Effects of a mixture of phytobiotic-rich herbal extracts on growth performance, blood metabolites, rumen fermentation, and bacterial population of dairy calves.

Forty-eight newborn Holstein dairy calves [40 ± 3.4 (SD) of kg of body weight (BW); 24 females and 24 males] were used in a completely randomized design to investigate the effects of a mixture of phytobiotic-rich herbal extract (Immunofin, IMPE) incorporated into milk on performance, ruminal fermentation, bacterial population, and serum biochemical metabolites during the preweaning period. Calves had free access to calf starter and clean water from d 6 until weaning. The treatments were the control (CON; without additive) and IMPE at 4, 8, and 12 mL/d. The treatments had no significant effect on total dry matter intake, weight gain, and BW at weaning. The incidence of diarrhea was lower in calves fed 8 mL of IMPE/d compared with CON. At weaning, body measurements (except for front leg circumference) were not affected by IMPE treatment. Relative to the CON group, front leg circumference was significantly decreased by IMPE supplementation. Serum IgG concentration was not significantly increased by IMPE supplementation compared with the CON group. Triglyceride concentration decreased in calves receiving 4, 8, and 12 mL/d of IMPE compared with the CON groups. In contrast to the CON group, serum albumin and total serum protein concentrations increased with IMPE supplementation. Calves receiving 4 mL/d of IMPE had a greater abundance of total bacteria, Ruminococcus albus, Ruminococcus flavefaciens, and Fibrobacter succinogenes compared with the other treatments. Molar proportions of acetate increased in calves fed IMPE (at 12 mL/d) compared with calves fed CON. Ruminal N-NH3 concentrations decreased linearly with the increase in IMPE supplementation. The results of the present study suggest that the addition of IMPE to milk may improve some health and immunity conditions, blood metabolite concentrations, and increase the abundance of some cellulolytic bacteria in the rumen of Holstein dairy calves. The use of IMPE may be an alternative to feeding antibiotics at subtherapeutic concentrations to improve calf health and immunity status.

Model-guided design of mammalian genetic programs.

Genetically engineering cells to perform customizable functions is an emerging frontier with numerous technological and translational applications. However, it remains challenging to systematically engineer mammalian cells to execute complex functions. To address this need, we developed a method enabling accurate genetic program design using high-performing genetic parts and predictive computational models. We built multifunctional proteins integrating both transcriptional and posttranslational control, validated models for describing these mechanisms, implemented digital and analog processing, and effectively linked genetic circuits with sensors for multi-input evaluations. The functional modularity and compositional versatility of these parts enable one to satisfy a given design objective via multiple synonymous programs. Our approach empowers bioengineers to predictively design mammalian cellular functions that perform as expected even at high levels of biological complexity.

Effects of wheat straw particle size as a free-choice provision on growth performance and feeding behaviors of dairy calves.

In the dairy calf feeding, supplementation of forage to the starter feed is commonly practiced. However, data are insufficient about how changes in particle size (PS) of forage affect calf performance and behavior in a free-choice forage provision system. This study aimed to assess the effects of supplementing wheat straw varying in PS on performance, skeletal growth characteristics, ruminal pH, nutritional behaviors, and blood metabolites of dairy calves. Forty-eight Holstein calves (43.8 ±â€¯3.2 kg of BW) from d 15 of age were randomly assigned to one of the four treatments (n = 12/treatment; six males and six females): (1) starter without wheat straw supplementation (CON), (2) CON supplemented with wheat straw chopped at 1 mm geometrical mean particle length (GMPL) (fine PS), (3) CON supplemented with wheat straw at 4 mm GMPL (medium PS), and (4) CON supplemented with wheat straw at 7 mm GMPL (long PS). The calves were given ad libitum access to feed and water throughout the study. All calves were weaned on d 56 of age and continued the experiment until d 90. The starter, wheat straw, and total solid feed intakes were not affected by GMPL of wheat straw; however, CON calves had a lower solid feed-, total DM- and NDF-intake than calves offered wheat straw. Further, ADG, weaning, and final BWs as well as feed efficiency were similar between treatments. No difference was observed in growth rate of hip height, hip width, body barrel, wither height, and heart girth among treatments, however, wheat straw supplemented calves tended to have greater body length at weaning. Blood concentration of serum ß-hydroxy butyrate was greater in wheat straw supplemented calves compared with CON calves on d 56 and 90. Calves supplemented with wheat straw spent more time eating starter and forage, lying and ruminating and less time for standing and non-nutritional behaviors compared with the CON calves on d 49 and 63 of the study. Moreover, calves offered wheat straw had greater ruminal pH than CON calves at 4 and 8 h after offering starter feed on d 35. In conclusion, supplementing wheat straw as a free-choice increased solid feed intake, rumen pH, and calves' welfare, however, PS of wheat straw had no effect.

Combining Geospatial Analysis with Dementia Risk Utilising General Practice Data: A Systematic Review.

Geographical information systems (GIS) and geospatial analysis techniques will help to identify significant dementia risk clusters (hotspots) across communities and will enable policy makers to target prevention interventions to the right place. This review synthesises the published literature on geospatial analysis techniques for quantifying and mapping dementia risk, and reviews available dementia risk assessment tools. A systematic literature review was undertaken in four medical and life sciences databases (PubMed, Cochrane Central, Embase, and Web of Sciences) from their inception to March 2017 for all articles relating to dementia. The search terms included: 'dementia', 'Alzheimer's disease', 'general practice database', 'family physician', 'AD risk assessment tools', 'Geographical Information Systems' and 'geospatial analysis', 'geographical variation' and 'spatial variation'. To date, most geospatial studies on dementia have been carried out retrospectively using population based data. An alternative approach is utilisation of a rich source of general practice (family physician) databases to predict dementia risk based on available dementia risk assessment tools. In conclusion, the estimated risks of dementia can thus be geo-attributed and mapped at a small scale using geographical information systems and geospatial analysis techniques to identify dementia risk clusters across the communities and refine our understanding of the interaction between socio-demographic and environmental factors, and dementia risk clusters. .

Hospital effect on infections after four major surgical procedures: outlier and volume-outcome analysis using all-inclusive state data.

BACKGROUND: Hospital volume is known to have a direct impact on the outcomes of major surgical procedures. However, it is unclear if the evidence applies specifically to surgical site infections. AIMS: To determine if there are procedure-specific hospital outliers [with higher surgical site infection rates (SSIRs)] for four major surgical procedures, and to examine if hospital volume is associated with SSIRs in the context of outlier performance in New South Wales (NSW), Australia. METHODS: Adults who underwent one of four surgical procedures (colorectal, joint replacement, spinal and cardiac procedures) at a NSW healthcare facility between 2002 and 2013 were included. The hospital volume for each of the four surgical procedures was categorized into tertiles (low, medium and high). Multi-variable logistic regression models were built to estimate the expected SSIR for each procedure. The expected SSIRs were used to compute indirect standardized SSIRs which were then plotted in funnel plots to identify hospital outliers. FINDINGS: One hospital was identified to be an overall outlier (higher SSIRs for three of the four procedures performed in its facilities), whereas two hospitals were outliers for one specific procedure throughout the entire study period. Low-volume facilities performed the best for colorectal surgery and worst for joint replacement and cardiac surgery. One high-volume facility was an outlier for spinal surgery. CONCLUSIONS: Surgical site infections seem to be mainly a procedure-specific, as opposed to a hospital-specific, phenomenon in NSW. The association between hospital volume and SSIRs differs for different surgical procedures.

A support vector machine model provides an accurate transcript-level-based diagnostic for major depressive disorder.

Major depressive disorder (MDD) is a critical cause of morbidity and disability with an economic cost of hundreds of billions of dollars each year, necessitating more effective treatment strategies and novel approaches to translational research. A notable barrier in addressing this public health threat involves reliable identification of the disorder, as many affected individuals remain undiagnosed or misdiagnosed. An objective blood-based diagnostic test using transcript levels of a panel of markers would provide an invaluable tool for MDD as the infrastructure-including equipment, trained personnel, billing, and governmental approval-for similar tests is well established in clinics worldwide. Here we present a supervised classification model utilizing support vector machines (SVMs) for the analysis of transcriptomic data readily obtained from a peripheral blood specimen. The model was trained on data from subjects with MDD (n=32) and age- and gender-matched controls (n=32). This SVM model provides a cross-validated sensitivity and specificity of 90.6% for the diagnosis of MDD using a panel of 10 transcripts. We applied a logistic equation on the SVM model and quantified a likelihood of depression score. This score gives the probability of a MDD diagnosis and allows the tuning of specificity and sensitivity for individual patients to bring personalized medicine closer in psychiatry.

New insight to IL-23/IL-17 axis in Iranian infected adult patients with gastritis: effects of genes polymorphisms on expression of cytokines.

BACKGROUND AND OBJECTIVE: Chronic inflammation is the hallmark of the pathogenesis of H. pylori-induced gastric cancer. IL-17A and IL-17F are inflammatory cytokines expressed by a novel subset of CD4+Th cells and play critical function in inflammation. We evaluated the relationship between IL-17A G197A, IL-17F A7488G and IL23R+2199 A/C polymorphisms with IL-6, IL-17, IL-21, IL-23 and TGF-ß1 mRNAs expression in regard to H. pylori infection with chronic gastritis. MATERIAL AND METHODS: Total RNA and genomic DNA were extracted from gastric biopsies of 58 H. pylori-infected patient with gastritis. Afterward, mucosal IL-6, IL-17, IL-21, IL-23 and TGF-ß1 mRNAs expression and polymorphisms in IL-17A G197A, IL-17F A7488G and IL-23R +2199A/Cin gastric biopsies were determined by real-time PCR and PCR-RFLP. RESULTS: Our results show that IL-17A G197A, IL-17F A7488G andIL23R +2199A/C polymorphisms have no effect on mucosal expression of IL-6, IL-17, IL-21 and TGF-ß1 mRNAs expression in H. pylori-infected patients with chronic gastritis. CONCLUSIONS: These results suggest that IL-17A G197A, IL-17F A7488G and IL23R +2199A/C polymorphisms no alter mucosal cytokine pattern in Iranian patients with H. pylori-associated gastritis diseases.

Evaluation of association between intima-media thickness of the carotid artery and risk factors for cardiovascular disease in patients on maintenance hemodialysis.

Cardiovascular disease is the most common cause of mortality and morbidity in patients with end-stage renal disease (ESRD). Atherosclerosis is a systemic disease, and carotid and coronary vessels are at comparable risk for developing pathologic changes. For this reason, increase in the thickness of the intima-media layers of carotid arteries can be a harbinger of coronary atherosclerosis and also a prognostic factor for cardiovascular accidents. In this study, we evaluated the status of carotid intima-media thickness (CIMT) in patients with ESRD on dialysis and analyzed its association with other risk factors for cardiovascular diseases. This cross-sectional study was conducted on patients referred for hemodialysis (HD) to the Taleghani Hospital (Shahid Beheshti University of Medical Sciences, Tehran, Iran) during 2007-2008. At the beginning, biochemical parameters and common cardiovascular risk factors were extracted from the patients' files, and then CIMT was measured by using B-Mode high-resolution ultrasonography, 1 cm proximal to the carotid bulb in the posterior wall. Finally, correlation between other risk factors and CIMT was made. One hundred patients with chronic and advanced renal disease were evaluated, including 46% females and 54% males. The mean age of these patients was 59.2 ± 13.1 years, with a range of 26-81 years. Correlations between CIMT and age (P = 0.023, r = 0.478), dialysis duration (P = 0.017, r = 0.435), number of cigarettes smoked (P = 0.026, r = 0.429), diastolic blood pressure (P = 0.013, r = 0.455) and fasting blood sugar (P = 0.045, r = 0.346) were significant. Risk factors for cardiovascular disease in patients on HD are of significant interest because of the high prevalence and frequency of the disease in this group of patients. However, in the present study, we were not able to find a very consistent and definite role for some risk factors in our patients. More studies are required to make clear the role of these factors in patients on HD.

Cytologic, immunocytologic, histopathologic and immunohistologic diagnosis of the poorly differentiated sertoli-leydig cell tumor.

BACKGROUND: Sertoli-Leydig cell tumors (SLCTs), also known as arrhenoblastomas, are tumors of the sex cord-stromal group of ovary and testis cancers. They comprise <1% of all ovarian tumors. They are divided into 6 categories based on the degree of differentiation and the presence of heterologous elements. However, <15% of these tumors are poorly differentiated. CASE: A 23-year-old unmarried female presented with an 8-month history of irregular menstrual cycle and abdominal pain. There were no clinical features suggesting virilization. The left salpingo-oophorectomy specimen revealed an oval ovarian mass of 11 × 7 × 4 cm in dimension. Grossly, the cut surface of the mass was yellowish white in color and solid in consistency and touch preparation was made. By applying cytology and immunocytochemistry techniques, a preliminary diagnosis suggestive of poorly differentiated SLCT was made. The tumor was confirmed as a poorly differentiated SLCT. CONCLUSION: Cytology and immunocytochemistry by WT-1, melan A, vimentin and calretinin are helpful in the diagnosis of poorly differentiated SLCTs.

Association of aplastic anaemia and Fanconi's disease with HLA-DRB1 alleles.

One of the most fascinating areas of research within the field of histocompatibility at present time concerns an observation that a major human histocompatibility system, human leucocyte antigen (HLA), is deeply involved in the development of a great number of diseases. Major histocompatibility complex is the most polymorphic system in the genome of different species. Recognition of HLA alleles could be useful in transplantation and disease studies. Genetic construct of HLA DRB1 was studied in Iranian normal populations and patients with aplastic anaemia and Fanconi's disease. DNA was extracted from the whole blood of 466 normal, 35 aplastic anaemia and 10 Fanconi's individuals. Then DRB1 gene polymorphism was studied by polymerase chain reaction-sequence-specific primer method. The HLA DRB1 gene analysis showed increase of DRB1*07 in aplastic anaemia patients compared to normal population (P = 0.02). According to this study, the frequency of DRB1*07 in normal individuals was 8.3, and in aplastic anaemia patients, 15.7%. Additionally, the frequency of DRB1*04 in normal, aplastic anaemia and Fanconi's individuals was 10, 5.7 and 20%, respectively. Our results of investigation showed correlation between some HLA alleles with the studied diseases. We reported the frequency of various DR types in aplastic and Fanconi's patients. This study could imply the possible role of HLA-DRB1*07 in the incidence of aplastic anaemia. Moreover, the frequency of DRB1*04, DRB1*03 and DRB1*15 alleles showed intermediate correlation with Fanconi's anaemia.

T cell cytokine polarity as a determinant of immunoglobulin A (IgA) glycosylation and the severity of experimental IgA nephropathy.

Immunoglobulin A (IgA) glycosylation, recognized as an important pathogenic factor in IgA nephropathy (IgAN), is apparently controlled by the polarity of T helper (Th) cytokine responses. To examine the role of cytokine polarity in IgAN, inbred mice were immunized by intraperitoneal priming with inactivated Sendai virus (SeV) emulsified in either complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA), which promote Th1- or Th2-immune response, respectively, and then boosted identically twice orally with aqueous suspensions of inactivated virus. Next, some mice were challenged intranasally with infectious SeV. Mice primed with CFA or IFA had equal reductions in nasal viral titre relative to non-immune controls, and equally increased serum levels of SeV-specific IgA antibody. Mice primed with CFA showed higher SeV-specific IgG than those with IFA. Splenocytes from mice primed with IFA produced copious amounts of interleukin (IL)-4 and IL-5, but little interferon-gamma and IL-2; those primed with CFA had reciprocal cytokine recall responses. Total serum IgA and especially SeV-specific IgA from mice primed with IFA showed a selective defect in sialylation and galactosylation. Although the frequency and intensity of glomerular deposits and haematuria did not differ, glomerulonephritis in mice primed with IFA and challenged with infectious virus was more severe than in those given CFA, as judged by serum creatinine level. We conclude that the polarity of T cell cytokines controls the pattern of IgA glycosylation and exerts direct or indirect effects on functional glomerular responses to immune complex deposition.

Phase development and sintering behaviour of biphasic HA-TCP calcium phosphate materials prepared from hydroxyapatite and bioactive glass.

The composites of hydroxyapatite (HA) with 2.5 and 5 wt% of a double oxide (50 mol% CaO and 50 mol% P(2)O(5)) glass were prepared using the conventional powder mixing and sintering method. The addition of the glass significantly enhanced the decomposition process of HA into alpha tricalcium phosphate (alpha-TCP) for bodies sintered at 1,300 and 1,350 degrees C and beta-TCP phases for the ones sintered at 1,200, 1,250 and 1,300 degrees C. Microstructural characteristics, phase development and thermal behaviour were studied by SEM, XRD and STA. The effects of TCP phase content and phase transformation from beta-TCP to alpha-TCP on the sintering are discussed. The characterizations revealed considerable content of TCP in the form of large semi-islands due to important reactions between the fine HA and the glass mixed powders.

Kidney transplantation: is there any place for refugees?

There are more than 8 million refugees worldwide with the Middle East bearing the brunt. Socioeconomic factors are the major obstacles that refugees encounter when seeking health care in the host country. It, therefore, comes as no surprise that refugees are denied equal opportunities for one of the most sophisticated and expensive medical procedures in the world, kidney transplantation. With respect to transplantation, refugees are caught between a rock and a hard place: as recipients they have to single-handedly clear many hurdles on the arduous road to renal transplantation and as donors they are left unprotected against human organ trafficking. It should be the moral responsibility of the host country to provide this population with a support network. The ways and means of establishing this network should be defined locally; nevertheless, enabling refugees to receive a transplant is the most basic step, which should be followed by the provision of financial support and follow-up facilities in a concerted effort to ensure the continued function of the invaluable graft. It is also necessary that refugees be protected from being an organ reservoir on the black market. There are no precise regional or international data available on kidney transplantation in refugees; among the Middle East Society for Organ Transplantation countries, only Iran, Saudi Arabia, Pakistan, and Turkey have thus far provided data on their respective kidney transplantation regulations and models. Other countries in the region should follow suit and design models tailored to the local needs and conditions. What could, indubitably, be of enormous benefit in the long term is the establishment of an international committee on transplantation in refugees.

Prediction of inpatient survival and graft loss in rehospitalized kidney recipients.

INTRODUCTION: Despite a sizeable amount of research conducted hitherto into predictors of renal transplantation outcomes, there are scarce, data on predictors of in-hospital outcomes of post-kidney transplant rehospitalization. This study sought to provide a user-friendly prediction model for inpatient mortality and graft loss among rehospitalized kidney recipients. METHOD: This retrospective review of 424 consecutive kidney recipients rehospitalized after kidney transplantation between the years 2000 and 2005 used multiple logistic regression analysis to evaluate predictors of hospitalization outcomes. RESULTS: Multivariate analysis showed that age at admission, diabetes mellitus as the cause of end-stage renal disease (ESRD), admission due to cerebrovascular accident (CVA), surgical complications were predictors of in-hospital death; age at transplantation, surgical complications, and rejection were predictors of graft loss. Equation for prediction of in-hospital death was Logit(death) -0.304 * age at transplantation (year) + 0.284 age at admission (year) + 1.621 admission for surgical complication + 4.001 admission for CVA-ischemic heart disease + 2.312 diabetes as cause of ESRD. Equation for prediction of in-hospital death was Logit(graft loss) = 0.041 age at transplantation (year) + 1.184 admission for graft rejection + 1.798 admission for surgical complication. CONCLUSIONS: Our prediction equations, using simple demographic and clinical variables, estimated the probability of inpatient mortality and graft loss among re-hospitalized kidney recipients.

Bone mineral density changes within 11 months of renal transplantation in Iranian patients.

BACKGROUND AND AIM: We studied bone mineral density (BMD) changes in Iranian patients with end-stage renal disease (ESRD) within 11 months after renal transplantation. METHODS: Among 68 ESRD candidates for renal transplantation, the BMD at the femur and the spine were assessed using a DEXA Norland scanner. Linear regression analysis was used to identify risk factors associated with low bone density. RESULTS: Mean BMD, T-score and Z-score of femur and spine were significantly reduced (at femur, 0.78 +/- 0.14, -2.4 +/- 1.1, -1.6 +/- 1.0; at spine, 142.25 +/- 105, -1.09 +/- 1.1, -1.07 +/- 0.9). Osteoporosis and osteopenia were found 55.2% and 36.2% at the femur and 8.6% and 58.6% at the spine, respectively. The BMD showed a significant negative association with age (r=0.615), female gender (r=0.394), and corticosteroid intake (r=0.286), and a positive association with weight (r=0.394) and body mass index (r=0.626). There was no significant association between BMD measurements and calcium, phosphorous, or parathyroid hormone levels. At 11 months follow-up, in 20 patients, the subject had lost a mean of 2.4% T-score and 2.8% Z-score at spine (P=.027 and .13, respectively), but did not experience significant declines at the femur. BMD showed a decrease in 80% of recipients in the spine area; there was a 15% BMD increase at the hip. CONCLUSION: Low bone density is common among ESRD Iranian patients. Early screening and treatment of this group is recommended. Significant loss in lumbar density occurred within 11 months of transplantation in more than one third of a prospective cohort of renal transplant recipients.

Nitric oxide mediates cyclosporine-induced apoptosis in cultured renal cells.

BACKGROUND: The clinical use of cyclosporine (CsA) is limited by its nephrotoxicity. Apoptosis, perhaps instigated by increased nitric oxide synthase (NOS) activity, may play a role in such toxicity. METHODS: Human mesangial cells, human tubular cells, human umbilical vein endothelial cells, or murine endothelial cells were cultured with CsA at final concentrations of 0 to 1000 ng/mL for 4 to 24 hours. As inhibitors of apoptosis, 0.01 mol/L L-nitromethylarginine (L-NAME) or 1 microg/mL cycloheximide (CHX) was added, whereas 0.01 mol/L sodium nitroprusside (as a nitric oxide donor) was used as a positive control. Apoptosis was assessed by using TUNEL method and by DNA fragmentation by electrophoresis. In addition, NOS enzymatic activity, Northern blots for inducible NOS (iNOS) mRNA, and immunohistochemically demonstrable iNOS protein were evaluated. RESULTS: Within 12 to 24 hours, CsA significantly increased the fraction (8 to 35%) of apoptotic cells in each cell line, according to the dose. Fragmentation of DNA confirmed apoptosis. L-NAME and CHX inhibited the phenomenon, whereas sodium nitroprusside enhanced it. Each cell line significantly increased NOS activity in response to CsA, an effect blunted by L-NAME and CHX. Neither inhibitor modified the increased iNOS mRNA expression elicited by CsA. Positive staining for both iNOS and p53 proteins was observed in all cell lines incubated with CsA that were inhibited by CHX; L-NAME inhibited only p53 staining. CONCLUSIONS: CsA induces apoptosis in various renal cell lines, and this effect is mediated by the induction of iNOS via p53. These effects may contribute to the acellular fibrosis characteristic of late CsA nephrotoxicity.

Proinflammatory cytokines regulate Fc alphaR expression by human mesangial cells in vitro.

IgA nephropathy (IgAN) is defined by the predominant deposition of IgA immune complexes (IC) in the glomerular mesangium. Interaction between IgA immune complexes and mesangial cells (MC) could be a linchpin for the genesis of IgAN. We studied the modulation of MC expression of IgA receptors (Fc alphaR) by selected cytokines. Binding of 125I-IgA to quiescent human MC showed 2.55 x 10(5) sites/cell with an affinity (Ka) of 3.2 x 10(7) M(-1). Addition of selected recombinant cytokines had no significant influence on Ka, but increased the number of sites/cell relative to unstimulated cells. Northern hybridization using the pHuFc alphaR cDNA probe showed time-dependent increases in mRNA expression in stimulated versus control cells. IL-6 and tumour necrosis factor-alpha (TNF-alpha) had a biphasic effect on the Fc alphaR mRNA level; at 48 h, IL-6 increased steady state mRNA levels about six-fold relative to control, TNF-alpha increased mRNA four-fold, and interferon-gamma (IFN-gamma) induced Fc alphaR mRNA two-fold. By reverse transcriptase-polymerase chain reaction (RT-PCR), the Fc alphaR expressed on human MC appears highly homologous to that expressed by U937 cells. Altered Fc alphaR expression in response to cytokines may influence the pathogenesis of IgAN by affecting deposition and/or clearance of IgA-IC in the mesangium.