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Background: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI., Methods: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface's applicator, and WBI was administered 3-5 weeks after surgery at a total dose of 26 Gy in five consecutive days., Results: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively., Conclusions: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC.

Background: Current pathways in early diagnosis of prostate cancer (PCa) can lead to unnecessary biopsy procedures. Here, we used telomere analysis to develop and evaluate ProsTAV®, a risk model for significant PCa (Gleason score >6), with the objective of improving the PCa diagnosis pathway., Methods: This retrospective, multicentric study analyzed telomeres from patients with serum PSA 3-10 ng/mL. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate telomere-associated variables (TAVs) in peripheral blood mononucleated cells. ProsTAV® was developed by multivariate logistics regression based on three clinical variables and six TAVs. The predictive capacity and accuracy of ProsTAV® were summarized by receiver operating characteristic (ROC) curves and its clinical benefit with decision curves analysis., Results: Telomeres from 1043 patients were analyzed. The median age of the patients was 63 years, with a median PSA of 5.2 ng/mL and a percentage of significant PCa of 23.9%. A total of 874 patients were selected for model training and 169 patients for model validation. The area under the ROC curve of ProsTAV® was 0.71 (95% confidence interval [CI], 0.62-0.79), with a sensitivity of 0.90 (95% CI, 0.88-1.0) and specificity of 0.33 (95% CI, 0.24-0.40). The positive predictive value was 0.29 (95% CI, 0.21-0.37) and the negative predictive value was 0.91 (95% CI, 0.83-0.99). ProsTAV® would make it possible to avoid 33% of biopsies., Conclusions: ProsTAV®, a predictive model based on telomere analysis through TAV, could be used to increase the prediction capacity of significant PCa in patients with PSA between 3 and 10 ng/mL., (© 2023 Wiley Periodicals LLC.)

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4 + and CD8 + T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7-55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, -0.52; p < 0.001) but not in VAC-ex (rho -0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4 + and CD8 + T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4 + and CD8 + T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC 50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4 + (p = 0.82) and CD8 + (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4 + or CD8 + T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents., (© 2022 Wiley Periodicals LLC.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination., (© 2022 Wiley Periodicals LLC.)

Objectives: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes., Methods: A prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively., Results: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8 + and/or CD4 + T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4 + and CD8 + T cells, respectively., Discussion: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine preoperative factors associated to myocardial injury after non-cardiac surgery (MINS) and to develop a prediction model of MINS., Design: Retrospective analysis., Setting: Tertiary hospital in Spain., Participants: Patients aged ≥45 years undergoing major non-cardiac surgery and with at least two measures of troponin levels within the first 3 days of the postoperative period. All patients were screened for the MANAGE trial., Primary and Secondary Outcome Measures: We used multivariable logistic regression analysis to study risk factors associated with MINS and created a score predicting the preoperative risk for MINS and a nomogram to facilitate bed-side use. We used Least Absolute Shrinkage and Selection Operator method to choose the factors included in the predictive model with MINS as dependent variable. The predictive ability of the model was evaluated. Discrimination was assessed with the area under the receiver operating characteristic curve (AUC) and calibration was visually assessed using calibration plots representing deciles of predicted probability of MINS against the observed rate in each risk group and the calibration-in-the-large (CITL) and the calibration slope. We created a nomogram to facilitate obtaining risk estimates for patients at pre-anaesthesia evaluation., Results: Our cohort included 3633 patients recruited from 9 September 2014 to 17 July 2017. The incidence of MINS was 9%. Preoperative risk factors that increased the risk of MINS were age, American Status Anaesthesiology classification and vascular surgery. The predictive model showed good performance in terms of discrimination (AUC=0.720; 95% CI: 0.69 to 0.75) and calibration slope=1.043 (95% CI: 0.90 to 1.18) and CITL=0.00 (95% CI: -0.12 to 0.12)., Conclusions: Our predictive model based on routinely preoperative information is highly affordable and might be a useful tool to identify moderate-high risk patients before surgery. However, external validation is needed before implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We have reviewed a considerable amount of recent scientific papers relating inflammation caused by air pollution with chronic and severe medical conditions. Furthermore, there are evidences relating organ inflammation caused by not only outdoor long-term but also short-term inhaled radioisotopes contained in high polluted air or in household natural radioactive background aerosols, in addition to SARS-COV-2 attached to bioaerosols, which are related with a worst evolution of severe acute respiratory syndrome patients. Reactive oxygen species (ROS) production induced by the interaction with environmental ionizing radiation contained in pollution is pointed out as a critical mechanism that predispose mainly to elder population, but not excluding young subjects, presenting previous chronic conditions of lung inflammation or neuroinflammation, which can lead to the most serious consequences., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Age is one of the most important prognostic factors associated to lethality in SARS-CoV-2 infection. In multivariate analysis, advanced age was an independent risk factor for death. Recent studies suggest a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis in SARS-CoV and SARS-CoV-2 infections. Increased NLRP3/ apoptosis-associated speck-like protein (ASC) mRNA expression and increased caspase-1 activity, have been observed in aged lung, provoking increased and heightened expression levels of mature Interleukin (IL)-1β and IL-18 in aged individuals. Aged individuals have a basal predisposition to over-react to infection, displaying an increased hyper-inflammatory cascade, that seems not to be fully physiologically controlled. NLRP3 inflammasome is over-activated in aged individuals, through deficient mitochondrial functioning, increased mitochondrial Reactive Oxigen Species (mtROS) and/or mitochondrial (mt)DNA, leading to a hyper-response of classically activated macrophages and subsequent increases in IL-1 β. This NLRP3 over-activated status in elderly individuals, is also observed in telomere dysfunctional mice models. In our opinion, the NLRP3 inflammasome plays a central role in the increased lethality observed in elderly patients infected by COVID-19. Strategies blocking inflammasome would deserve to be studied., Competing Interests: Conflict of Interest Authors declares no conflict of interest., (Copyright: © 2020 Lara et al.)

The COVID-19 pandemia is affecting people worldwide. Most of the patients suffered of a respiratory disease that will progress to an acute respiratory distress syndrome (ARDS). SARS-CoV-2 pneumonia severely ill patients, develop a systemic inflammatory response with a Cytokine Release Syndrome (CRS), that is characterized by a sudden increase in several pro-inflammatory cytokines, mainly IL-1, IL-6 and TNF-alfa by activated macrophages (M1 phenotype). Blocking IL-6 with tocilizumab and using respirator equipment seems to be a very important issue in this (SARS-CoV-2) pneumonia, but not all patients are referred to such treatments. Low dose radiotherapy (0,5 Gy), is an evidence-based anti-inflammatory treatment, that could modify the immune landscape in the lung affected of SARS-CoV-2 pneumonia, through macrophages polarization to alternatively activated Macrophages (M2 phenotype). Radiation-induced cancer risk could be assumed due to the very low dose used, the advanced age of the patients and the life-threatening condition of SARS-Cov2 pneumonia. LDRT is a cost-effective non-toxic treatment already available in most general hospitals. This fact allows that it would be used for the large number of patients that will suffer this disease, and that would not receive specific anti-IL-6 treatments in ICUs in low and middle income countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Breast cancer is the most common cancer pathology in women in the Western world. The median age at diagnosis is 60 years and in the coming decades it is estimated that the number of elderly women affected reaches an important percentage. This aging of the cancer population, associated with its inherent comorbidities and aggravated by the lack of consensus about the most appropriate treatment, make it difficult to administer an effective postoperative treatment in elderly women with a low-risk profile. An exhaustive geriatric evaluation is a sine qua non condition to opt for a specific type of treatment. To date, several options are available such as endocrine therapy (ET) alone, moderate/high hypofractionation and various accelerated partial breast irradiation (APBI) techniques. In this article, we provide information about each of them., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.08.38). The series “Radiotherapy for Breast Cancer in Advanced Age” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Breast cancer (BC) is the principal cause of cancer-related death in women. Metastatic patients are usually treated with a systemic therapy, but clinical results are limited. Oligometastatic subjects can benefit from high-precision radiotherapy techniques to potentially achieve a complete response. Currently, there is limited evidence of stereotactic ablative radiotherapy (SABR) treatments in elderly oligometastatic cancer patients. A review of the medical literature was performed in PubMed database to assess the current role of SABR in the treatment of breast oligometastases in elderly patients. SABR represents a feasible and safe therapeutic approach in oligometastatic elderly BC patients. Further studies are required to establish the optimum patient selection and treatment scheme., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.08.29). The series “Radiotherapy for Breast Cancer in Advanced Age” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2020 Translational Cancer Research. All rights reserved.)

Objectives: To move towards a more standardized approach in clinical practice to manage patients with castration-resistant prostate cancer (CRPC) in Spain., Methods: A panel of 18 Spanish experts in Urology with expertise managing CRPC followed a modified Delphi process with two rounds and a final face-to-face consensus meeting. The panel considered a total of 106 clinical questions divided into the following 6 sections: definition of CRPC, diagnosis of metastases by imaging techniques, symptoms of CRPC, progression of CRPC, M0 and M1 management and therapeutic sequencing., Results: A bone scan (BS) is recommended at diagnosis, at the onset of bone pain, and depending on PSA levels, but it is not sensitive enough to confirm or exclude bone metastases if there is bone pain. Whole-body MRI and axial MRI are more sensitive than BS and plain X-rays, but more expensive, so they have to be used in certain situations. There is CRPC progression when there is radiologic, clinical or confirmed PSA progression. Flare phenomenon appears in treatment with taxanes and abiraterone. It was agreed that in M0 CRPC patients no drug treatment is currently recommended, although in M1 CRPC patients the first-line therapy would be mainly enzalutamide/abiraterone and/or docetaxel, depending on the symptom burden., Conclusion: After the consensus, we provide a series of recommendations for Spanish physicians treating CRPC to address the disease characteristics,how to tailor patient management decisions, the use of imaging techniques, and how to handle disease progression appropriately to improve patients' quality of life.

Background: Evidence that periodontal disease is a possible risk factor for cognitive impairment may be explained by the inflammatory hypothesis. The aim of this study is to determine whether periodontitis is related to the amyloid β (Aβ) load in blood and the role of any such relationship in the association between Aβ and cognitive impairment., Methods: A case-control study was performed in elderly people diagnosed with cognitive impairment with or without dementia (cases group) and cognitively healthy elderly people (control group); data were collected on the medical and dental history of participants, and blood samples were drawn to determine Aβ levels using enzyme-linked immunosorbent assay., Results: The study included 166 patients and 122 control participants. Higher blood Aβ 1-42 levels (P = 0.01) and higher Aβ 42:40 ratio (P = 0.06) were observed in participants with severe attachment loss than in other participants. Periodontitis was a significant interaction variable, given that the association between Aβ 1-42 and Aβ 1-40 and cognitive impairment was only observed in patients with severe periodontitis. According to these data, periodontitis may be a modulating variable of the association between Aβ and cognitive impairment., Conclusions: Plasma Aβ 1-42 levels are higher in individuals who have severe periodontal disease. The presence of periodontitis may modify the association between Aβ and cognitive impairment.

Due to phylogenetic proximity to the human, zebrafish has been recognized as a reliable model to study Alzheimer's disease (AD) and other central nervous system disorders. Furthermore, metabotropic glutamate receptors have been previously reported to be impaired in brain from AD patients. Metabotropic glutamate 5 (mGlu 5 ) receptors are G-protein coupled receptors proposed as potential targets for therapy of different neurodegenerative disorders. Thus, MPEP (2-methyl-6-(phenylethynyl)pyridine hydrochloride), a selective noncompetitive mGlu 5 receptor antagonist, has been suggested for pharmacological treatment of AD. The aim of the present work was to quantify mGlu 5 receptors in brain from zebrafish and to study the possible modulation of these receptors by MPEP treatment. To this end, radioligand binding assay and open field test were used. Results showed a slightly higher presence of mGlu 5 receptors in brain from male than in that from female zebrafish. However, a significant increase of mGlu 5 receptor in male without variation in female was observed after MPEP treatment. This gender specific response was also observed in locomotor behavior, being significantly decreased only in male zebrafish. These results confirm the presence of mGlu 5 receptors in brain from zebrafish and their gender specific modulation by selective antagonist treatment and suggest a role of these receptors on locomotor activity, which is affected in many disorders. In addition, our data point to zebrafish as a useful model to study mGlu receptor function in both healthy and pathological conditions.

Synovial sarcoma (SS) is a high-grade, rare variant of soft tissue sarcoma (STS). The biphasic subtype is less common than the monophasic subtype. SS is very common around joint cavities in the extremities, but can be present elsewhere in the body. Tumor staging and therapeutic management are usually clear for a localized disease, but the proper management at the metastatic stage can be unclear. According to the literature, the histologic presence of an SS tumor thrombus affects tumor staging, making it unclear whether the tumor stage corresponds to localized or metastatic disease. An intravascular SS tumor exhibiting high metastatic potential is a rare finding that warrants thorough investigation. A 49-year-old woman presented with a biphasic SS intravascular tumor of the left inguinal area with femoral vessels involvement. Ten cases of intravascular SS have been reported in the literature and contain little information regarding the proper management of a local metastatic disease. Ours is a rare case of SS with an intravascular tumor occupying the femoral-iliac vein (as seen in metastatic disease) that has been treated as a local disease with a multidisciplinary therapeutic approach. As a result, our patient has been disease-free for two years and, during that time, has achieved an acceptable quality of life. We discuss the pertinent clinical findings of this rare tumor and review the literature of tumor thrombus by SS. We also present the multidisciplinary therapeutic approach realized and the history of this disease.

Night shift work has been classified as a probable human carcinogen based on experimental studies and limited human evidence on breast cancer. Evidence on other common cancers, such as prostate cancer, is scarce. Chronotype is an individual characteristic that may relate to night work adaptation. We evaluated night shift work with relation to prostate cancer, taking into account chronotype and disease severity in a population based case-control study in Spain. We included 1,095 prostate cancer cases and 1,388 randomly selected population controls. We collected detailed information on shift schedules (permanent vs. rotating, time schedules, duration, frequency), using lifetime occupational history. Sociodemographic and lifestyle factors were assessed by face-to-face interviews and chronotype through a validated questionnaire. We used unconditional logistic regression analysis adjusting for potential confounders. Subjects who had worked at least for one year in night shift work had a slightly higher prostate cancer risk [Odds Ratio (OR) 1.14; 95%CI 0.94, 1.37] compared with never night workers; this risk increased with longer duration of exposure (≥ 28 years: OR 1.37; 95%CI 1.05, 1.81; p-trend = 0.047). Risks were more pronounced for high risk tumors [D'Amico classification, Relative Risk Ratio (RRR) 1.40; 95%CI 1.05, 1.86], particularly among subjects with longer duration of exposure (≥28 years: RRR 1.63; 95%CI 1.08, 2.45; p-trend = 0.027). Overall risk was higher among subjects with an evening chronotype, but also increased in morning chronotypes after long-term night work. In this large population based study, we found an association between night shift work and prostate cancer particularly for tumors with worse prognosis., (© 2014 UICC.)

Argania spinosa is an example of an avoider tree growing under semi-arid conditions in Morocco. To assess what are the physiological strategies of this species, different variables were measured through an annual cycle in two populations located in the species' main distribution area. Results show the expected decrease of leaf water potential (psi) with an increase of water-use efficiency (A/gs) with the onset of the dry season. In summer, leaf conductance (g(s)) was sensitive to vapour pressure deficit (VPD), and stomatal closure occurred over 30 mbar of VPD. Surprisingly, carbon isotope discrimination (delta13C) maintained very low values over the year, with almost no relationship with any physiological or morphological variable. Hence Argania spinosa presents a complex set of mechanisms to avoid water deficit, but delta13C cannot be used as an ecological tracer of long term WUE.

Zebrafish is rapidly emerging as a promising model organism to study various central nervous system (CNS) disorders, including Alzheimer's disease (AD). AD is the main cause of dementia in the human population and there is an urgency to understand the causes of this neurodegenerative disease. In this respect, the development of new animal models to study the underlying neurodegenerative mechanisms of AD is an urgent need. In this review we analyze the current situation in the use of zebrafish as a model for AD, discussing the reasons to use this experimental paradigm in CNS investigation and analyzing the several strategies adopted to induce an AD-like pathology in zebrafish. We discuss the strategies of performing interventions to cause damage in the zebrafish brain by altering the major neurotransmitter systems (such as cholinergic, glutamatergic or GABAergic circuits). We also analyze the several transgenic zebrafish constructed for the AD study, discussing both the familial-AD models based on APP processing pathway (APP and presenilins) and in the TAU hyperphosphorylation, together with the genes involved in sporadic-AD, as apolipoprotein E. We conclude that zebrafish is in a preliminary stage of development in the AD field, and that the transgenic animals must be improved to use this fish as an optimal model for AD research. Furthermore, a deeper knowledge of the zebrafish brain and a better characterization of the injury caused by alterations in the major neurotransmitter systems are needed.

The present study was conducted to investigate the tolerance of Spartina densiflora to phenanthrene, and to test its ability in phenanthrene dissipation. A glasshouse experiment was designed to investigate the effect of phenanthrene from 0 to 1000 mg kg(-1) on growth and photosynthetic apparatus of S. densiflora by measuring chlorophyll fluorescence parameters, gas exchange and photosynthetic pigments. We also performed chemical analysis of plant samples, and determined the concentration of phenanthrene remaining in soil. S. densiflora survived to concentrations as high as 1000 mg kg(-1) phenanthrene in soil; in fact, there was no significant difference in RGR among the treatments after 30 days. Otherwise, phenanthrene affected photosynthetic apparatus at 100 and 1000 mg kg(-1); thus, the lower ΦPSII could be explained by the declined photosynthetic pigment concentrations. Soil extraction indicated a more marked rate of phenanthrene disappearance in the soil in the presence of S. densiflora., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The Andean Health Organization has been responsible for the coordination and evaluation of the malaria rapid diagnostic test strategy. This undertaking was organized to strengthen the malaria diagnostic capacity in ten provinces of Colombia., Objective: The implementation cycle of malaria rapid diagnostic tests was evaluated, along with its impact, performance, usage and coverage under the project "Malaria control in bordering areas of the Andean Region: a community cpproach" (PAMAFRO), as an integral part of the malaria control strategy., Materials and Methods: A descriptive retrospective study was organized in two stages. The first stage was an evaluation of the implementation of the rapid diagnostic test cycle. The second stage evaluated indicators of impact, performance, usage and coverage of this strategy. These evaluations were conducted from October 2007 to July 2008 in 10 Andean provinces of Colombia. A multi-criteria scoring method was applied to determine the critical variables., Results: The compliance in the implementation cycle for rapid diagnostic tests was 71%. Planning was the weakest component of the cycle with 50% of the goals accomplished. The critical variables with low compliance were as follows: study of rapid diagnostic test needs in the country (50%), study of rapid diagnostic test needs in each province (50%), rapid diagnostic test distribution according to needs (50%), assessment of health workers performance (50%), compliance with temperature and humidity requirements for storage of the rapid diagnostic tests at the provincial level (50%), logistics (67%) and supervision (25%)., Conclusion: Implementation strategies are important to strengthen the critical variables found asociated with low compliance.

Traditional studies of viral and bacterial infection and pathogenesis have generally relied on animal models that require the sacrifice of infected animals to determine viral or bacterial distributions and titers. The recent application of the in vivo bioluminescence imaging (BLI) to monitor the replication and tropism of pathogens expressing the luciferase (from firefly or Renilla) reporter proteins has been recently developed. This technology do not requires the sacrifice of the experimental animals, where the in vivo bioluminescence emissions in living animals permit the tracking of the infection. It has been demonstrated that the in vivo BLI is comparable to the classical approaches as measurements of in vitro light emission in organs of sacrificed animals. Moreover, molecular techniques such as PCR determinations show parallel results in pathogen quantification, where the concentrations of microbial DNA measured correlated with the magnitude of bioluminescence in vivo, and with the photon flux determined by the in vitro luciferase enzyme assay. These results show that BLI can be used for noninvasive, real-time monitoring of several infections of pathogens in living animals, supplying a new methodology in the study of pathogens in addition to conventional techniques for the characterization of infections.

Introduction: Ancient bone remains constitute an important source of biological information, and their genetic characterization allows the confirmation or rebuttal of human affiliations proposed on the basis of non-molecular approaches. Pre-Columbian history of the Eastern Andes in Colombia has been divided into three main periods: (i) an early colonization by groups of hunter-gatherers, (ii) an intermediate period "Herrera" characterized by primitive agriculture and (iii) a late stage of Chibcha-speaking groups, with agriculture and ceramics ("agroalfarero")., Objective: The mitochondrial DNA on ancient bone remains of the Herrera period were analyzed for comparison with modern and other ancient DNAs., Materials and Methods: Mitochondrial DNA was extracted from 11 Herrera individuals [approximately 2,000 years before present (YBP)] found in the Madrid 2-41 archaeological site near Bogotá, Colombia. A 192 bp segment of the hypervariable segment I was amplified and sequenced, following stringent archaic DNA authenticity criteria. The sequences were compared with those in American and European databases using bioinformatics tools., Results: All individuals had identical sequences and were classified as haplogroup B. This identity may be related to the type of ritual burial performed in the site, probably exclusively for members of a hierarchically important family of the ancient Herrera society. The search for homologous sequences in the American and European mtDNA data bases produced no identical coincidences, although a Brazilian Amazonic individual (approximately 4,000 YBP) was recorded with a matching sequence., Conclusion: Individuals buried in the Madrid 2-41 site were maternally closely related and showed a mtDNA sequence that is apparently absent in contemporary populations.

Introduction: To increase the accessibility of malaria diagnosis, the Instituto Nacional de Salud de Colombia undertook a field trial to evaluate the sensitivity and specificity of two rapid diagnostic tests., Objective: The sensitivity, specificity and concordance was compared for two rapid diagnostic tests for malaria, NOW ICT Malaria Pf/Pv and OptiMAL., Materials and Methods: A descriptive and concordance study was performed with 214 patients in the southwestern coastal city of Tumaco, Colombia, each of whom presented at least one of the symptoms of the classical malaria triad. Two strategies were applied for patient recruitment-one by passive search and a second through local health brigades., Results: NOW ICT showed a general sensitivity of 98.4% (95%CI: 90.3-99.9), and a general specificity of 98.0% (95%CI: 93.9-99.5). For Plasmodium falciparum, the sensitivity was 98.2% (95%CI: 89.4-99.9) and the specificity 98.1% (95%CI: 94.1-99.5). The sensitivity was lower (80.0%) when parasitemia ranged from 200 to 4,000 parasites/microl. The sensitivity and specificity of the NOW ICT for P. vivax malaria were 100%. The sensitivity for this test was not affected for the established ranges of parasitemia for P. vivax. The overall figures for OptiMAL were 95.2% (95%CI: 85.8-98.8) sensitivity and 99.3% (95%CI: 95.8-100.0) specificity. For P. falciparum malaria OptiMAL showed 94.7% (95%CI: 84.5-98.6) sensitivity and 99.4% (95%CI: 96.0-100.0) specificity. The sensitivity was lower (60.0%) when samples with 200-4,000 parasites/microl were tested. For P. vivax, OptiMAL presented a 66.7% (95%CI: 24.1-94.0) sensitivity, which diminished to 50% with a parasitemia between 300-2.500 parasites/microL., Conclusions: Good results for sensitivity and specificity were obtained for malaria diagnosis using NOW ICT and OptiMAL, with NOW ICT showing higher sensitivity and specificity values than OptiMAL.

Disseminated herpes simplex virus type 1 (HSV-1) infection during pregnancy is poorly described even though it is associated with high maternal and fetal morbidity and neonatal mortality in humans. In a previous paper using mice as a model, the authors demonstrated that HSV-1 is transmitted hematogenously from mother to offspring, the virus colonizing the central nervous system and provoking high mortality. In the present study, viral DNA levels in latently infected mothers were investigated during pregnancy and after delivery in mice. Samples from different organs were obtained before gestation (latency), three times during pregnancy (17, 4.5, and 1 day before delivery), and four times after delivery (1 day, 1 week, 1 and 2 months). A dramatic decrease in viral DNA concentration was observed during pregnancy, especially in the nervous system, with postnatal recovery to latent levels. All the brain regions studied showed similar trends. The viral copy numbers detected in mothers at delivery +1 day were independent of viral inoculum size. The spread of the virus to the above organs was examined immunohistochemically and, in general, more intense viral staining was observed after delivery in each. Because immunoglobulin levels can be modified by infections during pregnancy, the authors examined the levels of specific HSV-1 antibodies. Variation in HSV-1 DNA concentration was found to be associated with changes in the full spectrum of immunoglobulins (but especially immunoglobulin M [IgM]) over pregnancy, whereas at delivery -1 day a significant inverse relationship between immunoglobulins and HSV-1 DNA was observed. IgGs provided protection during the postnatal phase.

Herpes simplex virus type 1 (HSV-1) expresses an immediate-early protein, ICP47, that blocks the major histocompatibility complex class I antigen presentation pathway by binding to the transporter associated with antigen presentation (TAP). The result is the virus' evasion of the immune system. Although the interaction between ICP47 and TAP has been examined in vitro, this paper is the first to report their interaction in vivo. In C57BL/6 adult female mice, ICP47-defective virus (Delta ICP47, F strain) was less able to invade the organs studied than was wild-type HSV-1 F strain, showing that ICP47 influences general invasiveness. However, the neuroinvasiveness of the Delta ICP47 virus was recovered in TAP-deficient mice, indicating that the TAP-ICP47 interaction is specific to neural tissues. HSV-1 F strain showed no significant differences in their invasiveness in TAP-deficient and wild-type mice. Therefore, although ICP47 appears to be essential for invasion, the presence of TAP appears not to be crucial. Western blotting showed TAP1 expression to increase by at least fourfold in the brains and adrenal glands of infected mice. This suggests that TAP plays an important role in the host defense system. This increased expression may be particularly important in the encephalon since the baseline protein levels of this organ are low (ratio adrenal protein level/encephalon protein level > 100). However, Delta ICP47 virus provoked no significant increase in the brain TAP1 levels of wild-type mice because it could not invade this organ. These results suggest that ICP47 plays a role in infection, and that TAP1 production is regulated during viral challenge.

Traditional studies on viral neuroinvasiveness and pathogenesis have generally relied on murine models that require the sacrifice of infected animals to determine viral distributions and titers. The present paper reports the use of in vivo bioluminescence imaging to monitor the replication and tropism of KOS strain HSV-1 viruses expressing the firefly luciferase reporter protein in hematogenously infected mice. Following intraperitoneal injection, a comparison was made between real-time PCR determinations of HSV-1 DNA concentrations (requiring the sacrifice of the experimental animals) and in vivo bioluminescence emissions in living animals. For further comparison, in vitro light emission was also measured in the ovaries and adrenal glands of sacrificed mice. After infection, HSV-1 spread preferentially to the ovaries and adrenal glands (these organs showed the highest virus levels). Both the PCR and bioluminescence methods detected low viral loads in the nervous system, where the virus was restricted to the spinal cord. The concentrations of viral DNA measured correlated with the magnitude of bioluminescence in vivo, and with the photon flux determined by the in vitro luciferase enzyme assay. The results show that bioluminescence imaging can be used for non-invasive, real-time monitoring of HSV-1 hematogenous infection in living mice, but that coupling this methodology with conventional techniques aids in the characterization of the infection.

The aim of this study was to discuss the relevance of the Epstein-Barr virus (EBV) in the nasopharyngeal carcinoma (NPC), analyzing the variations of several molecules potentially involved in the pathogenesis of this cancer. EBV was detected in all the NPC samples by several techniques including PCR, in situ hybridization, and immunohistochemical methodologies. CD21 membrane receptor was absent after EBV infection, being a differential morphological feature of the tumoral cells. Latent membrane protein-1 (LMP1), an oncogenic viral product, was detected in a high percentage of samples, supporting a role for EBV in the pathogenesis of NPC. Bcl-2, an anti-apoptotic protein up-regulated by LMP1, was also overexpressed, coinciding with the majority of samples positive for LMP1. Finally, p53 presented abnormalities only in a low percentage of samples. These results reinforce the role of the EBV in the NPC discussing several potential mechanisms of pathogenesis in this neoplasia.

The mummy studied belonged to the prehispanic Guane society. According to the Mom 003 record of the Archaeological Museum of the House of the Marqués de San Jorge, it was found in a cave in the department of Santander, Colombia, and was donated to the Culture Promotion Fund of the Banco Popular more than 30 years ago. The gender of the mummy had been previously determined by PCR study of the Y chromosome; computerized tomography studies (CT) were carried out and samples of lung tissue, vertebral spine and skin were taken for studying tuberculosis. The CT scans clearly show the presence of spinal tuberculosis, accounting for its important angular cifosis or Pott's disease. DNA obtained from lung tissue was submitted to ribotyping with genes of the 16S ribosomal subunit, giving positive results. This finding demonstrates the presence of tuberculosis in prehispanic Colombia.

The objective of this study was to analyse the relationships between the Epstein-Barr virus (EBV) infection and the molecular abnormalities of the p53 oncoprotein in the nasopharyngeal carcinoma (NPC). Fifty-five NPC paraffin samples from a group of Spanish patients with EBV demonstrated presence by nested-PCR and non-isotopic in situ hybridisation, were analysed for p53 expression using immunohistochemistry. The positive samples by immunohistochemistry were studied for p53 gene alterations in the exon 5 by single strand conformation polymorphism (SSCP). Among the 55 specimens, 14 (25.5%) showed expression of p53 protein. All these positive samples corresponded to the late stage of the tumour. Of the 14 samples, p53 gene alterations were found only in three cases using SSCP. These results indicate that the p53 mutations are an infrequent event in NPC in Spanish patients needing exogenous factors as the EBV infection for the development of this malignancy.

Purpose: To electrophysiologically characterize alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptors in chick retinal membrane fragments, incorporated into Xenopus oocytes by direct microinjection., Methods: A 6-day retinal membrane suspension was injected into Xenopus oocytes by use of an electronic nanoliter injector. Fifteen to 40 hours after injection, the oocytes were assayed for kainate-elicited inward currents, under voltage-clamp conditions (membrane potential held at -70 mV). The structural incorporation of the retinal membrane fragments into the oocyte membrane was verified by specific immunofluorescent staining., Results: Chick retinal membrane fragments were efficiently grafted onto Xenopus oocytes after microinjection, with 22.9% +/- 7.6% of the oocyte membrane being stained with anti-chick retina antibody. Part of the retinal material was seen as patches of relatively uniform size (292.1 +/- 72.3 microm(2)). Bath-applied kainate induced dose-dependent (EC(50): 64 +/- 7 microM), nondesensitizing inward currents (15-90 nA) in the chimeric Xenopus oocytes. Sham-injected oocytes did not respond to kainate. Kainate-driven currents were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 1-(4-aminopropyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), but not by gamma-D-glutamylaminomethyl sulfonic acid (GAMS) or aminophosphonoheptanoate (AP7), suggesting the involvement of AMPA receptors in the observed responses. Guanine nucleotides (GNs) also blocked kainate currents in a concentration-dependent manner., Conclusions: An alternative oocyte microinjection technique to analyze the electrophysiological properties of glutamate receptors in chick retinal membranes is described. The results show the functional activity of putative AMPA-preferring receptors from chick retina and confirm, in the chick retinal model, the antagonistic behavior of guanine nucleotides toward glutamate receptors and their potential role as neuroprotective agents under excitotoxic conditions.