Leukocyte and platelet rich fibrin in the management of medication-related osteonecrosis of the jaw: A systematic review and meta-analysis.

BACKGROUND: Osteonecrosis of the jaw (ONJ) has a frequent adverse effect after the administration of nitrogenous bisphosphonates, as non-nitrogenous bisphosphonates are metabolized more rapidly and would produce this effect to a lesser extent. The objective of this study is to analyze the results obtained in the literature with the use of L-PRF in the treatment of ONJ through a systematic review and meta-analysis. MATERIAL AND METHODS: Medline (via PubMed), Cochrane, Web of Science and Grey Literature Database was screened from which 10 were selected. RESULTS: In the meta-analysis with full resolution, combining the use of L-PRF in the treatment of ONJ, a weighted proportion (PP) of 94.3% of complete resolution is obtained (95% CI: 91.2-97.4, p<0.001), with a low degree of heterogeneity, statistically significant (I2 = 29.02%; p<0.001). When analyzing the non-resolution data, a weighted proportion (PP) of 7.7% (95% CI: 3.6-11.9; p<0.001) was obtained with moderate heterogeneity (I2: 41.87%; p=0.112). In the meta-regression, no significant correlation was found between complete resolution and year of publication (intercept = 2.88, p=0.829). In consistency analysis no major changes in PP are identified when any of the studies are eliminated, demonstrating a high reliability in the combined results. CONCLUSION: L-PRF alone or in combination with other therapies in treatment of ONJ achieved high percentages of complete lesion resolution (94.3%). In studies where L-PRF is combined with other therapies, and where the effectiveness of the other therapy alone is analyzed, L-PRF has been shown higher percentages of resolution.

Effect of injectable trace mineral supplementation on peripheral polymorphonuclear leukocyte function, antioxidant enzymes, health, and performance in dairy cows in semi-arid conditions.

The objective of this study was to evaluate the effect of subcutaneous injections of 15 mg/mL Cu, 5 mg/mL Se, 60 mg/mL Zn, and 10 mg/mL Mn on health, performance, polymorphonuclear leukocyte (PMNL) function, circulating glutathione peroxidase (GPx) and superoxide dismutase (SOD) concentrations, and inflammation of dairy cows undergoing the transition period in high temperature-humidity index. A total of 923 multiparous cows from 2 commercial dairy farms were randomly allocated into 1 of 2 treatment groups as follows: control and injectable trace mineral supplementation (ITMS). Cows in the ITMS group received 7 mL of subcutaneous injections at dry-off (208 ± 3 d of gestation), 260 ± 3 d of gestation, and at 35 ± 3 d in milk (DIM). Data regarding health traits, reproductive performance, milk yield, and survivability were extracted from farm database software, and animals were followed-up until 300 DIM. For a subset of 142 cows from one herd, blood samples were collected at enrollment, and at 3 ± 1, 7 ± 1, 10 ± 1, and 35 ± 3 DIM to evaluate hematology, PMNL function, GPx and SOD concentrations, and circulating haptoglobin. Logistic regression was used to assess health and pregnancy per artificial insemination at first service. Cox proportional hazards models were used to evaluate hazard of pregnancy and culling. Mixed linear regression models accounting for repeated measures were used to assess all continuous variables collected over time. Parity, twinning, and previous gestation length were considered as potential confounders. Farm was included as a random effect. The ITMS cows tended to have lower incidence of metritis and stillbirth compared with control group. However, ITMS treatment did not influence the incidence of other diseases (e.g., mastitis, retained placenta), milk yield, reproductive performance, culling, and leukocyte count. Neutrophil-to-lymphocyte ratio, PMNL phagocytosis, and oxidative burst as well as intensity of the oxidative burst were greater for ITMS-treated cows in comparison to control cows. The ITMS cows had decreased expression of the adhesion molecule L-selectin on PMNL surface. The serum concentration of GPx and SOD were not affected by ITMS treatment. In conclusion, ITMS tended to reduce the incidence of metritis and stillbirth parturition, improved PMNL function, and improved the inflammatory status of dairy cows undergoing the transition period in high temperature-humidity index conditions. However, these findings did not translate into improved milk yield, reproductive performance, and survivability.

Association of blood calcium concentration in the first 3 days after parturition and energy balance metabolites at day 3 in milk with disease and production outcomes in multiparous Jersey cows.

Research exploring specific associations of markers of negative energy balance and Ca in postpartum Jersey cows with lactation performance is lacking. Our objectives were to evaluate the associations of total Ca concentration (tCa) measured at 1 through 3 d in milk (DIM) and free fatty acids (FFA), ß-hydroxybutyrate (BHB), and glucose measured at 3 DIM with (1) the risk of multiparous Jersey cows being diagnosed with early-lactation diseases and culling, (2) milk production in the first 9 wk of lactation, and (3) the risk of pregnancy in the first 150 DIM. A cohort study was performed in 1 dairy herd in Texas. Multivariable Poisson regression models were built to evaluate the association of the analytes of interest with the risks of early-lactation diseases and culling in the first 60 DIM (i.e., binary outcomes). Linear mixed models were used to evaluate the association of the analytes of interest with milk production within the first 9 wk of lactation, and a Cox proportional hazard model was built to assess the risk of pregnancy within 150 DIM. A total of 380 cows were used in the final analyses. Total Ca measured at 1 through 3 DIM was not associated with the risk of metritis. Cows with increased FFA and BHB had an increased risk of being diagnosed with metritis and clinical mastitis, respectively. Increased concentrations of glucose and FFA and decreased tCa at 3 DIM were associated with an increased risk of culling. Reduced tCa concentrations at 1 DIM (≤1.84 mmol/L) and 2 DIM (≤2.04 mmol/L) were associated with increased milk production across the first 9 wk of lactation compared with tCa concentrations above those thresholds. Total Ca was not associated with milk production when assessed at 3 DIM, whereas increased FFA (≥0.37 mmol/L) and decreased glucose (≤2.96 mmol/L) at 3 DIM were associated with increased milk production. None of the metabolites measured were associated with the risk of pregnancy in the first 150 DIM. Our results demonstrate that tCa concentration assessed in the first 3 DIM show temporary associations with milk production and culling in multiparous Jersey cows. Although increased concentration of FFA assessed at 3 DIM was associated with greater milk yield, it was a detrimental factor for the risk of metritis. This study attempted to better elucidate the relationship of tCa, FFA, BHB, and glucose assessed in early postpartum with health and performance of Jersey cows. Based on this study, assessments performed at 3 DIM using tCa concentration ≤1.99 mmol/L for increased risk of early-lactation culling and FFA ≥0.43 mmol/L for increased risk of metritis could be used as starting points. More studies evaluating the dynamics of energy balance markers and tCa in postpartum Jersey cows using a greater number of herds are needed to better inform dairy consultants on critical levels for exacerbated postpartum negative energy balance and subclinical hypocalcemia for the Jersey breed.

Short communication: Associations of serum biomarkers of stress and inflammation measured at arrival with health, mortality, and growth of calves transported within the first 4 days of life.

The objective of this study was to assess the association between serum concentrations of haptoglobin (Hp), cortisol, and l-lactate following transport of dairy heifer calves within their first week of life with health, mortality, and growth during the preweaning period. Blood samples were collected at arrival and included a cohort of 168 Jersey and Jersey-cross calves from 8 different sources located in Minnesota. All calves were raised at a single facility in New Mexico. Incidence of respiratory disease (BRD) and mortality during the preweaning period (60 d of life) were extracted from the farm's software database. Individual body weight was measured at birth and at weaning to estimate average daily gain. No simple linear correlations were found between the biomarkers. The incidence of BRD during the preweaning period was 7.7%. While cortisol and l-lactate serum concentrations were not associated with BRD, Hp was negatively associated with BRD. Receiving operating characteristic curve analysis was performed to determine the optimal threshold value for Hp [threshold ≤0.63 µmol/L (63 µg/mL), area under the curve = 0.65]. A Cox's proportional hazards model revealed that calves with Hp concentration ≤0.63 µmol/L were more likely to be diagnosed with BRD (hazard ratio = 5.0, 95% confidence interval = 1.3-19.0). A mixed linear model showed that calves with Hp concentration ≤0.63 µmol/L tended to have lower average daily gain (454.4 vs. 479.9 g/d) during the preweaning period than calves with Hp >0.63 µmol/L at arrival. Overall mortality of the cohort was 3.5%, and Hp was not associated with mortality. Although circulating concentrations of l-lactate and cortisol measured at arrival were not associated with BRD incidence during the preweaning period of heifer calves transported within the first 4 d of life, calves with serum Hp concentration >0.63 µmol/L were less likely to be diagnosed with BRD and tended to grow more than calves with Hp ≤0.63 µmol/L. Further research is needed to replicate these results in a larger cohort and to better understand the possible influence of greater inflammatory status at arrival on health and growth of calves transported to a calf-raising facility.

The association of cow-related factors assessed at metritis diagnosis with metritis cure risk, reproductive performance, milk yield, and culling for untreated and ceftiofur-treated dairy cows.

Our objective was to assess the association of cow-related factors with metritis cure risk and economically important outcomes. In this prospective cohort study nested inside a randomized clinical trial, cows enrolled in a clinical trial that aimed to evaluate an alternative metritis therapy that had available plasma samples collected at metritis diagnosis were included. Metritis was defined as fetid, watery, reddish-brownish discharge with or without fever, and cure was defined as the absence of metritis signs 12 d after diagnosis. Cows were randomly allocated to remain untreated (CON; n = 147) or receive subcutaneous injections of 6.6 mg/kg of ceftiofur crystalline-free acid at enrollment and 72 h later (CEF, n = 168). Additionally, a random subset of 150 nonmetritic cows (NMET) was also included to compare milk production, reproductive performance, and culling responses. Cow-related factors evaluated include plasma concentrations of nonesterified fatty acids, ß-hydroxybutyrate, and haptoglobin (Hp), parity, rectal temperature, and days in milk (DIM) at metritis diagnosis, vulvovaginal laceration (VL), BCS, dystocia, twins, and retained placenta. Among CON cows, DIM at metritis diagnosis was positively associated with metritis cure [threshold = 8, area under the curve (AUC) = 0.67], whereas plasma Hp concentration tended to be negatively associated with cure of metritis (threshold = 0.54 mg/mL, AUC = 0.64). Among CEF cows, DIM at metritis diagnosis (threshold = 5, AUC = 0.67) and dystocia were positively associated with metritis cure, whereas VL and Hp (threshold = 0.78 mg/mL, AUC = 0.76) were negatively associated with cure. For CON cows that were diagnosed with metritis after 8 DIM or had plasma Hp concentration ≤0.54 mg/mL, milk production, pregnancy, and culling risk were comparable to NMET cows. However, performance was impaired when cows that developed metritis at ≤8 DIM or had Hp >0.54 mg/mL were left untreated. Among CEF cows, Hp, DIM at metritis diagnosis, dystocia, and VL were associated with metritis cure. Milk yield, reproductive performance, and culling losses are more pronounced among CEF cows when metritis was diagnosed at ≤5 DIM, Hp >0.78 mg/mL, or if they had VL or dystocia. In conclusion, these data indicate that timing of the onset of metritis and inflammatory biomarkers could be used for the development of a selective therapy strategy for metritis, but more research is needed to identify more accurate predictors of metritis spontaneous cure and treatment failure.

Functional Interaction Between the ESCRT-I Component TSG101 and the HSV-1 Tegument Ubiquitin Specific Protease.

Similar to phosphorylation, transient conjugation of ubiquitin to target proteins (ubiquitination) mediated by the concerted action of ubiquitin ligases and de-ubiquitinating enzymes (DUBs) can affect substrate function. As obligate intracellular parasites, viruses rely on different cellular pathways for their own replication and the well conserved ubiquitin conjugating/de-conjugating system is not an exception. Viruses not only usurp the host proteins involved in the ubiquitination/de-ubiquitination process, but they also encode their own ubiquitin ligases and DUBs. Here we report that an N-terminal variant of the herpes simplex virus (HSV) type-1 large tegument protein VP1/2 (VP1/2(1-767)), encompassing an active DUB domain (herpesvirus tegument ubiquitin specific protease, htUSP), and TSG101, a component of the endosomal sorting complex required for transport (ESCRT)-I, functionally interact. In particular, VP1/2(1-767) modulates TSG101 ubiquitination and influences its intracellular distribution. Given the role played by the ESCRT machinery in crucial steps of both cellular pathways and viral life cycle, the identification of TSG101 as a cellular target for the HSV-1 specific de-ubiquitinating enzyme contributes to the clarification of the still under debate function of viral encoded DUBs highly conserved throughout the Herpesviridae family.

Sperm DNA fragmentation index does not correlate with the sperm or embryo aneuploidy rate in recurrent miscarriage or implantation failure patients.

BACKGROUND: The aneuploidy rate is higher in poor-quality sperm samples, which also have higher DNA fragmentation index values. The aim of this study was to assess the relationship between sperm DNA fragmentation in samples from infertile men belonging to couples with recurrent miscarriage or implantation failure and the aneuploidy rate in spermatozoa as well as in embryos from patients. METHODS: This prospective study evaluated DNA damage and the aneuploidy rate in fresh and processed (density gradient centrifugation) ejaculated sperm as well as the aneuploidy rate in biopsied embryos from fertility cycles. Fluorescence in situ hybridization was used for the aneuploidy analysis. Results were compared using linear regression and analysis of variance. RESULTS: A total of 154 embryos were evaluated from 38 patients undergoing PGD cycles; 35.2% of the embryos were chromosomally normal. Analysis of the same sperm samples showed an increased DNA fragmentation after sperm preparation in 76% of the patients. There was no correlation between DNA fragmentation and the aneuploidy rate in embryos or in fresh or processed sperm samples. CONCLUSIONS: Sperm DNA fragmentation is not related to chromosomal anomalies in embryos from patients with recurrent miscarriage or implantation failure. However, we cannot rule out the possibility that a relationship between DNA fragmentation and aneuploidy exists for other causes of infertility. Furthermore, the different methods used to evaluate DNA fragmentation may produce different results.

Cow-related factors associated with intramammary infections during the 1st week postpartum in primiparous dairy cows in certified organic herds.

The objectives if this exploratory study were to identify variables associated with intramammary infections (IMI) during the 1st week of lactation in primiparous organic dairy cows, and to evaluate the association of those variables with somatic cell count (SCC) linear scores and milk yield in early lactation. Nulliparous cows (n = 240) were evaluated for: udder edema, teat edema, milk leakage (ML) and udder hygiene at weeks 6, 4, 2, and 1 prepartum and 1st week postpartum; body condition score (BCS) at 6 weeks prepartum and 1st week postpartum; age at calving (days), gestation length, dystocia, stillbirth, calf sex were included in the analysis. Milk samples from the 1st week postpartum were cultured using standard laboratory techniques and bacterial growth was considered IMI. Intramammary infection was observed in 58.7% of cows, with Staphylococcus chromogenes and S. aureus being the most prevalent pathogens. Cows with ML at 1st week postpartum were at 3.42 greater odds of IMI (P < 0.01). Cows with prepartum BCS ≥ 3.75 were at 3.12 greater odds of IMI (P < 0.01). Cows with ML in the 1st week of lactation had increased SCC (P < 0.01) and lower milk production in the second month of lactation (P = 0.05). Intervention studies are needed to evaluate if monitoring prepartum BCS and ML at early postpartum can aid in the control of IMIs in heifers in organic dairies.

Associations between circulating levels of natural antibodies, total serum immunoglobulins, and polymorphonuclear leukocyte function in early postpartum dairy cows.

The objective of this study was to investigate the associations between natural antibodies (NAbs) and total serum immunoglobulins (Igs) concentrations (both from IgG and IgM isotypes), with variables of polymorphonuclear leukocytes (PMN) function of dairy cows in the early postpartum period. Seventy-five healthy postpartum dairy cows at 2 ± 1 days in milk were enrolled in a cross-sectional study. Natural and total antibodies in serum samples were measured by ELISA. Flow cytometry was used to determine the phagocytosis and oxidative burst capacities of PMN and the quantification of the adhesion molecule l-selectin. Leukocyte count and differentials, and serum haptoglobin were also measured. A positive correlation between NAbsIgM and total serum IgM and between NAbsIgM and NAbsIgG were found. Before performing the associations between circulating Igs concentrations and PMN function variables, cows were categorized into having low, medium or high circulating antibodies based on their NAbs and total Igs serum concentrations. None of the PMN variables assessed differed between low, medium, and high cows for both NAbsIgM and NAbsIgG. While associations between PMNs function and total IgG were not observed, some associations between total IgM concentrations and PMN activity were found. Cows with high serum IgM had greater phagocytic activity compared to cows in the low IgM group. Finally, the proportion of PMN that performed oxidative burst and PMN surface expression of l-selectin intensity was greater in high total IgM group when compared to medium and low groups. In conclusion, association between NAbs, and PMN activity variables were not observed, but total serum IgM was associated to some PMN function variables in early post-partum dairy cows.

Regional cerebral blood flow and cerebrovascular reactivity in IDDM.

OBJECTIVE: To investigate both rCBF and cerebrovascular reactivity, evaluated as pre- and post-ACZ rCBF differences in a group of IDDM patients with differences in duration of disease and severity of complications. RESEARCH DESIGN AND METHODS: rCBF was measured by the 133Xenon inhalation method in 20 IDDM patients and in 15 healthy control subjects before and after an intravenous injection of ACZ, a carbonic anhydrase inhibitor commonly used to assess cerebrovascular reactivity. RESULTS: Basal global CBF (the mean of 32 regional values) was within the normal range in all patients but 1, who showed slight hyperperfusion; moreover, in 3 patients with long-lasting disease, some hypoperfused regions were found. ANOVA showed an inverse correlation between basal global CBF (P < 0.01) and duration of diabetes, but no correlation with Hb, MABP, serum glucose concentration, or GHb. Compared with control subjects, the percentage of global CBF increment after ACZ administration was significantly impaired in 4 patients and gave a borderline response in 2 patients; 4 of these poor ACZ responders had retinopathy, and 1 had suffered from a TIA. Duration of diabetes, Hb, MABP, serum glucose concentration, and GHb did not correlate with the percentage of post-ACZ global CBF changes, and did not differ among the 6 poor ACZ responders and the other diabetic patients or control subjects. CONCLUSIONS: These results confirm that global CBF is within the normal range in most IDDM patients, although it is significantly influenced by the duration of diabetes; pathophysiological correlates of the altered cerebrovascular reactivity need to be further investigated. rCBF measurements, before and after ACZ administration, seem to represent a safe and reliable tool for assessing cerebrovascular function in IDDM.

In vivo biological activity of rocket extracts (Eruca vesicaria subsp. sativa (Miller) Thell) and sulforaphane.

Eruca is thought to be an excellent source of antioxidants like phenolic compounds, carotenoids, glucosinolates and their degradation products, such as isothiocyanates. Sulforaphane is one of the most potent indirect antioxidants of Eruca isolated until the date. In this work we investigate: (i) the safety and DNA protective activity of Eruca extracts and sulforaphane (under and without oxidative stress) in Drosophila melanogaster; and (ii) the influence on D. melanogaster life span treated with Eruca extracts and sulforaphane. Our results showed that among the four concentrations of Eruca extracts tested (from 0.625 to 5mg/ml), intermediate concentrations of the Es2 accession (1.25 and 2.5mg/ml) exhibited no genotoxic activity, as well as antigenotoxic activity (inhibition rate of 0.2-0.6) and the lowest concentration of Es2 and Es4 accessions (0.625 mg/ml) also enhanced the health span portion of the live span curves. Sulforaphane presented a high antigenotoxic activity in the SMART test of D. melanogaster and intermediate concentrations of this compound (3.75 µM) enhanced average healthspan. The results of this study indicate the presence of potent antigenotoxic factors in rocket, which are being explored further for their mechanism of action.

Regional cerebral blood flow in chronic stroke patients.

BACKGROUND AND PURPOSE: The aim of this study was to investigate regional cerebral blood flow parameters during the postacute phase of unilateral ischemic stroke and to correlate them with clinical data. METHODS: Regional cerebral blood flow was measured in 187 patients in the stabilized phase of stroke by the xenon-133 inhalation method with 32 extracranial detectors. Thirty-eight patients were reexamined after a mean +/- SD time of 32 +/- 21.4 months. RESULTS: The overall detection of hypoperfusion was 92.0%, with asymmetries as the most sensitive index, especially for patients with a lesser degree of neurological disability. Neurological disability score was strongly associated with regional cerebral blood flow in the affected hemisphere (p < 0.0001) and with asymmetries (p < 0.0001). The presence of carotid obstruction further decreased the regional cerebral blood flow in the affected hemisphere and significantly increased asymmetry (p < 0.0001). Subjects who had no hypoperfusion at absolute values analysis were more frequently free of carotid disease and had less severe disability than those who had bilateral or unilateral regional absolute cerebral blood flow reduction. In 38 patients without new cerebrovascular events, a significant (p = 0.005) reduction of hemispheric regional cerebral blood flow asymmetries was found on a follow-up examination. CONCLUSIONS: These data confirm the value of regional cerebral blood flow asymmetries in stroke detection and point out that important clinical information is also contained in absolute values analysis.