Porosity determination of Vienna sausages through digital images analysis.

BACKGROUND: This research aimed to determine the porosity and particle size distribution in canned Vienna-type sausages using digital image analysis (DIA) on photographs captured with a digital camera and applying a Monte Carlo simulation. The methodology determined morphometric parameters (area and Feret diameter) by DIA of transverse and longitudinal sections of canned sausages. Those images were previously contrast enhanced, color threshold adjusted, and binarized. Subsequently, the estimation of the pore volume was carried out from the inverse Gaussian distributions of Feret diameter and area, as well as the porosity, using Monte Carlo simulation. RESULTS: The pores had an average Feret diameter of 0.335 mm and an average area of 0.085 mm2 . The highest estimated bivariate kernel density was presented for the smallest pores (around 0.02 mm2 in area and 0.25 mm in diameter). Simulation average values of pore volume, assumed as a cylinder, and porosity were 1.455 mm3 and 0.737 respectively. The average porosity value was consistent with the value experimentally estimated by the indirect method, in concordance with the definition of porosity, which was 0.715, presenting a mean relative percentage error of 3.08% concerning the estimated experimental value as well. CONCLUSION: This research presents interesting perspectives for the quantitative analysis of the microstructure of food and biological materials through a novel, low-cost, reliable, and fast proposal. Moreover, this is the first study to report the porosity determination in canned sausages by DIA. © 2022 Society of Chemical Industry.

Distribution of planar cell polarity proteins in the developing avian retina.

Planar cell polarity (PCP) is evolutionary conserved and play a critical role in proper tissue development and function. During central nervous system development, PCP proteins exhibit specific patterns of distribution and are indispensable for axonal growth, dendritogenesis, neuronal migration, and neuronal differentiation. The retina constitutes an excellent model in which to study molecular mechanisms involved in neural development. The analysis of the spatiotemporal expression of PCP proteins in this model constitutes an useful histological approach in order to identify possible roles of these proteins in retinogenesis. Immunohistochemical techniques revealed that Frz6, Celsr1, Vangl1, Pk1, Pk3, and Fat1 were present in emerging axons from recently differentiated ganglion cells in the chicken retina. Except for Vangl1, they were also asymmetrically distributed in differentiated amacrine cells. Pk1 and Pk3 were restricted in the outer nuclear layer to the outer segment of photoreceptors. Vangl1 was also located in the cell somata of Müller glia. Given these findings together, the distribution of PCP proteins in the developing chicken retina suggest essential roles in axonal guidance during early retinogenesis and a possible involvement in the establishment of cell asymmetry and maintenance of retinal cell phenotypes.

A phenomenological-based semi-physical model of the kidneys and its role in glucose metabolism.

The kidneys play an important role in glucose homeostasis in three ways: Via endogenous glucose production from non-carbohydrate precursors (e.g. glutamine, lactate, alanine, glycerol) during both postprandial and post-absorptive states; via glucose filtration and reabsorption by the glomerulus and proximal tubule, respectively; and via glucose utilization and the elimination of its excess in the urine when glucose levels exceed 180mg/dl. The renal release of glucose into the circulation occurs mainly in the renal cortex and results from the glucose phosphorylating capacity of those renal cells, meaning that, cells in the renal cortex can form glucose-6-phosphate. Considering glucose filtration and reabsorption, the kidneys filtrate and reabsorb all circulating glucose, rendering the urine virtually glucose-free in a healthy person. Finally, the kidneys take up glucose from the circulation for energetic self-supply. Besides their role in glucose metabolism, the kidneys are the major site of insulin clearance from the systemic circulation, removing approximately 50% of peripheral insulin. In this regard, insulin clearance by kidneys occurs by degradation in the proximal tubule after being filtered in the glomerulus. All the aforementioned mechanisms affect the glucose concentration levels in the blood, preventing the parametrization of a mathematical model for patients with diabetes mellitus, in the implementation of an artificial pancreas. Aiming for a complete physiological model of the glucose homeostasis, a physiological submodel of the kidneys is presented in a way not described in the literature so far. This submodel is a phenomenological-based semi-physical model with a basic structure rooted in the conservation law and for which the parameters are interpretable. The model's results coincide well with the available clinical data reported for kidney functions associated with glucose and insulin.

Phenomenological-based model of glucose transport from liver to abdominal subcutaneous adipose tissue.

BACKGROUND: A good treatment for type 1 diabetes mellitus (T1DM) requires accurate measurements of blood glucose levels. Continuous glucose monitors (CGM) measure the glucose concentration in the interstitial fluid of the abdominal subcutaneous adipose tissue. However, glucose measured in the abdominal interstitial fluid does not represent blood glucose concentrations accurately due to the complex blood transport through the body and glucose diffusion in interstitial fluid. METHODS: To gain insight into this problem, a phenomenological-based semiphysical model (PBSM) of glucose transport by volumetric flow and diffusion from the bloodstream to interstitial fluid was constructed. A published 10-step modeling procedure was used to obtain a model for glucose transport time through the blood vessels and from the blood capillaries to the interstitial fluid, glucose diffusion within the interstitial fluid, and glucose diffusion through the semipermeable coating of the sensor needle. For this model, a healthy person is considered at rest with average parameters. RESULTS: The simulations performed using the PBSM allow obtaining the glucose transport time from the liver to the sensor needle. In this way, it is possible to reconstruct an accurate dynamic measurement of blood glucose from the measurements in the interstitial fluid of the abdominal subcutaneous adipose tissue. CONCLUSIONS: PBSMs with parameters interpretability illustrate the connection of glucose concentrations in the interstitial fluid with that currently in the blood. Implementing this model in a CGM will result in more reliable measurements of blood glucose levels for T1DM treatment.

Towards a phenomenological based model for predicting the hardness of a processed meat product.

This study aims to build a model for predicting the hardness of meat products by considering their protein fractions and protein structural changes during production. Protein solubility is considered an indicator of protein structural changes. The obtained model results show that structural changes of sarcoplasmic and myofibrillar proteins occur during production. The gelling capacity is formed by the effect of the three protein fractions, namely myofibrillar, sarcoplasmic and stromal. The obtained model allows the prediction of the hardness of meat products based on their protein fraction contents with error below 5%, thus reaching a significant adjustment between real process data and the simulated model.

Retinal differentiation in an altricial bird species, Taeniopygia guttata: An immunohistochemical study.

The bird retina offers an excellent model to investigate the mechanisms that coordinate the morphogenesis, histogenesis, and differentiation of neuron and glial cells. Although these developmental features have been intensively studied in the chicken (Gallus gallus, Linnaeus 1758), a precocial bird species, little is known about retinogenesis in altricial birds. The purpose of this study was to examine the differentiation of retinal cells in the altricial zebra finch (Taeniopygia guttata, Vieillot, 1817) and compare the results with those from previous studies in G. gallus. By using immunohistochemical techniques, the first differentiated TUJ1-/Isl1-positive neuroblasts were detected in the vitreal surface of the neuroblastic layer at later incubation times in T. guttata than in G. gallus (108 h vs 55 h). The immunoreactivity of these early differentiation markers coincided temporo-spatially with the appearance of the first PCNA-negative nuclei. Furthermore, the first visinin-positive photoreceptors (132 h vs 120 h) and the first Prox-1-immunoreactive neuroblasts (embryonic day 7.25 (E7.25) vs E6.5) were also detected at later embryonic stages in the retina of T. guttata than in the retina of G. gallus. At E13, one day before hatching, abundant PCNA- and pHisH3-immunoreactivities were detected in the T. guttata retina, while proliferation was almost absent in the G. gallus retina at perinatal stages. Therefore, these results suggest that cell differentiation in the retina is delayed in the altricial bird compared to precocial birds. Furthermore, the T. guttata retina was not completely developed at hatching, and abundant mitotically active precursor cells of retinal neurons were found, suggesting that retinal neurogenesis was intense at perinatal stages.

Senescence-associated ß-galactosidase activity in the developing avian retina.

BACKGROUND: Senescence-associated ß-galactosidase (SA-ß-GAL) histochemistry is the most commonly used biomarker of cellular senescence. These SA-ß-GAL-positive cells are senescent embryonic cells that are usually removed by apoptosis from the embryo, followed by macrophage-mediated clearance. RESULTS: Some authors have proposed that SA-ß-GAL activity in differentiated neurons from young and adult mammals cannot be uniquely attributed to cell senescence, whether in vivo or in vitro. Using the developing visual system of the chicken as a model, the present study found that SA-ß-GAL detected in the developing retina corresponded to lysosomal ß-galactosidase activity, and that SA-ß-GAL activity did not correlate with the chronotopographical distribution of apoptotic cells. However, SA-ß-GAL staining in the undifferentiated retina coincided with the appearance of early differentiating neurons. In the laminated retina, SA-ß-GAL staining was concentrated in the ganglion, amacrine, and horizontal cell layers. The photoreceptors and pigment epithelial cells also exhibited SA-ß-GAL activity throughout retinal development. We have also found that SA-ß-GAL staining strongly correlated p21 immunoreactivity. CONCLUSION: In conclusion, the results clearly show that SA-ß-GAL activity cannot be regarded as a specific marker of senescence during retinal development, and that it is mainly expressed in subpopulations of postmitotic neurons, which are nonproliferative cells, even at early stages of cell differentiation.

Phenomenological-Based model of human stomach and its role in glucose metabolism.

The stomach is a segment of the gastrointestinal (GI) tract which receives food from the esophagus, mixes it, breaks it down, and then passes it on to the small intestine in smaller portions. In the stomach, the main secretory functions and digestion process begin. However, the most critical and important function of the stomach in digestive physiology is perhaps gastric motility. In this way, the functions of the stomach are mainly three: (i) the storage of large quantities of food to be further processed in the duodenum, and lower intestinal tract, (ii) the mixing of this food with gastric secretions to form a semi-fluid mixture, and (iii) to slow down the emptying of that semi-fluid mixture into the small intestine at a rate suitable for proper digestion and absorption. Regarding the motor activity, the stomach must consume glucose to generate the power necessary to carry out the digestion process. Although glucose consumption in the stomach is relatively low, it can affect the glucose concentration in the bloodstream. In order to know the variations in the glucose levels in the bloodstream during the stomach digestion, a Phenomenological Based Semi-physical Model (PBSM) of the role of the stomach in the glucose homeostasis is developed. The simulation of the stomach model is able to mimic physiological results without risking the life of the patient, in order to test the impact of diverse medicines and foods on glucose homeostasis. The model may then be integrated to existing models of glucose homeostasis to improve the simulation scenario with respect to the glucose appearance from a mixed meal. Our model allows the change of the macronutrient composition and rheological properties of the meal as well as the digestion particularities of every subject. In this way, the integrated model will be fitted to real patient physiology providing a better model to use in, for example, automated insulin delivery systems like the artificial pancreas (AP).

Retinal histogenesis in an altricial avian species, the zebra finch (Taeniopygia guttata, Vieillot 1817).

Comparative developmental studies have shown that the retina of altricial fish and mammals is incompletely developed at birth, and that, during the first days of life, maturation proceeds rapidly. In contrast, precocial fish and mammals are born with fully differentiated retinas. Concerning birds, knowledge about retinal development is generally restricted to a single order of precocial birds, Galliformes, due to the fact that both the chicken and the Japanese quail are considered model systems. However, comparison of embryonic pre-hatchling retinal development between altricial and precocial birds has been poorly explored. The purpose of this study was to examine the morphogenesis and histogenesis of the retina in the altricial zebra finch (Taeniopygia guttata, Vieillot 1817) and compare the results with those from previous studies in the precocial chicken. Several maturational features (morphogenesis of the optic vesicle and optic cup, appearance of the first differentiated neurons, the period in which the non-apical cell divisions are observable, and the emergence of the plexiform layers) were found to occur at later stages in the zebra finch than in the chicken. At hatching, the retina of T. guttata showed the typical cytoarchitecture of the mature tissue, although features of immaturity were still observable, such as a ganglion cell layer containing many thick cells, very thin plexiform layers, and poorly developed photoreceptors. Moreover, abundant mitotic activity was detected in the entire retina, even in the regions where the layering was complete. The circumferential marginal zone was very prominent and showed abundant mitotic activity. The partially undifferentiated stage of maturation at hatching makes the T. guttata retina an appropriate model with which to study avian postnatal retinal neurogenesis.

Expression and function of the LIM-homeodomain transcription factor Islet-1 in the developing and mature vertebrate retina.

The LIM-homeodomain transcription factor Islet-1 (Isl1) has been widely used as a marker of different subtypes of neurons in the developing and mature retina of vertebrates. During retinal neurogenesis, early Isl1 expression is detected in the nuclei of neuroblasts that give rise to ganglion, amacrine, bipolar, and horizontal cells. In the mature retina, Isl1 expression is restricted to the nuclei of ganglion cells, cholinergic amacrine cells, ON-bipolar cells, and subpopulations of horizontal cells. Recent studies have explored the functional mechanisms of Isl1 during specification and differentiation of these retinal cell types. Thus, conditional inactivation of Isl1 in the developing mouse retina disrupts retinal function, and also results in optic nerve hypoplasia, marked reductions in mature ganglion, amacrine, and bipolar cells, and a substantial increase in horizontal cells. Furthermore, conditional knockout shows delayed ganglion cell axon growth, ganglion cell axon guidance error, and ganglion cell nerve fiber defasciculation. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different vertebrate retinal cell types. This review examines whether the expression pattern of Isl1 during vertebrate retinal development is conserved across vertebrate species, and discusses current understanding of the developmental functions of Isl1 in retinogenesis.

Model-based scale-up methodology for aerobic fed-batch bioprocesses: application to polyhydroxybutyrate (PHB) production.

This work presents a general model-based methodology to scale-up fed-batch bioprocesses. The idea behind this approach is to establish a dynamics hierarchy, based on a model of the process, that allows the designer to determine the proper scale factors as well as at which point of the fed-batch the process should be scaled up. Here, concepts and tools of linear control theory, such as the singular value decomposition of the Hankel matrix, are exploited in the context of process design. The proposed scale-up methodology is first described in a bioprocesses general framework highlighting its main features, key variables and parameters. Then, it is applied to a polyhydroxybutyrate (PHB) fed-batch bioreactor and compared with three empirical criteria, that are traditionally employed to determine the scale factors of these processes, showing the usefulness and distinctive features of this proposal. Moreover, this methodology provides theoretical support to a frequently used empirical rule: scale-up aerobic bioreactors at constant volumetric oxygen transfer coefficient. Finally, similar process dynamic behavior and PHB production set at the laboratory scale are predicted at the new operating scale, while it is also determined that is rarely possible to reproduce similar dynamic behavior of the bioreactor using empirical scale-up criteria.

Domestic dogs in indigenous Amazonian communities: Key players in Leptospira cycling and transmission?

BACKGROUND: Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. METHODOLOGY/PRINCIPAL FINDINGS: We sampled dogs from five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 7 serogroups were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16S rRNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n = 7), santarosai (n = 7), and interrogans (n = 1). CONCLUSIONS/SIGNIFICANCE: The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Histological and scanning electron microscope observations on the developing retina of the cuttlefish (Sepia officinalis Linnaeus, 1758).

In this work we present a detailed study of the major events during retinal histogenesis of the cuttlefish Sepia officinalis from early embryos to newly hatched animals and juveniles. For this purpose, we carried out morphometric and histological analyses using light and scanning electron microscopy. From St19, the first embryonic stage analysed, to St23/24 the embryonic retina is composed of a pseudostratified epithelium showing abundant mitotic figures in the more internal surface. At St24 the first photoreceptor nuclei appear in the presumptive inner segment layer, while an incipient layer of apical processes of the future rhabdomeric layer become visible at St25. From this stage onwards, both the rhabdomeric layer and the inner segment layer increase in size until postnatal ages. In contrast, the width of the supporting cell layer progressively decreases from St25/26 until postnatal ages. S. officinalis embryos hatched in a morphologically advanced state, showing a differentiated retina even in the last stages of the embryonic period. However, features of immaturity are still observable in the retinal tissue during the first postnatal weeks of life, such as the existence of mitotic figures in the apical region of the supporting cell layer and migrating nuclei of differentiating photoreceptors crossing the basal membrane to reach their final location in the inner segment layer. Therefore, postnatal retinal neurogenesis is present in juvenile specimens of S. officinalis.

MOXD1 is a lineage-specific gene and a tumor suppressor in neuroblastoma.

Neuroblastoma is a childhood developmental cancer; however, its embryonic origins remain poorly understood. Moreover, in-depth studies of early tumor-driving events are limited because of the lack of appropriate models. Herein, we analyzed RNA sequencing data obtained from human neuroblastoma samples and found that loss of expression of trunk neural crest-enriched gene MOXD1 associates with advanced disease and worse outcome. Further, by using single-cell RNA sequencing data of human neuroblastoma cells and fetal adrenal glands and creating in vivo models of zebrafish, chick, and mouse, we show that MOXD1 is a determinate of tumor development. In addition, we found that MOXD1 expression is highly conserved and restricted to mesenchymal neuroblastoma cells and Schwann cell precursors during healthy development. Our findings identify MOXD1 as a lineage-restricted tumor-suppressor gene in neuroblastoma, potentiating further stratification of these tumors and development of novel therapeutic interventions.

Islet-1 immunoreactivity in the developing retina of Xenopus laevis.

The LIM-homeodomain transcription factor Islet1 (Isl1) has been widely used as a marker of neuronal differentiation in the developing visual system of different classes of vertebrates, including mammals, birds, reptiles, and fish. In the present study, we analyzed the spatial and temporal distribution of Isl1-immunoreactive cells during Xenopus laevis retinal development and its relation to the formation of the retinal layers, and in combination with different markers of cell differentiation. The earliest Isl1 expression appeared at St29-30 in the cell nuclei of sparse differentiating neuroblasts located in the vitreal surface of the undifferentiated retina. At St35-36, abundant Isl1-positive cells accumulated at the vitreal surface of the neuroepithelium. As development proceeded and through the postmetamorphic juveniles, Isl1 expression was identified in subpopulations of ganglion cells and in subsets of amacrine, bipolar, and horizontal cells. These data together suggest a possible role for Isl1 in the early differentiation and maintenance of different retinal cell types, and Isl1 can serve as a specific molecular marker for the study of retinal cell specification in X. laevis.

Estimation of glucose rate of appearance in portal vein circulation using a phenomenological-based model.

The joint work of the stomach and the small intestine plays a fundamental role in human digestion. In the stomach, food is turned into a semi-fluid mixture that is slowly released into the small intestine, where most enzymatic reactions occur, and nutrients are absorbed as they become available. This whole process is closely related to glucose homeostasis, mainly because of the appearance of glucose in the portal system and the energetic expenditure of the process itself. The current phenomenological-based model describes such effects of the digestive process on blood glucose concentration. It considers enzymatic and mechanical transformations, energetic expenditure, and the impact of macro-nutrients, fiber, and water on overall digestion and glucose absorption. The model estimates the rate of glucose appearance in the portal vein and is intended to be further integrated into existing models for other human organs and used in model-based systems such as an artificial pancreas with automated insulin delivery.

Domestic dogs in indigenous Amazonian communities: key players in Leptospira cycling and transmission?

Background: Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. Methodology/Principal Findings: We sampled five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira, and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 10 serotypes were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16s rDNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n=7), santarosai (n=7), and interrogans (n=1). Conclusions/Significance: The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Markers of senescence are often associated with neuronal differentiation in the developing sensory systems.

It has been shown that senescent cells accumulate in transient structures of the embryo that normally degenerate during tissue development. A collection of biomarkers is generally accepted to define senescence in embryonic tissues. The histochemical detection of ß-galactosidase activity at pH 6.0 (ß-gal-pH6) is the most widely used assay for cellular senescence. Immunohistochemical detection of common mediators of senescence which block cell cycle progression, including p16, p21, p63, p15 or p27, has also been used to characterize senescent cells in the embryo. However, the reliability of this techniques has been discussed in recent publications because non-senescent cells are also labelled during development. Indeed, increased levels of senescent markers promote differentiation over apoptosis in developing neurons, suggesting that machinery used for the establishment of cellular senescence is also involved in neuronal maturation. Notably, it has recently been argued that a comparable state of cellular senescence might be adopted by terminally differentiated neurons. The developing sensory systems provide excellent models for studying if canonical markers of senescence are associated with terminal neuronal differentiation.

Retinal Development in a Precocial Bird Species, the Quail (Coturnix coturnix, Linnaeus 1758).

The quail (Coturnix coturnix, Linnaeus 1758), a notable model used in developmental biology, is a precocial bird species in which the processes of retinal cell differentiation and retinal histogenesis have been poorly studied. The purpose of the present research is to examine the retinogenesis in this bird species immunohistochemically and compare the results with those from previous studies in precocial and altricial birds. We found that the first PCNA-negative nuclei are detected at Stage (St) 21 in the vitreal region of the neuroblastic layer, coinciding topographically with the first αTubAc-/Tuj1-/Isl1-immunoreactive differentiating ganglion cells. At St28, the first Prox1-immunoreactive nuclei can be distinguished in the vitreal side of the neuroblastic layer (NbL), but also the first visinin-immunoreactive photoreceptors in the scleral surface. The inner plexiform layer (IPL) emerges at St32, and the outer plexiform layer (OPL) becomes visible at St35-the stage in which the first GS-immunoreactive Müller cells are distinguishable. Newly hatched animals show a well-developed stratified retina in which the PCNA-and pHisH3-immunoreactivies are absent. Therefore, retinal cell differentiation in the quail progresses in the stereotyped order conserved among vertebrates, in which ganglion cells initially appear and are followed by amacrine cells, horizontal cells, and photoreceptors. Müller glia are one of the last cell types to be born. Plexiform layers emerge following a vitreal-to-scleral gradient. Finally, our results suggest that there are no significant differences in the timing of different events involved in retinal maturation between the quail and the chicken, but the same events are delayed in an altricial bird species.

Analgesic effectiveness of dipyrone (metamizol) for postoperative pain after herniorrhaphy: a randomized, double-blind, dose-response study.

BACKGROUND: The efficacy of non-narcotic analgesics is mostly supported by randomized, placebo-controlled trials with no comparison with ordinary practice. Additionally, systematic reviews of these placebo-controlled trials have failed to determine clinically meaningful dose-response effect. METHODS: In this double-blind, randomized trial, patients undergoing elective inguinal, umbilical or epigastric herniorrhaphy under general anesthesia were assigned to receive 15 mg/kg (D15 group) vs. 40 mg/kg (D40 group) of dipyrone intravenously during surgery. The primary outcome was the incidence of moderate to severe pain with movement during the recovery room phase. The secondary outcomes were morphine consumption, incidence of vomiting, and Ramsay score (sedation scale). RESULTS: One hundred sixty-two patients were enrolled and analyzed for the primary and secondary outcomes. Relative to the D15 group, the D40 group showed a lower incidence of moderate to severe pain in the first 30 minutes (61% and 40%; P value < 0.05); lower cumulative morphine consumption during the recovery period (3.85 vs. 2.55 mg, P value < 0.006) as well as a lower incidence of vomiting (15.8% vs. 2.5%, P value < 0.005). In addition, more cases of sedation were recorded in the D15 group than in the D40 group (17 vs. 10 cases). There were no serious adverse effects attributed to dipyrone in either group. CONCLUSION: This trial shows a dose-response effect of 40 mg/kg over 15 mg/kg of intravenous dipyrone based on better movement-induced pain control, lower morphine consumption and fewer opioid-related side effects.