Insights into the mechanism of L-malic acid on drip loss of chicken meat under commercial conditions

Background A deterioration in the meat quality of broilers has attracted much more attention in recent years.L-malic acid(MA)is evidenced to decrease meat drip loss in broilers,but the underlying molecular mechanisms are still unclear.It’s also not sure whether the outputs obtained under experimental conditions can be obtained in a com-mercial condition.Here,we investigated the effects and mechanisms of dietary MA supplementation on chicken meat drip loss at large-scale rearing.Results Results showed that the growth performance and drip loss were improved by MA supplementation.Meat metabolome revealed that L-2-aminoadipic acid,β-aminoisobutyric acid,eicosapentaenoic acid,and nicotinamide,as well as amino acid metabolism pathways connected to the improvements of meat quality by MA addition.The transcriptome analysis further indicated that the effect of MA on drip loss was also related to the proper immune response,evidenced by the enhanced B cell receptor signaling pathway,NF-κB signaling pathway,TNF signaling pathway,and IL-17 signaling pathway.Conclusions We provided evidence that MA decreased chicken meat drip loss under commercial conditions.Metabolome and transcriptome revealed a comprehensive understanding of the underlying mechanisms.Together,MA could be used as a promising dietary supplement for enhancing the water-holding capacity of chicken meat.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial

BACKGROUND The prognostic value of the Systemic Inflammation Response Index(SIRI)in advanced pancreatic cancer is recognized,but its correlation with patients´nutritional status and outcomes remains unexplored.AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer.METHODS The PANTHEIA-Spanish Society of Medical Oncology(SEOM)study is a multicentric(16 Spanish hospitals),observational,longitudinal,non-interventional initiative,promoted by the SEOM Real World-Evidence work group.This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI.The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers.Patients with pathologically confirmed metastatic pancreatic adenocarcinoma,treated from January 2020 to January 2023,were included.The index was calculated using the product of neutrophil and monocyte counts,divided by lymphocyte counts,obtained within 15 days before initiation chemotherapy.This study evaluated associations between overall survival(OS),SIRI and weight loss.RESULTS A total of 50 patients were included.66%of these patients were male and the median age was 66 years.Metastasis sites:36%liver,12%peritoneal carcinomatosis,10%lung,and 42%multiple locations.Regarding the first line palliative chemotherapy treatments:50%received gemcitabine plus nab-paclitaxel;28%,modified fluorouracil,leucovorin,irinotecan and oxaliplatin,and 16%were administered gemcitabine.42%had a weight loss>5%in the three months(mo)preceding diagnosis.21 patients with a SIRI≥2.3×10^(3)/L exhibited a trend towards a lower median OS compared to those with a SIRI<2.3×10^(3)/L(4 vs 18 mo;P<0.000).Among 21 patients with>5%weight loss before diagnosis,the median OS was 6 mo,in contrast to 19 mo for those who did not experience such weight loss(P=0.003).Patients with a weight loss>5%showed higher SIRI levels.This difference was statistically significant(P<0.000).For patients with a SIRI<2.3×10^(3)/L,those who did not lose>5%of their weight had an OS of 20 mo,compared to 11 mo for those who did(P<0.001).No association was found between carbohydrate antigen 19-9 levels≥1000 U/mL and weight loss.CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss.An elevated SIRI is suggested as a predictor of survival,emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Remedies for loss and damage caused by climate change from the dimension of climate justice

Adverse consequences to the ecological system and human health caused by impacts potentially attributable to climate change have already drawn great and widespread concern of many scientists and international organizations.However,we still have a hard time determining exactly the impact of climate change on the environment or the damage that climate change inflicts on countries comprising small islands or low-lying lands in light of today's science and technology.The progress for dealing with the issue of loss and damage has been struggling for a long time from the beginning to the present.In this paper,the author begins by summarizing talks on the concept and the positions of commentators.The author is proposing that the development of future climate negotiations and rule-making process be based on global climate justice as a standard for measuring value.Also,the author proposes that a holistic view of climate justice be established.Generally,three aspects of climate justice can be derived.First,the dimension of human rights protection shows that protection of fundamental human rights is a logical precondition if small-island and low-lying countries are able to achieve climate justice.Second,the definite and traditional concepts of distributive justice and corrective justice hold the view that the principle of common but differentiated responsibilities should be upheld as a basic standard of allocating rights and duties associated with climate change.Third,climate justice requires that any state follow the "no-harm principle," which is regarded as an international customary rule.According to the principle,the obligation of states to prevent the use of their territory for causing trans-boundary harm to the environment shall be a violation of state responsibility,which incurs international punishment.Then we put forward three remedial approaches in light of climate justice,including the approach of State Responsibility(SR) based on the principles and rules of international human rights law and international environmental law.Based on clear rules,the judge can determine whether the damaging behavior or the damage perpetrated by a state party constitutes a state responsibility.The International Environmental Regulation(IEB),which means solving the problems within the framework established by the Conventions on Climate Change,takes advantage of the market mechanisms and incentives such as fund and insurance support system to relieve or compensate the loss and damage.International Environmental Dispute Settlement Mechanism(IEDSM),which includes the means such as consultations,negotiations,nonmandatory ways and international arbitration,international judicial ways to solve these disputes,functions as a procedural safeguard.As an active promoter of global climate governance,China should no doubt stand by the principle of Common But Differentiated Responsibility(CBDR) and take it as a basis for negotiations,actively strengthen the work of South-South cooperation,fulfill her international climate commitments without reservation,vigorously develop a low-carbon economy,and actively promote international negotiations on the subject of loss and damage.

Response of the Dominant Modes of Atmospheric Circulation in the Northern Hemisphere to a Projected Arctic Sea Ice Loss in 2007

This study revisits the Arctic sea ice extent(SIE) for the extended period of 1979-2015 based on satellite measurements and finds that the Arctic SIE experienced three different periods: a moderate sea ice decline period for 1979-1996, an accelerated sea ice decline period from 1997 to 2006, and large interannual variation period after 2007, when Arctic sea ice reached its tipping point reported by Livina and Lenton(2013). To address the response of atmospheric circulation to the lowest sea ice conditions with a large interannual variation, we investigated the dominant modes for large atmospheric circulation responses to the projected 2007 Arctic sea ice loss using an atmospheric general circulation model(ECHAM5). The response was obtained from two 50-yr simulations: one with a repeating seasonal cycle of specified sea ice concentration for the period of 1979-1996 and one with that of sea ice conditions in 2007. The results suggest more occurrences of a negative Arctic Oscillation(AO) response to the 2007 Arctic sea ice conditions, accompanied by an North Atlantic Oscillation(NAO)-type atmospheric circulation response under the largest sea ice loss, and more occurrences of the positive Arctic Dipole(AD) mode under the 2007 sea ice conditions, with an across-Arctic wave train pattern response to the largest sea ice loss in the Arctic. This study offers a new perspective for addressing the response of atmospheric circulation to sea ice changes after the Arctic reached the tipping point in 2007.

THE GENETIC-INDUCED HEARING lOSS CAN BLOCK THE EFFECT OF NOISE TRAUMA IN WAlTZING GUINEA PIG

The waltzing guinea pig may be a good model to investigate if genetic factor can change the sensitivity in noise-induced hearing loss. A total of 34 waltzig guinea pigs were studied and we found that there is no any significant increased sensitivity to noise trauma if the age-induced hearing loss was considered in waltz-ing guinea pig.

Risk of Hearing Loss Caused by Multiple Acoustic Impulses in the Framework of Biovariability

We consider the hearing loss injury among subjects in a crowd with a wide spectrum of individual intrinsic injury probabilities due to biovariability. For multiple acoustic impulses, the observed injury risk of a crowd vs the effective combined dose follows the logistic dose-response relation. The injury risk of a crowd is the average fraction of injured. The injury risk was measured in experiments as follows: each subject is individually exposed to a sequence of acoustic impulses of a given intensity and the injury is recorded;results of multiple individual subjects were assembled into data sets to mimic the response of a crowd. The effective combined dose was adjusted by varying the number of impulses in the sequence. The most prominent feature observed in experiments is that the injury risk of the crowd caused by multiple impulses is significantly less than the value predicted based on assumption that all impulses act independently in causing injury and all subjects in the crowd are statistically identical. Previously, in the case where all subjects are statistically identical (i.e., no biovariability), we interpreted the observed injury risk caused by multiple impulses in terms of the immunity effects of preceding impulses on subsequent impulses. In this study, we focus on the case where all sound exposure events act independently in causing injury regardless of whether one is preceded by another (i.e., no immunity effect). Instead, we explore the possibility of interpreting the observed logistic dose-response relation in the framework of biovariability of the crowd. Here biovariability means that subjects in the crowd have their own individual injury probabilities. That is, some subjects are biologically less or more susceptible to hearing loss injury than others. We derive analytically the distribution of individual injury probability that produces the observed logistic dose-response relation. For several parameter values, we prove that the derived distribution is mathematically a proper density function. We further study the asymptotic approximations for the density function and discuss their significance in practical numerical computation with finite precision arithmetic. Our mathematical analysis implies that the observed logistic dose-response relation can be theoretically explained in the framework of biovariability in the absence of immunity effect.

A Comparative Study on Efficacy of Fludrocortisones versus Glucocorticoids and Vasodilators in the Treatment of Idiopathic Sensorineural Cochlear Hearing Loss

Introduction and Objectives: The idiopathic sensorineural cochlear hearing loss is one of the most frequent human sensory deficits and there is no specific drug therapy for it. The possible hearing recovery is related with the reestablishment of normal ionic homeostasis of the endolymph controlled by the mineralocorticoid as could be demonstrate experimentally. The purpose of this clinical trial was to confirm the efficacy of mineralocorticoids to the recovery of hearing level in patients suffering idiopathic sensorineural hearing loss (SNHL) against the glucocorticoids and vasodilator drugs. Material and Methods: The research lasted three months and involved 90 patients allocated into four different groups: Placebo group, consisted of 20 patients (10 men and 10 women);the group consisting of 22 patients treated with glucocorticoid therapy (12 men and 10 female);the group treated with mineralocorticoid therapy encompassed 26 patients (13 males and 13 females) and the group of vasodilators formed by 22 patients (12 men and 10 women). The level of hearing loss was estimated by the tests Liminal Tone Audiometry (LTA) and Auditory Brainstem Response (ABR). Results: The main features in this research were overall better response in improving the hearing level with the mineralocorticoid therapy. This improvement in hearing levels was greater in women than in men, and a higher response was found in the left ear regardless of patient’s gender. Conclusions: The hearing gain was significantly superior in the mineralocorticoids group followed by the glucocorticoids group whereas the response to vasodilators was lesser and with no statistical significance.

Corporate Social Responsibility——From the Perspective of Polish Enterprises

Corporate social responsibility （CSR） is becoming more and more frequently emphasized part of management in the structure of Polish enterprises. These results from the fact that growing awareness of consumers, destructive impact of industry on the natural environment, economic scandals, unethical behavior among entrepreneurs, bring about redefining the principles of a business activity on the market by entrepreneurs. As a result of the above, such values as honesty, trust, or responsibility take on greater importance. Additionally, more and more often, Polish entrepreneurs pay attention to the influence of the company on the environment, the way the stakeholders are treated, while striving to maximize profit. The present paper looks into the subject of social responsibility from the point of view of Polish enterprises. To verify this objective, there was the analysis of the due literature performed, and also carried out the survey among 174 entrepreneurs running their business activity in the area of Southern Poland. The research tool used in the research was the questionnaire （PAPI and CAWI）. In the conducted research, there were factors analyzed referring to knowledge of social responsibility among the people holding both managerial and lower-level positions, in particular opinion, is it important for enterprises to be driven by ethical standards？ How to implement CSR in their structures？ How to understood concept of CSR？ What are the reasons for the implementation of CSR in the strategy of the company？ The considerations （both the theoretical and practical ones） confirmed that the Polish enterprises feel the increased need to implement the activities in the field of social responsibility, which, in the present conditions, constitutes an important part of running a business activity.

Governing for the Global Good the Greening of Diverse Responsibilities

This paper discusses methods for governing the global good. It holds that justice for both people and non-human creatures requires a change at the foundations of our view of life. What is needed is not only a few more government regulations or a little more international cooperation based on the unquestioned presupposition of the priority of national sovereignty and economic growth,but also a different perspective on our responsibilities for the wellbeing of the commons, recognizing that increasingly the environmental commons is global in scope and requires some transnational means of governance. It also holds that a"responsibilities"approach calls for the greening of all kinds of responsibility and not only those of national governments and international organizations.

Effect of Phopshate Fertilizer and Manure on Crop Yield, Soil P Accumulation, and the Environmental Risk Assessment

Phosphorus （P） applied from fertilizer and manure is important in increasing crop yield and soil fertility; however, excessive uses of phosphate fertilizer and manure may also increase P loss from agricultural soils, posing environmental impact. A long term experiment was conducted on a calcareous soil （meadow cinnamon） in Hebei Province, China, from 2003 to 2006 to investigate the effects of phosphate fertilizer and manure on the yield of Chinese cabbage, soil P accumulation, P sorption saturation, soluble P in runoff water, and P leaching. P fertilizer （P2O5） application at a rate of 360 kg ha^-1 or manure of 150 t ha^-1 significantly increased Chinese cabbage yield as compared to the unfertilized control. However, no significant yield response was found with excessive phosphate or manure application. Soil Olsen-P, soluble P, bioavailable P, the degree of phosphorus sorption saturation in top soil layer （0-20 cm）, and soluble P in runoff water increased significantly with the increase of phosphate fertilizer and manure application rates, whereas the maximum phosphorus sorption capacity （Qm） decreased with the phosphate fertilizer and manure application rates. Soil Olsen-P and soluble P also increased significantly in the sub soil layer （20-40 cm） with the high P fertilizer and manure rates. It indicates that excessive P application over crop demand can lead to a high environmental risk owing to the enrichment of soil Olsen-P, soluble P, bioavailable P, and the degree of phosphorus sorption saturation in agricultural soils.

Clinical impact of immunomonitoring in the treatment of inflammatory bowel disease

Despite improvement in outcomes, loss of response(LOR) to tumor necrosis factor-alpha (TNFα) therapies is a big concern in the management of inflammatory bowel disease. LOR is associated with flares of disease, increased hospitalisation rates, need for surgical interventions, and decline in quality of life. LOR may be multifactorial, but immunogenicity makes a significant contribution. Traditionally doses of anti-TNFα have been adjusted based on clinical response, using a standard approach. Immunomonitoring involves the measurement of anti-TNFα trough and antibody levels. It takes into account the underlying pharmacokinetics of anti-TNFα therapies. Expanding on this a treat to target approach may be used, where doses are intensified, or tailored to the individual based on the measurement of anti-TNFα trough and antibody levels. This review looks at the history, evolution, and clinical impact that immunomonitoring is having in the treatment of inflammatory bowel disease. It will focus on the role of immunomonitoring in helping to achieve long lasting deep remission and mucosal healing. It will explore the different options in terms of best measuring trough and antibody levels, explore possible advantages of immunomonitoring, and discuss its role in best optimising response, at induction, during the maintenance phase of treatment, as well as a role in withdrawing or switching therapy.

A preliminary study of the mechanism of compound hearing loss caused by ototoxic drugs combined with impulse noise

Background:Hearing loss(HL)is becoming increasingly common and is more commonly caused by noise,ototoxic substances,or a combination of ototoxic factors.However,so far,few studies have examined the mechanism by which compound factors cause HL.The only relevant study is about occupational ototoxic substances combined with environmental noise at 85-110 dB SPL.In this study,to address the shortcomings of existing research,we innovatively focused on HL induced by loud noise(impulse noise,>160 dB SPL)combined with common ototoxic drugs.The aim of this study was to establish and validate a mature animal model,and then to compare the characteristics of audiology,pathomorphology and molecular features,and to preliminarily predict pathogenesis in compound HL.Materials and Methods:We selected guinea pigs to construct in vivo HL model groups for different extents of exposure,including a blank control group,a single-drug group,a single-impulse noise group,and a compound group.The animal model of the mature compound HL group was established using gentamicin combined with impulse noise.We then performed audio-logical and pathological verification.We analyzed the auditory brainstem response(ABR),pathological morphology of the cochlea,and molecules(including important self-radicals,cytokines,and apoptosis signal trans-duction pathway proteins in the pathogenesis of drug-and noise-induced HL),compared the effect of different extents of exposure on HL,and preliminarily predict the pathogenic mechanism of compound HL.Results:Four groups of animal models were established successfully and verified by audiology and pathology.Regarding audiology,there were no sig-nificant differences in the ABR thresholds before exposure(p>0.05),but differences emerged among the groups after exposure.Notably,after 3,7,and 14 days of exposure,there were significant differences in the ABR thresholds between the compound group and both the drug and noise groups(p<0.01),and after 14 days,the HL of the compound group was much more severe(greater than the linear sum of single-factor HL group).Regarding the patho-morphology,compared with the control group,the cochleae were damaged to different degrees in the factor exposure groups.The drug group had the least severe HL,the noise group had serious HL(p<0.05),and the compound group had the most severe HL(p<0.01).The compound group's damage was greater than the linear sum of the single-factor group in many ways,such as the loss and damage of hair cells and cilia,disturbed morphology and arrangement of hair cells,protein metabolism,cell function,and structural defects on the epidermal plate(p<0.01).From a molecular perspective,the trend was similar to pathology and audiology,and the synergistic effect of ototoxic drugs and impulse noise significantly increased cytokine levels(IL-6,ICAM-1,8-OHDG,IL-1,and TNF-α),free radicals Malondialdehyde([MDA],▪OH,LPO,O•2ˉ),and the apoptosis signal transduction pathway protein.There were significant differences between the compound group and single-factor groups(p<0.05).Conclusion:Gentamicin,impulse noise,and compound factors were used to induce HL in animal models,which were verified by audiology and pathology,laying a foundation for future studies.After constructing the animal models,we found that 50 mg/kg of gentamicin for 10 days was a subinjury dose,and 50�impulse noise caused partial HL,but the two factors combined had a significant synergistic ototoxicity effect,which increased the level of oxidative stress and the waterfall response of inflammatory cytokines in the cochleae and enhanced the expression of apoptosis-related proteins,resulting in syn-ergistic pathomorphological and audiological injury.We preliminarily analyzed the pathogenic mechanism of compound HL,establishing the basis for further study of the mechanism,prevention,and treatment of this increasing global problem.

Impacts of different methylprednisolone administration routes in patients with sudden hearing loss or Meniere’s disease

Background:Evidence suggests that glucocorticoids are important in the treatment of sudden hearing loss(SHL)and Meniere’s disease(MD).However,different glucocorticoid administration methods may have a significant impact on treatment outcomes.Objective:This study aimed to investigate effects of different glucocorticoid administration methods on sudden hearing loss and Meniere’s disease.Methods:In this study,glucocorticoids were administered orally in 18 patients,by retroauricular injection in 15 patients and by intratympanic injection in 15 patients.White blood cell(WBC)count,serum Kt,fasting plasma glucose(FPG),body temperature,heart rate and blood pressure were used to evaluate effects of glucocorticoids on patients with hearing loss.Visual analog scale(VAS)of pain and sleep disorders were also surveyed,and pure tone audiometry(PTA)results were compared among groups to evaluate efficacy of different glucocorticoids administration methods.Result:WBC count,heart rate and blood pressure were higher in patients taking oral glucocorticoids,while body temperature,serum Kt and FPG levels did not change in all three groups.However,patients who received intratympanic injection of glucocorticoids experienced more pain,while those taking oral glucocorticoids reported more sleep impairment.Treatment efficacy on hearing loss was not significantly different among the three groups.Conclusion:These findings suggest that systemic glucocorticoid administration can result in greater whole body responses than local administration,but with similar hearing treatment efficacy.

Adalimumab induction therapy for ulcerative colitis with intolerance or lost response to infliximab: An open-label study

AIM: To evaluate the efficacy of adalimumab induction therapy in patients with ulcerative colitis who previously responded to infliximab and then lost response or became intolerant. METHODS: Ten patients with ulcerative colitis were enrolled in a 4-wk open-label trial. The patients received a loading dose of 160 mg adalimumab at wk 0 followed by 80 mg at wk 2. The primary efficacy measure was clinical improvement at wk 4, as defined by a decrease in clinical activity index (CAI) of more than 4. RESULTS: Four of 10 patients (40%) benefited from subsequent adalimumab therapy; one patient achieved remission (CAI < 4) and 3 had clinical improvement at wk 4. 6 patients had no response (60%); 2 of 6 (33.3%) subsequently underwent colectomy. This was accompanied by a decrease in median CRP concentration from 16.8 mg/mL at baseline to 3.85 mg/mL at wk 4, excluding two patients who underwent colectomy after two infusions of adalimumab. Among the 6 patients with severe colitis (CAI > 12) at baseline, none achieved remission and only one patient had clinical improvement at wk 4. CONCLUSION: The small advantage of adalimumab in patients with mild to moderate ulcerative colitis and lost response or intolerance to infliximab needs to be confirmed in randomised, double-blind, placebo- controlled trials.

Therapeutic drug monitoring in inflammatory bowel disease:The dawn of reactive monitoring

Inflammatory bowel disease(IBD)is a chronic condition that significantly affects the quality of life of its patients.Biologic drugs have been the mainstay treatment in the management of IBD patients but despite their significant contribution,there remains a proportion of patients that do not respond or lose response to treatment.Therapeutic drug monitoring(TDM)involves measuring levels of serum drug concentrations and anti-drug antibodies.TDM of biologic drugs initially emerged to understand treatment failure in other immune mediated inflammatory diseases.This was then introduced in IBD to rationalize primary non-response or secondary loss of response,given that low serum drug concentrations or the formation of anti-drug antibodies are variably associated with treatment failure.The aim of this narrative review is to provide an overview regarding the current use of TDM in clinical practice and to present the evidence available regarding its use in both proactive and reactive clinical settings in preventing and managing treatment failure.This review also presents the existing evidence regarding the association of various clinical outcomes with specific thresholds of drug concentrations,in everyday practice.A narrative review of published articles and conference abstracts regarding the use of TDM in IBD management,through an electronic search using PubMed and ScienceDirect.TDM has proven to be superior and more cost effective in guiding management of patients with treatment failure compared to empiric dose escalation or change in treatment.Despite a trend towards an association between clinical outcomes and drug concentrations,proactive TDM based strategies have not been shown to achieve clear benefit in long-term outcomes.In the clinical setting,TDM has proven to be useful in managing IBD patients,and its use in the reactive setting,as an additional tool to help manage patients with treatment failure,is being promoted as newer guidelines and consensus groups implement TDM as part of the management plan.

Optimization of Osmotic Drying Parameters for Button Mushroom (<i>Agaricus bisporus</i>)

Response surface methodology was used to investigate the effect of brine concentration (10% - 20%) solution temperature (35℃ - 55℃), and duration of osmosis (30 - 60 min) with respect to water loss (WL) and salt gain (SG). The solu- tion to sample ratio of 5/1 (w/w) was used. The Box-Behnken design of three variables and three levels including seventeen experiments formed by five central points were used for optimizing input parameters. Linear, quadratic and interaction effects of three variables were analyzed with respect to water loss and solid gain. For each response, second order polynomial models were developed using multiple regression analysis. Analysis of variance (ANOVA) was per- formed to check the adequacy and accuracy of the fitted models. The response surfaces and contour maps showing the interaction of process variables were constructed. The optimum operating conditions were: solution temperature 44.89℃, brine concentration of 16.53 per cent and duration of osmosis of 47.59 min. At this optimum point, water loss and salt gain were predicted to be 44.55 per cent and 2.98 percent respectively.

EFFECT OF ORIENTATION ON STRESS RESPONSE,FRICTION STRESS AND BACK STRESS DURING CYCLIC DEFORMATION IN Al SINGLE CRYSTALS

The symmetrical push-pull fatigue tests at strain amplitude of 2×10~3 with different slip orientation of Al single crystals,were carried out at room temperature in air.The peak stresses of various cycles were measured and the stress-strain hysteresis loops for selected cy- cles were recorded.The energy losses.friction stresses,back stresses and shape

Effect of Lipopolysaccharide-Induced Immune Responses on Pregnancy Loss in Ewes

An acute phase response induced by Gram-negative bacteria can reduce pregnancy rate. Early pregnant ewes were used to monitor effects of lipopolysaccharide (LPS), an endotoxin in the outer cell membrane of Gram-negative bacteria, on acute phase/innate immunity response. In Exp. 1, mixed breed ewes were assigned to receive either LPS or LPS and flunixin meglumine, an inhibitor of prostaglandin synthetase, intravenously on day 5 after mating. In Exp. 2, mixed breed ewes were assigned to receive an intravenous injection on day 5 after mating of either saline, LPS, recombinant human tumor necrosis factor (TNF)-α or LPS after pretreatment with dexamethasone. Pregnancy was diagnosed ultrasonographically on d 25, and live births were recorded at parturition. Challenge with LPS induced acute phase responses (fever, mucosal responses, lethargy and increased serum TNF, haptoglobin and?serum amyloid A) and decreased pregnancy rates. Predictably, flunixin meglumine attenuated fever but did not increase pregnancy rate in LPS-treated ewes. Similarly, exogenous TNF alone induced mucosal and serum amyloid A responses but did not affect pregnancy. Pre-treatment with dexamethasone blocked fever and mucosal and lethargic responses and attenuated increases in TNF and haptoglobin but did not ameliorate LPS-induced pregnancy loss. In summary, acute challenge with LPS mimics bacterial-induced pregnancy losses in early pregnant ewes. Although pretreatment with dexamethasone decreased clinical signs and some innate immune responses, neither it nor flunixin meglumine prevented LPS-induced pregnancy loss. That exogenous TNF alone did not promote pregnancy loss indicates that other cytokines also contribute to LPS-induced embryonic loss.

Analysis of the variability of auditory brainstem response components through linear regression

The analysis of the Auditory Brainstem Response (ABR) is of fundamental importance to the investigation of the auditory system behavior, though its interpretation has a subjective nature because of the manual process employed in its study and the clinical experience required for its analysis. When analyzing the ABR, clinicians are often interested in the identification of ABR signal components referred to as Jewett waves. In particular, the detection and study of the time when these waves occur (i.e., the wave latency) is a practical tool for the diagnosis of disorders affecting the auditory system. In this context, the aim of this research is to compare ABR manual/visual analysis provided by different examiners. Methods: The ABR data were collected from 10 normal-hearing subjects (5 men and 5 women, from 20 to 52 years). A total of 160 data samples were analyzed and a pair- wise comparison between four distinct examiners was executed. We carried out a statistical study aiming to identify significant differences between assessments provided by the examiners. For this, we used Linear Regression in conjunction with Bootstrap, as a method for evaluating the relation between the responses given by the examiners. Results: The analysis suggests agreement among examiners however reveals differences between assessments of the variability of the waves. We quantified the magnitude of the obtained wave latency differences and 18% of the investigated waves presented substantial differences (large and moderate) and of these 3.79% were considered not acceptable for the clinical practice. Conclusions: Our results characterize the variability of the manual analysis of ABR data and the necessity of establishing unified standards and protocols for the analysis of these data. These results may also contribute to the validation and development of automatic systems that are employed in the early diagnosis of hearing loss.

First Trimester Pregnancy Loss May Temporary Reduce the Ovarian Response during the Subsequent IVF Cycle

The aim of this study was to compare the in vitro fertilization (IVF) cycles ended by miscarriage with subsequent IVF cycles in relation to various IVF cycle parameters and pregnancy termination modalities. Comparison of pre-miscarriage to post-miscarriage IVF cycles parameters demonstrated that lower peak E2 levels (1087 ± 593 versus 1237 ± 676 pg/ml, respectively;p p p p p p < 0.05), and an increase in the conception rate (34.7% versus 42.2%, respectively) at the second post-miscarriage IVF cycle.