A meta-analysis of the effects of colostrum heat treatment on colostral viscosity, immunoglobulin G concentration, and the transfer of passive immunity in newborn dairy calves.

Newborn ruminants depend on colostrum intake immediately after birth to obtain immunoglobulins for effective transfer of passive immunity (TPI). As colostrum may also be a vehicle of infectious agents, heat treatment of raw colostrum is a practice aimed at eliminating or reducing its pathogen load. Despite the usefulness of heat treatment in preventing the transmission of infectious colostrum-borne diseases, heat treatment of colostrum may have some side effects. A systematic review and meta-analysis were conducted to summarize the effects of colostrum heat treatment on colostral viscosity and IgG concentration, and serum IgG concentration as a proxy for TPI in newborn calves fed raw versus heat-treated colostrum. Moderators were studied to identify sources of heterogeneity. Literature databases were searched for peer-reviewed articles published between 1946 and 2022. A Master of Science thesis was also included. Five, 21, and 19 original publications were quantitatively evaluated in 3 separate meta-analyses, based on predefined selection criteria. Two-level and 3-level random-effects meta-analysis revealed a significant overall effect of heat treatment on colostral viscosity and IgG concentration, and serum IgG concentration in newborns. Heat-treated colostrum had significantly higher viscosity (21.0 cP, 95% CI: 3.8 to 38.2) and lower IgG concentration (-7.4 g/L, 95% CI: -11.1 to -3.7) compared with raw colostrum. Overall, newborn calves fed heat-treated colostrum had higher serum IgG concentrations (2.8 g/L, 95% CI: 1.4 to 4.0) 24-48 h after birth than those fed with raw colostrum. Particularly, this positive effect on the serum IgG concentrations was seen when colostrum was heat-treated at ≤60°C (2.9 g/L, 95% CI: 0.9 to 4.2) and when the standard low-temperature low-time (LTLT) method was used for heat treatment (2.6 g/L, 95% CI: 0.1 to 5.1). Colostrum treated at >60-63.5°C tended to have higher viscosity (275.6 cP, 95% CI: -37.9 to 589.3) and had lower IgG concentration (-21.7 g/L, 95% CI: -27.3 to -16.1). Calves fed colostrum treated at this temperature range had significantly lower serum IgG (-4.2 g/L, 95% CI: -7.9 to -0.4) compared with those fed raw colostrum. Heat treatment of colostrum at 72-76°C was not associated with a significant increase in colostral viscosity (6.3 cP, 95% CI: -324.3 to 336.9) nor a reduction in IgG colostral concentration (-13.1 g/L, 95% CI: -26.5 to 0.2), but calves fed colostrum treated at this temperature range had a significant reduction in serum IgG (-11.3 g/L, 95% CI: -17.1 to -5.4). Feeding newborn calves with colostrum heat-treated at ≤60°C by the standard LTLT method, particularly within 2 h after birth, resulted in increased serum IgG concentration at 24-48 h of age. Importantly, delaying feeding of heat-treated colostrum to newborns beyond 2 h of age resulted in no significant difference in IgG serum levels compared with feeding raw colostrum, highlighting the importance of early administration of heat-treated colostrum to favor TPI. On-farm colostrum heat treating should achieve an equilibrium between pathogen elimination and the preservation of colostral immunoglobulins while minimizing undesired increases in viscosity. The beneficial effects of colostrum heat treatment on TPI can be negligible if colostrum feeding is not performed within 2 h after birth.

Epidemiological and clinicopathological findings in 15 fatal outbreaks of salmonellosis in dairy calves and virulence genes in the causative Salmonella enterica Typhimurium and Dublin strains.

Salmonella enterica is a major food-borne pathogen that affects cattle-rearing systems worldwide. Little information is available on the epidemiology and pathology of salmonellosis and the virulence genes (VGs) carried by Salmonella in spontaneous outbreaks in cattle. We describe epidemiological findings in 15 fatal outbreaks of salmonellosis in Uruguayan dairy farms and the age, clinical signs, and pathology in 20 affected calves. We also describe the serotypes and frequencies of 17 VGs in the causative Salmonella strains and explore their associations with epidemiological, clinical, and pathological findings. Salmonella Typhimurium and Dublin were identified in 11/15 and 4/15 outbreaks, respectively. The most frequent reason for consultation was digestive disease (8 outbreaks caused by S. Typhimurium), followed by sudden death (4 outbreaks, 3 caused by S. Dublin). Morbidity, mortality, and lethality ranged 4.8-100%, 3.8-78.9%, and 10-100%, without significant differences between serotypes. Diarrhea, the most common clinical sign (14 cases), was associated with the Typhimurium serotype (OR = 26.95), especially in ≤ 30-day-old calves with fibrinous enteritis as the main autopsy finding. The Dublin serotype affected ≥ 50-day-old calves and was associated with fibrinosuppurative splenitis (p = 0.01) and tubulointerstitial nephritis (OR = 48.95). The chances of the Dublin serotype increased significantly with age. There was low variability of VG across serotypes. The pefA gene was associated with the Typhimurium serotype (OR = 21.95), macroscopic enteritis (p = 0.03), and microscopic fibrinosuppurative splenitis (p = 0.04). Understanding the epidemiology, pathology, and virulence of S. enterica at the farm level is key to delineating prevention and control strategies to mitigate its impact on animal and human health.

Does Skilled Nursing Facility Trigger Tool used with Global Trigger Tool increase its value for adverse events evaluation?

OBJECTIVE: To assess the additional value in the evaluation of incidents and adverse events by adding the IHI Skilled Nursing Facility Trigger Tool (SNFTT) to the Institute for Healthcare Improvement's Global Trigger Tool (GTT) in an acute geriatric hospital. MATERIAL AND METHODS: A one-year retrospective study reviewing 240 electronic clinical records using the general GTT, either alone or combined with SNFTT. MAIN OUTCOME MEASURES: Number of triggers and identified adverse events (AEs), categories of severity and preventability of AEs, GTT incidence rates, and the number needed to alert (NNA). RESULTS: One hundred and thirty-seven AEs were identified in 107 patients (57.1 AEs per 100 admissions). Of these, 127 (92.7%) occurred 3 or more days after admissions; 49.6% of the harm events were preventable. The NNA for GTT plus SNFTT was 8.6. No significant difference was found using the general GTT alone versus the general GTT plus SNFTT in terms of the main outcome measures. Eleven categories of triggers were better identified when using GTT plus SNFTT because with GTT alone they were allocated to a category of "Other": 9 from the care module (C15) and 2 from the medication module (M13). CONCLUSIONS: The study demonstrates that adding the SNFTT to the GTT did not increase its effectiveness as regards the evaluation of AEs. However, some triggers are better described in SNFTT and now have now been added into the general GTT method in our hospital.

Effect of the administration of Lactobacillus spp. strains on neonatal diarrhoea, immune parameters and pathogen abundance in pre-weaned calves.

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.

Effects of feed withdrawal duration on animal behaviour, rumen microbiota and blood chemistry in feedlot cattle: implications for rumen acidosis.

Feed withdrawal (FW) is a frequent issue in open outdoor feedlot systems, where unexpected circumstances can limit the animals' access to food. The relationship among fasting period, animal behaviour during feed reintroduction (FR) and acidosis occurrence has not been completely elucidated. Twenty steers fitted with rumen catheters were fed a high-concentrate diet (concentrate : forage ratio 85 : 15) and were challenged by a protocol of FW followed by FR. The animals were randomly assigned to one of the four treatments: FW for 12 h (T12), 24 h (T24), 36 h (T36) or no FW (control group) followed by FR. The steers' behaviour, ruminal chemistry, structure of the ruminal microbial community, blood enzymes and metabolites and ruminal acidosis status were assessed. Animal behaviour was affected by the FW-FR challenge ( P < 0.05). Steers from the T12, T24 and T36 treatments showed a higher ingestion rate and a lower frequency of rumination. Although all animals were suspected to have sub-acute ruminal acidosis (SARA) prior to treatment, a severe case of transient SARA arose after FR in the T12, T24 and T36 groups. The ruminal pH remained below the threshold adopted for SARA diagnosis ( pH value = 5.6) for more than three consecutive hours (24, 7 and 19 h in the T12, T24 and T36 treatments, respectively). The FW-FR challenge did not induce clinical acute ruminal acidosis even though steers from the T36 treatment presented ruminal pH values that were consistent with this metabolic disorder (pH threshold for acute acidosis = 5.2). Total mixed ration reintroduction after the withdrawal period reactivated ruminal fermentation as reflected by changes in the fermentation end-products. Ruminal lactic acid accumulation in steers from the T24 and T36 treatments probably led to the reduction of pH in these groups. Both the FW and the FR phases may have altered the structure of the ruminal microbiota community. Whereas fibrolytic bacterial groups decreased relative abundance in the restricted animals, both lactic acid producer and utiliser bacterial groups increased ( P < 0.05). The results demonstrated a synchronisation between Streptococcus (lactate producer) and Megasphaera (lactate utiliser), as the relative abundance of both groups increased, suggesting that bacterial resilience may be central for preventing the onset of metabolic disturbances such as ruminal acidosis. A long-FW period (36 h) produced rumen pH reductions well below and lactic acid concentration increased well above the accepted thresholds for acute acidosis without any perceptible clinical signs.

Aortitis sifilítica e insuficiencia valvular aórtica: presentación de un caso / Syphilitic aortitis and aortic regurgitation: a case report

Se presenta el caso de un varón de 60 años de doble lesión aórtica que fue sometido a recambio valvular aórtico. Durante la intervención se observó engrosamiento e inflamación de la pared de la aorta ascendente. El análisis serológico resultó positivo para Treponema pallidum. El estudio histológico de la pared aórtica y de la válvula demostró infiltrado inflamatorio mixto linfoplasmocitario. La insuficiencia aórtica sifilítica constituye una complicación infrecuente de la sífilis terciaria que debe ser sospechada en presencia de inflamación aórtica

We report the case of a a 60-year-old male with double aortic lesion who underwent an aortic valve replacement. Thickening and inflammation of the ascending aorta wall was observed. Serological analyses were positive for Treponema pallidum. The histological study of the aortic wall and aortic valve showed mixed inflammatory lymphoplasmacytic infiltrate. Syphilitic aortic insufficiency is a rare complication of tertiary syphilis but should be suspected in the presence of aortic inflammation

Urocystitis and Ureteritis in Holstein Calves with Septicaemia Caused by Salmonella enterica Serotype Dublin.

Salmonellosis is an enteric or multisystemic disease of global distribution that affects numerous animal species. Although Salmonella enterica has been associated with urinary tract lesions in man, information on urocystitis/ureteritis in cattle caused by salmonellae is lacking. This communication describes lesions of the inferior urinary tract in four Holstein calves with septicaemia caused by S. enterica subsp. enterica serotype Dublin. Examination of the urinary bladder revealed either diffuse irregular thickening (three cases) or petechiation (one case) of the mucosa. On histopathological examination, urocystitis with submucosal histiocytic, lymphocytic and plasmacytic infiltration and neutrophil transmigration through the urothelium was noted in all cases. In one case, a fibrinosuppurative ureteritis was detected. Salmonella Dublin was identified by culture, 16S rDNA sequencing and serotyping and Salmonella antigen was detected intralesionally by immunohistochemistry. Other lesions, indicative of septicaemia included hepatitis, enteritis, pericarditis, splenitis, lymphadenitis and pneumonia. We conclude that S. Dublin can be uropathogenic in cattle with septicaemia.

Probiotic properties of native Lactobacillus spp. strains for dairy calves.

The use of native microorganisms with probiotic capacity is an alternative tool for the treatment and prevention of several diseases that affect animals, such as neonatal calf diarrhoea. The selection of probiotic strains within a collection is based on different in vitro and in vivo assays, which predict their potential. The aim of this study was to characterise a group of native Lactobacillus spp. strains isolated from faeces of healthy calves using an in vitro approach and to assess their ability to colonise the gastrointestinal tract (GIT) of calves. Native Lactobacillus spp. strains were evaluated on their capacity to survive low pH conditions and bile salts presence, biofilm formation and adhesion to both mucus and Caco-2 cells. Based on the in vitro characterisation, four strains (Lactobacillus johnsonii TP1.1, Lactobacillus reuteri TP1.3B, L. johnsonii TP1.6 and Lactobacillus amylovorus TP8.7) were selected to evaluate their capacity to colonise and persist in the GIT of calves. The assessment of enteric persistence involved an in vivo assay with oral administration of probiotics and quantification in faeces of the administered bacterial species with real-time quantitative PCR (qPCR). The study was conducted using 15 calves (1-month-old) which were divided into five groups of three animals, four of which were treated with four different selected strains and one was the control group. Strains TP1.3B and TP1.6 managed to persist in treated animals until ten days after the end of the administration period, indicating that they could be promising candidates for the design of probiotics for calves.

Council of Europe Black Sea Area Project: International Cooperation for the Development of Activities Related to Donation and Transplantation of Organs in the Region.

BACKGROUND: In 2011, the European Directorate for the Quality of Medicines & Healthcare of the Council of Europe launched a 3-year collaborative project to address the organ shortage and improve access to transplant health services in Council of Europe member states in the Black Sea area (Armenia, Azerbaijan, Bulgaria, Georgia, Moldova, Romania, Turkey, Ukraine, and the Russian Federation) through the development of safe and ethical donation and transplantation programs. OBJECTIVE: Support the development of donation and transplantation programs through close interstate cooperation between national health organizations and relevant stakeholders. METHODOLOGY: Several work packages (WP) were established: WP1, project coordination (European Directorate for the Quality of Medicines & Healthcare); WP2, development and implementation of an effective legislative and financial framework (Czech Republic and France); WP3, establishment of National Transplant Authorities (Italy and Portugal); and WP4, clinical practices (DTI Foundation). Data collection, surveys, and expert visits allowed for the collection of first-hand information from each participant country at national, regional, and hospital levels. RESULTS: Data analysis showed the positive impact of the project represented by a tendency to increase the total donation rates (per million people) in the participant countries (2011 vs 2013): Azerbaijan, +7.3; Armenia, -0.7; Georgia, +3.3; Bulgaria, +0.9; Moldova, +2.5; Ukraine:, +0.8; Romania, +2.3; and Turkey, +2.7. CONCLUSIONS: Increases in total donation rates are the result of a number of initiatives in the Black Sea area, including the stepwise implementation of legislative, organizational and institutional country-specific recommendations tailored by the CoE, efforts of the respective Ministries of Health in each country and synergism with other European projects in the region. These countries should invest further in implementing the recommendations that emerged from this project to improve their organ donation and transplantation programs and progress toward self-sufficiency.

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

OBJECTIVE: To analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns. STUDY DESIGN: The original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment. RESULTS: Two hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window. CONCLUSION: Despite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives.

Very late presentation of a disorder of sex development.

Disorders of sex development generally present in the neonatal period with ambiguity of external genitalia. We report a very old male patient presenting at 75 years because of panhypopituitarism and a large nonsecreting pituitary macroadenoma secondary to long-standing primary hypogonadism due to 46,XX sex reversal disorder now first diagnosed. Sex development disorders may go unrecognised for the entire life span, despite infertility and long-standing primary gonadic failure may lead to uncommon complications.

The role of 5-hydroxymethylcytosine in development, aging and age-related diseases.

DNA methylation at the fifth position of cytosines (5mC) represents a major epigenetic modification in mammals. The recent discovery of 5-hydroxymethylcytosine (5hmC), resulting from 5mC oxidation, is redefining our view of the epigenome, as multiple studies indicate that 5hmC is not simply an intermediate of DNA demethylation, but a genuine epigenetic mark that may play an important functional role in gene regulation. Currently, the availability of platforms that discriminates between the presence of 5mC and 5hmC at single-base resolution is starting to shed light on the functions of 5hmC. In this review, we provide an overview of the genomic distribution of 5hmC, and examine recent findings on the role of this mark and the potential consequences of its misregulation during three fundamental biological processes: cell differentiation, cancer and aging.

Ultrastructure of pheochromocytoma: undescribed morphologic features.

We examined samples of human pheochromocytoma from 11 patients aged 30-70 years including one case of malignant pheochromocytoma with a view to identifying previously unreported ultrastructural details.We identified two types of nuclear inclusions consisting of irregularly shaped singular or multiple granulofibrillar formations with a typical concentric halo, on the one hand, and accumulations of egg-shaped structures consisting of granules and microfilaments, on the other. In some of the tumor cells, membrane-covered inclusions containing parallel laminar elements arranged in a paracrystalline, periodic fashion, or mega-mitrochondriae characterized by increased electrodensity of their matrix, and fibrillary material in the spaces between the cristae were present. A frequent finding consisted of typical ciliary formations, while rough/smooth tubular aggregates of different size occurred less frequently. Finally, we were able to demonstrate the uptake of norepinephrine by smooth muscle fibers in the periphery of arterial vessels as evidenced by linear accumulations of membrane-covered granules separating bands of contractile smooth muscle components in the peripheral layers of arterial vessels close to norepinephrine producing neoplastic cells.These findings represent ultrastructural features that contribute to further elucidating the ultrastructural characteristics of the human pheochromocytoma.

[Benchmarking in patient identification: An opportunity to learn]. / Benchmarking en la identificación de pacientes: una oportunidad para aprender.

OBJECTIVE: To perform a benchmarking on the safe identification of hospital patients involved in "Club de las tres C" (Calidez, Calidad y Cuidados) in order to prepare a common procedure for this process. MATERIAL AND METHODS: A descriptive study was conducted on the patient identification process in palliative care and stroke units in 5medium-stay hospitals. The following steps were carried out: Data collection from each hospital; organisation and data analysis, and preparation of a common procedure for this process. RESULTS: The data obtained for the safe identification of all stroke patients were: hospital 1 (93%), hospital 2 (93.1%), hospital 3 (100%), and hospital 5 (93.4%), and for the palliative care process: hospital 1 (93%), hospital 2 (92.3%), hospital 3 (92%), hospital 4 (98.3%), and hospital 5 (85.2%). CONCLUSIONS: The aim of the study has been accomplished successfully. Benchmarking activities have been developed and knowledge on the patient identification process has been shared. All hospitals had good results. The hospital 3 was best in the ictus identification process. The benchmarking identification is difficult, but, a useful common procedure that collects the best practices has been identified among the 5 hospitals.

Pilot scale nanofiltration treatment of olive mill wastewater: a technical and economical evaluation.

The treatment of large volumes of olive mill wastewater is presently a challenge. This study reports the technical and economical feasibility of a sequential treatment of olive mill wastewater comprising a dissolved air flotation pre-treatment and nanofiltration. Different pilot nanofiltration assays were conducted in a concentration mode up to different volume reduction factors (29, 45, 58, and 81). Data attained demonstrated that nanofiltration can be operated at considerably high volume reduction factors and still be effective towards the removal of several components. A flux decline of approximately 50% was observed at the highest volume reduction factor, mainly due to increase of the osmotic pressure. Considerably high rejections were obtained across all experiments for total suspended solids (83 to >99%), total organic carbon (64 to 99%), chemical oxygen demand (53 to 77%), and oil and grease (67 to >82%). Treated water was in compliance with European legal limits for discharge regarding total suspended solids and oil and grease. The potential recovery of phenolic compounds was evaluated and found not relevant. It was demonstrated that nanofiltration is economically feasible, involving operation costs of approximately 2.56-3.08 €/m3, depending on the working plan schedule and volume reduction factor, and requiring a footprint of approximately 52 m2 to treat 1000 m3 of olive mill wastewater.

The effect of exposure to nanoparticles and nanomaterials on the mammalian epigenome.

Human exposure to nanomaterials and nanoparticles is increasing rapidly, but their effects on human health are still largely unknown. Epigenetic modifications are attracting ever more interest as possible underlying molecular mechanisms of gene-environment interactions, highlighting them as potential molecular targets following exposure to nanomaterials and nanoparticles. Interestingly, recent research has identified changes in DNA methylation, histone post-translational modifications, and noncoding RNAs in mammalian cells exposed to nanomaterials and nanoparticles. However, the challenge for the future will be to determine the molecular pathways driving these epigenetic alterations, the possible functional consequences, and the potential effects on health.

[Compliance with the surgical safety checklist and surgical events detected by the Global Trigger Tool]. / Cumplimiento del listado de verificación quirúrgica y los eventos quirúrgicos detectados mediante la herramienta del Global Trigger Tool.

INTRODUCTION: The implementing of the WHO Surgical Safety Checklist (SSC) has helped to improve patient safety. The aim of this study was to assess the level of compliance of the SSC, and incorporating the non-compliances as «triggers¼ in the Global Trigger Tool (GTT). SETTING: Acute Geriatric Hospital (200 beds). Retrospective study, study period: 2011-2014. The SSC formulary and the methodology of the GTT were used for the analysis of electronic medical records and the compliance with the SSC. The NCCP MERP categories were used to assess the severity of the harm. RESULTS: Out of all the electronic medical records (EMR), a total of 227 (23.6%) discharged patients (1.7% of interventions in the four year study period) were analysed. All (100%) of the EMR included the SSC, with 94.4% of the items being completed, and 28.2% of SSC had all items completed in the 3 phases of the process. Surgical adverse events decreased from 16.3% in 2011 to 9.4% in 2014 (P=.2838, not significant), and compliance with all items of SSC was increased from 18.6% to 39.1% (P=.0246, significant). CONCLUSIONS: The GTT systematises and evaluates, at low cost, the triggers and incidents/ AEs found in the EMR in order to assess the compliance with the SSC and consider non-compliance of SSC as «triggers¼ for further analysis. This strategy has never been referred to in the GTT or in the SCC formulary.

Relationships among growth mechanism, structure and morphology of PEALD TiO2 films: the influence of O2 plasma power, precursor chemistry and plasma exposure mode.

Titanium dioxide (TiO2) thin films have generated considerable interest over recent years, because they are functional materials suitable for a wide range of applications. The efficient use of the outstanding functional properties of these films relies strongly on their basic characteristics, such as structure and morphology, which are affected by deposition parameters. Here, we report on the influence of plasma power and precursor chemistry on the growth kinetics, structure and morphology of TiO2 thin films grown on Si(100) by plasma-enhanced atomic layer deposition (PEALD). For this, remote capacitively coupled 13.56 MHz oxygen plasma was used to act as a co-reactant during the ALD process using two different metal precursors: titanium tetrachloride (TiCl4) and titanium tetraisopropoxide (TTIP). Furthermore, we investigate the effect of direct plasma exposure during the co-reactant pulse on the aforementioned material properties. The extensive characterization of TiO2 films using Rutherford backscattering spectroscopy, ellipsometry, x-ray diffraction (XRD), field-emission scanning electron microscopy, and atomic force microscopy (AFM) have revealed how the investigated process parameters affect their growth per cycle (GPC), crystallization and morphology. The GPC tends to increase with plasma power for both precursors, however, for the TTIP precursor, it starts decreasing when the plasma power is greater than 100 W. From XRD analysis, we found a good correlation between film crystallinity and GPC behavior, mainly for the TTIP process. The AFM images indicated the formation of films with grain size higher than film thickness (grain size/film thickness ratio ≈20) for both precursors, and plasma power analysis allows us to infer that this phenomenon can be directly related to the increase of the flux of energetic oxygen species on the substrate/growing film surface. Finally, the effect of direct plasma exposure on film structure and morphology was evidenced showing that the grid removal causes a drastic reduction in the grain size, particularly for TiO2 synthesized using TiCl4.

Liver X Receptor Agonist Modifies the DNA Methylation Profile of Synapse and Neurogenesis-Related Genes in the Triple Transgenic Mouse Model of Alzheimer's Disease.

The liver X receptor agonist, GW3965, improves cognition in Alzheimer's disease (AD) mouse models. Here, we determined if short-term GW3965 treatment induces changes in the DNA methylation state of the hippocampus, which are associated with cognitive improvement. Twenty-four-month-old triple-transgenic AD (3xTg-AD) mice were treated with GW3965 (50 mg/kg/day for 6 days). DNA methylation state was examined by modified bisulfite conversion and hybridization on Illumina Infinium Methylation BeadChip 450 k arrays. The Morris water maze was used for behavioral analysis. Our results show in addition to improvement in cognition methylation changes in 39 of 13,715 interrogated probes in treated 3xTg-AD mice compared with untreated 3xTg-AD mice. These changes in methylation probes include 29 gene loci. Importantly, changes in methylation status were mainly from synapse-related genes (SYP, SYN1, and DLG3) and neurogenesis-associated genes (HMGB3 and RBBP7). Thus, our results indicate that liver X receptors (LXR) agonist treatment induces rapid changes in DNA methylation, particularly in loci associated with genes involved in neurogenesis and synaptic function. Our results suggest a new potential mechanism to explain the beneficial effect of GW3965.

Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα.

B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPα with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by 'epigenetic memory'. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies.