Ionic Fragmentation of the Halothane Molecule Induced by EUV and Soft X-ray Radiation.

EUV and soft X-ray-induced photofragmentation of the halothane (CF3CHBrCl) molecule has been investigated using time-of-flight mass spectrometry in the coincidence mode (PEPICO) covering the valence region and vicinity of the bromine 3d, chlorine 2p, and carbon 1s edges. Total and partial ion yields have been recorded as a function of photon energy. At lower photon energies, the heavier singly charged molecular fragments predominate in the mass spectra. On the other hand, there is a strong tendency to the atomization of the molecule at higher photon energies. Despite the different chemical environments experienced by the two carbon atoms, weak site-specific fragmentation is observed. In addition, ab initio quantum mechanical calculations at the MP2 level and a series of computations with multiconfigurational self-consistent field have been performed to describe the inner-shell states.

Cerebral sinovenous thrombosis as a cause of subdural hemorrhage in the pediatric population: Is there a correlation?

PURPOSE: Cerebral sinovenous thrombosis is an increasingly recognized cause of stroke in children and neonates. Its true incidence appears to be underestimated. Despite being a rare event, certain studies have found a correlation between subdural hemorrhage and cerebral sinus thrombosis. The literature suggests that spontaneous cerebral sinovenous thrombosis in the pediatric population may lead to the occurrence of a subdural hemorrhage. In this report, we present a case of cerebral venous thrombosis associated with chronic subdural hematoma and review the literature to highlight the importance of these conditions. CASE REPORT: An 11-year-old boy was admitted in the neurosurgery department with headache and a neurological examination without changes. The imaging studies identified a heterogeneous subdural collection in the fronto-temporo-parietal region. The patient underwent surgical drainage of the subdural hematoma, and the procedure was performed without complications. The magnetic resonance and angiography showed an extensive thrombosis of the superior sagittal sinus, extending downward to the occipital sinus and partially to the right transverse sinus. CONCLUSIONS: Appropriate management in the diagnosis and an early treatment of dural sinus thrombosis associated with subdural hemorrhage can reduce the risk of recurrence and improve the clinical outcome.

Use of thermography in the long-term evaluation of scrotal surface temperature and its impact on seminal quality in stallions.

Scrotal surface thermography is a non-invasive method for assessing testicular thermoregulation in stallions; however, few studies have explored the application of this technique concerning the thermal physiology of equine reproductive systems. This study aimed to evaluate the consistency of testicular thermoregulation in stallions over a year using thermography to measure the scrotal surface temperature (SST). Moreover, we assessed the best region for measuring the surface body temperature compared with the SST. Ten light-breed stallions were used in the experiment. Thermographic images of the scrotal and body surfaces (neck and abdomen) were captured. Fresh, cooled and frozen-thawed semen samples were evaluated to verify the impact of thermoregulation on semen quality. Testicular thermoregulation was maintained throughout the year in stallions amidst changes in the external temperature, as evidenced by the weak correlation between the SST and ambient temperature. A lower correlation was observed between the environmental temperature and body surface temperature (BTS) obtained from the abdomen (BTS-A; R = .4772; p < .0001) than with that obtained from the neck (BTS-N; R = .7259; p < .0001). Moreover, both BTS-A and SST were simultaneously captured in a single image. The consistent quality of the fresh, cooled and frozen semen suggests efficient thermoregulation in stallions throughout the year.

Longitudinal association of sleep quality with physical performance measures: SABE cohort study, Brazil.

OBJECTIVES: The aim of this study was to investigate the longitudinal association of sleep with physical performance in a representative sample of non-institutionalised older adults residing in the municipality of São Paulo, Brazil. STUDY DESIGN: Prospective cohort study. METHODS: The current longitudinal study used data extracted from the Health, Well-being, and Aging Study (Estudo Saúde Bem-Estar e Envelhecimento [SABE]). The study population consisted of individuals aged ≥60 years who participated in the study in 2010 or 2015. Dependent variables included the Short Physical Performance Battery (SPPB) and gait speed. Independent variables of interest were self-reported sleep difficulty, daytime sleepiness and sleep quality. The longitudinal association between sleep variables and the outcomes was evaluated using Generalised Estimating Equations (GEE) Models adjusted for covariates. All the variables, except age, sex and schooling, were assessed at baseline and follow-up visits (2010 and 2015). RESULTS: The analyses included 2205 observations from 1559 individuals. The population mean age was 72 years in 2010 and 71 years in 2015, with a higher prevalence of women in both years. Between 2010 and 2015, there was a decline in the SPPB score and gait speed. Daytime sleepiness was negatively associated with the SPPB score [Coef.: -0.38 (95% confidence interval {CI}: -0.56, -0.21)] and gait speed [Coef.: -0.03 (95% CI: -0.05, -0.01)]. Poor sleep quality was negatively associated with the SPPB score [Coef.: -0.29 (95% CI: -0.57, -0.01)] and gait speed [Coef.: -0.03 (95% CI: -0.06, -0.00)]. CONCLUSIONS: Daytime sleepiness and poor sleep quality are associated with compromised physical performance in non-institutionalised older adults, and this association remained consistent over time.

Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

Evolution and divergence of the genetic lineage Desmodus rotundus/Artibeus lituratus of rabies virus in São Paulo State.

The last record of a rabies case caused by the dog-specific rabies virus (RABV) lineage in dogs or cats in São Paulo State was in 1998. From 2002 to 2021, 57 cases of rabies in these animals were reported, and the vast majority (51) were genetically characterized as belonging to the Desmodus rotundus/Artibeus lituratus RABV lineage. However, it is not currently possible to infer which of these bats is the source of infection by genome sequencing of RABV isolates. The aims of this study were (a) to characterize the Desmodus rotundus/Artibeus lituratus lineage to determine the relationships between the RABV lineages and each reservoir, (b) to assess the phylogeny and common ancestors of the RABV lineages found in D. rotundus and A. lituratus, and (c) to further understand the epidemiology and control of rabies. In this study, we genetically analyzed 70 RABV isolates from São Paulo State that were received by the Virology Laboratory of the Pasteur Institute of São Paulo between 2006 and 2015. Of these isolates, 33 were associated with the hematophagous bat D. rotundus and 37 with the fruit bat A. lituratus. A genomic approach using phylogenetic analysis and nucleotide sequence comparisons demonstrated that these isolates belonged to the same genetic lineage of RABV. We also found that, in São Paulo State, the D. rotundus/A. lituratus lineage could be subdivided into at least four phylogenetic sublineages: two associated with D. rotundus and two with A. lituratus. These results are of importance for the epidemiological surveillance of rabies in São Paulo.

Raising the suspicion of a non-autochthonous infection: identification of Leishmania guyanensis from Costa Rica exhibits a Leishmaniavirus related to Brazilian north-east and French Guiana viral genotypes.

BACKGROUND: Costa Rica has a history of neglecting prevention, control and research of leishmaniasis, including limited understanding on Leishmania species causing human disease across the country and a complete lack of knowledge on the Leishmania RNA virus, described as a factor linked to the worsening and metastasis of leishmanial lesions. OBJECTIVES: The aim of this work was to describe a case of cutaneous leishmaniasis by Leishmania (Viannia) guyanensis, bearing infection with Leishmaniavirus 1 (LRV1) in Costa Rica, raising the suspicion of imported parasites in the region. METHODS: The Leishmania strain was previously identified by routine hsp70 polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in Costa Rica and subsequently characterised by isoenzyme electrophoresis and Sanger sequencing in Brazil. Screening for LRV1 was conducted with a dual RT-PCR approach and sequencing of the fragment obtained. FINDINGS: Since 2016 Costa Rica performs Leishmania isolation and typing as part of its epidemiological surveillance activities. Amongst 113 strains typed until 2019, only one was characterised as a L. (V.) guyanensis, corresponding to the first confirmed report of this species in the country. Interestingly, the same strain tested positive for LRV1. Sequencing of the viral orf1 and 2, clustered this sample with other LRV1 genotypes of South American origin, from the Northeast of Brazil and French Guiana. MAIN CONCLUSION: The unique characteristics of this finding raised the suspicion that it was not an autochthonous strain. Notwithstanding its presumed origin, this report points to the occurrence of said endosymbiont in Central American Leishmania strains. The possibility of its local dispersion represents one more challenge faced by regional health authorities in preventing and controlling leishmaniasis.

Oral health related-quality of life before and during the COVID-19 pandemic in patients with non-alcoholic fatty liver disease.

BACKGROUND: Since the beginning of the COVID-19 pandemic, the number of medical appointments and the offer and use of oral health services have decreased sharply with the lockdown period. Restriction to regular dental care can increase the risk of oral diseases, capable of affecting general health and oral health-related quality of life, particularly among medically compromised patients. This study aimed to assess health-related quality of life (HRQoL) and oral health-related quality of life (OHRQoL) of patients with non-alcoholic liver disease (NAFLD) before and during the COVID-19 pandemic. MATERIAL AND METHODS: Prospective cohort of 58 patients with NAFLD followed up from March 2020 (before the pandemic) to December 2021 (during the pandemic). RAND 36-Item Health Survey and Oral Health Impact Profile 14 (OHIP-14) questionnaires were used to assess HRQoL and OHRQoL, respectively, in the two points of time. RESULTS: The scores of all scales HRQoL and of the question about health change in the last year decreased substantially with the advent of the pandemic. Large (>0.50) effect sizes were estimated for the scales Role functioning/physical, Pain, General health, and Energy/fatigue. Patients who had COVID-19 presented better HRQoL and OHIP-14 mean scores than those who did not have the disease. The OHIP-14 total score increased 3.6 points with the advent of the pandemic, representing a large effect size (0.62). Patients presented high probability (84.3%) of increasing OHIP14 score during the pandemic. CONCLUSIONS: The HRQoL and the OHRQoL scores of NAFLD patients decreased substantially with the advent of the pandemic. However, these decreases were not associated with the COVID-19 disease by itself, but probably to other factors related to the deep social changes brought by the social isolation measures to combat the pandemic.

Scalp arteriovenous malformations - 20 years of experience in a tertiary healthcare centre.

BACKGROUND: Scalp arteriovenous malformations (SAVM) are extremely uncommon vascular malformations, with only ~200 cases published in the English language in the past years. The objective of the present study was to describe the experience of a single reference service in neurosurgery. METHODS: This is a descriptive and retrospective study conducted at our institution, which included cases of SAVM treated between 2001 and 2022. All information were extracted from the medical records of our institution. Patient confidentiality was preserved. Furthermore, an illustrative case has been described in detail. RESULTS: Seven patients were included. The male-to-female ratio was 2.5: 1 and the mean age was 23.3 (3-42) years. Most cases (56.4%) were spontaneous and the lesions were located in the frontal (28.7%) and parietal (28.7%) regions. All lesions were supplied by more than one feeder, with the superficial temporal and occipital arteries being the most commonly involved (71.5%). Six patients underwent preoperative embolization, and 56.4% patients had scalp necrosis. Five patients underwent surgical resection, all without recurrence and with good postoperative evolution. CONCLUSIONS: More than one artery was involved in all cases, and the properties of the involved vessel influences the approach strategy. Surgical treatment is curative, and preoperative embolization helps reduce bleeding during the surgery. Complete resection of the lesions prevents associated complications, such as bleeding or recurrence. Scalp necrosis is a frequent complication in the treatment of these lesions, and a multidisciplinary approach involving reconstructive plastic surgery should always be considered.

Enhanced Cavity Optomechanics with Quantum-Well Exciton Polaritons.

Semiconductor microresonators embedding quantum wells can host tightly confined and mutually interacting excitonic, optical, and mechanical modes at once. We theoretically investigate the case where the system operates in the strong exciton-photon coupling regime, while the optical and excitonic resonances are parametrically modulated by the interaction with a mechanical mode. Owing to the large exciton-phonon coupling at play in semiconductors, we predict an enhancement of polariton-phonon interactions by 2 orders of magnitude with respect to mere optomechanical coupling: a near-unity single-polariton quantum cooperativity is within reach for current semiconductor resonator platforms. We further analyze how polariton nonlinearities affect dynamical backaction, modifying the capability to cool or amplify the mechanical motion.

Protective role of Portuguese natural mineral waters on skin aging: in vitro evaluation of anti-senescence and anti-oxidant properties.

Natural mineral waters (NMWs) emerge from the earth as springs and their beneficial therapeutic effect has been empirically recognized in different countries. Portugal has diverse NMW resources that are sought for the relief of different afflictions including dermatological complications. However, there is a lack of scientific validation supporting this empiric knowledge. In this study, we aimed to screen the in vitro bioactivity of Portuguese NMWs with different chemical profiles, namely sulfurous/bicarbonate/sodic (SBS), bicarbonate/magnesium, sulfated/calcic, sulfurous/chlorinated/sodic, sulfurous/bicarbonate/fluoridated/sodic, and chlorinated/sodic, focusing on aging-related skin alterations. Mouse skin fibroblasts and macrophages were exposed to culture medium prepared in different NMWs. Cellular viability was evaluated by MTT assay and etoposide-induced senescence was analyzed through the beta-galactosidase staining kit. Wound healing was investigated by the scratch assay, and phototoxicity/photoprotection after UVA irradiation was evaluated using a neutral red solution. ROS production was quantified using the 2'7'-dichlorofluorescin diacetate dye, and the activity of superoxide dismutase (SOD) was analyzed by a commercial kit after lipopolysaccharide exposure. NMWs within the SBS profile demonstrated anti-senescence activity in skin fibroblasts, along with a variable effect on cellular viability. Among the tested NMWs, two decreased cellular senescence and preserved cell viability and were therefore selected for subsequent studies, together with a SBS NMW with therapeutic indications for dermatologic diseases. Overall, the selected NMW promoted wound healing in skin fibroblasts and activated SOD in macrophages, thus suggesting an anti-oxidant effect. None of the NMWs prevented phototoxicity after UV irradiation. Our results shed a light on the anti-aging potential of Portuguese NMW, supporting their putative application in cosmetic or medical products.

Transcranial Doppler findings in a population with clinical probable reversible cerebral vasoconstriction syndrome.

OBJECTIVE: To describe transcranial Doppler (TCD) findings in a population with clinical probable RCVS. Exploratory objectives included the study of clinical characteristics of probable RCVS patients with and without spasm detected by TCD. METHODS: Cross-sectional cohort study of patients with thunderclap headache (TCH) without subarachnoid hemorrhage (SAH) of our neurology and headache center between 2010 and 2019, selecting patients with clinical diagnosis of probable RCVS (negative angiography study) by ICHD-3 criteria and with at least two TCD studies. RESULTS: From 114 TCH patients, 36/114 had probable RCVS by ICHD-3 criteria and had at least two TCD studies available. The mean age at RCVS onset was 42.9years (21-72years); 29/36 (80.6%) were female, 7/28 (25%) had cardiovascular risk factors and 20/36 (55.6%) had history of migraine. Most common triggers were stressful emotion, drugs, valsalva maneuvers and sexual activity. Five/36 (13.9%) had complications and 3/36 (8.3%) had late recurrence. Initial TCD was performed on average of 16 (6-26) days after headache onset. Twenty-nine had vasospasm on TCD, presenting mean flow velocity of MCA (VMCA) of 135.7±17.0cm/s and mean maximum VMCA of 138.3±17.2. Vasospasm was mild in 21/29 patients (72.4%) and moderate in 8/29 (27.6%). Complete VMCA normalization occurred on average 41 (30-70) days after headache onset and 24 (11-47) days after initial TCD. The group of patients with vasospasm detected by TCD had more female patients (26/29, 89.7% vs. 3/7, 42.8%, P=0.016), and more TCH attacks (mean of 3.6 vs. 2.14, P=0.049). CONCLUSION: TCD may be a useful tool in the identification of vasospasm in patients with probable RCVS, supporting the diagnosis of RCVS in patients presenting with recurrent TCH without SAH.

Incidence and risk factors for osteoporotic non-vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The São Paulo Ageing and Health (SPAH) study.

We ascertained the incidence of non-vertebral fracture in a low-income Brazilian elderly cohort. To the best of our knowledge, this is the first population-based study to demonstrate the frequency of non-vertebral fracture in elderly Latin Americans. Age, prior fracture, and bone mineral density (BMD) at hip were predictors of fracture. INTRODUCTION: No data on incidence of osteoporotic non-vertebral fracture have been reported in low-income countries where the population's aging has been faster. Even in developed countries, currently available prospective data on major fracture rates beyond hip are scarce. The aim of this study is to describe the incidence and risk factors for non-vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. METHODS: Seven hundred seven older adults (449 women, 258 men) were evaluated at baseline and after a mean follow-up of 4.3 ± 0.8 years. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. New non-vertebral fracture (hip, proximal humerus, rib, forearm) was determined during the follow-up. Multivariate Poisson regression models were used to identify independent predictors of fracture. RESULTS: The age-standardized incidence of non-vertebral fracture was 1562.3/100,000 (1085.7-2248.1/100,000) person-years (pyr) in women and 632.8/100,000 (301.7-1327.3/100,000) in men. Concerning to hip fractures, the incidence was 421.2/100,000 (210.7-842.3/100,000) pyr in women and 89.9/100,000 (12.7-638.5/100,000) in men. In a multivariate analysis, age (RR 2.07, 95% CI 1.13-3.82, p = 0.019, each 10-year increase), prior non-vertebral fracture (RR 3.08, 95% CI 1.36-6.95, p = 0.007), and total hip BMD (RR 1.68, 95% CI 1.11-2.56, p = 0.015, each 1 SD decrease) were predictors of new non-vertebral fracture. In men, fitting a model of risk factors for fracture was prevented by the limited number of events in male sample. CONCLUSION: This is the first population-based study to ascertain the incidence of major non-vertebral fractures in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, and hip BMD were predictors of the short-term incidence of fracture.

Blood biomarkers associated with inflammation predict poor prognosis in cerebral venous thrombosis:: a multicenter prospective observational study.

BACKGROUND AND PURPOSE: Experimental studies suggest inflammation can contribute to blood barrier disruption and brain injury in cerebral venous thrombosis (CVT). We aimed to determine whether blood biomarkers of inflammation were associated with the evolution of brain lesions, persistent venous occlusion or functional outcome in patients with CVT. METHODS: Pathophysiology of Venous Infarction-Prediction of Infarction and Recanalization in CVT (PRIORITy-CVT) was a multicenter prospective cohort study of patients with newly diagnosed CVT. Evaluation of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) concentrations in peripheral blood samples was performed at admission in 62 patients. Additional quantification of interleukin (IL)-6 was performed at day 1, 3 and 8 in 35 patients and 22 healthy controls. Standardized magnetic resonance imaging was performed at day 1, 8 and 90. Primary outcomes were early evolution of brain lesion, early recanalization and functional outcome at 90 days. RESULTS: Interleukin-6 levels were increased in patients with CVT with a peak at baseline. IL-6, NLR and CRP levels were not related with brain lesion outcomes or early recanalization but had a significant association with unfavourable functional outcome at 90 days (IL-6: OR = 1.28, 95% CI: 1.05-1.56, P = 0.046; NLR: OR = 1.39, 95% CI: 1.4-1.87, P = 0.014; CRP: OR = 1.756, 95% CI: 1.010-3.051, P = 0.029). Baseline IL-6 had the best discriminative capacity, with an area under the receiver operating characteristic curve to predict unfavourable functional outcome of 0.74 (P = 0.031). CONCLUSIONS: Increased baseline levels of NLR, CRP and IL-6 may serve as new predictive markers of worse functional prognosis at 90 days in patients with CVT. No association was found between inflammatory markers and early evolution of brain lesion or venous recanalization.

Short telomeres drive pessimistic judgement bias in zebrafish.

The role of telomerase reverse transcriptase has been widely investigated in the contexts of ageing and age-related diseases. Interestingly, decreased telomerase activities (and accelerated telomere shortening) have also been reported in patients with emotion-related disorders, opening the possibility for subjective appraisal of stressful stimuli playing a key role in stress-driven telomere shortening. In fact, patients showing a pessimistic judgement bias have shorter telomeres. However, in humans the evidence for this is correlational and the causal directionality between pessimism and telomere shortening has not been established experimentally yet. We have developed and validated a judgement bias experimental paradigm to measure subjective evaluations of ambiguous stimuli in zebrafish. This behavioural assay allows classification of individuals in an optimistic-pessimistic dimension (i.e. from individuals that consistently evaluate ambiguous stimuli as negative to others that perceive them as positive). Using this behavioural paradigm we found that telomerase-deficient zebrafish (tert-/-) were more pessimistic in response to ambiguous stimuli than wild-type zebrafish. The fact that individuals with constitutive shorter telomeres have pessimistic behaviours demonstrates for the first time in a vertebrate model a genetic basis of judgement bias.

Biosurfactant production of Piper hispidum endophytic fungi.

AIMS: To evaluate the production of biosurfactants by fungi isolated from the Amazonian species Piper hispidum (Piperaceae), and to determine the physico-chemical properties of the crude biosurfactant obtained from the most promising fungi. METHODS AND RESULTS: A total of 117 endophytic fungi were isolated, and 50 were used to verify the production of biosurfactants. Of these, eight presented positive results in the drop collapse test, and emulsification index ranging from 20 to 78%. The most promising fungi, Ph III 23L and Ph II 22S (identified as Aspergillus niger and Glomerella cingulata, respectively) were recultivated for extraction and analysis of the biosurfactant's physico-chemical characteristics. The cultivation broth that presented the greatest decrease in surface tension (36%) was that of the A. niger, which reduced it from 68·0 to 44·0 mN m-1 . The lowest critical micellar concentration value was found for the same endophyte (14·93 mg ml-1 ). CONCLUSIONS: Endophytes of P. hispidum proved to be interesting producers of biosurfactants and presented promising physico-chemical characteristics for applications in diverse industrial sectors. SIGNIFICANCE AND IMPACT OF THE STUDY: Piper hispidum endophytic fungi can be used as a new source of biosurfactants, as these molecules present a significant market due to their wide industrial applications.

Death from drought in tropical forests is triggered by hydraulics not carbon starvation.

Drought threatens tropical rainforests over seasonal to decadal timescales, but the drivers of tree mortality following drought remain poorly understood. It has been suggested that reduced availability of non-structural carbohydrates (NSC) critically increases mortality risk through insufficient carbon supply to metabolism ('carbon starvation'). However, little is known about how NSC stores are affected by drought, especially over the long term, and whether they are more important than hydraulic processes in determining drought-induced mortality. Using data from the world's longest-running experimental drought study in tropical rainforest (in the Brazilian Amazon), we test whether carbon starvation or deterioration of the water-conducting pathways from soil to leaf trigger tree mortality. Biomass loss from mortality in the experimentally droughted forest increased substantially after >10 years of reduced soil moisture availability. The mortality signal was dominated by the death of large trees, which were at a much greater risk of hydraulic deterioration than smaller trees. However, we find no evidence that the droughted trees suffered carbon starvation, as their NSC concentrations were similar to those of non-droughted trees, and growth rates did not decline in either living or dying trees. Our results indicate that hydraulics, rather than carbon starvation, triggers tree death from drought in tropical rainforest.

High-Fat Diet Induces Disruption of the Tight Junction-Mediated Paracellular Barrier in the Proximal Small Intestine Before the Onset of Type 2 Diabetes and Endotoxemia.

BACKGROUND/AIM: A link between an impaired intestinal barrier, endotoxemia, and the pathogenesis of metabolic diseases, such as type 2 diabetes mellitus (T2DM), has been proposed. In previous work, we have demonstrated that the tight junction (TJ)-mediated intestinal barrier in ileum/colon was marginally changed in prediabetic mice; therefore, it does not seem to mainly contribute to the T2DM onset. In this study, the TJ-mediated epithelial barrier in the duodenum and jejunum was evaluated in mice during the development of type 2 prediabetes. METHODS/RESULTS: HF diet induced prediabetes after 60 days associated with a significant rise in intestinal permeability to the small-sized marker Lucifer yellow in these mice, with no histological signs of mucosal inflammation or rupture of the proximal intestine epithelium. As revealed by immunofluorescence, TJ proteins, such as claudins-1, -2, -3, and ZO-1, showed a significant decrease in junctional content in duodenum and jejunum epithelia, already after 15 days of treatment, suggesting a rearrangement of the TJ structure. However, no significant change in total cell content of these proteins was observed in intestinal epithelium homogenates, as assessed by immunoblotting. Despite the changes in intestinal permeability and TJ structure, the prediabetic mice showed similar LPS, zonulin, and TNF-α levels in plasma or adipose tissue, and in intestinal segments as compared to the controls. CONCLUSION: Disruption of the TJ-mediated paracellular barrier in the duodenum and jejunum is an early event in prediabetes development, which occurs in the absence of detectable endotoxemia/inflammation and may contribute to the HF diet-induced increase in intestinal permeability.

Methionine precursor effects on lactation performance of dairy cows fed raw or heated soybeans.

Two experiments were conducted to evaluate the effect of isopropyl ester of 2-hydroxy-4-(methylthio) butanoic acid (HMBi) on lactation performance of dairy cows. Experiment 1 evaluated the effect of HMBi in diets with 15.3% crude protein (CP) and with different proportions of rumen-degradable and undegradable protein. Variation in rumen-degradable and undegradable protein was achieved by replacing raw with heated soybeans. Experiment 2 was an on-farm trial to evaluate HMBi with a large number of observations and using a farm-formulated diet (17.2% CP). In experiment 1, 20 Holsteins at 100 ± 41 d in milk were allocated to 5 replicated 4 × 4 Latin squares with 21-d periods. Treatments were formed by a 2 × 2 factorial arrangement of raw or heated soybeans with or without HMBi. Paper capsules with HMBi were orally administered twice daily to each cow. Dosage of HMBi was 7.6 g of digestible Met/cow per day. There was no interaction between soybean type and HMBi. Heat-treated soybeans increased the yields of milk, protein, fat, and lactose, and reduced urea N in milk and plasma (PUN) compared with raw soybeans. Rumen microbial yield, dry matter intake (DMI), and the total-tract apparent digestibility of nutrients did not differ between soybean types. There was no evidence for HMBi-driven effects on DMI, milk and components yield, or diet digestibility. Urinary purine derivative excretion and PUN concentration were reduced in HMBi-fed cows compared with cows fed diets without HMBi. In experiment 2, 294 Holstein cows were blocked by parity and milk yield, and randomly assigned to HMBi (8.9 g of digestible Met/cow per day) or control. The final data set had 234 cows (215 ± 105 days in milk; 96 primiparous and 138 multiparous; 114 on control and 120 on HMBi) housed in 4 freestall groups (1 group/treatment per parity). The freestall group was the experimental unit for DMI, diet and orts composition, and feed availability. The HMBi supplement was top dressed for 28 d on the first daily meal of each cow, immediately after feed delivery of the same batch of feed to all 4 freestall groups (3 times per day). Sample collection and feed analysis occurred during the last 5 d. Spot urine samples and blood samples from each cow were obtained for analysis of the urinary allantoin to creatinine ratio and PUN. Feed availability, the contents of CP and neutral detergent fiber in diets and orts, and DMI did not differ. Cows fed with HMBi had greater milk protein yield and concentration compared with control and had no change in milk fat and lactose. Rumen microbial yield was greater and PUN was lower in HMBi-fed cows compared with control. In experiment 1, HMBi decreased rumen microbial yield and did not affect lactation performance, but it increased ruminal microbial yield and the secretion of milk protein in experiment 2. These results suggest that lactation response to HMBi may be partially mediated by ruminal events. Heated soybeans increased the efficiency of N utilization and the yields of milk, protein, fat, and lactose, but did not interact with HMBi supplementation.

The evolution of ADAM gene family in eukaryotes.

The ADAM (A Disintegrin And Metalloprotease) gene family encodes proteins with adhesion and proteolytic functions. ADAM proteins are associated with diseases like cancers. Twenty ADAM genes have been identified in humans. However, little is known about the evolution of the family. We analyzed the repertoire of ADAM genes in a vast number of eukaryotic genomes to clarify the main gene copy number expansions. For the first time, we provide compelling evidence that early-branching green algae (Mamiellophyceae) have ADAM genes, suggesting that they originated in the last common ancestor of eukaryotes, before the split of plants, fungi and animals. The ADAM family expanded in early metazoans, with the most significative gene expansion happening during the first steps of vertebrate evolution. We concluded that most of mammal ADAM diversity can be explained by gene duplications in early bone fish. Our data suggest that ADAM genes were lost early in green plant evolution.