Is low back pain a risk/prognostic factor for the development and/or progression of temporomandibular disorders? A systematic review with meta-analysis.

OBJECTIVES: To evaluate the association between low back pain (LBP) and painful temporomandibular disorders (TMDs). METHODS: Systematic review of observational studies. Searches were conducted using OVID MEDLINE, CINHAL, Web of Science and PUBMED databases up to 21 October 2022. Qualitative and quantitative analyses were performed. Risk of bias (RoB) was assessed using the Quality in Prognosis Studies tool (QUIPS). RESULTS: Eight studies were included in the present review with meta-analysis. The first onset of TMDs was more likely in patients with previous chronic LBP (hazard ratio (HR) 1.53 [95% confidence interval (CI): 1.28; 1.83, p < .00001]). In addition, patients with chronic LBP had 3.25 times the odds (OR) [95% CI: 1.94; 5.43, p < .00001] of having chronic TMDs than those who did not have chronic LBP. In addition, the higher the exposure to chronic LBP, the higher the risk of developing a first onset of TMDs. CONCLUSIONS: Chronic LBP can be considered a risk/contributing factor for painful TMDs. Although there is a high certainty in the evidence linking chronic LBP with the risk of a first onset of TMDs, there are insufficient studies to draw definitive conclusions. Furthermore, while an association between chronic LBP and chronic TMDs and a dose-effect was observed between these two conditions, a limited number of studies and evidence exist to support these findings. Future studies are needed to increase the body of evidence.

Assessment of a computed tomography imaging spectrometer using an optimized expectation-maximization algorithm.

We designed and built a homemade computed tomography imaging spectrometer (CTIS) of 250×250pixels of spatial resolution and 2 nm spectral resolution. The optical design considers a CTIS optical array coupled to a digital reflex camera. We reconstructed the intensity spectra of a fluorescent source, the diffuse reflectance of a ColorChecker, and samples of Capsicum annuum of three different colors, using the expectation-maximization sequential algorithm, optimized utilizing an array of indices to reduce the reconstruction time. The results obtained with a ColorChecker indicate a high positive correlation of 0.9745 with an average residual difference of 1.31% concerning the spectra obtained with a commercial integrating sphere spectrometer. The feasibility of the proposed CTIS system shows how to detect and evaluate the physiological changes resulting from the decomposition of the green fruit of the Capsicum annuum in a range from 500 to 650 nm.

Body size phenotypes comprehensively assess cardiometabolic risk and refine the association between obesity and gut microbiota.

OBJECTIVE: The gut microbiota associates with obesity and related disorders, but recent meta-analyses have found that this association is, at best, of small effect. We argue that such analyses are flawed by the use of body mass index (BMI) as sole proxy for disease, and explore a classification method that distinguishes the cardiometabolic health status of individuals to look for more comprehensive associations between gut microbes and health. DESIGN: We analyzed a 441 community-dwelling cohort on which we obtained demographic and health information, anthropometry and blood biochemistry data that served to categorize participants according to BMI, cardiometabolic health status and body size phenotypes. In addition, the participants donated fecal samples from which we performed 16S rRNA gene sequencing to analyze the gut microbiota. RESULTS: We observed that health-related variables deteriorate with increased BMI, and that there are further discrepancies within a given BMI category when distinguishing cardiometabolically healthy and unhealthy individuals. Regarding the gut microbiota, both obesity and cardiovascular disease associate with reductions in α-diversity; having lean, healthy individuals the most diverse microbiotas. Moreover, the association between the gut microbiota and health stems from particular consortia of microbes; the prevalence of consortia involving pathobionts and Lachnospiraceae are increased in obese and cardiometabolically abnormal subjects, whereas consortia including Akkermansia muciniphila and Methanobrevibacter, Oscillospira and Dialister have higher prevalence in cardiometabolically healthy and normoweight participants. CONCLUSIONS: The incorporation of cardiometabolic data allows a refined identification of dissimilarities in the gut microbiota; within a given BMI category, marker taxa associated with obesity and cardiometabolic disease are exacerbated in individuals with abnormal health status. Our results highlight the importance of the detailed assessment and classification of individuals that should be carried out prior to the evaluation of obesity treatments targeting the gut microbiota.

Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes.

Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011-2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy ( n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy ( n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

Neutrophil CD64 expression, procalcitonin and presepsin are useful to differentiate infections from flares in SLE patients with SIRS.

Background/Objective Differentiating systemic lupus erythematosus (SLE) activity from infections in febrile patients is difficult because of similar initial clinical presentation. The aim of this study is to evaluate the usefulness of a number of biomarkers for differentiating infections from activity in SLE patients admitted with systemic inflammatory response (SIRS). Methods Patients with SLE and SIRS admitted to the emergency room were included in this study. Measurements of different markers including procalcitonin, neutrophil CD64 expression and presepsin, were performed. Infection was considered present when positive cultures and/or polymerase chain reaction were obtained. Sensitivity and specificity were calculated for all biomarkers. Results Twenty-seven patients were admitted, 23 women (82.5%), mean age 33.2 years. An infectious disease was confirmed in 12 cases. Markers for SLE activity including anti-DNA titers by IIF ( p = 0.041) and enzyme-linked immunosorbent assay ( p = 0.009) were used for differentiating SLE flares from infection. On the contrary, increased procalcitonin ( p = 0.047), neutrophil CD64 expression by flow cytometry ( p = 0.037) and presepsin ( p = 0.037) levels were observed in infected SLE patients. Conclusions High neutrophil CD64 expression, presepsin and procalcitonin levels are useful to differentiate infections from activity in SLE patients. In most cases, a positive bioscore that includes these three markers demonstrate the presence of an infectious disease.

Self-fertilization, long-distance flash invasion and biogeography shape the population structure of Pseudosuccinea columella at the worldwide scale.

Population genetic studies are efficient for inferring the invasion history based on a comparison of native and invasive populations, especially when conducted at species scale. An expected outcome in invasive populations is variability loss, and this is especially true in self-fertilizing species. We here focus on the self-fertilizing Pseudosuccinea columella, an invasive hermaphroditic freshwater snail that has greatly expanded its geographic distribution and that acts as intermediate host of Fasciola hepatica, the causative agent of human and veterinary fasciolosis. We evaluated the distribution of genetic diversity at the largest geographic scale analysed to date in this species by surveying 80 populations collected during 16 years from 14 countries, using eight nuclear microsatellites and two mitochondrial genes. As expected, populations from North America, the putative origin area, were strongly structured by selfing and history and harboured much more genetic variability than invasive populations. We found high selfing rates (when it was possible to infer it), none-to-low genetic variability and strong population structure in most invasive populations. Strikingly, we found a unique genotype/haplotype in populations from eight invaded regions sampled all over the world. Moreover, snail populations resistant to infection by the parasite are genetically distinct from susceptible populations. Our results are compatible with repeated introductions in South America and flash worldwide invasion by this unique genotype/haplotype. Our study illustrates the population genetic consequences of biological invasion in a highly selfing species at very large geographic scale. We discuss how such a large-scale flash invasion may affect the spread of fasciolosis.

Kidney transplantation for end-stage renal disease in lupus nephritis, a very safe procedure: a single Latin American transplant center experience.

Background Lupus nephritis (LN) is one of the most frequent complications of SLE and occurs in up to 50% of cases depending on the studied population. Of these, approximately 20% progress to end-stage renal disease (ESRD), with the treatment of choice being a kidney transplant. Objective The objective of this study was to describe the clinical outcome of patients transplanted due to LN, compared with patients transplanted for other causes, in a Latin American population from the Fundación Valle del Lili in Cali, Colombia. Methods Observational, retrospective case study with controls matched by age, sex and type of donor in a single center between 1996 and 2014. Results Sixty-five kidney transplants were performed in patients with LN and ESRD. The survival of patients with LN was 98% at 1, 10 and 15 years ( p = .99). For controls by age and sex, survival was also 98% at 15 years post-transplant, and for controls by donor, the survival rate was 100% at 5 years and 98% at 15 years. Graft survival in patients with LN to 1, 5 and 15 years was 92%, 83% and 71%, respectively; for controls by age and sex, it was 90%, 84% and 64%, respectively, and for the controls by donor, it was 89%, 86% and 79%, respectively ( p = .7718). There were no statistically significant differences found in the cumulative incidence of acute graft rejection in the first year, but it was found that acute rejection is a factor that relates to the loss of function of the renal graft ( p = .032). Of the patients transplanted for LN, two (3.1%) experienced a recurrence of the disease. One patient died after a diagnosis of recurrence of LN due to an infection. Conclusions Kidney transplantation is a good option for patients with ESRD due to LN. In this Hispanic population, the survival of patients, graft survival, and cumulative incidence of graft rejection are not different from those of other transplanted patients. In addition, recurrence of LN was rare, showing the benefits of renal transplantation in LN patients with ESRD.

Hepatic expression of aminoadipate semialdehyde synthase is unchanged by postruminal lysine supply in lactating dairy cows.

Lysine supply is potentially limiting for milk production in dairy cows. The availability of Lys to the mammary gland and other tissues is a function of the quantity of metabolizable Lys supplied and Lys catabolism by the liver. Likewise, Lys catabolism may be influenced by Lys supply. This study evaluated the effect of increased postruminal Lys supply on the expression of aminoadipate semialdehyde synthase (AASS, a committing step in Lys catabolism in the liver) and ornithine transcarbamoylase and argininosuccinate synthase (key urea cycle enzymes that are responsive to protein supply). Eight multiparous peak Holstein cows were used in a replicated 4 × 4 Latin square. Cows were fed a Lys-limiting ration and infused postruminally with 0, 9, 27, or 63 g/d of Lys. The study consisted of 10 d of pretreatment followed by 10 d of Lys infusion. On the last day of each period, liver and milk samples were collected for mRNA analysis, and blood samples were collected for analysis of amino acids and Lys metabolites. Milk protein percent increased by 5.9%, plasma Lys increased by 74%, and α-aminoadipic acid increased by 51% with postruminal infusion of 63 g/d Lys compared with 0 g/d. Expression of AASS, ornithine transcarbamoylase, and argininosuccinate synthase mRNA in liver did not differ with postruminal infusion of Lys. Milk fat globule mRNA for major milk proteins and AASS were not affected by Lys infusion. Postruminal infusion of Lys resulted in an 86% greater increase in AASS mRNA in the liver compared with mammary mRNA. These changes suggest that hepatic Lys metabolism is not responsive to Lys supply at the transcription level, and that the availability of Lys to extrahepatic tissue may be determined by hepatic Lys metabolism.

Bladder cancer in Spain 2011: population based study.

PURPOSE: We estimate the annual incidence of bladder cancer in Spain and describe the clinical profile of patients with bladder cancer enrolled in a population based study. MATERIALS AND METHODS: Using the structure of the Spanish National Health System as a basis, in 2011 the AEU (Spanish Association of Urology) conducted this study with a representative sample from 26 public hospitals and a reference population of 10,146,534 inhabitants, comprising 21.5% of the Spanish population. RESULTS: A total of 4,285 episodes of bladder cancer were diagnosed, of which 2,476 (57.8%) were new cases and 1,809 (42.2%) were cases of recurrence, representing an estimated 11,539 new diagnoses annually in Spain. The incidence of bladder cancer in Spain, age adjusted to the standard European population, was 20.08 cases per 100,000 inhabitants (95% CI 13.9, 26.3). Of patients diagnosed with a first episode of bladder cancer 84.3% were male, generally older than 59 years (81.7%) with a mean ± SD age of 70.5 ± 11.4 years. Of these patients 87.5% presented with some type of clinical symptom, with macroscopic hematuria (90.8%) being the most commonly detected. The majority of primary tumors were nonmuscle invasive (76.7%) but included a high proportion of high grade tumors (43.7%). According to the ISUP (International Society of Urologic Pathology)/WHO (2004) classification 51.1% was papillary high grade carcinoma. Carcinoma in situ was found in 2.2% of primary and 5.8% of recurrent cases. CONCLUSIONS: The incidence of bladder cancer in Spain, age adjusted to the standard European population, confirms that Spain has one of the highest incidences in Europe. Most primary nonmuscle invasive bladder cancer corresponded to high risk patients but with a low detected incidence of carcinoma in situ.

Visual odometry in the wolf spider Lycosa tarantula (Araneae: Lycosidae).

The wolf spider Lycosa tarantula homes using path integration. The angular component of the displacement is measured using a polarized-light compass associated with the functioning of the anterior median eyes. However, how L. tarantula estimates the linear component of the displacement was not known prior to this investigation. The ability of L. tarantula to gauge the distance walked after being displaced from its burrow was investigated using experimental channels placed in an indoor setup. Firstly, we manipulated the perception of visual stimuli by covering all the spider's eyes. Secondly, we changed the optic flow supplied by a black-and-white grating (λ=2 cm) perceived either in the lateral or in the ventral field of view. Finally, the period of the lateral or ventral grating was changed from λ=2 cm to λ=1 cm. Our results indicate that visual information contributes to distance estimation because when the spider's eyes were covered, the spiders tended to search for the burrow at very variable distances. This visual information is created by the motion of the image as the spider walks, the motion in the lateral field of view being the most important. The preference of a lateral optic flow over the ventral flow can be explained by the difference in the resolution capacity of the posterior lateral eyes and the anterior lateral eyes.

Current vision on diagnosis and comprehensive care in hepatic encephalopathy.

The first clinical guidelines on hepatic encephalopathy were published in 2009. Almost 14 years since that first publication, numerous advances in the field of diagnosis, treatment, and special condition care have been made. Therefore, as an initiative of the Asociación Mexicana de Gastroenterología A.C., we present a current view of those aspects. The manuscript described herein was formulated by 24 experts that participated in six working groups, analyzing, discussing, and summarizing the following topics: Definition of hepatic encephalopathy; recommended classifications; epidemiologic panorama, worldwide and in Mexico; diagnostic tools; conditions that merit a differential diagnosis; treatment; and primary and secondary prophylaxis. Likewise, these guidelines emphasize the management of certain special conditions, such as hepatic encephalopathy in acute liver failure and acute-on-chronic liver failure, as well as specific care in patients with hepatic encephalopathy, such as the use of medications and types of sedation, describing those that are permitted or recommended, and those that are not.

Volume of hippocampal activation as a determining factor for the lateralisation of the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy.

INTRODUCTION: Approximately 30% of patients with mesial temporal lobe epilepsy (MTLE) will develop drug resistance, which requires early surgical treatment. The success of the surgical procedure largely depends on the correct lateralisation of the epileptogenic zone, which can only be determined in 70% of patients with such conventional diagnostic tools as video electroencephalography and volumetric structural magnetic resonance imaging. We evaluated the performance of a memory functional magnetic resonance imaging (fMRI) paradigm in lateralising the epileptogenic zone in patients with drug-resistant MTLE. METHODS: We included 18 patients with MTLE attended at the Instituto Neurológico Colombiano in Medellin (Colombia) between 2018 and 2019. The volume of functional activation in both temporal lobes was determined with a memory fMRI paradigm. A concordance analysis was performed to compare the performance of fMRI against that of conventional tests. RESULTS: In patients with left MTLE, lower total activation was found in the hemisphere ipsilateral to the epileptogenic zone as compared to the contralateral hemisphere (121.15 ± 16.48 voxels vs 170.23 ± 17.8 voxels [P < .001]), showing substantial concordance with conventional tests. Patients with right MTLE displayed lower hippocampal activation ipsilateral to the epileptogenic zone (18.5 ± 3.38 voxels vs 27.8 ± 3.77 voxels in the contralateral hippocampus [P = .048]), showing moderate concordance with conventional tests. CONCLUSIONS: These findings suggest that lower functional activation as determined by a memory fMRI paradigm has a high level of concordance with conventional tests for lateralising the epileptogenic zone in patients with drug-resistant MTLE.

[Mirror and action observation therapy in children with unilateral spastic cerebral palsy: a feasibility study]. / Terapia en espejo y de observación de la acción en niños con parálisis cerebral espástica unilateral: estudio de viabilidad.

INTRODUCTION: Unilateral spastic cerebral palsy affects upper extremity function. Mirror and home-based action observation therapies may be useful in its treatment. The aim has been to evaluate the feasibility of action observation therapy and mirror therapy programmes combined with home action observation in children with unilateral spastic cerebral palsy. SUBJECTS AND METHODS: The feasibility study included children (6-12 years old), randomly assigned to two groups: action observation therapy and mirror therapy and action observation. Twenty-hour home sessions were conducted, including unimanual and bimanual activities. Feasibility of interventions and procedures, and spontaneous use (Assisting Hand Assessment scale) and functionality (Jebsen Taylor Hand Function Test) of the upper extremity were assessed. RESULTS: Twenty-five families were recruited, with 17 meeting the inclusion criteria. Twelve children (8.75 ± 2.38 years) participated in the study. All families completed the interventions, with no adverse effects. The total intervention dose was above 96%. After the intervention, clinically relevant changes were found in both groups in spontaneous use of the upper extremity, as well as in functionality in the action observation therapy group. CONCLUSIONS: Action observation therapy and mirror therapy combined with action observation therapy are considered feasible to be applied at home and aimed at children with unilateral spastic cerebral palsy.

TITLE: Terapia en espejo y de observación de la acción en niños con parálisis cerebral espástica unilateral: estudio de viabilidad.Introducción. La parálisis cerebral espástica unilateral afecta a la función de la extremidad superior. Las terapias en espejo y de observación de la acción domiciliaria pueden ser útiles en su tratamiento. El objetivo ha sido evaluar la viabilidad de programas de terapia de observación de la acción y terapia en espejo combinada con observación de la acción domiciliaria en niños con parálisis cerebral espástica unilateral. Sujetos y métodos. El estudio de viabilidad incluyó a niños (6-12 años), asignados aleatoriamente a dos grupos: terapia de observación de la acción y terapia en espejo y observación de la acción. Se realizaron 20 sesiones domiciliarias de una hora, y se incluyeron actividades unimanuales y bimanuales. Se evaluó la viabilidad de las intervenciones y procedimientos, y el uso espontáneo (escala Assisting Hand Assessment) y la funcionalidad (Jebsen Taylor Hand Function Test) de la extremidad superior. Resultados. Se reclutaron 25 familias, y 17 cumplieron los criterios de inclusión. Doce niños (8,75 ± 2,38 años) participaron en el estudio. Todas las familias completaron las intervenciones y no existieron efectos adversos. La dosis total de intervención fue superior al 96%. Tras la intervención, se hallaron cambios clínicamente relevantes en ambos grupos en el uso espontáneo de la extremidad superior, así como en la funcionalidad en el grupo de terapia de observación de la acción. Conclusiones. La terapia de observación de la acción y la terapia en espejo combinada con terapia de observación de la acción se consideran viables para aplicarse en el hogar y dirigidas a niños con parálisis cerebral espástica unilateral.

Ordered transcriptional factor recruitment and epigenetic regulation of tnf-alpha in necrotizing acute pancreatitis.

Tauhe expression of the critical initiator cytokine TNF-alpha was strongly upregulated in vivo in acute necrotic pancreatitis (AP) in rodents and in vitro in TNF-alpha activated acinar AR42J cells. Upregulation of tnf-alpha, inos, icam-1 and il-6 occurred both in TNF-alpha receptor 1 and 2 knock-out mice, but not in TNF-alpha knock-out mice, in cerulein-induced acute pancreatitis. Chromatin immunoprecipitation analysis showed that transcriptional factors (ELK-1, SP1, NF-kappaB and EGR-1) and chromatin modification complexes (HDAC1, HDAC2, GCN5, PCAF and CBP) were recruited and/or released from the promoter in a strictly ordered mechanism. Activation of tnf-alpha gene was also accompanied by an ordered increased level of histone H3K9, H3K14 and H3K18-acetylation and H3K4 methylation, as well as H4K5 acetylation. A better knowledge of the molecular mechanisms that control tnf-alpha gene regulation will provide deeper understanding of the initiation and development of the inflammatory processes occurring in acute pancreatitis triggered by TNF-alpha cytokine.

Effects of jugular-infused lysine, methionine, and branched-chain amino acids on milk protein synthesis in high-producing dairy cows.

In addition to lysine and methionine, current ration-balancing programs suggest that branched-chain amino acid (BCAA) supply may also be limiting in dairy cows. The objective of this study was to investigate whether BCAA, leucine, isoleucine, and valine become limiting for milk protein synthesis when methionine and lysine supply were not limiting. Nine multiparous Holstein cows with an average milk production of 53.5±7.1 kg/d were randomly assigned to 7-d continuous jugular infusions of saline (CTL), methionine and lysine (ML; 12 g and 21 g/d, respectively), or ML plus leucine, isoleucine, and valine (ML+BCAA; 35 g, 15 g, and 15 g/d, respectively) in a 3×3 Latin square design with 3 infusion periods separated by 7-d noninfusion periods. The basal diet consisted of 40% corn silage, 14% alfalfa hay, and a concentrate mix, and respectively supplied lysine, methionine, isoleucine, leucine, and valine as 6.1, 1.8, 4.7, 8.9, and 5.3% of metabolizable protein. Dry matter intake (23.9 kg/d), milk yield (52.8 kg/d), fat content (2.55%), fat yield (1.33 kg/d), lactose content (4.77%), lactose yield (2.51 kg/d), and milk protein efficiency (0.38) were similar across treatments. Protein yield and protein content were not significantly different between ML (1.52 kg/d and 2.88%, respectively) and ML+BCAA (1.51 kg/d and 2.83%, respectively), but they were significantly greater than that of CTL (1.39 kg/d and 2.71%). Cows that received ML+BCAA had less milk urea nitrogen content (10.9 mg/dL) compared with milk of CTL cows (12.4 mg/dL) and ML cows (11.8 mg/dL). Whereas high-producing cows responded positively to methionine and lysine supplementation, no apparent benefits of BCAA supplementation in milk protein synthesis were found. Infusion of BCAA may have stimulated synthesis of other body proteins, probably muscle proteins, as evidenced by decreased milk urea nitrogen.

Cytotoxic and antioxidant activities of selected Lamiales species from Mexico.

CONTEXT: Methanol extracts obtained from eight species belonging to four families of the Lamiales order native to Mexico were investigated for biological action. OBJECTIVE: Cytotoxicity and antioxidant activity of methanol extracts have been investigated. MATERIALS AND METHODS: Cytotoxic activity was evaluated by the sulphorhodamine B protein staining assay against KB (nasopharyngeal), HEp-2 (larynx), HF-6 (colon), MCF7 (breast), PC-3 (prostate), and Ca Ski (cervix) carcinoma cell lines. To analyze the antioxidant activity, common stable radicals chromogens, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS+) and DPPH (1,1-diphenyl-2-picrylhydrazyl) were used. The ferric reducing antioxidant power (FRAP) and the total phenolic content of the samples were also determined. RESULTS: Some of the extracts, such as Limosella aquatica L. (Scrophulariaceae), Mimulus glabratus Kunth. (Phrymaceae), Pedicularis mexicana Zucc. ex Benth. (Orobanchaceae), and Penstemon campanulatus (Cav.) Willd. (Plantaginaceae) displayed remarkably selective cytotoxic activity. However, the extract from Veronica americana (Raf.) Schwein (Plantaginaceae) showed the highest activity with IC50 values of 1.46 and 0.169 g/ µL on PC-3 and HF-6 cells, respectively. With the exception of M. glabratus, all the extracts showed different degrees of antioxidant activity with IC50 values from 0.89 up to 1.8 in the ABTS assay; from 0.49 up to 1.25 mg/mL in the DPPH assay and with the FRAP evaluation, 36 to 68 equivalents in mM of FeSO4. V. americana also showed the highest antoxidant activity with IC50 values from 0.491 and 0.892 mg/mL, on DPPH and ABTS assays, respectively. DISCUSSION AND CONCLUSION: These findings demonstrated that the species studied have great potential cytotoxic and antioxidant activity.

Regulation of dual leucine zipper kinase activity through its interaction with calcineurin.

Hyperglycemia enhancing the intracellular levels of reactive oxygen species (ROS) contributes to dysfunction and progressive loss of beta cells and thereby to diabetes mellitus. The oxidation sensitive calcium/calmodulin dependent phosphatase calcineurin promotes pancreatic beta cell function and survival whereas the dual leucine zipper kinase (DLK) induces apoptosis. Therefore, it was studied whether calcineurin interferes with DLK action. In a beta cell line similar concentrations of H2O2 decreased calcineurin activity and activated DLK. DLK interacted via its φLxVP motif (aa 362-365) with the interface of the calcineurin subunits A and B. Mutation of the Val prevented this protein protein interaction, hinting at a distinct φLxVP motif. Indeed, mutational analysis revealed an ordered structure of DLK's φLxVP motif whereby Val mediates the interaction with calcineurin and Leu maintains an enzymatically active conformation. Overexpression of DLK wild-type but not the DLK mutant unable to bind calcineurin diminished calcineurin-induced nuclear localisation of the nuclear factor of activated T-cells (NFAT), suggesting that both, DLK and NFAT compete for the substrate binding site of calcineurin. The calcineurin binding-deficient DLK mutant exhibited increased DLK activity measured as phosphorylation of the downstream c-Jun N-terminal kinase, inhibition of CRE-dependent gene transcription and induction of apoptosis. These findings show that calcineurin interacts with DLK; and inhibition of calcineurin increases DLK activity. Hence, this study demonstrates a novel mechanism regulating DLK action. These findings suggest that ROS through inhibition of calcineurin enhance DLK activity and thereby lead to beta cell dysfunction and loss and ultimately diabetes mellitus.

Regulation of protein synthesis in mammary glands of lactating dairy cows by starch and amino acids.

The objective of this study was to evaluate local molecular adaptations proposed to regulate protein synthesis in the mammary glands. It was hypothesized that AA and energy-yielding substrates independently regulate AA metabolism and protein synthesis in mammary glands by a combination of systemic and local mechanisms. Six primiparous mid-lactation Holstein cows with ruminal cannulas were randomly assigned to 4 treatment sequences in a replicated incomplete 4 x 4 Latin square design experiment. Treatments were abomasal infusions of casein and starch in a 2 x 2 factorial arrangement. All animals received the same basal diet (17.6% crude protein and 6.61 MJ of net energy for lactation/kg of DM) throughout the study. Cows were restricted to 70% of ad libitum intake and abomasally infused for 36 h with water, casein (0.86 kg/d), starch (2 kg/d), or a combination (2 kg/d starch+0.86 kg/d casein) using peristaltic pumps. Milk yields and composition were assessed throughout the study. Arterial and venous plasma samples were collected every 20 min during the last 8h of infusion to assess mammary uptake. Mammary biopsy samples were collected at the end of each infusion and assessed for the phosphorylation state of selected intracellular signaling molecules that regulate protein synthesis. Animals infused with casein had increased arterial concentrations of AA, increased mammary extraction of AA from plasma, either no change or a trend for reduced mammary AA clearance rates, and no change in milk protein yield. Animals infused with starch had increased milk and milk protein yields, increased mammary plasma flow, reduced arterial concentrations of AA, and increased mammary clearance rates and net uptake of some AA. Infusions of starch increased plasma concentrations of glucose, insulin, and insulin-like growth factor-I. Starch infusions increased phosphorylation of ribosomal protein S6 and endothelial nitric oxide synthase, consistent with changes in milk protein yields and plasma flow, respectively. Phosphorylation of the mammalian target of rapamycin was increased in response to starch only when casein was also infused. Thus, cell signaling molecules involved in the regulation of protein synthesis differentially responded to these nutritional stimuli. The hypothesized independent effects of casein and starch on animal metabolism and cell signaling were not observed, presumably because of the lack of a milk protein response to infused casein.

Dietary supplementation with anti-IL-10 antibody during a severe Eimeria challenge in broiler chickens.

Attenuation of host IL-10 activity during Eimeria infection may elicit a robust Th1 response to eliminate the parasite from the gut epithelium. An experiment was conducted to study the effects of feeding IL-10 neutralizing antibody delivered via a dried egg product (DEP) on growth performance, immune responsivity, and gut health outcomes during a severe challenge with either Eimeria acervulina (study 1) or Eimeria tenella (study 2) following FDA CVM #217 protocol to test anticoccidial products. A total of 720 male Ross 308 chicks were used in each study, with 15 replicate cages of 12 birds and the following 4 treatments: sham-inoculated (uninfected) control diet (UCON), Eimeria-infected control diet (ICON), and Eimeria-infected control diet supplemented with DEP at 2 levels (165 [I-165] or 287 [I-287] U/tonne in study 1 and 143 [I-143] or 287 [I-287] U/tonne in study 2). Individual birds assigned to infected treatment groups received a single oral dose of either 200,000 E. acervulina (study 1) or 80,000 E. tenella (study 2) oocysts at 12 d of age (i.e., d post inoculation [DPI] 0), whereas uninfected birds were sham-inoculated with tap water. A one-way ANOVA was performed on outcomes including growth performance, hematology, serum chemistry profiles, immunophenotyping profiles, and intestinal lesion scores. In both studies, DPI 0 to 7 weight gain, feed intake, and feed conversion ratio were worse (P < 0.05) in all infected groups compared with the UCON group. Compared with ICON, DEP supplementation elicited no differences on overall growth performance. Histopathology and lesion scores revealed severe damage to the gut epithelium owing to the Eimeria challenge, yet DEP supplementation did not improve these outcomes or oocyst shedding, hematological measurements, or serum chemistry. However, DEP supplementation improved (P < 0.05) the percentage of circulating CD3+ cells at 6 DPI in study 2. These results indicate that DEP does not appear to elicit a coccidiostatic effect during a severe infection with E. acervulina or E. tenella.