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Post-consumer waste management systems have proven insufficient to meet the growing global demand. In this context, adopting alternative pathways that complement established practices, such as chemical recycling, becomes essential. Accordingly, this study evaluated the potential of the co-pyrolysis process to manage polyethylene terephthalate (PET) residues and waste cooking oil (WCO), converting them into industrial inputs. Three mixing ratios between PET and WCO were evaluated, assessing their synergistic effects through kinetic studies and comprehensive characterization of the final liquid product. The interaction between PET and WCO in the evaluated mixtures reduced the activation energy of thermal degradation by ∼ 40 % compared to raw PET, improving the energy viability of the process. The addition of WCO to the thermal conversion of PET favored the cracking of the polymer, thus the yield of the pyrolytic liquid increased from 44.41 % by weight to 59.38 % in the PW (2:1) mixture, 71.06 % in PW (1:1) and 79.86 % in PW (1:2). The synergistic interaction between the feedstocks led to an increase in terephthalic acid (TPA) production compared to the individual pyrolysis of PET. When PET and WCO were mixed in proportions of 2:1, 1:1, and 1:2, TPA production increased by 167 %, 73 % and 58 %, respectively. Moreover, the production of highly aromatic compounds was inhibited during co-pyrolysis, favoring the formation of less aromatic species. The results showed that the simultaneous management of wastes from co-pyrolysis offers advantages to the production process, presenting itself as a promising approach for the management and production of chemical inputs from PET and WCO., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The management of complex, intra- and extrahepatic portal vein thrombosis (PVT) after liver transplantation (LT) is challenging. Although most of the patients remain asymptomatic or oligosymptomatic in the chronic setting, some of them may develop severe portal hypertension and related complications, notably gastrointestinal (GI) bleeding. In the emergency scenario, clinical and endoscopic treatments as well as intensive support constitute the bases of conservative management, while more definitive treatment options such as surgical shunting and retransplantation are related to high morbidity rates. Transjugular intrahepatic portosystemic shunt (TIPS) was largely considered of limited role due to technical difficulties arising from extensive PVT. Recently, however, new minimally invasive image-guided techniques emerged, allowing portal vein recanalization and TIPS creation simultaneously (TIPS-PVR), even in complex PVT pretransplant patients., Methods: Herein, we describe a novel indication for TIPS-PVR in a post-LT adolescent presenting with life-threatening, refractory GI bleeding., Results: The patient presented with complete resolution of the hemorrhagic condition after the procedure, with no deterioration of hepatic function or hepatic encephalopathy. Follow-up Doppler ultrasound after TIPS-PVR showed normal hepatopetal venous flow within the stents, and no evidence of complications, including intraperitoneal or peri splenic bleeding., Conclusions: This report describes the feasibility of TIPS-PVR in the post-LT scenario complicated by extensive PVT. In this case, a complete resolution of the life-threatening GI bleeding was achieved, with no major complications. Other patients with complex chronic PVT might benefit from the use of the described technique, but further studies are required to determine the correct timing and indications of the procedure, eventually before the occurrence of life-threatening complications., (© 2023 Wiley Periodicals LLC.)

Background: Implementing cognitive assessment in older people admitted to hospital with hip fracture-lying in bed, experiencing pain-is challenging. We investigated the value of a quick and easy-to-administer 10-point Cognitive Screener (10-CS) in predicting 1-year functional recovery and survival after hip surgery., Methods: Prospective cohort study comprising 304 older patients (mean age = 80.3 ± 9.1 years; women = 72%) with hip fracture consecutively admitted to a specialized academic medical center that supports secondary hospitals in Sao Paulo Metropolitan Area, Brazil. The 10-CS, a 2-minute bedside tool including temporal orientation, verbal fluency, and three-word recall, classified patients as having normal cognition, possible cognitive impairment, or probable cognitive impairment on admission. Outcomes were time-to-recovery activities of daily living (ADLs; Katz index) and mobility (New Mobility Score), and survival during 1-year after hip surgery. Hazard models, considering death as a competing risk, were used to associate the 10-CS categories with outcomes after adjusting for sociodemographic and clinical measures., Results: On admission, 144 (47%) patients had probable cognitive impairment. Compared to those cognitively normal, patients with probable cognitive impairment presented less postsurgical recovery of ADLs (77% vs 40%; adjusted sub-hazard ratio [HR] = 0.44; 95% confidence interval [CI] = 0.32-0.62) and mobility (50% vs 30%; adjusted sub-HR = 0.52; 95% CI = 0.34-0.79), and higher risk of death (15% vs 40%; adjusted HR = 2.08; 95% CI = 1.03-4.20) over 1-year follow-up., Conclusions: The 10-CS is a strong predictor of functional recovery and survival after hip fracture repair. Cognitive assessment using quick and easy-to-administer screening tools like 10-CS can help clinicians make better decisions and offer tailored care for older patients admitted with hip fracture., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Appearance modification is ancient, universal and influences other and self-perceptions. It has been rarely addressed how expectation of appearance modification would affect women's self-perception. We analyzed self-assessments of women without makeup and after having makeup professionally applied at four increasing levels (light, moderate, heavy 1, and heavy 2 makeup). In the simulation phase, women were treated with colorless cosmetics. Fifty Brazilian women (M age  = 24.26 years; SD = 5.53) rated themselves on attractiveness, health, self-esteem, femininity, satisfaction with appearance, age, dominance, confidence, and competence in all experimental conditions. Women in the simulation phase considered themselves more feminine, healthier, and with higher self-esteem than without makeup. In the real makeup phases, these ratings were higher than in the simulation phase. Appearance satisfaction and attractiveness did not differ between simulation and the real makeup phases, both being higher than without makeup. Confidence increased only in real makeup phases, but there was no effect on competence. Thus, real appearance modification and/or an expectation thereof can differently affect specific domains of self-evaluation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this work, the production of renewable hydrocarbons was explored by the means of waste cottonseed oil (WCSO) micropyrolysis at 500 °C. Catalytic upgrading of the pyrolysis vapors was studied using α-Al 2 O 3 , γ-Al 2 O 3, Mo-Co/γ-Al 2 O 3 , and Mo-Ni/γ-Al 2 O 3 catalysts. The oxygen removal efficiency was much lower in non-catalytic pyrolysis (18.0%), whilst γ-Al 2 O 3 yielded a very high oxygen removal efficiency (91.8%), similar to that obtained with Mo-Co/γ-Al 2 O 3 (92.8%) and higher than that attained with Mo-Ni/γ-Al 2 O 3 (82.0%). Higher conversion yields into total renewable hydrocarbons were obtained with Mo-Co/γ-Al 2 O 3 (61.9 wt.%) in comparison to Mo-Ni/γ-Al 2 O 3 (46.6%). GC/MS analyses showed a relative chemical composition of 31.3, 86.4, and 92.6% of total renewable hydrocarbons and 58.7, 7.2, and 4.2% of oxygenated compounds for non-catalytic bio-oil (BOWCSO), BOMoNi and BOMoCo, respectively. The renewable hydrocarbons that were derived from BOMoNi and BOMoCo were mainly composed by olefins (35.3 and 33.4%), aromatics (31.4 and 28.9%), and paraffins (13.8 and 25.7%). The results revealed the catalysts' effectiveness in FFA decarbonylation and decarboxylation, as evidenced by significant changes in the van Krevelen space, with the lowest O/C ratio values for BOMoCo and BOMoNi (O/C = 0-0.10) in relation to the BOWCSO (O/C = 0.10-0.20), and by a decrease in the presence of oxygenated compounds in the catalytic bio-oils.

Neglected tropical diseases such as Chagas disease and leishmaniasis affect millions of people around the world. Both diseases affect various parts of the globe and drugs traditionally used in therapy against these diseases have limitations, especially with regard to low efficacy and high toxicity. In this context, the class of bisphosphonate-based compounds has made significant advances regarding the chemical synthesis process as well as the pharmacological properties attributed to these compounds. Among this spectrum of pharmacological activity, bisphosphonate compounds with antiparasitic activity stand out, especially in the treatment of Chagas disease and leishmaniasis caused by Trypanosoma cruzi and Leishmania spp., respectively. Some bisphosphonate compounds can inhibit the mevalonate pathway, an essential metabolic pathway, by interfering with the synthesis of ergosterol, a sterol responsible for the growth and viability of these parasites. Therefore, this review aims to present the information about the importance of these compounds as antiparasitic agents and as potential new drugs to treat Chagas disease and leishmaniasis.

Candida species are common in the human oral microbiota and may cause oral candidiasis (OC) when the microbiota equilibrium is disturbed. Immunosuppressed individuals are susceptible to oral infections as individuals with Down syndrome (IDS) due to particularities of their mouth morphoanatomy, saliva and comorbidities. This study aimed to analyze the molecular epidemiology of Candida spp. from the oral cavity of IDS and their relatives. A case-control study with 80 IDS and 80 non-syndromic (non-DS) was evaluated by oral swab collection for culture on Sabouraud dextrose agar, selection of yeast colonies to Gram staining and culturing on chromogenic media. DNA extraction was performed with the phenol/chloroform method for screening of 6 Candida species medically important in PCR, applying SPSS for statistics. We confirmed four species in 46 IDS without use of antimicrobials (57.54%), with a high prevalence of C. albicans/Ca (93.48%/43) and 3 C. glabrata/Cg (6.52%), being 25 of these IDS (31.25%) colonized by species other than C. albicans: Ca + Cg (16), Ca + C. tropicalis/Ct (7) and Ca + C. krusei/Ck (2). Only 10 non-DS were colonized by one species (11.25%): 6 C. albicans, 2 C. glabrata, 1 C. tropicalis and 1 C. krusei. Previous OC was reported by 39 IDS (48.75%), being 33 positives for Candida spp. (84.61%) and 17 with active OC (21.25%). Five non-DS reported OC previously and had no active lesions. Behavioral changes and buccal health programs directed to IDS may help prevent OC and its recurrence, providing information on oral hygiene for self-care.

Background: Limited time and resources hinder the use of comprehensive geriatric assessment in acute contexts. We investigated the predictive value of a 10-minute targeted geriatric assessment (10-TaGA) for adverse outcomes over 6 months among acutely ill older outpatients., Methods: Prospective study comprising 819 acutely ill outpatients (79.2 ± 8.4 years; 63% women) in need of intensive management (eg, intravenous therapy, laboratory test, radiology) to avoid hospitalization. The 10-TaGA provided a validated measure of cumulative deficits. Previously established 10-TaGA cutoffs defined low (0-0.29), medium (0.30-0.39), and high (0.40-1) risks. To estimate whether 10-TaGA predicts new dependence in activities of daily living and hospitalization over the next 6 months, we used hazard models (considering death as competing risk) adjusted for standard risk factors (sociodemographic factors, Charlson comorbidity index, and physician estimates of risk). Differences among areas under receiver operating characteristic curves (AUROC) examined whether 10-TaGA improves outcome discrimination when added to standard risk factors., Results: Medium- and high-risk patients, according to 10-TaGA, presented a higher incidence of new activities of daily living dependence (21% vs 7%, adjusted subhazard ratio [aHR] = 2.4, 95% CI = 1.3-4.5; 40% vs 7%, aHR = 5.0, 95% CI = 2.8-8.7, respectively) and hospitalization (27% vs 13%, aHR = 2.0, 95% CI = 1.2-3.3; 37% vs 13%, aHR = 2.9, 95% CI = 1.8-4.6, respectively) than low-risk patients. The 10-TaGA remarkably improved the discrimination of models that incorporated standard risk factors to predict new activities of daily living dependence (AUROC = 0.76 vs 0.71, p < .001) and hospitalization (AUROC = 0.71 vs 0.68, p < .001)., Conclusions: The 10-TaGA is a practical and efficient comprehensive geriatric assessment tool that improves the prediction of adverse outcomes among acutely ill older outpatients., (© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To estimate whether a 10-minute Targeted Geriatric Assessment (10-TaGA) adds utility to sociodemographic characteristics and comorbidities in predicting one-year mortality in busy acute care settings. We have also compared the performance of 10-TaGA with the Identification of Seniors at Risk (ISAR) scale., Design: Prospective cohort study., Setting: Geriatric day hospital specializing in acute care in Brazil., Participants: 751 older adults aged 79.4 ± 8.4 years (64% female), presenting non-surgical, medical illness requiring hospital-level care (e.g., intravenous therapy, laboratory test, radiology) for ≤ 12 hours., Measurements: The 10-TaGA, an easy-to-administer screening tool based on the comprehensive geriatric assessment (CGA), provided a measure of cumulative deficits ranging from 0 (no deficits) to 1 (highest deficit) on admission. Standard risk factors, including sociodemographics (age, gender, ethnicity, income) and the Charlson comorbidity index, were evaluated. The ISAR, a well-validated screening tool, was used for comparison., Results: During one year of follow-up, 130 (17%) participants died. Compared to the ISAR, 10-TaGA offered better accuracy in identifying older patients at risk of death (area under the receiver operating characteristic curve: [AUC] 0.70 vs 0.65; P = 0.03). In a Cox regression model adjusted for sociodemographics and comorbidities, each 0.1 increment in the 10-TaGA score (range 0-1) was associated with increased mortality (hazard ratio = 1.42, 95% confidence interval 1.27-1.59). The addition of 10-TaGA markedly improved the discrimination of the model, which already incorporated standard risk factors (AUC 0.76 vs 0.71; P = 0.005); adding ISAR (AUC 0.73 vs 0.71; P = 0.09) did not have this marked effect., Conclusion: The 10-TaGA is an independent predictor of one-year mortality in acute care patients. This multidimensional screening tool offers better accuracy than ISAR when differentiating between older people at low and high risk of death in healthcare settings where providers have limited time and resources., Competing Interests: All authors declare no conflict of interest to disclose.

Objectives: To develop and examine the validity and reliability of a targeted geriatric assessment (TaGA) for busy healthcare settings., Design: The TaGA was developed through the consensus of experts (Delphi technique), and we investigated its construct validity and reliability in a cross-sectional study., Setting: Geriatric day hospital specializing in acute care in Brazil., Participants: Older adults (N = 534) aged 79.5 ± 8.4, 63% female, consecutively admitted to the geriatric day hospital., Measurements: The Frailty Index (FI), Physical Frailty Phenotype, and Identification of Seniors at Risk (ISAR) were used to explore the TaGA's validity. External scales were used to investigate the validity of each matched TaGA domain. The interrater reliability and time to complete the instrument were tested in a 53-person subsample., Results: In 3 rounds of opinion, experts achieved consensus that the TaGA should include 10 domains (social support, recent hospital admissions, falls, number of medications, basic activities of daily living, cognitive performance, self-rated health, depressive symptoms, nutritional status, gait speed). They arrived at sufficient agreement on specific tools to assess each domain. A single numerical score from 0 to 1 expressed the cumulative deficits across the 10 domains. The TaGA score was highly correlated with the FI (Spearman coefficient = 0.79, 95% confidence interval (CI)=0.76-0.82) and discriminated between frail and nonfrail individuals better than the ISAR (area under the receiver operating characteristic curve 0.84 vs 0.72; P < .001). The TaGA score also had excellent interrater reliability (intraclass correlation coefficient = 0.92, 95% CI=0.87-0.95). Mean TaGA administration time was 9.5 ± 2.2 minutes., Conclusion: The study presents evidence supporting the TaGA's validity and reliability. This instrument may be a practical and efficient approach to screening geriatric syndromes in fast-paced healthcare settings. Future research should investigate its predictive value and effect on care., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

Objective: Comparison of frailty instruments in low-middle income countries, where the prevalence of frailty may be higher, is scarce. In addition, less complex diagnostic tools for frailty are important in these settings, especially in acutely ill patients, because of limited time and economic resources. We aimed to compare the performance of 3 frailty instruments for predicting adverse outcomes after 1 year of follow-up in older adults with an acute event or a chronic decompensated disease., Design: Prospective cohort study., Setting: Geriatric day hospital (GDH) specializing in acute care., Participants: A total of 534 patients (mean age 79.6 ± 8.4 years, 63% female, 64% white) admitted to the GDH., Measurements: Frailty was assessed using the Cardiovascular Health Study (CHS) criteria, the Study of Osteoporotic Fracture (SOF) criteria, and the FRAIL (fatigue, resistance, ambulation, illnesses, and loss of weight) questionnaire. Monthly phone contacts were performed over the course of the first year to detect the following outcomes: incident disability, hospitalization, fall, and death. Multivariable Cox proportional hazard regression models were performed to evaluate the association of the outcomes with frailty as defined by the 3 instruments. In addition, we compared the accuracy of these instruments for predicting the outcomes., Results: Prevalence of frailty ranged from 37% (using FRAIL) to 51% (using CHS). After 1 year of follow-up, disability occurred in 33% of the sample, hospitalization in 40%, fall in 44%, and death in 16%. Frailty, as defined by the 3 instruments was associated with all outcomes, whereas prefrailty was associated with disability, using the SOF and FRAIL instruments, and with hospitalization using the CHS and SOF instruments. The accuracy of frailty to predict different outcomes was poor to moderate with area under the curve varying from 0.57 (for fall, with frailty defined by SOF and FRAIL) to 0.69 (for disability, with frailty defined by CHS)., Conclusions: In acutely ill patients from a low-middle income country GDH acute care unit, the CHS, SOF, and FRAIL instruments showed similar performance in predicting adverse outcomes., (Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

An extensive proteostatic network comprised of molecular chaperones and protein clearance mechanisms functions collectively to preserve the integrity and resiliency of the proteome. The efficacy of this network deteriorates during aging, coinciding with many clinical manifestations, including protein aggregation diseases of the nervous system. A decline in proteostasis can be delayed through the activation of cytoprotective transcriptional responses, which are sensitive to environmental stress and internal metabolic and physiological cues. The homeodomain-interacting protein kinase (hipk) family members are conserved transcriptional co-factors that have been implicated in both genotoxic and metabolic stress responses from yeast to mammals. We demonstrate that constitutive expression of the sole Caenorhabditis elegans Hipk homolog, hpk-1, is sufficient to delay aging, preserve proteostasis, and promote stress resistance, while loss of hpk-1 is deleterious to these phenotypes. We show that HPK-1 preserves proteostasis and extends longevity through distinct but complementary genetic pathways defined by the heat shock transcription factor (HSF-1), and the target of rapamycin complex 1 (TORC1). We demonstrate that HPK-1 antagonizes sumoylation of HSF-1, a post-translational modification associated with reduced transcriptional activity in mammals. We show that inhibition of sumoylation by RNAi enhances HSF-1-dependent transcriptional induction of chaperones in response to heat shock. We find that hpk-1 is required for HSF-1 to induce molecular chaperones after thermal stress and enhances hormetic extension of longevity. We also show that HPK-1 is required in conjunction with HSF-1 for maintenance of proteostasis in the absence of thermal stress, protecting against the formation of polyglutamine (Q35::YFP) protein aggregates and associated locomotory toxicity. These functions of HPK-1/HSF-1 undergo rapid down-regulation once animals reach reproductive maturity. We show that HPK-1 fortifies proteostasis and extends longevity by an additional independent mechanism: induction of autophagy. HPK-1 is necessary for induction of autophagosome formation and autophagy gene expression in response to dietary restriction (DR) or inactivation of TORC1. The autophagy-stimulating transcription factors pha-4/FoxA and mxl-2/Mlx, but not hlh-30/TFEB or the nuclear hormone receptor nhr-62, are necessary for extended longevity resulting from HPK-1 overexpression. HPK-1 expression is itself induced by transcriptional mechanisms after nutritional stress, and post-transcriptional mechanisms in response to thermal stress. Collectively our results position HPK-1 at a central regulatory node upstream of the greater proteostatic network, acting at the transcriptional level by promoting protein folding via chaperone expression, and protein turnover via expression of autophagy genes. HPK-1 therefore provides a promising intervention point for pharmacological agents targeting the protein homeostasis system as a means of preserving robust longevity.

Background: Hip fractures resulting from falls increase substantially with advancing age and less than half of older hip fracture survivors regain their former levels of mobility. There is increasing evidence that rehabilitation interventions with exercises that goes beyond the sub-acute phase or even in a later stage of care have a positive impact on various functional abilities. The purpose of this study is to determine if exercise program training for people who have suffered a fall-related hip fracture will improve functional mobility when compared with usual care., Methods: A randomized controlled trial with blinded assessors and intention-to-treat analysis will be undertaken. We will recruit 82 older adults, 60 years or over who have suffered a hip fracture due to a fall in the previous 6 to 24 months. Participants randomized to the Intervention Group (IG) will undertake a physical exercise program involving progressive and challenging balance training and neuromuscular and functional training of the lower limbs, conducted at home by physiotherapists, once a week, lasting about one hour, in the first, second and third month after randomization and will be taught to perform exercises at home, twice a week, using a booklet. Visits to monitor and progress the home exercise program will be conducted once a month, from the fourth to the sixth month and each 2 months until the end of the follow up at the 12 th month, i.e., a total of 18 sessions. Participants will receive monthly phone calls to encourage exercise adherence. The control group will receive usual care. The primary outcome will be mobility-related disability and participants will be assessed at baseline, and at 3 months, 6 and 12 months. Participants will receive monthly phone calls to ask about falls and exercise adherence. Adverse effects will be monitored., Discussion: This study proposes a home-based exercise program, which may in part overcome some barriers for rehabilitation, such as difficulties with public transportation and lack of a caregiver to accompany older patients to sessions. If a positive effect is observed this program has the potential to be incorporated into the public health system and contribute to building a pathway of care for older people with hip fracture., Trial Registration: Clinicaltrials.gov Identifier: NCT02295527 .

Older adults have a greater risk of experiencing functional decline and iatrogenic complications during hospitalization than younger individuals. Geriatric day hospitals (GDHs) have been implemented mainly for rehabilitation. The goal of the current study was to expand the GDH spectrum of care to prevent hospital admissions in this population. This study details an innovative model of GDH care that offers short-term, nonrehabilitative treatment to older adults who have experienced an acute event, those with a decompensated chronic disease, or those in need of a minor procedure that would be unattainable in a regular outpatient setting. During the 6-hour visits made weekly for up to 2 months, participants receive integrated evaluations of their various health domains, education, and rapid access to examinations and procedures based on a multidisciplinary approach. In the first 6 years, 2,322 individuals attended the GDH. The analysis of a representative sample (n = 645) revealed that 81% were treated in the GDH without the need for another type of hospital care. This percentage was high for the different reasons for referral (infection, 71%; delirium, 73%; decompensated chronic disease, 81%). Between baseline and discharge, participants maintained their functional status, and their self-reported health improved. This study represents the first step in describing the role of the GDH as a possible alternative to emergency department use or hospitalization for older adults. Future studies are needed to determine the optimal individual for this model of care and to ensure its cost-effectiveness., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

Background: although the importance of identifying hip fracture patients with high risk for delirium has been well established, considerable controversy exists over the choice of the screening tool. The most commonly used cognitive screeners take an excessive amount of time and include drawing tasks that can be troublesome for individuals with hip fracture who are invariably lying in bed., Objective: to evaluate the properties of the 10-point Cognitive Screener (10-CS), a 2-min bedside tool, for predicting delirium in older adults with hip fracture., Design: prospective cohort study., Setting: a tertiary referral hospital in São Paulo, Brazil., Subjects: non-delirious older adults with hip fracture (n = 147)., Methods: the 10-CS was administered as a baseline predictor. The test is composed of three-item temporal orientation (date, month, year), category fluency (animals in 1 min) and three-word recall. Incident delirium has been diagnosed according to the Confusion Assessment Method (CAM) that was administered daily from admission to discharge., Results: during hospitalisation, 61 (41.5%) patients developed delirium. The 10-CS presented excellent accuracy for predicting delirium, with an area under ROC curve of 0.83 (95% CI 0.76-0.89). After adjusting for demographic and clinical variables, participants with probable cognitive impairment (score ≤ 5) were more likely to develop delirium (HR = 7.48; 95% CI 2.2-25.4) compared with participants with a normal score. Lower scores on the 10-CS were also independently associated with a longer length of stay., Conclusions: the 10-CS is an easy-to-use bedside tool with adequate properties to stratify the risk of delirium in older adults with hip fracture., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The objective of this study was to evaluate the influence of enriched environment on spatial memory acquisition in mice of three different age groups. Weanling, young, and young adult female Swiss mice were housed in a standard control or enriched environment for 50 days, and their spatial memory was tested with the Morris Water Maze. We did not observe an experimental effect for spatial memory acquisition, and there was neither an effect of time of analysis nor an interaction between experimental group and time of analysis. Regarding effects of experimental group and training day in relation to latency in finding the hidden platform, we did find an effect in the experimental young adult mice group (p = 0.027), but there was no interaction between these factors in all three groups. Based on these findings environmental enrichment did not enhance spatial memory acquisition in female Swiss mice in the tested age groups.

Objectives: . The 28-joint DAS (DAS28), clinical disease activity index (CDAI) and simplified disease activity index (SDAI) are indices frequently used to assess disease activity in RA patients. Cut-off values were defined to classify the states of RA disease activity: remission, low, moderate and high. The aim of this work was to assess disease activity states classified by DAS28, CDAI and SDAI and to analyse their agreement in the Rheumatic Diseases Portuguese Register Reuma.pt., Methods: . A total of 2795 patients and 14 440 visits were selected from Reuma.pt for analysis. Pearson's correlation coefficients (PCCs) were calculated for the three indices. McNemar's chi-squared tests, PCCs and kappa statistics were performed to analyse and compare the distribution of visits among all disease activity states and indices., Results: A strong correlation was found between the three indices throughout the 14 440 visits: r = 0.874 for DAS28/CDAI, r = 0.877 for DAS28/SDAI and r = 0.984 for CDAI/SDAI (all PCCs with P < 0.0001). However, when categorization in the different disease activity states was analysed, McNemar's chi-squared tests and PCCs revealed significant disagreement between the cut-offs of the three indices., Conclusion: DAS28, CDAI and SDAI cut-offs do not translate into the same clinical information in Reuma.pt. Although this might be expected for the original DAS28 cut-offs, when compared with CDAI and SDAI significant disagreement was also found for the DAS28 modified cut-offs. For visits where patients are in CDAI or SDAI remission, we also find disagreement between these two indices, which may contradict previous conclusions that acute phase reactants add little to composite disease activity indices for RA., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

This research was conducted with patients who sought emergency care at a Comprehensive Primary Care Clinic (CIAP IV) at the Dental School of Minas Gerais Federal University and at the Dental Center of a medium-sized city in the state of Minas Gerais. The scope of this article is to identify how the social representations of this issue are generated through the metaphors used by patients to express toothache. A total of 35 individuals of both genders who sought emergency care for toothache participated in the study. Content theme analysis was used. Social representations of toothache are generated as people resort to their life experiences to find words to express the problem. Prior sensations and feelings, and even imaginary situations, generate metaphors to attempt to explain the suffering. Toothache is often compared with the worst feelings ever experienced by individuals. Toothache represents great suffering for people seeking emergency dental care. This fact may help to develop further public oral health policies, bearing in mind that a socially deprived population is more often afflicted by toothache.

Biotechnological drugs have become a fundamental resource for the treatment of rheumatic patients. Patent expiry of some of these drugs created the opportunity for biopharmaceutical manufacturers to develop biosimilar drugs intended to be as efficacious as the originator product but with a lower cost to healthcare systems. Due to the complex manufacturing process and highly intricate structure of biologicals, a biosimilar can never be an exact copy of its reference product. Consequently, regulatory authorities issued strict preclinical and clinical guidelines to ensure safety and efficacy equivalence and, in September 2013, the biosimilar of infliximab was the first biosimilar monoclonal antibody to be authorized for use in the European Union. The current document is a position statement of the "Sociedade Portuguesa de Reumatologia" (Portuguese Society of Rheumatology) on the use of biosimilar drugs in rheumatic diseases. Two systematic literature reviews were performed, one concerning clinical trials and the other one concerning international position papers on biosimilars. The results were presented and discussed in a national meeting and a final position document was discussed, written and approved by Portuguese rheumatologists. Briefly, this position statement is contrary to automatic substitution of the originator by the biosimilar, defends either a different INN or the prescription by brand name, supports that switching between biosimilars and the originator molecule should be done after at least 6 months of treatment and based on the attending physician decision and after adequate patient information, recommends the registration of all biosimilar treated patients in Reuma.pt for efficacy, safety and immunogenicity surveillance, following the strategy already ongoing for originators, and opposes to extrapolation of indications approved to the originator to completely different diseases and/or age groups without adequate pre-clinical, safety or efficacy data.

The nematode C. elegans is attracted to nutritious bacteria and is repelled by pathogens and toxins. Here we show that RNAi and toxin-mediated disruption of core cellular activities, including translation, respiration, and protein turnover, stimulate behavioral avoidance of normally attractive bacteria. RNAi of these and other essential processes induces expression of detoxification and innate immune effectors, even in the absence of toxins or pathogens. Disruption of core processes in non-neuronal tissues was sufficient to stimulate aversion behavior, revealing a neuroendocrine axis of control that additionally required serotonergic and Jnk kinase signaling pathways. We propose that surveillance pathways overseeing core cellular activities allow animals to detect invading pathogens that deploy toxins and virulence factors to undermine vital host functions. Variation in cellular surveillance and endocrine pathways controlling behavior, detoxification, and immunity selected by past toxin or microbial interactions could underlie aberrant responses to foods, medicines, and microbes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Since the last half of the nineteenth century, molecular graphs have been present in several branches of chemistry. When used for molecular structure representation, they have been compared after mapping the corresponding graphs into mathematical objects. However, direct molecular comparison of molecular graphs is a research field less explored. The goal of this mini-review is to show some distance and similarity coefficients which were proposed to directly compare molecular graphs or which could be useful to do so.

A beta-N-Acetylhexosaminidase (EC 3.2.1.52) was purified from hepatic extracts of Sotalia fluviatilis, order Cetacea. The protein was purified by using ammonium sulfate fractionation and four subsequent chromatographies (Biogel A 1.5 m, Chitin, Deae-Biogel and hydroxyapatite resins). After these purification steps, the enzyme was purified 380.5-fold with an 8.4% yield. The molecular mass (10 kDa) was estimated by SDS-PAGE and MALDI-TOF analysis. A Km of 2.72 mM and Vmax 9.5 x 10(-6) micromol/(min x mg) were found for this enzyme, determined by p-nitrophenyl-beta-D: -hexosaminide substrate digestion. Optimal pH and temperature for beta-N-Acetylhexosaminidase activity were 5.0 and 60 degrees C, respectively. Enzyme activity was inhibited by sodium selenate (Na(2)SeO(4)), mercuric chloride (HgCl(2)) and sodium dodecyl sulfate (C(12)H(25)SO(4)Na), and activated by zinc, calcium, barium and lithium ions. Characterization of the beta-N-Acetylhexosaminidase in Sotalia fluviatilis can be a basis for physiological studies in this species.

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment should be considered in RA patients with a disease activity score 28 (DAS 28) superior to 3.2 despite treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 6 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regimens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, characterized by a DAS28 lower than 3.2, without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of 0.6 in the DAS28 score. After 6 months of treatment response criteria is defined as a decrease of more than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opinion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituximab or tocilizumab).

Rictor is a component of the target of rapamycin complex 2 (TORC2). While TORC2 has been implicated in insulin and other growth factor signaling pathways, the key inputs and outputs of this kinase complex remain unknown. We identified mutations in the Caenorhabditis elegans homolog of rictor in a forward genetic screen for increased body fat. Despite high body fat, rictor mutants are developmentally delayed, small in body size, lay an attenuated brood, and are short-lived, indicating that Rictor plays a critical role in appropriately partitioning calories between long-term energy stores and vital organismal processes. Rictor is also necessary to maintain normal feeding on nutrient-rich food sources. In contrast to wild-type animals, which grow more rapidly on nutrient-rich bacterial strains, rictor mutants display even slower growth, a further reduced body size, decreased energy expenditure, and a dramatically extended life span, apparently through inappropriate, decreased consumption of nutrient-rich food. Rictor acts directly in the intestine to regulate fat mass and whole-animal growth. Further, the high-fat phenotype of rictor mutants is genetically dependent on akt-1, akt-2, and serum and glucocorticoid-induced kinase-1 (sgk-1). Alternatively, the life span, growth, and reproductive phenotypes of rictor mutants are mediated predominantly by sgk-1. These data indicate that Rictor/TORC2 is a nutrient-sensitive complex with outputs to AKT and SGK to modulate the assessment of food quality and signal to fat metabolism, growth, feeding behavior, reproduction, and life span.

A novel family of antimicrobial peptides, named raniseptins, has been characterized from the skin secretion of the anuran Hypsiboas raniceps. Nine cDNA molecules have been successfully cloned, sequenced, and their respective polypeptides were characterized by mass spectrometry and Edman degradation. The encoded precursors share structural similarities with the dermaseptin prepropeptides from the Phyllomedusinae subfamily and the mature 28-29 residue long peptides undergo further proteolytic cleavage in the crude secretion yielding consistent fragments of 14-15 residues. The biological assays performed demonstrated that the Rsp-1 peptide has antimicrobial activity against different bacterial strains without significant lytic effect against human erythrocytes, whereas the peptide fragments generated by endoproteolysis show limited antibiotic potency. MALDI imaging mass spectrometry in situ studies have demonstrated that the mature raniseptin peptides are in fact secreted as intact molecules within a defined glandular domain of the dorsal skin, challenging the physiological role of the observed raniseptin fragments, identified only as part of the crude secretion. In this sense, stored and secreted antimicrobial peptides may confer distinct protective roles to the frog.

Previous work on the DNA damage checkpoint in Saccharomyces cerevisiae has shown that two complexes independently sense DNA lesions: the kinase Mec1-Ddc2 and the PCNA-like 9-1-1 complex. To test whether colocalization of these components is sufficient for checkpoint activation, we fused these checkpoint proteins to the LacI repressor and artificially colocalized these fusions by expressing them in cells harboring Lac operator arrays. We observed Rad53 and Rad9 phosphorylation, Sml1 degradation, and metaphase delay, demonstrating that colocalization of these sensors is sufficient to activate the checkpoint in the absence of DNA damage. Our tethering system allowed us to establish that CDK functions in the checkpoint pathway downstream of damage processing and checkpoint protein recruitment. This CDK dependence is likely, at least in part, through Rad9, since mutation of CDK consensus sites compromised its checkpoint function.

Ionizing radiation (IR) can cause various lesions in DNA, which induce the increase of p53 expression levels in order to repair radiation induced damage. Thus, the correlation between the increase of p53 expression and an irradiation may constitute a fast and powerful method of individual monitoring in cases of accidental or suspected exposures to IR. In this context, the aim of this research was to evaluate changes in lymphocyte p53 expression levels, based on flow cytometry, after in vitro irradiation of peripheral blood samples. For the measurement of such expression levels of p53 protein, an investigation was carried out in order to establish a methodology of analysis based on flow cytometry. Hence, relationships among levels of expression of p53 protein with the absorbed dose have been verified. The results presented in this report emphasized flow cytometry as an important tool for the fast evaluation of p53 protein expression levels as bioindicator of individual exposure to acute ionizing radiation.

The coffee berry borer, Hypothenemus hampei (Ferrari), is an important devastating coffee pest worldwide. Both trypsin and chymotrypsin enzyme activities from H. hampei larval midgut can be inactivated by proteinaceous enzyme-inhibitors. A serine proteinase inhibitor belonging to the Bowman-Birk class was purified from a wild accession of Phaseolus coccineus L. seeds. The inhibitor (PcBBI1) is a cysteine-rich protein that is heat-stable at alkaline pH. MALDI-TOF/MS analysis showed that PcBBI1 occurs in seeds as a monomer (8689 Da) or dimer (17,378 Da). Using in vitro inhibition assays, it was found that PcBBI1 has a high inhibitory activity against H. hampei trypsin-like enzymes, bovine pancreatic chymotrypsin, and trypsin. According to this, PcBBI1 could be a promising tool to make genetically modified coffee with resistance to coffee berry borer.

Antimicrobial peptides are considered part of the innate immune system of the majority of living organisms. Most of these molecules are small, cationic and show amphiphilic nature. The skin secretions of Leptodactylus syphax were extracted by mild electrical stimulation and its semipreparative reverse-phase chromatography was resolved in more than 40 fractions. Among these fractions, an antimicrobial peptide was isolated and its amino acid sequence determined by de novo sequencing. Six other truncated forms were characterized in skin secretion. The longest one (25 amino acid residues), named syphaxin (SPX), is amidated at the C-terminal, and shares strong sequence similarity with antimicrobial peptides found in the skin secretion of leptodactylid frogs. Two of the truncated peptides (SPX(1-22) and SPX(1-16)) were tested against Escherichia coli and Staphylococcus aureus, showing low minimal inhibitory concentration (MIC) and no significant toxicity towards blood cells, including both leukocytes and erythrocytes, based on their direct incubation in whole blood at the highest MIC concentration (64 microg/mL).

The endophytic bruchid pest Callosobruchus maculatus causes severe damage to storage cowpea seeds, leading to economical losses. For this reason the use of alpha-amylase inhibitors to interfere with the pest digestion process has been an interesting alternative to control bruchids. With this aim, alpha-amylase inhibitors from baru seeds (Dipteryx alata) were isolated by affinity chromatographic procedures, causing enhanced inhibition of C. maculatus and Anthonomus grandis alpha-amylases. To attempt further purification, this fraction was applied onto a reversed-phase HPLC column, generating four peaks with remarkable inhibition toward C. maculatus alpha-amylases. SDS-PAGE and MALDI-ToF analysis identified major proteins of approximately 5.0, 11.0, 20.0 and 55 kDa that showed alpha-amylase inhibition. Results of in vivo bioassays using artificial seeds containing 1.0% (w/w) of baru crude extract revealed 40% cowpea weevil larvae mortality. These results provide evidence that several alpha-amylase inhibitors classes, with biotechnological potential, can be isolated from a single plant species.

The development of new and more efficacious therapeutic agents, though expensive and potentially toxic, helped to implement objective measures to quantify the improvement and to monitor the evolution of inflammatory rheumatic diseases. The aim of our protocol (PMAIJ) is to supply rheumatologists and paediatricians with a useful tool for follow-up of juvenile arthritis patients using validated instruments for the evaluation of activity, functional capacity and response to treatment. PMAIJ has 2 pages. The first page is filled only at the initial evaluation; the second page is filled at first and in all the appointments after that. The application of this protocol would contribute to the standardization of procedures in different Paediatric Rheumatology Centres and would help to obtain useful information on the clinical evolution of JIA patients followed in Portugal.

This article presents the guidelines for the management of osteoporosis established by the Portuguese Society of Rheumatology and the Portuguese Society of Metabolic Bone Diseases. The document is the result of the consensus achieved after systematic review of the literature and open discussion in nationa meetings of both societies of draft documents presented by the authors. The recommendations include aspects related to diagnosis, clinical evaluation, prevention, treatment and monitoring of post-menopausal and male osteoporosis. The guidelines aim to achieve the reduction of osteoporotic fractures throug validated clinical practices that will allow the correct use of diagnostic and therapeutic resources. The consensus will be reviewed as needed whenever new scientific evidence is available.

Bradykinin related peptides (BRPs) present in the water-soluble secretion and freshly dissected skin fragments of Phyllomedusa hypochondrialis were investigated by mass spectrometry techniques. Eighteen BRPs, along with their post-translational modifications, were characterized in the secretion by de novo MS/MS sequencing and direct MALDI imaging experiments of the frog skin. These molecules revealed strong sequence similarities to the main plasma kinin of some mammals and reptiles. Such a diversity of molecules, within the same peptide family, belonging to a single amphibian species may be related to functional specializations of these peptides and a variety of corresponding receptors that might be present in a number of different predators. Also, a novel analog, [Val]1,[Thr]6-bradykinyl-Gln,Ser had its biological activity positively detected in cell culture expressing the human bradykinin B2 receptor and in guinea pig ileum preparations.

Toxicity and toxin identification in Colomesus asellus, an Amazonian (Brazil) freshwater puffer fish. By using four different techniques--mouse bioassay, ELISA, HPLC and mass spectrometry-we evaluated the toxicity in the extracts of C. asellus, a freshwater puffer fish from the rivers of the Amazon, and identified for the first time the components responsible for its toxicity. The T20G10 monoclonal antibody raised against TTX, and employed in an indirect competitive enzyme immunoassay, showed very low affinity for the C. asellus extracts, indicating that TTX and its analogs are not the main toxic components of the extracts. This antibody was efficient in detecting presence of TTX in a total extract of Sphoeroides spengleri, which is one of the most toxic puffer fish found in the Atlantic coast. Extracts of C. asellus were toxic when administered intraperitonially into mice with an average toxicity of 38.6+/-12 mouse unit (MU)/g, while HPLC analysis indicated a lower toxin content (7.6+/-0 5MU/g). The HPLC profile showed no traces of TTX, but only the presence of PSPs (STX, GTX 2 and GTX 3). These toxins were also confirmed by electrospray ionization mass spectrometry.

This study compared 50 Latino and 50 White American students' perceptions of the severity of 25 psychological problems, their willingness to seek help for these problems, and their preferences for caregivers. Each group received a modified version of the Personal Problems Inventory. Latino students rated depression, financial concerns, and discrimination as more severe problems; their preference for mental health workers consistently significantly exceeded those of White students, although both groups preferred seeking help from family and community resources. Findings suggest the possibility of a greater role for therapists serving Latino students than currently exists.

Background: Unrepaired DNA double-stranded breaks (DSBs) can result in the whole or partial loss of chromosomes. Previously, we showed that the ends of broken chromosomes remain associated. Here, we have examined the machinery that holds broken chromosome ends together, and we have explored the behavior of broken chromosomes as they pass through mitosis., Results: Using GFP-localized arrays flanking an HO endonuclease site, we examined the association of broken chromosome ends in yeast cells that are checkpoint-arrested in metaphase. This association is partially dependent upon Rad50 and Rad52. After 6-8 hr, cells adapted to the checkpoint and resumed mitosis, segregating the broken chromosome. When this occurred, we found that the acentric fragments cosegregated into either the mother or daughter cell 95% of the time. Similarly, pedigree analysis showed that postmitotic repair of a broken chromosome (rejoining the centric and acentric fragments) occurred in either the mother or daughter cell, but rarely both, consistent with a model in which both acentric sister chromatid fragments are passaged into the same nucleus., Conclusions: These data suggest two related phenomena: an intrachromosomal association that holds the halves of a single broken sister chromatid together in metaphase and an interchromosomal force that tethers broken sister chromatids to each other and promotes their missegregation. Strikingly, the interchromosomal association of DNA breaks also promotes the missegregation of centromeric chromosomal fragments, albeit to a lesser extent than acentric fragments. The DNA break-induced missegregation of acentric and centric chromosome fragments provides a novel mechanism for the loss of heterozygosity that precedes tumorigenesis in mammalian cells.

Background: Carcinoma of the cervix and a prolapsed uterus are common diseases in underdeveloped countries, but their association is quite rare., Case: We report here the clinical characteristics of two Brazilian patients with carcinoma of the uterine cervix associated with a third-degree prolapsed uterus. The patients, respectively aged 69 and 73 years, were admitted with an ulcerated prolapsed uterus. Biopsy of the ulcerated cervical lesion confirmed epidermoid carcinoma. The patients underwent radical vaginal hysterectomy complemented with external irradiation. The first patient was lost to follow-up, whereas the second is alive, with no signs of disease, 2 years after surgery., Conclusion: When operable invasive cervical carcinoma is found in association with full prolapse, radical vaginal hysterectomy complemented with radiotherapy seems to be an adequate therapeutic option., (©2002 Elsevier Science.)

The Ddc1/Rad17/Mec3 complex and Rad24 are DNA damage checkpoint components with limited homology to replication factors PCNA and RF-C, respectively, suggesting that these factors promote checkpoint activation by "sensing" DNA damage directly. Mec1 kinase, however, phosphorylates the checkpoint protein Ddc2 in response to damage in the absence of all other known checkpoint proteins, suggesting instead that Mec1 and/or Ddc2 may act as the initial sensors of DNA damage. In this paper, we show that Ddc1 or Ddc2 fused to GFP localizes to a single subnuclear focus following an endonucleolytic break. Other forms of damage result in a greater number of Ddc1-GFP or Ddc2-GFP foci, in correlation with the number of damage sites generated, indicating that Ddc1 and Ddc2 are both recruited to sites of DNA damage. Interestingly, Ddc2 localization is severely abrogated in mec1 cells but requires no other known checkpoint genes, whereas Ddc1 localization requires Rad17, Mec3, and Rad24, but not Mec1. Therefore, Ddc1 and Ddc2 recognize DNA damage by independent mechanisms. These data support a model in which assembly of multiple checkpoint complexes at DNA damage sites stimulates checkpoint activation. Further, we show that although Ddc1 remains strongly localized following checkpoint adaptation, many nuclei contain only dim foci of Ddc2-GFP, suggesting that Ddc2 localization may be down-regulated during resumption of cell division. Lastly, visualization of checkpoint proteins localized to damage sites serves as a useful tool for analysis of DNA damage in living cells.

This article provides an overview of the main problems that ethics committees deal with when analysing clinical trials. Some characteristics of the different phases are discussed as well as some particular problems of the Portuguese law.

We report on the observation of sex-restricted, non-Mendelian inheritance over a region of mouse Chromosome (Chr) 11, occurring in the offspring of crosses between two commonly used Mus musculus-derived inbred strains, C57BL/6J and DBA/2J. In the surviving backcross progeny of reciprocal matings between (C57BL/6J x DBA/2J)F1 hybrids and the C57BL/6J parental strain, we observed the preferential appearance of C57BL/6J alleles along a region of Chr 11. The deviation from Mendelian predictions was observed only in female offspring from both reciprocal backcrosses, and not in males from either cross. The sex-specificity of the observed non-Mendelian inheritance points to an explanation based on embryonic or neonatal lethality. Our data add to previously obtained evidence for a Chr 11 locus or loci with sex-specific and allele-specific effects on viability.

Mice from various inbred strains consume alcoholic beverages at highly reproducible and strain-specific levels. While most mice consume alcohol in moderate amounts, C57BL/6J animals exhibit sustained oral ingestion of high levels of alcohol in the presence of competing water and food. We now report a genetic investigation of this phenotype as one potential model for alcoholism. An intercross-backcross breeding protocol was used to identify two recessive alcohol preference quantitative trait loci (QTLs) that are both sex-restricted in expression. A comparison of our results with those of an earlier morphine preference study argues against the hypothesis of a single unified phenotype defined by a preference for all euphoria-producing drugs.

This is a retrospective analysis of 148 patients with histologically proven carcinoma of the cervix, stage III, treated with irradiation. All patients received external irradiation with cobalt 60 followed by intracavitary radium application. The median age was 55 years. Squamous cell carcinoma was found in 96.5% of the cases. The 8-year actuarial survival rate was 41%. Bilateral parametrial invasion proved to be a strong prognostic factor. Patients with unilateral disease had a survival rate of 43% whereas in those with bilateral involvement it was only 15% (P less than 0.005). The total pelvic failure rate was 29.5%. The overall incidence of distant metastasis was 11%. The complication rate (minor and major complications) was high, with vaginal stenosis (22.5%), proctitis (21.5%), cystitis (13.5%), and fistulae (4%) occurring in 33, 32, 20, and 6 patients, respectively. New treatment modalities are urgently needed for advanced carcinoma of the cervix. Bilateral parametrial involvement is an unfavorable prognostic factor and this should be kept in mind when designing new protocols.