Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes.

PURPOSE: To report oncologic outcomes of patients undergoing salvage cryotherapy (SCT) for local recurrence of prostate cancer (PCa) and to establish a nadir PSA (nPSA) value that best defines long-term oncologic success. METHODS: Retrospective study of men who underwent SCT for local recurrence of PCa between 2008 and 2020. SCT was performed in men with biochemical recurrence (BCR), after primary treatment and with biopsy-proven PCa local recurrence. Survival analysis with Kaplan-Meier and Cox models was performed. We determined the optimal cutoff nPSA value after SCT that best classifies patients depending on prognosis. RESULTS: Seventy-seven men who underwent SCT were included. Survival analysis showed a 5-year biochemical recurrence-free survival (BRFS), androgen deprivation therapy-free survival (AFS), and metastasis-free survival (MFS) after SCT of 48.4%, 62% and 81.3% respectively. On multivariable analysis for perioperative variables associated with BCR, initial ISUP, pre-SCT PSA, pre-SCT prostate volume and post-SCT nPSA emerged as variables associated with BCR. The cutoff analysis revealed an nPSA < 0.5 ng/ml to be the optimal threshold that best defines success after SCT. 5-year BRFS for patients achieving an nPSA < 0.5 vs nPSA ≥ 0.5 was 64% and 9.5% respectively (p < 0.001). 5-year AFS for men with nPSA < 0.5 vs ≥ 0.5 was 81.2% and 12.2% (p < 0.001). Improved 5-year MFS for patients who achieved nPSA < 0.5 was also obtained (89.6% vs 60%, p = 0.003). CONCLUSION: SCT is a feasible rescue alternative for the local recurrence of PCa. Achieving an nPSA < 0.5 ng/ml after SCT is associated with higher long-term BRFS, AFS and MFS rates.

Genetic dissection of tomato rootstock effects on scion traits under moderate salinity.

KEY MESSAGE: Rootstock HKT1 genotype affected fruit [Na(+)] and non-commercial fruit yield; QTL analysis of rootstock-mediated scion nutrition is a powerful forward genetic approach to identify wild genes for rootstock breeding. The present study approaches the QTL dissection of rootstock effects on a commercial hybrid variety grafted on a population of RILs derived from Solanum pimpinellifolium, genotyped for 4370 segregating SNPs from the SolCAP tomato panel and grown under moderate salinity. Results are compared to those previously obtained under high salinity. The most likely functional candidate genes controlling the scion [Na(+)] were rootstock HKT1;1 and HKT1;2 as it was previously reported for non-grafted genotypes. The higher fruit [Na(+)] found when rootstock genotype was homozygote for SpHKT1 supports the thesis that scion HKT1 is loading Na(+) into the phloem sap in leaves and unloading it in sink organs. A significant increment of small, mostly seedless, fruits was found associated with SlHKT1 homozygous rootstocks. Just grafting increased the incidence of blossom end rot and delayed fruit maturation but there were rootstock RILs that increased commercial fruit yield under moderate salinity. The heritability and number of QTLs involved were lower and different than those found under high salinity. Four large contributing (>17%) rootstock QTLs, controlling the leaf concentrations of B, K, Mg and Mo were detected whose 2 Mbp physical intervals contained B, K, Mg and Mo transporter-coding genes, respectively. Since a minimum of 3 QTLs (two of them coincident with leaf K and Ca QTLs) were also found governing rootstock-mediated soluble-solids content of the fruit under moderate salinity, grafting desirable crop varieties on stress-tolerant rootstocks tenders an opportunity to increase both salt tolerance and quality.

Eating through time: Understanding dietary practices across late prehistory in the northeastern Iberian Peninsula.

OBJECTIVE: This study seeks to contribute to the current understanding of dietary variation in the late Prehistory of the northeastern Iberian Peninsula by examining buccal dental microwear patterns alongside archeological data from the same populations. MATERIALS AND METHODS: Teeth from 84 adult individuals from eight distinct samples spanning the Middle-Late Neolithic to the Middle Bronze Age (Cova de l'Avi, Cova de Can Sadurní, Cova de la Guineu, Cova Foradada, Cova del Trader, Roc de les Orenetes, Cova del Gegant, Cova dels Galls Carboners) were analyzed using optical microscopy to examine buccal dental microwear patterns. RESULTS: The analysis did not reveal clear chronological contrasts in the dietary habits of these samples. Nevertheless, significant differences emerged among the samples, leading to their classification into two distinct sets based on the abrasiveness of the diet informed by the microwear patterns. These findings offer similarities and differences among samples in the Iberian Peninsula, shedding light on the diverse lifestyles of these individuals. DISCUSSION: Integrating our new results with other available proxies points to a multifaceted specialization in dietary patterns among these samples, influenced by factors such as habitat, resource selection, and available technology. By contextualizing the results within the broader context of the Iberian Peninsula, this research discerns shared characteristics and distinctive adaptations in the dietary practices and subsistence strategies of these groups. Ultimately, this study contributes to a deeper understanding of the intricate interplay between culture and environment in shaping human diets throughout late Prehistory.

The Early-Middle Pleistocene environmental and climatic change and the human expansion in Western Europe: A case study with small vertebrates (Gran Dolina, Atapuerca, Spain).

The dispersal of hominins may have been favored by the opening of the landscape during the Early-Middle Pleistocene transition (EMP) in Western Europe. The structure of the small-vertebrate assemblages of the archaeo-paleontological karstic site of Gran Dolina in Atapuerca (Burgos, Spain) shows important environmental and climatic changes in the faunal succession, across the Matuyama-Brunhes boundary at 780 ka. These changes are interpreted to indicate impoverishment of the forests, along with an increase in dry meadows, and open lands in general that entailed a tendency towards the loss of diversity in small-vertebrate communities above the EMP. We evaluate variation in diversity of the faunal succession of Gran Dolina using Shannon's Second Theorem as an index of ecosystem structure. The long cultural-stratigraphic sequence of Gran Dolina during the EMP is somewhat similar in its completeness and continuity to that in the locality of Gesher Benot Ya'aqov in the Upper Jordan Valley. We also evaluate related data including faunal and floral (pollen) succession. Both localities present cold, dry and humid, warm fluctuations at the transition between the Early and the Middle Pleistocene. Comparisons between these sites present opportunities to understand large-scale climatic changes.

Genetic analysis of physiological components of salt tolerance conferred by Solanum rootstocks. What is the rootstock doing for the scion?

Grafting desirable crop varieties on stress-tolerant rootstocks provides an opportunity to increase crop salt tolerance. Here, a commercial hybrid tomato variety was grafted on two populations of recombinant inbred lines developed from a salt-sensitive genotype of Solanum lycopersicum var. cerasiforme, as female parent, and two salt-tolerant lines, as male parents, from S. pimpinellifolium, the P population, and S. cheesmaniae, the C population, to identify an easy screening method for identifying rootstocks conferring salt tolerance in terms of fruit yield. Potential physiological components of salt tolerance were assessed in the scion: leaf biomass, [Na(+)], nutrition, water relations and xylem ABA concentration. A significant correlation between scion fruit yield and scion leaf fresh weight, water potential or the ABA concentration was found in the C population under salinity, but the only detected QTL did not support this relationship. The rootstocks of the P population clearly affected seven traits related to the sodium, phosphorous and copper concentrations and water content of the scion leaf, showing heritability estimates around 0.4 or higher. According to heritability estimates in the P population, up to five QTLs were detected per trait. QTLs contributing over 15% to the total variance were found for P and Cu concentrations and water content of the scion leaf, and the proportion of fresh root weight. Correlation and QTL analysis suggests that rootstock-mediated improvement of fruit yield in the P population under salinity is mainly explained by the rootstock's ability to minimise perturbations in scion water status.

A hominid from the lower Pleistocene of Atapuerca, Spain: possible ancestor to Neandertals and modern humans.

Human fossil remains recovered from the TD6 level (Aurora stratum) of the lower Pleistocene cave site of Gran Dolina, Sierra de Atapuerca, Spain, exhibit a unique combination of cranial, mandibular, and dental traits and are suggested as a new species of Homo-H. antecessor sp. nov. The fully modern midfacial morphology of the fossils antedates other evidence of this feature by about 650, 000 years. The midfacial and subnasal morphology of modern humans may be a retention of a juvenile pattern that was not yet present in H. ergaster. Homo antecessor may represent the last common ancestor for Neandertals and modern humans.

Size variation in Middle Pleistocene humans.

It has been suggested that European Middle Pleistocene humans, Neandertals, and prehistoric modern humans had a greater sexual dimorphism than modern humans. Analysis of body size variation and cranial capacity variation in the large sample from the Sima de los Huesos site in Spain showed instead that the sexual dimorphism is comparable in Middle Pleistocene and modern populations.

Lower Pleistocene hominids and artifacts from Atapuerca-TD6 (Spain)

Human remains dating to more than 780,000 years ago are associated with a rich faunal and lithic assemblage in the Pleistocene cave site of Gran Dolina (TD), Sierra de Atapuerca, Burgos, Spain. The micromammal species represent the late Biharian (Mimomys savini zone), and the lithic objects represent pre-Acheulean technology (Mode 1) and comes from the TD6 level below the Matuyama-Brunhes boundary. The Gran Dolina hominid fossils cannot be comfortably accommodated in any of the defined Homo species. They could be considered a primitive form of Homo heidelbergensis, but a new species might be named in the future if the sample is enlarged. The new human fossil evidence demonstrates that Western Europe was settled at least since the late early Pleistocene.

Coprology of Panthera tigris altaica and Felis bengalensis euptilurus from the Russian Far East.

Fecal samples from the Siberian tiger (Panthera tigris altaica) and the Amur cat (Felis bengalensis euptilurus) from Far Eastern Russia, were examined for parasites. A natural sedimentation methodology was used and a complete examination of all the sediment was performed. This fecal investigation allowed us to isolate and identify several developmental stages of gastrointestinal, hepatic, and respiratory parasites. Five parasites were found from P. t. altaica: 11 trematodes (Platynosomum fastosum) and 4 nematodes (Strongyloides sp., Ancylostomatidae, Toxascaris leonina, and Toxocara cati). Five parasites were found from F. b. euptilurus: 1 cestode (Diplopylidium sp.) and 4 nematodes (Trichuris sp., Ancylostomatidae, Toxascaris leonina, and Aelurostrongylus abstrusus). In addition, trophozoites of the amoeba Acanthamoeba sp. were detected in tiger feces.

Genetic analysis of rootstock-mediated nitrogen (N) uptake and root-to-shoot signalling at contrasting N availabilities in tomato.

Selecting rootstocks for high nitrogen acquisition ability may allow decreased N fertilizer application without reducing tomato yields, minimizing environmental nitrate pollution. A commercial hybrid tomato variety was grafted on a genotyped population of 130 recombinant inbred lines (RILs) derived from Solanum pimpinellifolium, and compared with self- and non-grafted controls under contrasting nitrate availabilities (13.8 vs 1.0mM) in the nutrient solution. Grafting itself altered xylem sap composition under N-sufficient conditions, particularly Na+ (8.75-fold increase) concentration. N deprivation decreased shoot dry weight by 72.7% across the grafted RIL population, and one RIL rootstock allowed higher total leaf N content than the best of controls, suggesting more effective N uptake. Sixty-two significant QTLs were detected by multiple QTL mapping procedure for leaf N concentration (LNC), vegetative growth, and the xylem sap concentrations of Mn and four phytohormone groups (cytokinins, gibberellins, salicylic acid and jasmonic acid). Only three LNC QTLs could be common between nitrogen treatments. Clustering of rootstock QTLs controlling LNC, leaf dry weight and xylem sap salicylic acid concentration in chromosome 9 suggests a genetic relationship between this rootstock phytohormone and N uptake efficiency. Some functional candidate genes found within 2 Mbp intervals of LNC and hormone QTLs are discussed.

Factors Affecting Pseudomonas savastanoi pv. savastanoi Plant Inoculations and Their Use for Evaluation of Olive Cultivar Susceptibility.

ABSTRACT Pseudomonas savastanoi pv. savastanoi causes olive knot disease, which is present in most countries where olive trees are grown. Although the use of cultivars with low susceptibility may be one of the most appropriate methods of disease control, little information is available from inoculation assays, and cultivar susceptibility assessments have been limited to few cultivars. We have evaluated the effects of pathogen virulence, plant age, the dose/response relationship, and the induction of secondary tumors in olive inoculation assays. Most P. savastanoi pv. savastanoi strains evaluated were highly virulent to olive plants, but interactions between cultivars and strains were found. The severity of the disease in a given cultivar was strongly dependent of the pathogen dose applied at the wound sites. Secondary tumors developed in noninoculated wounds following inoculation at another position on the stem, suggesting the migration of the pathogen within olive plants. Proportion and weight of primary knots and the presence of secondary knots were evaluated in 29 olive cultivars inoculated with two pathogen strains at two inoculum doses, allowing us to rate most of the cultivars as having either high, medium, or low susceptibility to olive knot disease. None of the cultivars were immune to the disease.

Intervention thresholds for Aphis spiraecola (Hemiptera: Aphididae) on Citrus clementina.

The production of clementine fruit was affected by varying densities of Aphis spiraecola Patch (Hemiptera: Aphididae) maintained on four groups of clementine, Citrus clementina Hort. ex Tan., trees individually isolated in mesh cages. A formula relating the number of aphids per square meter of canopy per group of trees to yield loss in that group of trees was obtained, permitting us to calculate the economic injury levels (EILs) and economic thresholds (ETs) for treatment against A. spiraecola, i.e., EIL, ET, environmental economic injury level (EEIL), and environmental economic threshold (EET). In an example case with current values, EIL = 370, ET = 322, EEIL = 614, and EET = 533 aphids per m2 of canopy. Formulae designed for easier use in the field were obtained to express each of these thresholds. The formulae are compared with those obtained for Aphis gossypii Glover in a previous study; the intervention thresholds for A. spiraecola are slightly higher than those found for A. gossypii.

New interpretation of the Gran Dolina-TD6 bearing Homo antecessor deposits through sedimentological analysis.

Gran Dolina is a cavity infilled by at least 25 m of Pleistocene sediments. This sequence contains the TD6 stratigraphic unit, whose records include around 170 hominin bones that have allowed the definition of a new species, Homo antecessor. This fossil accumulation was studied as a single assemblage and interpreted as a succession of several human home bases. We propose a complete stratigraphic context and sedimentological interpretation for TD6, analyzing the relationships between the sedimentary facies, the clasts and archaeo-palaeontological remains. The TD6 unit has been divided into three sub-units and 13 layers. Nine sedimentary facies have been defined. Hominin remains appear related to three different sedimentary facies: debris flow facies, channel facies and floodplain facies. They show three kinds of distribution: first a group of scattered fossils, then a group with layers of fossils in fluvial facies, and third a group with a layer of fossils in mixed fluvial and gravity flow facies. The results of this work suggest that some of these hominin remains accumulated in the cave by geological processes, coming from the adjacent slope above the cave or the cave entry, as the palaeogeography and sedimentary characteristics of these allochthonous facies suggest.

Medical Students for Tissue Procurement, a 10-Year Experience in a Large University Hospital: An Exportable Model?

OBJECTIVE: The objective of this study was to describe tissue procurement activity performed during 10 years (2004-2014) by trained medical students in a large university hospital. METHODS: In this study, third to sixth year medical students were trained as in-hospital Tissue Coordinators (Tc) to perform tissue procurement activity on a 24/7 schedule supervised by an on-call senior Transplant Coordinator (sTC) in a large university hospital. Tc duty consisted of detection, initial evaluation of all hospital deaths, donor's family approach for tissue donation, and retrieval logistics organization, including corneal tissue retrieval after training and certification. They also assist sTC in organ procurement activity. RESULTS: A total of 18,931 deaths were prospectively evaluated, 79% of whom (n = 14,879) presented medical contraindications for tissue donation. Of the remaining 4052 (21%) potential tissue donors (PTD), 2522 (62%) were not converted into real donors, mostly due to family refusal (66%; n = 1650) followed by detection system failure and other logistical issues (34%; n = 872). A total of 2814 corneal units, 225 skin donations, 327 muscleskeletal tissue donations, 91 blood vessels donations, and 177 heart valve donations were obtained from the remaining 1530 (38%) real donors. Tissue potentiality increased from 19% to 43% throughout the study period as a consequence of the fluctuating acceptance criteria used by tissue banks depending on tissue demand. CONCLUSIONS: The tissue donation program performed by trained students was successful in achieving a high and sustainable tissue donation rate in a large university hospital.

Sclerosis in bisphosphonate-related osteonecrosis of the jaws and its correlation with the clinical stages: study of 43 cases.

We analysed the degree of sclerosis in the different stages of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and studied the relation between the grade of sclerosis, the clinical symptoms, and the depth of lucency. We compared 43 patients with mandibular BRONJ with a control group of 40 cases with no bony lesions. The presence of sclerotic bone, cortical irregularities, radiolucency, fragmentation or sequestration, periostitis, and narrowing of the mandibular canal were studied from computed tomographic (CT) scans using the program ImageJ 1.47v (National Institute of Health, Bethesda, USA) to measure the radiolucency, width of the cortices, and degree of sclerosis. Patients with BRONJ had more severe sclerosis than controls (p<0.01). There was also a significant difference among the different stages of BRONJ, with the highest values found in stage III (p=0.02). The degree of sclerosis differed according to sex, type of bisphosphonate, and the clinical characteristics such as pain, or suppuration, but not significantly so (p>0.05). We conclude that the degree of sclerosis increases with the clinical stage of BRONJ, and is correlated with the depth of lucency.

A cytogenetic follow-up study of thyroid cancer patients treated with 131I.

To determine the genotoxic risk associated with therapeutic exposure to 131I, we studied the presence of micronuclei (MN) in binucleated peripheral blood lymphocytes of a group of 22 women, patients of thyroid cancer, who received 131I sodium iodide orally as an adjuvant after total thyroidectomy. The cytogenetic study was conducted following annual check-up, the patients having received the therapeutic dose between 1 and 5 years before the study. The results show that there are no significant differences in MN frequency between the patients and the control group, the latter composed of 19 unexposed women. These findings could indicate that any possible genetic damage induced by therapeutic exposure to 131I is eliminated after a period of 1 year.

The safety of olanzapine compared with other antipsychotic drugs: results of an observational prospective study in patients with schizophrenia (EFESO Study). Pharmacoepidemiologic Study of Olanzapine in Schizophrenia.

INTRODUCTION: Results of controlled clinical trials should be confirmed through safety and effectiveness studies in nonselected patient cohorts treated according to routine clinical practice. METHOD: Outpatients with schizophrenia (ICD-10 criteria) entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Safety was evaluated through the collection of spontaneous adverse events and a specific questionnaire for extrapyramidal symptoms. Global clinical status was measured through the Clinical Global Impressions-Severity (CGI-S) and the Global Assessment of Functioning (GAF) scales. RESULTS: From the 2967 patients included, 2128 patients were treated with olanzapine as monotherapy or combined with other drugs (olanzapine group), and 821 were treated with other antipsychotic drugs as monotherapy or combined with other drugs (control group). There were no statistical differences between treatment groups at baseline regarding age, gender, disease duration, or severity of symptoms. Olanzapine was well tolerated and effective in this study. Overall incidence of adverse events was significantly lower in the olanzapine group compared with the control group (p < .001). Somnolence and weight gain were significantly more frequent in the olanzapine group, and akathisia, dystonia, extrapyramidal syndrome, hypertonia, hypokinesia, and tremor were significantly higher in the control group. Clinical improvement at endpoint, measured through the mean change in the CGI-S and the GAF, was significantly higher in the olanzapine group compared with the control group (p = .004). CONCLUSION: These results show that olanzapine is safe and effective in nonselected schizophrenic outpatients and are consistent with the efficacy and safety profile that olanzapine has shown in previous controlled clinical trials.

Genotoxicity of humic acid in cultured human lymphocytes and its interaction with the herbicides alachlor and maleic hydrazide.

The genotoxicity of humic acid and its possible interaction with the herbicides alachlor and maleic hydrazide have been evaluated in cultured human lymphocytes from two donors. Humic acid and the two herbicides have been tested (alone and combined) for sister-chromatid exchange (SCE) induction. In addition, the effect of two different preincubation times, 2 and 24 hr, was analyzed. The results indicate that humic acid and the herbicides alachlor and maleic hydrazide appear to significantly enhance the frequency of SCE, the effect of the herbicides being more pronounced. With reference to the possible interaction of humic acid with the herbicides, the results do not show a common pattern, although mainly an additive effect was obtained. Nevertheless, there is some evidence suggesting that antagonism may occur, especially in the combined treatment of humic acid and maleic hydrazide.

Selective serotonin reuptake inhibitors in the treatment of paediatric anxiety disorders: a review.

Anxiety disorders (obsessive-compulsive disorder, social phobia/selective mutism, panic disorder, separation anxiety, generalized anxiety disorder, simple phobia and post-traumatic stress disorder) are the most prevalent psychiatric disorders in children and adolescents. The selective serotonin reuptake inhibitors (SSRIs)--citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline--have demonstrated efficacy in treating anxiety disorders in adults. Although less information is available on the use of these agents in the paediatric population, research into the SSRIs for childhood anxiety disorders is increasing. This article reviews current literature, including case reports as well as open and controlled trials, on the effectiveness and tolerability of the SSRIs in the paediatric population. It also discusses developmental differences in children that should be considered in the utilisation of the SSRIs in paediatric patients.