Disruption of BMP4 signaling is associated with laryngeal birth defects in a mouse model.

Laryngeal birth defects are considered rare, but they can be life-threatening conditions. The BMP4 gene plays an important role in organ development and tissue remodeling throughout life. Here we examined its role in laryngeal development complementing similar efforts for the lung, pharynx, and cranial base. Our goal was to determine how different imaging techniques contribute to a better understanding of the embryonic anatomy of the normal and diseased larynx in small specimens. Contrast-enhanced micro CT images of embryonic larynx tissue from a mouse model with Bmp4 deletion informed by histology and whole-mount immunofluorescence were used to reconstruct the laryngeal cartilaginous framework in three dimensions. Laryngeal defects included laryngeal cleft, laryngeal asymmetry, ankylosis and atresia. Results implicate BMP4 in laryngeal development and show that the 3D reconstruction of laryngeal elements provides a powerful approach to visualize laryngeal defects and thereby overcoming shortcomings of 2D histological sectioning and whole mount immunofluorescence.

Climatic and calf-related risk factors associated with failure of transfer of passive immunity in Holstein calves in a hot environment.

This retrospective observational study aimed to assess the effect of temperature-humidity index (THI) at calving and in the last trimester of pregnancy and calve-related factors affecting passive transfer of maternal immunoglobulin using Brix refractometry in Holstein calves. Blood samples from 4411 Holstein calves from a single large dairy farm in spring 2022 were used. A subset of data containing 6318 calvings was used to determine the effect of climatic conditions on the occurrence of agammaglobulinemia. Risk factors predictive of failure of passive transfer (FPT) were calculated using multiple logistic models. Females were 1.4 times more likely not to have FPT (56%; Brix% > 8 equivalent to ≥ 10 g/L IgG) than males (47.2%). Calves born as singles increased the likelihood of not presenting FPT (52.6%) than calves born as twins (42.9%). Calves from cows with no dystocic delivery had a lower risk for FPT (odds ratio = 2.3) than calves from cows with dystocia. Agammaglobulinemia was 1.5 and 1.8 times more likely to occur in calves with THI ≥ 80 and ≥ 82 in the last trimester of gestation and at calving, respectively, than in calves not experiencing heat stress. Agammaglobulinemia was twice as likely to occur in male than in female calves. Calves with birth weight ≥ 37 kg and gestation length ≥ 275 kg were less likely to present agammaglobulinemia than lighter calves and calves with shorter gestation periods. This study raises questions for management practices in Holstein calves undergoing in utero heat stress and around calving to avoid agammaglobulinemia.

Disseminated lymphangiomas as a cutaneous manifestation of Noonan syndrome.

Lymphangioma is a known, but rare manifestation of Noonan syndrome. We present the case of disseminated and circumscribed cutaneous lymphangiomas in the context of Noonan syndrome. Oral rapamycin is a promising treatment in these extensive and morbidity-causing cases.

Low phase noise beams for Raman transitions with a phase modulator and a highly birefringent crystal.

We present a technique to excite Raman transitions with minimum phase noise. A phase modulator generates the Raman beams and a long calcite crystal rotates the polarization of the sidebands by 90° with respect to the carrier. That polarization converts the destructive interference of the Raman pairs into constructive interference, opening the possibility to drive both co-propagating and counter-propagating transitions at high detuning with the same setup. The technique has low phase noise and a low sensitivity to vibrations or temperature fluctuations. We apply it to drive velocity insensitive Raman transitions. The crystal can be also configured to filter out one of the sidebands.

The combination of resveratrol and conjugated linoleic acid attenuates the individual effects of these molecules on triacylglycerol metabolism in adipose tissue.

PURPOSE: The combination of resveratrol + conjugated linoleic acid (RSV + CLA) did not show the body fat-lowering effect exhibited by these molecules when administered separately. This study aimed to find metabolic explanations for this situation in an experimental model of diet-induced obesity. METHODS: Thirty-six male Wistar rats were divided into four groups: rats treated with saline (control), resveratrol (RSV), conjugated linoleic acid (CLA) and a combination of these molecules (RSV + CLA). RESULTS: Rats treated with RSV + CLA did not show the reduction in heparin-releasable lipoprotein lipase (HR-LPL) and fatty acid synthase activities observed in RSV group or the increased HSL expression found in RSV and CLA groups. These animals showed reduced sirtuin 1 expression and CLA isomer amounts in adipose tissue. Finally, intracellular Ca(2+) concentration was increased. CONCLUSION: The attenuation of the effects induced in adipose tissue triacylglycerol metabolism by RSV and CLA separately, such as the decrease in lipogenesis and fatty acid uptake and the increase in lipolysis, contributes to explain the lack of body fat-lowering effect of the combination RSV + CLA.

Effects of resveratrol and its derivative pterostilbene on brown adipose tissue thermogenic activation and on white adipose tissue browning process.

The main function of brown adipose tissue (BAT) is thermogenesis, a process mediated by uncoupling protein 1 (UCP1), which is located in the inner mitochondrial membrane and acts uncoupling oxidative phosphorylation from ATP production, thereby dissipating energy as heat. White adipose tissue can also express UCP1 positive cells due to a process known as browning. This phenomenon could also increase the thermogenic effect in the classical brown adipose depots. BAT thermogenesis depends, among other factors on both, nutritional conditions and food availability. Indeed, some studies have found that BAT recruitment and function are enhanced by some food components. The present study focuses on the effects of resveratrol and pterostilbene, two phenolic compounds belonging to the stilbene group, on BAT thermogenic activation and white adipose tissue browning process. The reported studies, carried out in cell cultures and animal models, show that both resveratrol and pterostilbene induce thermogenic capacity in interscapular BAT by increasing mitochondriogenesis, as well as enhancing fatty acid oxidation and glucose disposal. In addition, resveratrol seems to promote browning by activating peroxisome proliferator-activated receptor (PPAR), while the lack of changes in mitochondrial biogenesis suggests that probably the browning process occurs by direct resveratrol-mediated upregulation of ucp1 mRNA expression.

New target with low photoneutron yield for LINAC radiotherapy applications.

This paper presents three new materials composed of TiXV0,035XCuX-1,035 (X = 2, 4 and 6%), is proposed as Linear Accelerator target. Its response to electron beam based on photoneutron production, is assessed by MC simulation and nuclear track-etch methodology. The outcome is compared to a tungsten target irradiated by energetic 16 MeV electron beam. Photoneutron yield, of two energy groups (thermal and epithermal) were determined via converter matter 10B (98%) and Cd-filter by PADC-track density comparison. The multi-metal Ti2V0,07Cu97.93 target related to therapy beam quality, resulted advantageous in comparison to that provided by W-target, commonly used in the LINAC.

Seasonal variation of the S-index as it relates to the concentration of 222Rn inside a bunker that stores radioactive material.

In this work, the seasonal variation of the concentration of radon in soil and its contribution to concentrations inside of a bunker used for the storage and operation of radioactive material was studied. The measurements obtained inside and outside of the installation allowed establish a method for the calculation of the diffusion coefficient for the concrete, variable that directly influences the concentration of radon gas inside of the bunker. With the obtained results of the gamma dose rate and the concentration of radon inside the bunker, the S-index was calculated in order to determine whether the bunker would require some remediation process. The high radon gas concentration rates to which workers are exposed led to study the relative risk of contracting lung cancer (RRLC).

Gender and socio-cultural determinants of TB-related stigma in Bangladesh, India, Malawi and Colombia.

SETTING: Tuberculosis (TB) control programmes in Bangladesh, India, Malawi and Colombia. OBJECTIVE: Assess indicators of TB-related stigma and socio-cultural and gender-related features of illness associated with stigma. DESIGN: Semi-structured Explanatory Model Interview Catalogue (EMIC) interviews were administered to 100 or more patients at each site, assessing categories of distress, perceived causes and help seeking. Indicators of self-perceived stigma were analysed individually and in a validated index, which was compared across sites and between men and women at each site. Cultural epidemiological explanatory variables for stigma and interactions with female sex were analysed at each site. Qualitative illness narratives were examined to explain the role and context of explanatory variables. RESULTS: The overall stigma index was highest in India, lowest in Malawi and greater for women in Bangladesh. In India and Malawi, women were more likely to be concerned about impact on marital prospects. Associations with HIV/AIDS were linked to TB stigma in Malawi, where sexual contact as a perceived cause was more associated with stigma for men and less for women. CONCLUSION: Stigma both influences and indicates the effectiveness of TB control. Cultural epidemiological methods clarify cross-cutting and local features of stigma and gender for TB control.

Enhancement of VP6 immunogenicity and protective efficacy against rotavirus by VP2 in a genetic immunization.

VP2/VP6 virus like particles (VLPs) are very effective in inducing protection against the rotavirus infection in animal models. Individually, VP6 can also induce protection. However, there is no information about the immunogenicity of VP2. The aim of this work was to evaluate the efficacy of DNA vaccines codifying for VP2 or VP6, alone or combined, to induce protection against the rotavirus infection. Murine rotavirus VP2 and VP6 genes were cloned into the pcDNA3 vector. Adult BALB/c mice were inoculated three times by intramuscular (i.m.) injections with 100 or 200µg of pcDNA3-VP2 or pcDNA3-VP6 alone or co-administered with 100µg of pcDNA3-VP2/100µg of pcDNA3-VP6. Two weeks after the last inoculation, mice were challenged with the wild type murine rotavirus strain epizootic diarrhea of infant mice (EDIMwt). We found that both plasmids, pcDNA3-VP2 and pcDNA3-VP6, were able to induce rotavirus-specific serum antibodies, but not intestinal rotavirus-specific IgA; only 200µg of pcDNA3-VP6 induced 35% protection against the infection. A similar level of protection was found when mice were co-administered with 100µg of pcDNA3-VP2/100µg of pcDNA3-VP6 (1:1 ratio). However, the best protection (up to 58%) occurred when mice were inoculated with 10µg of pcDNA3-VP2/100µg of pcDNA3-VP6 (1:10 ratio). These results indicate that the DNA plasmid expressing VP6 is a better vaccine candidate that the one expressing VP2. However, when co-expressed, VP2 potentiates the immunogenicity and protective efficacy of VP6.

[The microbial pattern of the catheter exit-site infection in peritoneal dialysis: A non-diphtheria Corynebacteria emergence?]. / Patrón microbiológico de la infección del cateter peritoneal: aumento de Corynebacterium sp?

BACKGROUND: A prospective cohort study was undertaken to compare the rates of the infecting microorganisms of the peritoneal catheter exit-site in three periods of the prophylactic protocol of a peritoneal dialysis program. All patients treated for more than one month on Peritoneal Dialysis were included: Fourty-eight in Period 1 (P1), 48 in Period 2 (P2), and 54 in Period 3 (P3). Each period was of 3 years. METHODS: Infection prophylaxis protocol: P1: hydrogen peroxide or povidone iodine and non-occlusive dressing; P2: sterile water (boiled water) instead of antiseptic agents, semi-permeable dressing for taking showers, and nasal mupirocine prophylaxis for Staphylococcus aureus carriers; P3: equal to P2, plus local application of antibiotics in equivocal exit-site for infection and argentic nitrate in granulation tissue. MAIN OUTCOME MEASURE: The rates of catheter infection and microorganisms causing infection were analysed by means of the Poisson regression method. Chi-square and ANOVA when appropriate. RESULTS: The proportion of catheters implanted by nephrologist or surgeon (p<0.01) and modality treatment by CAPD or CCPD (p<0.0001) were significantly different in the three periods, while the Staph. Aureus carrieres was in the limit of significance (p=0.048). Throughout the three periods, a significantly decreasing rate of total (P=0.0035) and acute infections (P<0.001), Staph. aureus (P=0.003) and peritonitis (P=0.0025) were found. The Pseudomonas aer. (P=0.006) and Gram negative Bacteria (P=0.023) decreased significantly in P2. The multiple factor analysis included eight factors: sex, age group, ESRD, DM, catheter implantation (nephrologist, surgeon), modality treatment (CAPD, CCPD), manufacturer and prophylaxis period as possible predictors of the catheter infections, the specific microorganisms and the peritonitis. That analysis revealed the prophylaxis period as the main predictive factor of the improvements found (p<0.02,- p<0.001). In contrast, the Corynebacteria spp. increased significantly (P=0.008) throughout the three periods. One half of the Corynebacteria in each period could be considered colonisers. The other half caused true infections, but not one of those episodes required catheter intervention. The non-diphtheria Corynebacteria increase was found related with the continuous cycling Peritoneal Dialysis treatment in multiple factor analysis (p=0.0023) and in the proportion analysis (P=0.039, c2). CONCLUSION: The progressive protocol applied obtained good results, without the continued use of local antiseptics or antibiotics at the exit-site. However, the non-diphtheria Corynebacteria sp. infection increment favours the consideration of an antiseptic agent for the exit-site care.

Are calanco landforms similar to river basins?

In the past badlands have been often considered as ideal field laboratories for studying landscape evolution because of their geometrical similarity to larger fluvial systems. For a given hydrological process, no scientific proof exists that badlands can be considered a model of river basin prototypes. In this paper the measurements carried out on 45 Sicilian calanchi, a type of badlands that appears as a small-scale hydrographic unit, are used to establish their morphological similarity with river systems whose data are available in the literature. At first the geomorphological similarity is studied by identifying the dimensionless groups, which can assume the same value or a scaled one in a fixed ratio, representing drainage basin shape, stream network and relief properties. Then, for each property, the dimensionless groups are calculated for the investigated calanchi and the river basins and their corresponding scale ratio is evaluated. The applicability of Hack's, Horton's and Melton's laws for establishing similarity criteria is also tested. The developed analysis allows to conclude that a quantitative morphological similarity between calanco landforms and river basins can be established using commonly applied dimensionless groups. In particular, the analysis showed that i) calanchi and river basins have a geometrically similar shape respect to the parameters Rf and Re with a scale factor close to 1, ii) calanchi and river basins are similar respect to the bifurcation and length ratios (λ=1), iii) for the investigated calanchi the Melton number assumes values less than that (0.694) corresponding to the river case and a scale ratio ranging from 0.52 and 0.78 can be used, iv) calanchi and river basins have similar mean relief ratio values (λ=1.13) and v) calanchi present active geomorphic processes and therefore fall in a more juvenile stage with respect to river basins.

[A burden questionnaire for caregivers of peritoneal dialysis patients]. / Cuestionario de sobrecarga de cuidadores de pacientes de diálisis peritoneal.

INTRODUCTION: Despite the interest generated by the increasing number of studies that measure Quality of Life among patients and caregivers, few of these studies measure the caregivers burden in Peritoneal Dialysis (PD). OBJECTIVE: The main target of this study was to create a burden measure questionnaire applicable amongst caregivers of PD patients. INCLUSION CRITERIA: 1) Patients had to be in PD treatment for more than 3 months; 2) Patients had to receive help with the PD treatment from a caregiver. The study was divided into 3 phases: 1st) design and use of the initial questionnaire; 2nd) a test-retest on a modified scale; and 3rd) to provide the questionnaire-3 to two collaborative centres with similar PD programs. Four groups of caregivers were established: A1:23, A2:17, B:7 and C:16 caregivers. We applied 5 scales (5): 1--Patient Dependence on caregiver, from caregivers' view (D); 2--Complete caregiver burden (CB), including 12 items which measure the caregivers' subjective burden, 3--Reduced caregiver burden (RB), as the one before but with only 8 items, 4--Repercussions on the caregiver (R), which measures objective burden; 5--Specific PD tasks (ST), a scale that measures the effort the tasks implied in the PD treatment represent for the caregiver. RESULTS: We studied 63 caregivers (table I): mean age: 53.43 (SD = 12.3); Sex: Females: 86.4%, Males: 13.6%, corresponding to 63 patients: mean age: 59.79 (SD = 15.9); Sex: Males: 80.3%, Females: 19.7%. Valuable results for reliability, unidimensionality, and discrimination were obtained in the 1st and 2nd phases, except for burden scale which was compound of two factors; then one of those factors was suppressed. In the 3rd phase, ANOVA did not show any differences between centres (table II). Consequently, all caregivers could be analysed together. Reliability results for each one of the third phase scales (table III) were: D: Cronbach alpha = 0,886; CB: alpha = 0,894; RB: alpha = 0,857; R: alpha = 0,892; ST: alpha = 0,62. Although the ST scale obtained an acceptable reliability, it was suppressed in the 3rd phase due to the low correlation with other scales and the fact that it was not applicable to all caregivers. Finally, a direct correlation was found between third phase scales (table IV): D-RB: r = 0.502, p < or = 0.001; D-R: r = 0.599, p < or = 0.001; RB-R: r = 0.775, p < or = 0.001. We must headlight that both Burden scales, and the Repercussion scale, obtained a direct correlation with the Dependency scale. CONCLUSION: A questionnaire has been created to measure burden and repercussions on caregivers of peritoneal dialysis patients. It can already be applied, as requirements of both reliability and validity are fulfilled. This questionnaire can be a useful tool to prevent caregivers' burnout.

MicroRNAs involved in the browning process of adipocytes.

The present review focuses on the role of miRNAs in the control of white adipose tissue browning, a process which describes the recruitment of adipocytes showing features of brown adipocytes in white adipose tissue. MicroRNAs (miRNAs) are a class of short non-coding RNAs (19-22 nucleotides) involved in gene regulation. Although the main effect of miRNAs is the inhibition of the translational machinery, thereby preventing the production of the protein product, the activation of protein translation has also been described in the literature. In addition to modifying translation, miRNAs binding to its target mRNAs also trigger the recruitment and association of mRNA decay factors, leading to mRNA destabilization, degradation, and thus to the decrease in expression levels. Although a great number of miRNAs have been reported to potentially regulate genes that play important roles in the browning process, only a reduced number of studies have demonstrated experimentally an effect on this process associated to changes in miRNA expressions, so far. These studies have shown, by using either primary adipocyte cultures or experimental models of mice (KO mice, mice overexpressing a specific miRNA), that miR-196a, miR-26, and miR-30 are needed for browning process development. By contrast, miR-155, miR-133, miR-27b, and miR-34 act as negative regulators of this process [corrected]. Further studies are needed to fully describe the miRNA network-involved white adipose tissue browning regulation.

Differential contribution of the hippocampus in two different demanding tasks at early stages of hepatic encephalopathy.

The hippocampus has been established as a site of plasticity during the acquisition of spatial memory. The memory for spatial locations is impaired in patients who develop hepatic encephalopathy (HE). We wondered how the hippocampus can manage different hippocampal-dependent tasks in a type B model of the early evolutive phases of HE induced by triple portal vein ligation. We used a one-trial object-place recognition task that involves making judgements about whether a stimulus was encountered before in that location and a reversal learning task performed in the Morris water maze that involves reward-guided behavior and decision making. Our behavioral results showed impairments in the acquisition of both tasks by the portal hypertension group compared with the sham-operated group. To label brain areas related to these tasks, we marked the expression of the c-Fos protein and revealed high c-Fos immunoreactivity in cornu ammonis 1 (CA1), cornu ammonis 3 (CA3) and entorhinal (Ent) cortex of the PH group compared with the SHAM group in the object-place recognition task and a decrease in c-Fos-positive cells in the reversal task in the CA1, CA3, dentate gyrus (DG), cingulate (CG), prelimbic (PL), and infralimbic (IL) cortices in the PH group compared with the SHAM group. In conclusion, the study corroborated the pivotal role of the hippocampus in spatial memory deficits found in the early stages of type B HE and noted its differential contribution in each of the tasks.

The recognition of a novel-object in a novel context leads to hippocampal and parahippocampal c-Fos involvement.

Contextual memory implies recognition based on the association between past and present events experienced. It is important for daily functioning and dysfunctional in many neuropsychological disturbances. The network related to this memory is still open for debate, even though it has been associated with medial temporal lobe regions, including the perirhinal, entorhinal and temporal association cortices, as well as the hippocampus and prefrontal cortex. Our work tries to elucidate whether a change in the context, such as differences in the amount of stimuli presented on the walls and floor of an open field during object exploration, affects the recognition of an object that has been experienced before, and whether this context manipulation could be linked to changes in c-Fos expression. For this purpose, we used a one-trial novel-object recognition task. The animals were divided into two different experimental conditions; in the OR-NORMAL group, the sample and probe test were performed in the same context. However, in the OR-CONTEXT group, the probe test was performed in a different context. Our results showed that the OR-NORMAL group presented a greater exploration of objects than the OR-CONTEXT group. However, both groups presented significant exploration of the novel object. To label the brain regions involved in novel-object recognition under these conditions, we marked the expression of c-Fos protein. Results suggest that a neural circuit that includes the hippocampus, entorhinal and temporal association cortices is involved in the recognition of the novel-object in a novel context.

How demanding is the brain on a reversal task under day and night conditions?

Reversal learning has been studied as the process of learning to inhibit previously rewarded actions. These behavioral studies are usually performed during the day, when animals are in their daily period rest. However, how day or night affects spatial reversal learning and the brain regions involved in the learning process are still unknown. We conducted two experiments using the Morris Water Maze under different light-conditions: naïve group (CN, n=8), day group (DY, n=8), control DY group (CDY, n=8) night group (NG, n=8), and control NG group (CNG, n=7). Distance covered, velocity and latencies to reach the platform were examined. After completing these tasks, cytochrome c-oxidase activity (CO) in several brain limbic system structures was compared between groups. There were no behavioral differences in the time of day when the animals were trained. However, the metabolic brain consumption was higher in rats trained in the day condition. This CO increase was supported by the prefrontal cortex, thalamus, dorsal and ventral striatum, hippocampus and entorhinal cortex, revealing their role in the performance of the spatial reversal learning task. Finally, the orbitofrontal cortex has been revealed as a key structure in reversal learning execution.