Exposure to bisphenols, parabens, and benzophenones in colostrum breast milk of Panamanian women: A pilot study from the PA-MAMI cohort.

BACKGROUND: Breast milk is the optimal source of nutrition for infants but can also expose them to endocrine-disrupting chemicals (EDCs), among other environmental contaminants. AIM: To determine concentrations of non-persistent phenolic EDCs (three bisphenols, four parabens [PBs], and six benzophenones [BPs]), in colostrum samples from Panamanian mothers and to examine associated reproductive, sociodemographic, and life-style factors. METHODS: Dispersive liquid-liquid microextraction was used to measure concentrations of bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS), methyl- (MeP), ethyl- (EtP), propyl- (n-PrP), and butyl-paraben (n-BuP), and benzophenones BP-1, BP-2, BP-3, BP-6, BP-8, and 4-hydroxy-BP in colostrum milk samples from 36 mothers. An ad hoc questionnaire was used to collect data on potential influentially variables, and multiple linear and logistic regression analyses were conducted. RESULTS: Two or more tested EDCs were detected in 36 colostrum samples (100 %), at least four in 14 samples (38.9 %), and at least six in 4 samples (11.1 %). The most frequently detected compounds were BPA (91.7 %), BP-8 (63.9 %), MeP (47.2 %), and BPF (41.7 %). The median concentration was 3.45 ng/mL for BP-8 and 1.37 ng/mL for BPA. No concentrations of n-PrP, BP-1, BP-6, or 4-hydroxy-BP were detected. Associations were observed between phenolic EDC concentrations and maternal place of residence, consumption frequency of poultry, fish, fresh cheese, fruit, yogurt and chocolate, intake of nutritional supplements, and application of some personal care products. CONCLUSIONS: Bisphenols, parabens, and benzophenones were widely present in colostrum milk samples from Panamanian women. Preventive measures are needed to maximize the benefits of breastfeeding.

Supercooling preservation of vascularized composite allografts through CPA optimization, thermal tracking, and stepwise loading techniques.

Vascularized composite allografts (VCAs) present unique challenges in transplant medicine, owing to their complex structure and vulnerability to ischemic injury. Innovative preservation techniques are crucial for extending the viability of these grafts, from procurement to transplantation. This study addresses these challenges by integrating cryoprotectant agent (CPA) optimization, advanced thermal tracking, and stepwise CPA loading strategies within an ex vivo rodent model. CPA optimization focused on various combinations, identifying those that effectively suppress ice nucleation while mitigating cytotoxicity. Thermal dynamics were monitored using invasive thermocouples and non-invasive FLIR imaging, yielding detailed temperature profiles crucial for managing warm ischemia time and optimizing cooling rates. The efficacy of stepwise CPA loading versus conventional flush protocols demonstrated that stepwise (un)loading significantly improved arterial resistance and weight change outcomes. In summary, this study presents comprehensive advancements in VCA preservation strategies, combining CPA optimization, precise thermal monitoring, and stepwise loading techniques. These findings hold potential implications for refining transplantation protocols and improving graft viability in VCA transplantation.

Placental concentrations of xenoestrogenic organochlorine pesticides and polychlorinated biphenyls and assessment of their xenoestrogenicity in the PA-MAMI mother-child cohort.

BACKGROUND: Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCB), they have contributed to the exposure of women to persistent organic pollutants (POPs). These compounds can cross the placental barrier and interfere with the hormonal system of newborns. AIM: To determine concentrations of OCPs and PCBs and their xenoestrogenic activity in placentas of women from the PA-MAMI cohort of Panama. METHODS: Thirty-nine placenta samples from women in the Azuero peninsula (Panama) were analyzed. Five OCPs [p-p'-dichlorodiphenyldichloroethylene (p-p'-DDE), beta-hexachlorohexane (ß-HCH), γ-hexachlorohexane (lindane), hexachlorobenzene (HCB) and mirex] and three PCB congeners (PCB-138, PCB-153 and PCB-180) were quantified in placenta extracts. The xenoestrogenic activity of extracts was assessed with the E-Screen bioassay to estimate the total effective xenoestrogen burden (TEXB). RESULTS: All placental samples were positive for at least three POP residues and >70% for at least six. The frequencies of quantified OCPs ranged from 100% for p,p'-DDE and HCB to 30.8% for ß-HCH. The highest median concentration was for lindane (380.0 pg/g placenta), followed by p,p'-DDE (280.0 pg/g placenta), and HCB (90.0 pg/g placenta). Exposure to p,p'-DDE was associated with greater meat consumption, suggesting that animal fat is a major source of exposure to DDT metabolites. The frequency of detected PCBs ranged between 70 and 90%; the highest median concentration was for PCB 138 (17.0 pg/g placenta), followed by PCB 153 (16.0 pg/g placenta). All placentas were positive in the estrogenicity bioassay with a median TEXB-α of 0.91 pM Eeq/g of placenta. Exposure to lindane was positively associated with the xenoestrogenicity of TEXB- α, whereas this association was negative in the case of exposure to PCB 153. CONCLUSIONS: To our best knowledge, this study contributes the first evidence on the presence of POPs and xenoestrogenic burden in placentas from Latin-American women. Given concerns about the consequences of prenatal exposure to these compounds on children's health, preventive measures are highly recommended to eliminate or minimize the risk of OCP exposure during pregnancy.

Concentrations of bisphenols, parabens, and benzophenones in human breast milk: A systematic review and meta-analysis.

BACKGROUND: Breast milk is the main source of nutrition for infants but may be responsible for their exposure to environmental chemicals, including endocrine-disrupting chemicals. AIM: To review available evidence on the presence and concentrations of bisphenols, parabens (PBs), and benzophenones (BPs) in human milk and to explore factors related to exposure levels. METHODS: A systematic review was carried out using Medline, Web of Science, and Scopus databases, conducting a comprehensive search of peer-reviewed original articles published during the period 2000-2020, including epidemiological and methodological studies. Inclusion criteria were met by 50 studies, which were compiled by calculating weighted detection frequencies and arithmetic mean concentrations of the chemicals. Their risk of bias was assessed using the ROBINS-I checklist. RESULTS: Among the 50 reviewed studies, concentrations of bisphenols were assessed by 37 (74.0%), PBs by 21 (42.0%), and BPs by 10 (20.0%). Weighted detection frequencies were 63.6% for bisphenol-A (BPA), 27.9-63.4% for PBs, and 39.5% for benzophenone-3 (BP-3). Weighted mean concentrations were 1.4 ng/mL for BPA, 0.2-14.2 ng/mL for PBs, and 24.4 ng/mL for BP-3. Mean concentrations ranged among studies from 0.1 to 3.9 ng/mL for BPA, 0.1 to 1063.6 ng/mL for PBs, and 0.5 to 72.4 ng/mL for BP-3. The highest concentrations of BPA and PBs were reported in samples from Asia (versus America and Europe). Higher BPA and lower methyl-paraben concentrations were observed in samples collected after 2010. Elevated concentrations of these chemicals were associated with socio-demographic and lifestyle factors in eight studies (16.0%). Two epidemiological studies showed moderate/serious risk of bias. CONCLUSIONS: This systematic review contributes the first overview of the widespread presence and concentrations of bisphenols, PBs, and BPs in human breast milk, revealing geographical and temporal variations. The methodological heterogeneity of published studies underscores the need for well-conducted studies to assess the magnitude of exposure to these chemicals from human milk.

Divergent molecular and growth responses of young "Cabernet Sauvignon" (Vitis vinifera) plants to simple and mixed infections with Grapevine rupestris stem pitting-associated virus.

Grapevine rupestris stem pitting associated virus (GRSPaV) is one of the most widely distributed viruses; even so, little is known about its effect on Vitis vinifera. To provide new insights, the effects of single and mixed GRSPaV infections on the V. vinifera cultivar "Cabernet Sauvignon" were studied by evaluating growth parameters, such as measurements of the total plant length, the number and distance of internodes and the number of leaves per shoot. In addition, parameters relating to gas exchange, i.e., the stomatal conductance, net photosynthetic rate, internal CO2 concentration and leaf transpiration, were also assessed. All the measurements were performed in one- and two-year-old plants with a single GRSPaV infection or mixed infections of GRSPaV and Grapevine fanleaf virus (GFLV). The results show that the plant phytosanitary status did not significantly alter the growth and gas exchange parameters in one-year-old plants. However, in two-year-old plants, single GRSPaV infections increased shoot elongation, which was accompanied by the overexpression of genes associated with the gibberellic acid response pathway. The gas exchange parameters of these plants were negatively affected, despite exhibiting higher LHCII gene expression. Plants with mixed infections did not have modified growth parameters, although they presented a greater reduction in the primary photosynthetic parameters evaluated with no change in LHCII expression. The results presented here confirm the co-evolution hypothesis for V. vinifera and GRSPaV during the early stages of plant development, and they provide new evidence about the effects of GRSPaV and GFLV co-infections on the "Cabernet Sauvignon" cultivar.

Platelet thrombus formation in eHUS is prevented by anti-MBL2.

E. coli associated Hemolytic Uremic Syndrome (epidemic hemolytic uremic syndrome, eHUS) caused by Shiga toxin-producing bacteria is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury that cause acute renal failure in up to 65% of affected patients. We hypothesized that the mannose-binding lectin (MBL) pathway of complement activation plays an important role in human eHUS, as we previously demonstrated that injection of Shiga Toxin-2 (Stx-2) led to fibrin deposition in mouse glomeruli that was blocked by co-injection of the anti-MBL-2 antibody 3F8. However, the markers of platelet thrombosis in affected mouse glomeruli were not delineated. To investigate the effect of 3F8 on markers of platelet thrombosis, we used kidney sections from our mouse model (MBL-2+/+ Mbl-A/C-/-; MBL2 KI mouse). Mice in the control group received PBS, while mice in a second group received Stx-2, and those in a third group received 3F8 and Stx-2. Using double immunofluorescence (IF) followed by digital image analysis, kidney sections were stained for fibrin(ogen) and CD41 (marker for platelets), von-Willebrand factor (marker for endothelial cells and platelets), and podocin (marker for podocytes). Electron microscopy (EM) was performed on ultrathin sections from mice and human with HUS. Injection of Stx-2 resulted in an increase of both fibrin and platelets in glomeruli, while administration of 3F8 with Stx-2 reduced both platelet and fibrin to control levels. EM studies confirmed that CD41-positive objects observed by IF were platelets. The increases in platelet number and fibrin levels by injection of Stx-2 are consistent with the generation of platelet-fibrin thrombi that were prevented by 3F8.

Characterization and Pathogenicity of Botryosphaeriaceae Species Obtained from Avocado Trees with Branch Canker and Dieback and from Avocado Fruit with Stem End Rot in Chile.

Several species of the Botryosphaeriaceae family have been associated with branch canker, dieback, and stem end rot in avocado (Persea americana Mill.). In Chile, the incidence of diseases affecting the avocado tree increased from 2011 to 2016, which coincided with a severe drought that affected avocado production. Moreover, distant countries importing avocados from Chile also reported an increase of stem end rot of ripe avocados. Therefore, the aims of this study were to identify the pathogen species associated with branch canker, dieback, and stem end rot of avocado in Chile and to study their pathogenicity. This study was conducted between 2015 and 2016 in 'Hass' avocado orchards located in the main avocado-producing regions in Chile. A diverse collection of fungal species was recovered from both necrotic woody tissue and necrotic tissue on harvested ripe fruit. On the basis of morphology and phylogenetic analyses of the internal transcribed spacer region (ITS1-5.8S-ITS2) and the translation elongation factor 1-α (TEF1-α) gene, eight species in the Botryosphaeriaceae family were identified: Diplodia mutila, D. pseudoseriata, D. seriata, Dothiorella iberica, Lasiodiplodia theobromae, Neofusicoccum australe, N. nonquaesitum, and N. parvum. For each of these species, pathogenicity studies were conducted on 1-year-old healthy Hass avocado plants. All isolates produced brown gum exudate and caused necrosis in the vascular system 3 weeks after inoculation. N. nonquaesitum, N. parvum, and D. pseudoseriata were the most virulent species. Necrotic lesions and cavities with white mycelia near the peduncle union were observed on Hass avocado fruit inoculated postharvest. L. theobromae, N. australe, and N. parvum were significantly more virulent than the other tested species in the Botryosphaeriaceae family. This study identified and characterized the pathogenicity of Botryosphaeriaceae species in Chile, which will prove useful to future research on these pathogens directed at establishing effective control strategies in avocado.

RNA expression profiling of nonhuman primate renal allograft rejection identifies tolerance.

Tolerance induction to prevent allograft rejection is a long-standing clinical goal. However, convincing and dependable tolerance identification remains elusive. Hypothesizing that intragraft RNA expression is informative in both rejection and tolerance, we profile intrarenal allograft RNA expression in a mixed chimerism renal allograft model of cynomolgus monkeys and identify biologically significant tolerance. Analysis of 67 genes identified 3 dominant factors, each with a different pattern of gene expressions, relating to T cell-mediated rejection (TCMR), chronic antibody-mediated rejection (CAMR), or Tolerance. Clustering these 3 factors created 9 groups. One of the 9 clustered groups, the Tolerance cluster, showed the lowest probability of terminal rejection, the longest duration of allograft survival, and the lowest relative risk of terminal rejection. The Tolerance factor consists of a novel set of gene expressions including cytokine and immunoregulatory genes adding mechanistic insights into tolerance. The Tolerance factor could not be identified within current pathologic diagnostic categories. The TCMR and CAMR factors are dominant to the Tolerance factor, causing rejection even if the Tolerance factor is present. These 3 factors determine the probability of terminal rejection or tolerance. This novel a posteriori approach permits identification of pathways of rejection, including tolerance.

RNA expression profiling of renal allografts in a nonhuman primate identifies variation in NK and endothelial gene expression.

RNA transcript expression estimates are a promising method to study the mechanisms and classification of renal allograft rejections. Here we use the Nanostring platform to profile RNA expression in renal allografts in a nonhuman primate (NHP), the Cynomolgus monkey. We analyzed protocol and indication 278 archival renal allograft samples, both protocol and indication from 76 animals with diagnoses of chronic antibody-mediated rejection (CAMR), acute cellular rejection (TCMR), and MIXED (both CAMR and TCMR), plus normals and samples with no pathological rejection using a Cynomolgus-specific probe set of 67 genes. Analysis identified RNA expression heterogeneity of endothelial and NK genes within CAMR and TCMR, including the stages of CAMR. Three factors were partitioned into additional groups. One group with the longest allograft survival time is pure CAMR without NK or CD3. Three mixed groups show variation in NK and CD3. TCMR was split into 2 groups with variation in NK genes. Additional validation of the complete gene-set correlated many of the genes with diagnoses of CAMR, MIXED, and TCMR rejections and with Banff histologic criteria defined in human subjects. These NHP data demonstrate the utility of RNA expression profiling to identify additional heterogeneity of endothelial and NK RNA gene expressions.

Prolonged Survival Following Pig-to-Primate Liver Xenotransplantation Utilizing Exogenous Coagulation Factors and Costimulation Blockade.

Since the first attempt of pig-to-primate liver xenotransplantation (LXT) in 1968, survival has been limited. We evaluated a model utilizing α-1,3-galactosyltransferase knockout donors, continuous posttransplant infusion of human prothrombin concentrate complex, and immunosuppression including anti-thymocyte globulin, FK-506, methylprednisone, and costimulation blockade (belatacept, n = 3 or anti-CD40 mAb, n = 1) to extend survival. Baboon 1 remained well until postoperative day (POD) 25, when euthanasia was required because of cholestasis and plantar ulcers. Baboon 2 was euthanized following a seizure on POD 5, despite normal liver function tests (LFTs) and no apparent pathology. Baboon 3 demonstrated initial stable liver function but was euthanized on POD 8 because of worsening LFTs. Pathology revealed C4d positivity, extensive hemorrhagic necrosis, and a focal cytomegalovirus inclusion. Baboon 4 was clinically well with stable LFTs until POD29, when euthanasia was again necessitated by plantar ulcerations and rising LFTs. Final pathology was C4d negative and without evidence of rejection, inflammation, or thrombotic microangiopathy. Thus, nearly 1-mo rejection-free survival has been achieved following LXT in two of four consecutive recipients, demonstrating that the porcine liver can support life in primates for several weeks and has encouraging potential for clinical application as a bridge to allotransplantation for patients with acute-on-chronic or fulminant hepatic failure.

Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts: Validation of Human Histological and Molecular Phenotypes.

Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0.92). This three-gene set correlated with classic features of AMR, including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association between three-gene set expression and AMR and highlighted the ambiguity of v lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR). Elevated three-gene set expression corresponded with the development of immunopathological evidence of rejection and often preceded it. Many recipients demonstrated mixed AMR and TCMR, suggesting that this represents the natural pattern of rejection. These data provide NHP animal model validation of recent updates to the Banff classification including the assessment of molecular markers for diagnosing AMR.

Immunosuppression With CD40 Costimulatory Blockade Plus Rapamycin for Simultaneous Islet-Kidney Transplantation in Nonhuman Primates.

The lack of a reliable immunosuppressive regimen that effectively suppresses both renal and islet allograft rejection without islet toxicity hampers a wider clinical application of simultaneous islet-kidney transplantation (SIK). Seven MHC-mismatched SIKs were performed in diabetic cynomolgus monkeys. Two recipients received rabbit antithymocyte globulin (ATG) induction followed by daily tacrolimus and rapamycin (ATG/Tac/Rapa), and five recipients were treated with anti-CD40 monoclonal antibody (mAb) and rapamycin (aCD40/Rapa). Anti-inflammatory therapy, including anti-interleukin-6 receptor mAb and anti-tumor necrosis factor-α mAb, was given in both groups. The ATG/Tac/Rapa recipients failed to achieve long-term islet allograft survival (19 and 26 days) due to poor islet engraftment and cytomegalovirus pneumonia. In contrast, the aCD40/Rapa regimen provided long-term islet and kidney allograft survival (90, 94, >120, >120, and >120 days), with only one recipient developing evidence of allograft rejection. The aCD40/Rapa regimen was also tested in four kidney-alone transplant recipients. All four recipients achieved long-term renal allograft survival (100% at day 120), which was superior to renal allograft survival (62.9% at day 120) with triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). The combination of anti-CD40 mAb and rapamycin is an effective and nontoxic immunosuppressive regimen that uses only clinically available agents for kidney and islet recipients.

Exoenzymes and metabolites related to the nematicidal effect of rhizobacteria on Xiphinema index Thorne & Allen.

AIMS: To identify enzymes and metabolites in the rhizobacteria filtrates that have a nematicidal effect on Xiphinema index and perform molecular characterization of the strains evaluated. METHODS AND RESULTS: A series of four bacteria selected for their nematicidal potential were considered for in vitro, biochemical and molecular studies. The direct effect of the bacterial filtrates was evaluated in vitro on X. index juveniles and adults. Hydrogen sulphide and hydrogen cyanide liberation and protease, chitinase, collagenase and lipase activity were verified in the strains. Up to five housekeeping genes and one ITS 16S-23S rRNA were analysed. All bacterial filtrates presented 54-100% mortality when evaluated during up to 72 h of nematode exposure. Strains presented protease activity; two of them (strains FB833T and FR203A) showed reliable collagenase and chitinase activities, respectively, and three of them showed strong lipolytic activity (FB833T, FR203A and FS213P). Strain Bacillus megaterium FB133M had no lipase activity and presented the lowest nematicidal effect. Bacillus amyloliquefaciens FR203A had the largest lethal effect. CONCLUSION: The rhizobacteria strains evaluated in this study possess nematicidal compounds, which may offer an interesting alternative for X. index control. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of exoenzymes and metabolites associated with nematicidal effect of rhizobacteria on X. index, which can be a possible alternative for control of this plant-parasitic nematode.

The Effects of Exogenous Administration of Human Coagulation Factors Following Pig-to-Baboon Liver Xenotransplantation.

We sought to determine the effects of exogenous administration of human coagulation factors following pig-to-baboon liver xenotransplantation (LXT) using GalT-KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor VIIa (1 µg/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large-vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor VIIa. Further studies are warranted because this regimen may allow for prolonged survival following LXT.

Effects of Lung Cotransplantation on Cardiac Allograft Tolerance Across a Full Major Histocompatibility Complex Barrier in Miniature Swine.

A 12-day course of high-dose tacrolimus induces tolerance of major histocompatibility complex-mismatched lung allografts in miniature swine but does not induce tolerance of heart allografts unless a kidney is cotransplanted. To determine whether lungs share with kidneys the ability to induce cardiac allograft tolerance, we investigated heart-lung cotransplantation using the same induction protocol. Hearts (n = 3), heart-kidneys (n = 3), lungs (n = 6), and hearts-lungs (n = 3) were transplanted into fully major histocompatibility complex-mismatched recipients treated with high-dose tacrolimus for 12 days. Serial biopsy samples were used to evaluate rejection, and in vitro assays were used to detect donor responsiveness. All heart-kidney recipients and five of six lung recipients demonstrated long-term graft survival for longer than 272 days, while all heart recipients rejected their allografts within 35 days. Tolerant recipients remained free of alloantibody and showed persistent donor-specific unresponsiveness by cell-mediated lympholysis/mixed-lymphocyte reaction. In contrast, heart-lung recipients demonstrated rejection of both allografts (days 47, 55, and 202) and antidonor responsiveness in vitro. In contrast to kidneys, lung cotransplantation leads to rejection of both heart and lung allografts, indicating that lungs do not have the same tolerogenic capacity as kidneys. We conclude that cells or cell products present in kidney, but not heart or lung allografts, have a unique capacity to confer unresponsiveness on cotransplanted organs, most likely by amplifying host regulatory mechanisms.

Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model.

The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI)-treated donor lymphoid cell infusion (ECDI-DLI) with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor-specific T cell hyporesponsiveness and a transient absence of donor-specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.

Pretransplant IgG reactivity to apoptotic cells correlates with late kidney allograft loss.

Preexisting serum antibodies have long been associated with graft loss in transplant recipients. While most studies have focused on HLA-specific antibodies, the contribution of non-HLA-reactive antibodies has been largely overlooked. We have recently characterized mAbs secreted by B cell clones derived from kidney allograft recipients with rejection that bind to apoptotic cells. Here, we assessed the presence of such antibodies in pretransplant serum from 300 kidney transplant recipients and examined their contribution to the graft outcomes. Kaplan-Meier survival analysis revealed that patients with high pretransplant IgG reactivity to apoptotic cells had a significantly increased rate of late graft loss. The effect was only apparent after approximately 1 year posttransplant. Moreover, the association between pretransplant IgG reactivity to apoptotic cells and graft loss was still significant after excluding patients with high reactivity to HLA. This reactivity was almost exclusively mediated by IgG1 and IgG3 with complement fixing and activating properties. Overall, our findings support the view that IgG reactive to apoptotic cells contribute to presensitization. Taking these antibodies into consideration alongside anti-HLA antibodies during candidate evaluation would likely improve the transplant risk assessment.

[Blood pressure variability in 24 hours in obese and non-obese adolescents with breast development 4 and 5 of Tanner's criteria]. / Variabilidad de la presión arterial en 24 horas en adolescentes obesas y no-obesas con desarrollo mamario 4 y 5 de los criterios de Tanner.

OBJECTIVE: The aim of the study was to investigate the blood pressure variability during 24 h by using ambulatory blood pressure monitoring (ABPM) in a group of obese and non-obese female adolescents with breast development status 4 and 5 of Tanner´s criteria. METHODS: A cross-sectional study was conducted at the Cardiovascular Research Institute, Mexico. All subjects underwent 24 h non-invasive ABPM recording device. Pubertal status was determined by breast development. MEASUREMENTS: office systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR). Height, weight, body mass index (BMI), waist and hip circumferences, arm circumference, waist to hip ratio (W/H), and skinfold thickness measurements: triceps, subscapular, abdominal and supraspinal. RESULTS: Fifty-nine adolescents 13-16 years old; 29 obese (BMI 31.2±4.0), and 30 non- obese (BMI 21.2±2.2). Obese vs. non-obese: Office SBP 116.9 vs. 105.9±9.3 mmHg (p<0.001); ABPM in 24 h: SBP 113.8±6.3 vs. 107.6±5.7 mmHg (p<0.001); diurnal SBP 117.3 mmHg vs. 111.2 mmHg (p<0.001); nocturnal SBP 105.5±8 vs. 99.4 mmHg; absolute variability in 24 h DBP 10.0±1.8 vs. 8.7±1.5 (p<0.003); coefficient of variation 24 h DBP 17.3±3 vs. 15.4±2.6% (p<0.05); systolic non-dipper 16 (55.2%) vs. 9 (30%) (p<0.05); pulse pressure 24 h 49.3±8 vs. 43.5±9 mmHg (p<0.01). CONCLUSION: Obese adolescents are presenting changes in BP variability during 24-h in comparison with nonobese adolescents; it also includes higher pulse pressure. Thus, these can be early indicators for the development of hypertension or other cardiovascular diseases in the adult life.

Nano and micro reoriented domains and their relation with the crystal structure in the New Fe1.5Zn1.5B7O13Cl boracite.

New iron-zinc chlorine single crystals of Fe1.5Zn1.5B7O13Cl boracite were grown by chemical transport reactions in closed quartz ampoules, at a temperature of 1173 K. The crystal structure was characterized by X-ray powder diffraction (XRD) using the Rietveld refinement method and belongs to the trigonal/rombohedral system with space group R3c (No. 161). The cell parameters were a = 8.5726(1) angstroms, c = 21.0116(4) angstroms, V = 1337.26(3) angstroms3 and Z = 6. The refinement successfully proceeded and ended with sound merit figure values chi2 = 2.25, R(B) = 6.12%. Chemical analysis was performed with X-ray energy dispersive spectroscopy (EDS) and X-ray fluorescence (XRF). Ferroelectric nano and micro reoriented domains were found in this material using polarizing optical microscopy (PLM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The examination by TEM showed that in the trigonal/rombohedral system of Fe1.5Zn1.5B7O13Cl nanodomain structures exist. Thin (50-100 nm) mostly planar domains parallel to (100) were frequently observed in Fe1.5Zn1.5B7O13Cl boracite.

First Report of Alfalfa mosaic virus Infection in Viburnum tinus in Chile.

Viburnum tinus L., commonly known as laurustinus, is an ornamental shrub that is widely used as a garden plant and flower crop. V. tinus is popular because of its desirable characteristics such as evergreen foliage, tolerance to pruning, winter blooms, and its adaptation to cold temperate zones. It is also relatively easy to grow and is commonly used as a windbreak. Infection of this ornamental species by Alfalfa mosaic virus (AMV) has been associated with yellow mottling or variegated leaf coloring, including light green and white, and has been referred to as the "Viburnum Calico" (1,4). In April 2011, at the onset of winter in the Southern Hemisphere, intense yellow spotting and mottling was observed on V. tinus leaves in the San Joaquin Campus at Pontificia Universidad Catolica de Chile. Presence of Aphis spiraecola Patch was observed on the shrubs, however, in the area it is also common to find other aphid species such as Toxoptera aurantii (Boyer de Fonscolombe) and A. fabae Scopoli. Leaf tissue samples from 10 asymptomatic and 10 symptomatic plants were examined for the presence of AMV by tissue-blot immunoassay with a commercially available polyclonal antibody (Agdia Inc., Elkhart, IN) along with the Goat affinity purified anti-rabbit IgG conjugated (Whole Molecule) (Molecular Probes, Invitrogen Corp., Carlsbad, CA). First-strand cDNA synthesis and PCR were performed with specific primers CP-AMV1 and CP-AMV2 (3). AMV was detected in all symptomatic leaves and also in two of the asymptomatic tissue analyzed by tissue blot assay. Reverse transcription (RT)-PCR produced 753-bp amplicons in all samples that were positive to AMV by tissue printing. No amplification product was observed when water control or seronegative samples were used as templates in the RT-PCR assays. Two amplicons were directly sequenced in both directions to confirm the identification of AMV in the leaf samples. The sequences obtained were homologous and BLASTN analysis of the submitted sequence (GenBank Accession No. JN040542) showed 99% nucleotide sequence identity to an AMV isolate described from Nicotiana tabacum L. (GenBank Accession No. FJ527749). These results demonstrate the presence of AMV in V. tinus in Chile. This pathogen has also been described to be affecting V. tinus in France (1) and V. lucidum Mill. in Spain (2). In Chile, V. tinum is increasingly grown as an ornamental plant. Therefore, care should be taken to ensure that the propagative materials of V. tinum are devoid of AMV infection to prevent further spread of this virus. References: (1) L. Cardin et al. Plant Dis. 90:1115, 2006. (2) M. Cebrián et al. Plant Dis. 92:1132, 2008. (3) M. Finetti-Sialer et al. J. Plant Pathol. 79:115, 1997. (4) H. E. Williams et al. Phytopathology 61:1305, 1971.