different weight bearings. A further aim was to analyze any changes in plantar pressure distribution characteristics on gait during walking and stopping, Twelve males were required to complete foot morphology scans and three types of gait tests with 0%, 10%, 20% and 30% of additional body weight. The dynamic gait tests included walking, planned and unplanned gait termination. Foot morphology details and plantar pressure data were collected from subjects using the Easy-Foot-Scan and Footscan pressure platform. No significant differences were observed in static arch index when adding low levels of additional body weight (10%). There were no significant changes observed in dynamic arch index when loads were added in the range of 20% to 30%, except in unplanned gait termination. Significant maximal pressure increases were observed in the rearfoot during walking and in both the forefoot and rearfoot during planned gait termination. In addition, significant maximum pressure increases were shown in the lateral forefoot and midfoot during unplanned gait termination when weight was increased. Findings from the study indicated that excessive weight bearing could lead to a collapse of the arch structure and, therefore, increases in plantar loading. This may result in foot injuries, especially during unplanned gait termination.

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<![CDATA[Long-term effect of the Brazilian Workers’ Food Program on the nutritional status of manufacturing workers: A population-based prospective cohort study]]> https://www.researchpad.co/product?articleinfo=N23375fc9-a89d-407e-9d06-75f348bd7d78

Background

The Brazilian Workers Food Program (WFP) is a public policy program of nutritional assistance to workers, with the main objective of improving nutritional conditions, which was implemented 40 years ago and serves over 21.4 million workers.

Objectives

To compare the long-term change in anthropometric indicators of the nutritional status and dietary intake between workers of manufacturing industries adherent to and non-adherent to the WFP.

Methods

A prospective cohort study, based on a combined stratified and multistage probability sampling, was carried out, with two waves with a 4-year interval. The change in body mass index (BMI), waist circumference (WC) and dietary intake at lunch by the 24-hour recall method were compared between groups with analysis of covariance.

Results

A total of 273 workers in 16 industries from an initial cohort of 1069 workers in 26 industries of the State of Rio Grande do Norte in Brazil were evaluated in the two waves. The mean age was 37±10 years and 53.1% were male, with no differences between groups in age and sex distribution. BMI increased in both groups (0.44 kg/m2 in non-WFP, p = 0.003, and 0.56 kg/m2 in WFP, p = 0.0006) and WC increased in the WFP group (1.50 cm, p = 0.0006). BMI change over time did not show statistical differences between groups (p = 0.54) but WC had a greater increase in the WFP group (difference 1.37 cm, p = 0.047). There were no differences between groups in the change over time of the dietary intake.

Conclusion

BMI and WC increased over time in manufacturing workers of industries both adherent and non-adherent to the WFP, but with a greater increase of WC in the WFP group. In order to achieve the objectives of the WFP, there will be a need for periodic evaluation and monitoring of nutritional indicators in these workers and implementation of monitoring and enforcement actions of the WFP.

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<![CDATA[Investigation of synovial fluid induced Staphylococcus aureus aggregate development and its impact on surface attachment and biofilm formation]]> https://www.researchpad.co/product?articleinfo=Nf13f73b5-5132-41b9-b894-3d4dd0a113b1

Periprosthetic joint infections (PJIs) are a devastating complication that occurs in 2% of patients following joint replacement. These infections are costly and difficult to treat, often requiring multiple corrective surgeries and prolonged antimicrobial treatments. The Gram-positive bacterium Staphylococcus aureus is one of the most common causes of PJIs, and it is often resistant to a number of commonly used antimicrobials. This tolerance can be partially attributed to the ability of S. aureus to form biofilms. Biofilms associated with the surface of indwelling medical devices have been observed on components removed during chronic infection, however, the development and localization of biofilms during PJIs remains unclear. Prior studies have demonstrated that synovial fluid, in the joint cavity, promotes the development of bacterial aggregates with many biofilm-like properties, including antibiotic resistance. We anticipate these aggregates have an important role in biofilm formation and antibiotic tolerance during PJIs. Therefore, we sought to determine specifically how synovial fluid promotes aggregate formation and the impact of this process on surface attachment. Using flow cytometry and microscopy, we quantified the aggregation of various clinical S. aureus strains following exposure to purified synovial fluid components. We determined that fibrinogen and fibronectin promoted bacterial aggregation, while cell free DNA, serum albumin, and hyaluronic acid had minimal effect. To determine how synovial fluid mediated aggregation affects surface attachment, we utilized microscopy to measure bacterial attachment. Surprisingly, we found that synovial fluid significantly impeded bacterial surface attachment to a variety of materials. We conclude from this study that fibrinogen and fibronectin in synovial fluid have a crucial role in promoting bacterial aggregation and inhibiting surface adhesion during PJI. Collectively, we propose that synovial fluid may have conflicting protective roles for the host by preventing adhesion to surfaces, but by promoting bacterial aggregation is also contributing to the development of antibiotic tolerance.

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<![CDATA[Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis]]> https://www.researchpad.co/product?articleinfo=Nd170950f-0b0f-46af-a42d-6b06a3bc49ed

Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.

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<![CDATA[Uptake and speciation of zinc in edible plants grown in smelter contaminated soils]]> https://www.researchpad.co/product?articleinfo=N21b4cc8f-fdc5-4198-8cfa-2868c1971919

Heavy metal accumulation in edible plants grown in contaminated soils poses a major environmental risk to humans and grazing animals. This study focused on the concentration and speciation of Zn in different edible plants grown in soils contaminated with smelter wastes (Spelter, WV, USA) containing high levels of the metals Zn, Cu, Pb, Cd. Their accumulation was examined in different parts (roots, stem, and leaves) of plants and as a function of growth stage (dry seed, sprouting seed, cotyledon, and leaves) in the root vegetables radish, the leafy vegetable spinach and the legume clover. Although the accumulation of metals varied significantly with plant species, the average metal concentrations were [Zn] > [Pb] > [Cu] > [Cd]. Metal uptake studies were complemented with bulk and micro X-ray absorption spectroscopy (XAS) at Zn K-edge and micro X-ray fluorescence (μXRF) measurements to evaluate the speciation and distribution of Zn in these plant species. Dynamic interplay between the histidine and malate complexation of Zn was observed in all plant species. XRF mapping of spinach leaves at micron spatial resolution demonstrated the accumulation of Zn in vacuoles and leaf tips. Radish root showed accumulation of Zn in root hairs, likely as ZnS nanoparticles. At locations of high Zn concentration in spinach leaves, μXANES suggests Zn complexation with histidine, as opposed to malate in the bulk leaf. These findings shed new light on the dynamic nature of Zn speciation in plants.

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<![CDATA[Influence of the tubular network on the characteristics of calcium transients in cardiac myocytes]]> https://www.researchpad.co/product?articleinfo=N7f446290-780e-4486-a1de-95187c6060a1

Transverse and axial tubules (TATS) are an essential ingredient of the excitation-contraction machinery that allow the effective coupling of L-type Calcium Channels (LCC) and ryanodine receptors (RyR2). They form a regular network in ventricular cells, while their presence in atrial myocytes is variable regionally and among animal species We have studied the effect of variations in the TAT network using a bidomain computational model of an atrial myocyte with variable density of tubules. At each z-line the t-tubule length is obtained from an exponential distribution, with a given mean penetration length. This gives rise to a distribution of t-tubules in the cell that is characterized by the fractional area (F.A.) occupied by the t-tubules. To obtain consistent results, we average over different realizations of the same mean penetration length. To this, in some simulations we add the effect of a network of axial tubules. Then we study global properties of calcium signaling, as well as regional heterogeneities and local properties of sparks and RyR2 openings. In agreement with recent experiments in detubulated ventricular and atrial cells, we find that detubulation reduces the calcium transient and synchronization in release. However, it does not affect sarcoplasmic reticulum (SR) load, so the decrease in SR calcium release is due to regional differences in Ca2+ release, that is restricted to the cell periphery in detubulated cells. Despite the decrease in release, the release gain is larger in detubulated cells, due to recruitment of orphaned RyR2s, i.e, those that are not confronting a cluster of LCCs. This probably provides a safeguard mechanism, allowing physiological values to be maintained upon small changes in the t-tubule density. Finally, we do not find any relevant change in spark properties between tubulated and detubulated cells, suggesting that the differences found in experiments could be due to differential properties of the RyR2s in the membrane and in the t-tubules, not incorporated in the present model. This work will help understand the effect of detubulation, that has been shown to occur in disease conditions such as heart failure (HF) in ventricular cells, or atrial fibrillation (AF) in atrial cells.

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<![CDATA[Reference values of physiological 18F-FET uptake: Implications for brain tumor discrimination]]> https://www.researchpad.co/product?articleinfo=N80bdbd58-ef10-47b0-8bc3-8bde8c3b2b52

Purpose

The aim of this study was to derive reference values of 18F-fluoro-ethyl-L-tyrosine positron emission tomography (18F-FET-PET) uptake in normal brain and head structures to allow for differentiation from tumor tissue.

Materials and methods

We examined the datasets of 70 patients (median age 53 years, range 15–79), whose dynamic 18F-FET-PET was acquired between January 2016 and October 2017. Maximum standardized uptake value (SUVmax), target-to-background standardized uptake value ratio (TBR), and time activity curve (TAC) of the 18F-FET-PET were assessed in tumor tissue and in eight normal anatomic structures and compared using the t-test and Mann-Whitney U-test. Correlation analyses were performed using Pearson or Spearman coefficients, and comparisons between several variables with Pearson’s chi-squared tests and Kruskal-Wallis tests as well as the Benjamini-Hochberg correction.

Results

All analyzed structures showed an 18F-FET uptake higher than background (threshold: TBR > 1.5). The venous sinuses and cranial muscles exhibited a TBR of 2.03±0.46 (confidence interval (CI) 1.92–2.14), higher than the uptake of caudate nucleus, pineal gland, putamen, and thalamus (TBR 1.42±0.17, CI 1.38–1.47). SUVmax, TBR, and TAC showed no difference in the analyzed structures between subjects with high-grade gliomas and subjects with low-grade gliomas, except the SUVmax of the pineal gland (t-tests of the pineal gland: SUVmax: p = 0.022; TBR: p = 0.411). No significant differences were found for gender and age.

Conclusion

Normal brain tissue demonstrates increased 18F-FET uptake compared to background tissue. Two distinct clusters have been identified, comprising venous structures and gray matter with a reference uptake of up to SUVmax of 2.99 and 2.33, respectively.

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<![CDATA[Assessment of availability, awareness and perception of stakeholders regarding preschool vision screening in Kumasi, Ghana: An exploratory study]]> https://www.researchpad.co/product?articleinfo=N637f6c02-dcec-48f9-ae4a-5e42bca666db

Background

Regardless of the importance of preschool vision screening (PSVS), there is limited data on the current state of these programs in Africa (particularly Ghana). This study sought to investigate the level of awareness and perception of stakeholders regarding PSVS, its availability and related policies/programmes in the Kumasi Metropolis, Ghana.

Methods

This descriptive cross-sectional study included 100 systematically sampled preschools in the metropolis (using probability proportional-to-size method); 72 private schools and 28 public schools. Convenience sampling was used to recruit stakeholders of preschools (teachers, head teachers, proprietors, administrators, directors, and educationists), and were interviewed using a well-structured questionnaire. Questionnaires were administered to all eligible respondents who were present at the time of data collection.

Results

A total of 344 respondents participated in the study; 123 (35.8%) males and 221 (64.2%) females. The overall mean age of respondents was 37.63 ±12.20 years (18–71 years). Of the respondents, 215 (62.5%), 94 (27.3%), and 35 (10.2%) were enrolled from private schools, public schools, and Metropolitan Education Directorate, respectively. 73.8% of respondents reported the absence of routine PSVS in schools whereas 90.1% reported no written policies for PSVS in schools. Only 63.6% of respondents were aware of PSVS whereas more than half (59.6%) of all respondents perceived PSVS to be very important for preschoolers. Private school ownership was significantly associated with availability of PSVS whereas age, teachers, private school ownership, and preschool experience > 10 years were significantly associated with awareness of PSVS (P < 0.05). However, there was no significant association between sociodemographic factors and perception of PSVS.

Conclusion

PSVS is largely unavailable in most Ghanaian schools. Majority of stakeholders were aware of PSVS and agreed to its implementation and incorporation into schools’ health programmes. There is the need to implement a national programme/policy on preschool vision screening in Ghana.

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<![CDATA[Changes in human health parameters associated with an immersive exhibit experience at a zoological institution]]> https://www.researchpad.co/product?articleinfo=N69289aa2-a5fc-4464-abf6-42bfa80ae1ee

Zoological institutions often use immersive, naturalistic exhibits to create an inclusive atmosphere that is inviting for visitors while providing for the welfare of animals in their collections. In this study, we investigated physiological changes in salivary cortisol and blood pressure, as well as psychological changes among visitors before and after a walk through the River’s Edge, an immersive, naturalistic exhibit at the Saint Louis Zoo. Study participants had a significant reduction in salivary cortisol and blood pressure after walking through the exhibit. Psychological assessments of mood found that most visitors felt happier, more energized, and less tense after the visit. Additionally, participants who spent more time in River’s Edge, had visited River’s Edge prior to the study, and had seen more exhibits at the Zoo prior to entering River’s Edge experienced greater psychological and/or physiological benefits. We conclude that immersive, naturalistic exhibits in zoos can elicit positive changes in physiological and psychological measures of health and well-being and argue for a greater scientific focus on the role of zoos and other green spaces in human health.

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<![CDATA[Opposing effects of HNP1 (α-defensin-1) on plasma cholesterol and atherogenesis]]> https://www.researchpad.co/product?articleinfo=Ndf7081dd-c312-4392-aa9c-ddf6cf67dfa0

Atherosclerosis, the predominant cause of death in well-resourced countries, may develop in the presence of plasma lipid levels within the normal range. Inflammation may contribute to lesion development in these individuals, but the underlying mechanisms are not well understood. Transgenic mice expressing α-def-1 released from activated neutrophils develop larger lipid and macrophage-rich lesions in the proximal aortae notwithstanding hypocholesterolemia caused by accelerated clearance of α-def-1/low-density lipoprotein (LDL) complexes from the plasma. The phenotype does not develop when the release of α-def-1 is prevented with colchicine. However, ApoE-/- mice crossed with α-def-1 mice or given exogenous α-def-1 develop smaller aortic lesions associated with reduced plasma cholesterol, suggesting a protective effect of accelerated LDL clearance. Experiments were performed to address this seeming paradox and to determine if α-def-1 might provide a means to lower cholesterol and thereby attenuate atherogenesis. We confirmed that exposing ApoE-/- mice to α-def-1 lowers total plasma cholesterol and decreases lesion size. However, lesion size was larger than in mice with total plasma cholesterol lowered to the same extent by inhibiting its adsorption or by ingesting a low-fat diet. Furthermore, α-def-1 levels correlated independently with lesion size in ApoE-/- mice. These studies show that α-def-1 has competing effects on atherogenesis. Although α-def-1 accelerates LDL clearance from plasma, it also stimulates deposition and retention of LDL in the vasculature, which may contribute to development of atherosclerosis in individuals with normal or even low plasma levels of cholesterol. Inhibiting α-def-1 may attenuate the impact of chronic inflammation on atherosclerotic vascular disease.

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<![CDATA[Neuroprotective effects of exogenous erythropoietin in Wistar rats by downregulating apoptotic factors to attenuate N-methyl-D-aspartate-mediated retinal ganglion cells death]]> https://www.researchpad.co/product?articleinfo=N85685bba-c047-422b-abfc-358a98ed1fe7

The aim of this study was to investigate whether exogenous erythropoietin (EPO) administration attenuates N-methyl-D-aspartate (NMDA)-mediated excitotoxic retinal damage in Wistar rats. The survival rate of retinal ganglion cells (RGCs) were investigated by flat mount analysis and flow cytometry. A total of 125 male Wistar rats were randomly assigned to five groups: negative control, NMDA80 (i.e., 80 nmoles NMDA intravitreally injected), NMDA80 + 10ng EPO, NMDA80 + 50ng EPO, and NMDA80 + 250ng EPO. The NMDA80 + 50ng EPO treatment group was used to evaluate various administrated points (pre-/co-/post- administration of NMDA80). Meanwhile, the transferase dUTP Nick-End Labeling (TUNEL) assay of RGCs, the inner plexiform layer (IPL) thickness and the apoptotic signal transduction pathways of μ-calpain, Bax, and caspase 9 were assessed simultaneously using an immunohistochemical method (IHC). When EPO was co-administered with NMDA80, attenuated cell death occurred through the downregulation of the apoptotic indicators: μ-calpain was activated first (peak at ~18hrs), followed by Bax and caspase 9 (peak at ~40hrs). Furthermore, the images of retinal cross sections have clearly demonstrated that thickness of the inner plexiform layer (IPL) was significantly recovered at 40 hours after receiving intravitreal injection with NMDA80 and 50ng EPO. Exogenous EPO may protect RGCs and bipolar cell axon terminals in IPL by downregulating apoptotic factors to attenuate NMDA-mediated excitotoxic retinal damage.

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<![CDATA[Drug induced pancreatitis: A systematic review of case reports to determine potential drug associations]]> https://www.researchpad.co/product?articleinfo=N8c4889da-2d62-467b-8b66-b271dff2cf8d

Objective

A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations.

Methods

A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency.

Results

Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis.

Discussion

Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations.

Registration

CRD42017060473.

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<![CDATA[Role of intraoperative oliguria in risk stratification for postoperative acute kidney injury in patients undergoing colorectal surgery with an enhanced recovery protocol: A propensity score matching analysis]]> https://www.researchpad.co/product?articleinfo=N90678846-11a4-456d-84dc-7e3677d2f27e

Background

The enhanced recovery after surgery (ERAS) protocol for colorectal cancer resection recommends balanced perioperative fluid therapy. According to recent guidelines, zero-balance fluid therapy is recommended in low-risk patients, and immediate correction of low urine output during surgery is discouraged. However, several reports have indicated an association of intraoperative oliguria with postoperative acute kidney injury (AKI). We investigated the impact of intraoperative oliguria in the colorectal ERAS setting on the incidence of postoperative AKI.

Patients and methods

From January 2017 to August 2019, a total of 453 patients underwent laparoscopic colorectal cancer resection with the ERAS protocol. Among them, 125 patients met the criteria for oliguria and were propensity score (PS) matched to 328 patients without intraoperative oliguria. After PS matching had been performed, 125 patients from each group were selected and the incidences of AKI were compared between the two groups. Postoperative kidney function and surgical outcomes were also evaluated.

Results

The incidence of AKI was significantly higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (26.4% vs. 11.2%, respectively, P = 0.002). Also, the eGFR reduction on postoperative day 0 was significantly greater in the intraoperative oliguria than non-intraoperative oliguria group (−9.02 vs. −1.24 mL/min/1.73 m2 respectively, P < 0.001). In addition, the surgical complication rate was higher in the intraoperative oliguria group than in the non-intraoperative oliguria group (18.4% vs. 9.6%, respectively, P = 0.045).

Conclusions

Despite the proven benefits of perioperative care with the ERAS protocol, caution is required in patients with intraoperative oliguria to prevent postoperative AKI. Further studies regarding appropriate management of intraoperative oliguria in association with long-term prognosis are needed in the colorectal ERAS setting.

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<![CDATA[Constitutive hydrogen inhalation prevents vascular remodeling via reduction of oxidative stress]]> https://www.researchpad.co/product?articleinfo=Ne1330967-900e-43ee-b1f2-140543b0d511

Molecular hydrogen is thought to have an inhibitory effect on oxidative stress, thereby attenuating the onset and progression of various diseases including cardiovascular disease; however, few reports have assessed the preventive effect of constitutive inhalation of hydrogen gas on of vascular remodeling. Here, we investigated the effect of constitutive inhalation of hydrogen gas on vascular neointima formation using a cuff-induced vascular injury mouse model. After constitutive inhalation of compressed hydrogen gas (O2 21%, N2 77.7%, hydrogen 1.3%) or compressed air only (O2 21%, N2 79%) by C57BL/6 mice for 2 weeks from 8 weeks of age in a closed chamber, inflammatory cuff injury was induced by polyethylene cuff placement around the femoral artery under anesthesia, and hydrogen gas administration was continued until sampling of the femoral artery. Neointima formation, accompanied by an increase in cell proliferation, was significantly attenuated in the hydrogen group compared with the control group. NADPH oxidase NOX1 downregulation in response to cuff injury was shown in the hydrogen group, but the expression levels of NADPH oxidase subunits, p40phox and p47phox, did not differ significantly between the hydrogen and control groups. Although the increase in superoxide anion production did not significantly differ between the hydrogen and control groups, DNA damage was decreased as a result of reduction of reactive oxygen species such as hydroxyl radical (⋅OH) and peroxynitrite (ONOO-) in the hydrogen group. These results demonstrate that constitutive inhalation of hydrogen gas attenuates vascular remodeling partly via reduction of oxidative stress, suggesting that constitutive inhalation of hydrogen gas at a safe concentration in the living environment could be an effective strategy for prevention of vascular diseases such as atherosclerosis.

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<![CDATA[Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions]]> https://www.researchpad.co/product?articleinfo=N24a1d01a-2f11-47b7-a628-8330af6f7455

Recent advances in canine intestinal organoids have expanded the option for building a better in vitro model to investigate translational science of intestinal physiology and pathology between humans and animals. However, the three-dimensional geometry and the enclosed lumen of canine intestinal organoids considerably hinder the access to the apical side of epithelium for investigating the nutrient and drug absorption, host-microbiome crosstalk, and pharmaceutical toxicity testing. Thus, the creation of a polarized epithelial interface accessible from apical or basolateral side is critical. Here, we demonstrated the generation of an intestinal epithelial monolayer using canine biopsy-derived colonic organoids (colonoids). We optimized the culture condition to form an intact monolayer of the canine colonic epithelium on a nanoporous membrane insert using the canine colonoids over 14 days. Transmission and scanning electron microscopy revealed a physiological brush border interface covered by the microvilli with glycocalyx, as well as the presence of mucin granules, tight junctions, and desmosomes. The population of stem cells as well as differentiated lineage-dependent epithelial cells were verified by immunofluorescence staining and RNA in situ hybridization. The polarized expression of P-glycoprotein efflux pump was confirmed at the apical membrane. Also, the epithelial monolayer formed tight- and adherence-junctional barrier within 4 days, where the transepithelial electrical resistance and apparent permeability were inversely correlated. Hence, we verified the stable creation, maintenance, differentiation, and physiological function of a canine intestinal epithelial barrier, which can be useful for pharmaceutical and biomedical researches.

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<![CDATA[Streptococcal H2O2 inhibits IgE-triggered degranulation of RBL-2H3 mast cell/basophil cell line by inducing cell death]]> https://www.researchpad.co/product?articleinfo=Nadf2e0c3-9608-4100-a6fa-f03310d30959

Mast cells and basophils are central players in allergic reactions triggered by immunoglobulin E (IgE). They have intracellular granules containing allergic mediators (e.g., histamine, serotonin, inflammatory cytokines, proteases and β-hexosaminidase), and stimulation by IgE-allergen complex leads to the release of such allergic mediators from the granules, that is, degranulation. Mast cells are residents of mucosal surfaces, including those of nasal and oral cavities, and play an important role in the innate defense system. Members of the mitis group streptococci such as Streptococcus oralis, are primary colonizers of the human oral cavity. They produce hydrogen peroxide (H2O2) as a by-product of sugar metabolism. In this study, we investigated the effects of streptococcal infection on RBL-2H3 mast cell/basophil cell line. Infection by oral streptococci did not induce degranulation of the cells. Stimulation of the RBL-2H3 cells with anti-dinitrophenol (DNP) IgE and DNP-conjugated human serum albumin triggers degranulation with the release of β-hexosaminidase. We found that S. oralis and other mitis group streptococci inhibited the IgE-triggered degranulation of RBL-2H3 cells. Since mitis group streptococci produce H2O2, we examined the effect of S. oralis mutant strain deficient in producing H2O2, and found that they lost the ability to suppress the degranulation. Moreover, H2O2 alone inhibited the IgE-induced degranulation. Subsequent analysis suggested that the inhibition of degranulation was related to the cytotoxicity of streptococcal H2O2. Activated RBL-2H3 cells produce interleukin-4 (IL-4); however, IL-4 production was not induced by streptococcal H2O2. Furthermore, an in vivo study using the murine pollen-induced allergic rhinitis model suggested that the streptococcal H2O2 reduces nasal allergic reaction. These findings reveal that H2O2 produced by oral mitis group streptococci inhibits IgE-stimulated degranulation by inducing cell death. Consequently, streptococcal H2O2 can be considered to modulate the allergic reaction in mucosal surfaces.

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<![CDATA[Host immune responses during Taenia solium Neurocysticercosis infection and treatment]]> https://www.researchpad.co/product?articleinfo=Nc0d0d75e-fba6-45d6-a2e4-1505f9de6f1c

Taenia solium cysticercosis and taeniasis (TSCT), caused by the tapeworm T. solium, is a foodborne and zoonotic disease classified since 2010 by WHO as a neglected tropical isease. It causes considerable impact on health and economy and is one of the leading causes of acquired epilepsy in most endemic countries of Latin America, Sub-Saharan Africa, and Asia. There is some evidence that the prevalence of TSCT in high-income countries has recently increased, mainly due to immigration from endemic areas. In regions endemic for TSCT, human cysticercosis can manifest clinically as neurocysticercosis (NCC), resulting in epileptic seizures and severe progressive headaches, amongst other neurological signs and/or symptoms. The development of these symptoms results from a complex interplay between anatomical cyst localization, environmental factors, parasite’s infective potential, host genetics, and, especially, host immune responses. Treatment of individuals with active NCC (presence of viable cerebral cysts) with anthelmintic drugs together with steroids is usually effective and, in the majority, reduces the number and/or size of cerebral lesions as well as the neurological symptoms. However, in some cases, treatment may profoundly enhance anthelmintic inflammatory responses with ensuing symptoms, which, otherwise, would have remained silent as long as the cysts are viable. This intriguing silencing process is not yet fully understood but may involve active modulation of host responses by cyst-derived immunomodulatory components released directly into the surrounding brain tissue or by the induction of regulatory networks including regulatory T cells (Treg) or regulatory B cells (Breg). These processes might be disturbed once the cysts undergo treatment-induced apoptosis and necrosis or in a coinfection setting such as HIV. Herein, we review the current literature regarding the immunology and pathogenesis of NCC with a highlight on the mobilization of immune cells during human NCC and their interaction with viable and degenerating cysticerci. Moreover, the immunological parameters associated with NCC in people living with HIV/AIDS and treatments are discussed. Eventually, we propose open questions to understand the role of the immune system and its impact in this intriguing host–parasite crosstalk.

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