Is zoonotic Plasmodium vivax malaria an obstacle for disease elimination?

BACKGROUND: The groundwork for malaria elimination does not currently consider the potential of Plasmodium zoonotic cycles that involve non-human primates (NHPs) in sylvatic environments. Since vivax malaria is less responsive to control measures, finding Plasmodium vivax infected NHPs adds even more concern. METHODS: Both Free-living monkeys in forest fragments inside the urban area and captive monkeys from a local zoo had blood samples tested for Plasmodium species. RESULTS: In this study, among the Neotropical monkeys tested, three (4.4%), one captive and two free-living, were found to be naturally infected by P. vivax. CONCLUSION: This important finding indicates that it is necessary to estimate the extent to which P. vivax NHP infection contributes to the maintenance of malaria transmission to humans. Therefore, the discussion on wildlife conservation and management must be incorporated into the malaria elimination agenda.

Hyperbaric oxygen as an adjuvant treatment for patients with COVID-19 severe hypoxaemia: a randomised controlled trial.

BACKGROUND: Hyperbaric oxygen (HBO2) therapy has been proposed to treat hypoxaemia and reduce inflammation in COVID-19. Our objective was to analyse safety and efficacy of HBO2 in treatment of hypoxaemia in patients with COVID-19 and evaluate time to hypoxaemia correction. METHODS: This was a multicentre, open-label randomised controlled trial conducted in Buenos Aires, Argentina, between July and November 2020. Patients with COVID-19 and severe hypoxaemia (SpO2 ≤90% despite oxygen supplementation) were assigned to receive either HBO2 treatment or the standard treatment for respiratory symptoms for 7 days. HBO2 treatment was planned for ≥5 sessions (1 /day) for 90 min at 1.45 atmosphere absolute (ATA). Outcomes were time to normalise oxygen requirement to SpO2 ≥93%, need for mechanical respiratory assistance, development of acute respiratory distress syndrome and mortality within 30 days. A sample size of 80 patients was estimated, with a planned interim analysis after determining outcomes on 50% of patients. RESULTS: The trial was stopped after the interim analysis. 40 patients were randomised, 20 in each group, age was 55.2±9.2 years. At admission, frequent symptoms were dyspnoea, fever and odynophagia; SpO2 was 85.1%±4.3% for the whole group. Patients in the treatment group received an average of 6.2±1.2 HBO2 sessions. Time to correct hypoxaemia was shorter in treatment group versus control group; median 3 days (IQR 1.0-4.5) versus median 9 days (IQR 5.5-12.5), respectively (p<0.010). OR for recovery from hypoxaemia in the HBO2 group at day 3 compared with the control group was 23.2 (95% CI 1.6 to 329.6; p=0.001) Treatment had no statistically significant effect on acute respiratory distress syndrome, mechanical ventilation or death within 30 days after admission. CONCLUSION: Our findings support the safety and efficacy of HBO2 in the treatment of COVID-19 and severe hypoxaemia. TRIAL REGISTRATION NUMBER: NCT04477954.

Allergen challenge-induced changes in bone-marrow responses to leukotriene D4, nonsteroidal anti-inflammatory drugs and cytokines.

Context: In nonallergic (naive) mice, type I cysteinyl-leukotriene receptors (CysLT1R) mediate the stimulatory effects of cytokines (eotaxin/CCL11, interleukin[IL] - 13), and nonsteroidal anti-inflammatory drugs (NSAID; indomethacin, aspirin) on eosinophil production by IL-5-stimulated bone-marrow. In ovalbumin (OVA)-sensitized mice, airway challenge-induced bone-marrow eosinophilia and eosinopoiesis are prevented by pretreatment with blockers of adrenal glucocorticoid signaling (RU486, metyrapone) or cysteinyl-leukotriene (CysLT) signaling (montelukast).Objective: To define whether allergen challenge modifies subsequent bone-marrow responses to CysLT, NSAID, and cytokines which act through type 1 CysLT receptor (CysLT1R).Methods: We examined the effects of sensitization/challenge, and of in vivo blockade of endogenous glucocorticoid or CysLT signaling, on ex vivo responses to CysLT1R-dependent stimuli.Results and discussion: Challenge abolished the stimulatory ex vivo responses to CysLT1R-dependent agents in the eosinophil lineage. In cultured bone-marrow of naive, sensitized and sensitized/challenged mice, responses to leukotriene D4 (LTD4) in eosinophil differentiation ex vivo shifted from stimulatory (without challenge) to suppressive (following challenge). Both stimulatory and suppressive LTD4 effects were blocked by montelukast. The suppressive LTD4 effect was accounted for by accelerated maturation followed by apoptosis of eosinophils. RU486/metyrapone or montelukast pretreatments before challenge prevented the challenge-induced change in subsequent responses to all these agents. Hence, allergen challenge has two separate effects on bone-marrow: (a) it enhances eosinopoiesis in vivo and upregulates ex vivo responses to IL-5; (b) it promotes a faster, but self-limiting, response to LTD4 and CysLT1R-dependent stimuli.Conclusion: Allergen challenge modifies eosinopoiesis through systemic (glucocorticoid- and CysLT1R-dependent) mechanisms, increasing responses to IL-5 but restricting responses to subsequent CysLT1R stimulation.

[Costs attributable to obesity, hypertension, and diabetes in the Unified Health System, Brazil, 2018Costos atribuibles a la obesidad, la hipertensión y la diabetes en el Sistema Único de Salud de Brasil, 2018]. / Custos atribuíveis a obesidade, hipertensão e diabetes no Sistema Único de Saúde, Brasil, 2018.

OBJECTIVE: To estimate the cost attributable to arterial hypertension, diabetes and obesity in the Unified Health System of Brazil in 2018. METHOD: The study estimated the cost attributable to non-communicable chronic diseases based on relative risk and population prevalence of hypertension, diabetes, and obesity, considering the cost of hospitalizations, outpatient procedures, and medications distributed by the SUS to treat these diseases. Cost data were obtained from SUS information systems. The analysis explored the cost of disease according to sex and age in the adult population. RESULTS: The total cost of hypertension, diabetes, and obesity in the SUS reached R$ 3.45 billion (95%CI: 3.15-3.75) in 2018, that is, more than US$ 890 million. Of this amount, 59% referred to the treatment of hypertension, 30% to diabetes, and 11% to obesity. The age group from 30 to 69 years accounted for 72% of the total costs, and women accounted for 56%. When obesity was considered separately as a risk factor for hypertension and diabetes, the cost attributable to this diseases reached R$ 1.42 billion (95%CI: 0.98-1.87), i.e., 41% of the total cost. CONCLUSIONS: The estimates of costs attributable to the main chronic diseases associated with inadequate diet revealed a heavy economic burden of these disorders for the SUS. The data show the need to prioritize integrated and intersectoral policies for the prevention and control of hypertension, diabetes, and obesity, and may support the advocacy for interventions such as fiscal and regulatory measures to ensure that the objectives of the United Nations Decade of Action on Nutrition are met.

OBJETIVO: Estimar los costos atribuibles a la hipertensión arterial, la diabetes y la obesidad en el Sistema Único de Salud (SUS) de Brasil en el 2018. MÉTODOS: Se estimaron los costos atribuibles a las enfermedades crónicas no transmisibles a partir de los riesgos relativos y de las tasas de prevalencia poblacional de hipertensión, diabetes y obesidad, teniendo en cuenta los costos de hospitalización, los procedimientos ambulatorios y los medicamentos distribuidos por el SUS para el tratamiento de esas enfermedades. Los datos de costos se obtuvieron en los sistemas de información de salud disponibles en el SUS. En el análisis se exploraron los costos de las enfermedades según el sexo y la edad de la población adulta. RESULTADOS: Los costos totales atribuibles a la hipertensión, la diabetes y la obesidad en el SUS alcanzaron R$ 3,450 milliones (IC 95%: de 3,15 a 3,75) en el 2018, o sea, más de US$ 890 millones. De esos costos, 59% correspondió al tratamiento de la hipertensión, 30% al de la diabetes y 11% al de la obesidad. En total, 72% de los costos correspondieron a personas de 30 a 69 años y 56%, a mujeres. Al considerarse por separado la obesidad como factor de riesgo de hipertensión y diabetes, los costos atribuibles a esa enfermedad alcanzaron R$ 1.420 millones (IC 95%: de 0,98 a 1,87), o sea, 41% del total. CONCLUSIONES: Las estimaciones de los costos atribuibles a las principales enfermedades crónicas relacionadas con la alimentación inadecuada ponen de manifiesto la pesada carga económica de esas enfermedades para el SUS. Los datos muestran la necesidad de priorizar políticas integradas e intersectoriales para la prevención y el control de la hipertensión, la diabetes y la obesidad, y permiten apoyar la defensa de intervenciones como medidas fiscales y regulatorias para alcanzar los objetivos del Decenio de las Naciones Unidas de Acción sobre la Nutrición.

Modality transition on renal replacement therapy and quality of life of patients: a 10-year follow-up cohort study.

PURPOSE: Despite advance in renal replacement therapy (RRT), patients with chronic end-stage renal disease (ESRD) face various limitations, and renal transplantation (Tx) is the treatment that impacts most on quality of life (QoL). This study aimed to assess changes in QoL in a cohort of ESRD dialysis patients. METHODS: Sociodemographic, clinical, nutritional, lifestyle, and QoL data were collected from 712 patients at baseline (time 1) and after 10 years of follow-up (time 2) for patients surviving. The QoL was assessed through the 36-Item Short Form Health Survey (SF-36) and the multiple linear regression model was used to analyze the factors associated with change in QoL. RESULTS: A total of 205 survivors were assessed and distributed into three groups according to current RRT (Dialysis-Dialysis, Dialysis-Tx, and Dialysis-Tx-Dialysis). At time 1, only age was significantly different among groups; at time 2, transplant patients sustained greater social participation, job retention, and improvement in SF-36 scores. The factors associated with change in QoL were more time on dialysis interfering negatively on physical functioning (p = 0.002), role-physical limitations (p  = 0.002), general health (p  = 0.007), social functioning (p = 0.02), role-emotional (p = 0.003), and physical components ( p = 0.002); non-participation in social groups at times 1 and 2 reducing vitality (p = 0.02) scores; and having work at time 2, increasing vitality (p = 0.02) and mental health (p  = 0.02) scores. CONCLUSIONS: QoL was shown to be dynamic throughout the years of RRT, transplantation being the treatment with more benefits to the ESRD. More time on dialysis and limited social and occupational routine were associated with a reduction in QoL.

Blockage of Eosinopoiesis by IL-17A Is Prevented by Cytokine and Lipid Mediators of Allergic Inflammation.

Interleukin- (IL-) 17A, a pleiotropic mediator of inflammation and autoimmunity, potently stimulates bone-marrow neutrophil production. To explore IL-17A effects on eosinopoiesis, we cultured bone-marrow from wild-type mice, or mutants lacking inducible nitric oxide synthase (iNOS-/-), CD95 (lpr), IL-17RA, or IL-4, with IL-5, alone or associated with IL-17A. Synergisms between IL-17A-activated, NO-dependent, and NO-independent mechanisms and antagonisms between IL-17A and proallergic factors were further examined. While IL-17A (0.1-10 ng/mL) had no IL-5-independent effect on eosinopoiesis, it dose-dependently suppressed IL-5-induced eosinophil differentiation, by acting during the initial 24 hours. Its effectiveness was abolished by caspase inhibitor, zVAD-fmk. The effect of IL-17A (0.1-1 ng/mL) was sensitive to the iNOS-selective inhibitor aminoguanidine and undetectable in iNOS-/- bone-marrow. By contrast, a higher IL-17A concentration (10 ng/mL) retained significant suppressive effect in both conditions, unmasking a high-end iNOS-independent mechanism. Lower IL-17A concentrations synergized with NO donor nitroprusside. Eosinopoiesis suppression by IL-17A was (a) undetectable in bone-marrow lacking IL-17RA or CD95 and (b) actively prevented by LTD4, LTC4, IL-13, and eotaxin. Sensitivity to IL-17A was increased in bone-marrow lacking IL-4; adding IL-4 to the cultures restored IL-5 responses to control levels. Therefore, effects of both IL-17A and proallergic factors are transduced by the iNOS-CD95 pathway in isolated bone-marrow.

The In Vivo Granulopoietic Response to Dexamethasone Injection Is Abolished in Perforin-Deficient Mutant Mice and Corrected by Lymphocyte Transfer from Nonsensitized Wild-Type Donors.

Exogenously administered glucocorticoids enhance eosinophil and neutrophil granulocyte production from murine bone-marrow. A hematological response dependent on endogenous glucocorticoids underlies bone-marrow eosinophilia induced by trauma or allergic sensitization/challenge. We detected a defect in granulopoiesis in nonsensitized, perforin-deficient mice. In steady-state conditions, perforin- (Pfp-) deficient mice showed significantly decreased bone-marrow and blood eosinophil and neutrophil counts, and colony formation in response to GM-CSF, relative to wild-type controls of comparable age and/or weight. By contrast, peripheral blood or spleen total cell and lymphocyte numbers were not affected by perforin deficiency. Dexamethasone enhanced colony formation by GM-CSF-stimulated progenitors from wild-type controls, but not Pfp mice. Dexamethasone injection increased bone-marrow eosinophil and neutrophil counts in wild-type controls, but not Pfp mice. Because perforin is expressed in effector lymphocytes, we examined whether this defect would be corrected by transferring wild-type lymphocytes into perforin-deficient recipients. Short-term reconstitution of the response to dexamethasone was separately achieved for eosinophils and neutrophils by transfer of distinct populations of splenic lymphocytes from nonsensitized wild-type donors. Transfer of the same amount of splenic lymphocytes from perforin-deficient donors was ineffective. This demonstrates that the perforin-dependent, granulopoietic response to dexamethasone can be restored by transfer of innate lymphocyte subpopulations.

Roles of 5-lipoxygenase and cysteinyl-leukotriene type 1 receptors in the hematological response to allergen challenge and its prevention by diethylcarbamazine in a murine model of asthma.

Diethylcarbamazine (DEC), which blocks leukotriene production, abolishes the challenge-induced increase in eosinopoiesis in bone-marrow from ovalbumin- (OVA-) sensitized mice, suggesting that 5-lipoxygenase (5-LO) products contribute to the hematological responses in experimental asthma models. We explored the relationship between 5-LO, central and peripheral eosinophilia, and effectiveness of DEC, using PAS or BALB/c mice and 5-LO-deficient mutants. We quantified eosinophil numbers in freshly harvested or cultured bone-marrow, peritoneal lavage fluid, and spleen, with or without administration of leukotriene generation inhibitors (DEC and MK886) and cisteinyl-leukotriene type I receptor antagonist (montelukast). The increase in eosinophil numbers in bone-marrow, observed in sensitized/challenged wild-type mice, was abolished by MK886 and DEC pretreatment. In ALOX mutants, by contrast, there was no increase in bone-marrow eosinophil counts, nor in eosinophil production in culture, in response to sensitization/challenge. In sensitized/challenged ALOX mice, challenge-induced migration of eosinophils to the peritoneal cavity was significantly reduced relative to the wild-type PAS controls. DEC was ineffective in ALOX mice, as expected from a mechanism of action dependent on 5-LO. In BALB/c mice, challenge significantly increased spleen eosinophil numbers and DEC treatment prevented this increase. Overall, 5-LO appears as indispensable to the systemic hematological response to allergen challenge, as well as to the effectiveness of DEC.

5-lipoxygenase-dependent recruitment of neutrophils and macrophages by eotaxin-stimulated murine eosinophils.

The roles of eosinophils in antimicrobial defense remain incompletely understood. In ovalbumin-sensitized mice, eosinophils are selectively recruited to the peritoneal cavity by antigen, eotaxin, or leukotriene(LT)B4, a 5-lipoxygenase (5-LO) metabolite. 5-LO blockade prevents responses to both antigen and eotaxin. We examined responses to eotaxin in the absence of sensitization and their dependence on 5-LO. BALB/c or PAS mice and their mutants (5-LO-deficient ALOX; eosinophil-deficient GATA-1) were injected i.p. with eotaxin, eosinophils, or both, and leukocyte accumulation was quantified up to 24 h. Significant recruitment of eosinophils by eotaxin in BALB/c, up to 24 h, was accompanied by much larger numbers of recruited neutrophils and monocytes/macrophages. These effects were abolished by eotaxin neutralization and 5-LO-activating protein inhibitor MK886. In ALOX (but not PAS) mice, eotaxin recruitment was abolished for eosinophils and halved for neutrophils. In GATA-1 mutants, eotaxin recruited neither neutrophils nor macrophages. Transfer of eosinophils cultured from bone-marrow of BALB/c donors, or from ALOX donors, into GATA-1 mutant recipients, i.p., restored eotaxin recruitment of neutrophils and showed that the critical step dependent on 5-LO is the initial recruitment of eosinophils by eotaxin, not the secondary neutrophil accumulation. Eosinophil-dependent recruitment of neutrophils in naive BALB/c mice was associated with increased binding of bacteria.

Detection of Zika Virus in Aedes aegypti and Aedes albopictus Mosquitoes Collected in Urban Forest Fragments in the Brazilian Amazon.

Zika virus (ZIKV) is an RNA flavivirus (Flaviviridae family) endemic in tropical and subtropical regions that is transmitted to humans by Aedes (Stegomyia) species mosquitoes. The two main urban vectors of ZIKV are Aedes aegypti and Aedes albopictus, which can be found throughout Brazil. This study investigated ZIKV infection in mosquito species sampled from urban forest fragments in Manaus (Brazilian Amazon). A total of 905 non-engorged female Ae. aegypti (22 specimens) and Ae. albopictus (883 specimens) were collected using BG-Sentinel traps, entomological hand nets, and Prokopack aspirators during the rainy and dry seasons between 2018 and 2021. All pools were macerated and used to inoculate C6/36 culture cells. Overall, 3/20 (15%) Ae. aegypti and 5/241 (2%) Ae. albopictus pools screened using RT-qPCR were positive for ZIKV. No supernatants from Ae. aegypti were positive for ZIKV (0%), and 15 out of 241 (6.2%) Ae. albopictus pools were positive. In this study, we provide the first-ever evidence of Ae. albopictus naturally infected with ZIKV in the Amazon region.

Subcutaneous Emphysema after a Dental Procedure.

Subcutaneous emphysema is the presence of air beneath the skin's soft tissues. It can result from medical conditions, trauma or iatrogenic causes. The occurrence of subcutaneous emphysema after a dental procedure is rare. Although it is mostly a benign and self-limiting complication, the consequences may be severe and life-threatening. We report the case of a 20-year-old man who presented to the emergency department with swelling of his face and neck after dental treatment. The diagnosis of subcutaneous emphysema and pneumomediastinum was made based on physical examination and a computerized tomography scan. LEARNING POINTS: Subcutaneous emphysema is a rare complication of dental procedures.It is mostly benign and self-limiting, although the consequences may be severe and potentially life-threatening.Early diagnosis and accurate treatment based on understanding its characteristics are important in the prognosis.

Mastodon footprints found to be water erosion in the Quebrada de Chalán (Licto, Ecuador).

The Chalan ravine is a deep bed creek that runs through Licto (Ecuador). It has been known since the 19th century for the abundance of paleontological remains of Pleiostocene fauna and megafauna in its profiles, where entire remains of mastodons were recovered. The abundance of these remains made one of the high areas, where marmites exist in different forms, was traditionally considered as mastodon footprints. Archaeological prospecting, geographic information system (GIS) technology, unmanned aerial vehicle (UAV), photogrammetry, and the geological study of the place, allowed us to determine that the mythical traces of mastodon were marmites made by the water erosion produced in the same ravine over time.

Automated analysis of bone-conduction cortical auditory evoked potential in normal-hearing neonates.

INTRODUCTION: The cortical auditory evoked potential allows the possibility of objectively evaluating the entire auditory system, which is desirable in the pediatric population. Bone conduction auditory stimulation is recommended in the differential diagnosis of conductive hearing loss. However, there are not many studies of cortical auditory evoked potential using bone conduction. OBJECTIVE: The aim of this study was to characterize the response of cortical auditory evoked potential through bone conduction in normal-hearing neonates using an automated response analysis equipment. METHODS: This study included 30 normal-hearing neonates, without risk factors for hearing loss. The equipment used was the HEARlab automated response analysis and the cortical responses were evaluated at the frequencies of 500-4000Hz through bone conduction, at intensity ranging from 0 to 60dBnHL. The latencies and amplitudes were manually marked by experienced judges. RESULTS: Cortical auditory evoked potential responses were detected in 100% of the evaluated subjects and there was no difference regarding the cortical response of the neonates in relation to the variables of gender, ear and masking use. At an intensity of 60 dBnHL for the frequencies of 500, 1000, 2000 and 4000Hz the latencies were 234; 241; 239 and 253ms and the amplitudes were 15.6; 8.4; 6.2; 6.3µV. The mean thresholds were 23.6; 28; 31 and 33.1dBnHL, respectively. CONCLUSION: It was possible to measure the cortical auditory evoked potential response in the neonatal population using bone vibrator as sound transducer and to draw the profile of the cortical auditory evoked potential latencies and amplitudes by frequencies at the intensity of 60dBnHL and at the threshold.

5-lipoxygenase- and Glucocorticoid-dependent eosinophilia in a novel surgical model in mice.

BACKGROUND: Subcutaneous implants of heat-coagulated egg white (egg white implants, EWI) induce intense local eosinophilia and prime for hyperreactivity following airway ovalbumin challenge. The roles of allergen sensitization, surgical trauma-induced glucocorticoids, and the 5-lipoxygenase (5-LO) pathway were hitherto unexplored in this model, in which quantitative recovery and large-scale purification of the eosinophils from the inflammatory site for functional and immunopharmacological studies are difficult to achieve. METHODS: We overcame this limitation by shifting the implantation site to the peritoneal cavity (EWIp), thereby enabling quantitative leukocyte retrieval. RESULTS: By day 7 post-surgery, eosinophil counts reached ~ 30% of all leukocytes recovered. Eosinophilia was prevented by: a) induction of allergen-specific oral tolerance to ovalbumin, the main allergen in egg white; b) inactivation of the 5-lipoxygenase pathway; c) blockade of endogenous glucocorticoid signaling by pretreatment with metirapone plus mifepristone before surgery. Highly purified eosinophils (~99% pure) could be obtained from the peritoneal exudate of EWIp-carrier mice in 2 simple, antibody-free steps. Preparative-scale yields, suitable for most biochemical, pharmacological, and molecular applications, were routinely obtained, and could be further enhanced through addition of pre-or post-surgery immunization steps (active or adoptive). The recovered eosinophils were fully functional in vivo, as demonstrated by the transfer of purified eosinophils into eosinophil-deficient Δdbl-GATA-1-KO mice, which upon subsequent challenge with eotaxin-1 present secondary accumulation of neutrophils, but not of mononuclear phagocytes. CONCLUSION: These findings document glucocorticoid-, allergen- and 5-lipoxygenase-dependent eosinophilia, which makes EWIp carriers an abundant source of pure, nontransgenic eosinophils for immunopharmacological studies.

Adaptation of the stomatherapy service during the COVID-19 pandemic: an experience report.

OBJECTIVE: To report the experience of adapting the stomatherapy service during the COVID-19 pandemic. METHOD: Experience report related to adaptations in the work routine in times of COVID-19 pandemic, from March to May 2020, in a specialized stomatherapy center in a city in the South of Brazil. RESULTS: The work routines were adapted to suit the protection measures for workers and users who used stomatherapy services. Some assistance processes were implemented to make users' access to care more flexible, and to modify routines to increase the safety of health professionals and users. CONCLUSION: The need to adapt the physical area, rethink the dynamics of care, use personal protective equipment, and guidance for servers and patients were of fundamental importance to continue attending the population safely in times of pandemic.

The ability to survive mitosis in the presence of microtubule poisons differs significantly between human nontransformed (RPE-1) and cancer (U2OS, HeLa) cells.

We used live cell imaging to compare the fate of human nontransformed (RPE-1) and cancer (HeLa, U2OS) cells as they entered mitosis in nocodazole or taxol. In the same field, and in either drug, a cell in all lines could die in mitosis, exit mitosis and die within 10 h, or exit mitosis and survive > or =10 h. Relative to RPE-1 cells, significantly fewer HeLa or U2OS cells survived mitosis or remained viable after mitosis: in nocodazole concentrations that inhibit spindle microtubule assembly, or in 500 nM taxol, 30% and 27% of RPE-1 cells, respectively, died in or within 10 h of exiting mitosis while 90% and 49% of U2OS and 78% and 81% of HeLa died. This was even true for clinically relevant taxol concentrations (5 nM) which killed 93% and 46%, respectively, of HeLa and U2OS cells in mitosis or within 10 h of escaping mitosis, compared to 1% of RPE-1 cells. Together these data imply that studies using HeLa or U2OS cells, harvested after a prolonged block in mitosis with nocodazole or taxol, are significantly contaminated with dead or dying cells. We also found that the relationship between the duration of mitosis and survival is drug and cell type specific and that lethality is related to the cell type and drug used to prevent satisfaction of the kinetochore attachment checkpoint. Finally, work with a pan-caspase inhibitor suggests that the primary apoptotic pathway triggered by nocodazole during mitosis in RPE-1 cells is not active in U2OS cells. Cell Motil. Cytoskeleton 2008. (c) 2008 Wiley-Liss, Inc.

Impact of clinical, sociodemographic and quality of life factors on dialysis patient survival: a nine-year follow-up cohort study.

Although renal replacement therapy has contributed to the survival of chronic kidney failure (CKF) patients, mortality remains a major concern. This study aimed to identify the factors associated with mortality in a prospective cohort of CKF patients. Sociodemographic, clinical, nutritional, lifestyle and quality of life data were collected from 712 patients. The instruments used were the Short-Form Health Survey (SF-36), Global Subjective Assessment (GSA) and Charlson Comorbidity Index (CCI) questionnaires. A total of 444 patients died during the study. After five years of follow-up, factors such as not being married (hazard ratio - HR = 1.289, 95%CI: 1.001; 1.660), a low frequency of leisure activities (HR = 1.321; 95%CI: 1.010; 1.727) and not being transplanted (HR = 7.246; 95%CI: 3.359; 15.630) remained independently associated with the risk of mortality. At the end of the follow-up period, factors such as not being married (HR = 1.337, 95%CI: 1.019; 1.756), not being transplanted (HR = 7.341, 95%CI: 3.829; 14.075) and having a worse nutritional status (HR = 1.363, 95%CI: 1.002; 1.853) remained independently associated with an increased risk of mortality, whereas a high schooling level (10 to 12 years, HR = 0.578, 95%CI: 0.344; 0.972; and over 12 years, HR = 0.561, 95%CI: 0.329; 0.956) and a better SF-36 physical functioning score (HR = 0.992, 95%CI: 0.987; 0.998) were protective factors associated with survival. The survival of patients with CKF is associated with factors not restricted to the clinical spectrum. The following factors were associated with high mortality: not being married, low schooling level, a limited social routine, a longer time on dialysis, worse nutritional status, and worse physical functioning.

Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint.

In the presence of unattached/weakly attached kinetochores, the spindle assembly checkpoint (SAC) delays exit from mitosis by preventing the anaphase-promoting complex (APC)-mediated proteolysis of cyclin B, a regulatory subunit of cyclin-dependent kinase 1 (Cdk1). Like all checkpoints, the SAC does not arrest cells permanently, and escape from mitosis in the presence of an unsatisfied SAC requires that cyclin B/Cdk1 activity be inhibited. In yeast , and likely Drosophila, this occurs through an "adaptation" process involving an inhibitory phosphorylation on Cdk1 and/or activation of a cyclin-dependent kinase inhibitor (Cdki). The mechanism that allows vertebrate cells to escape mitosis when the SAC cannot be satisfied is unknown. To explore this issue, we conducted fluorescence microscopy studies on rat kangaroo (PtK) and human (RPE1) cells dividing in the presence of nocodazole. We find that in the absence of microtubules (MTs), escape from mitosis occurs in the presence of an active SAC and requires cyclin B destruction. We also find that cyclin B is progressively destroyed during the block by a proteasome-dependent mechanism. Thus, vertebrate cells do not adapt to the SAC. Rather, our data suggest that in normal cells, the SAC cannot prevent a slow but continuous degradation of cyclin B that ultimately drives the cell out of mitosis.

Depression and anxiety among patients undergoing dialysis and kidney transplantation: a cross-sectional study.

BACKGROUND: Depression and anxiety are the most prevalent psychological disorders among end-stage renal disease patients and are associated with various conditions that result in poorer health outcomes, e.g. reduced quality of life and survival. We aimed to investigate the prevalences of depression and anxiety among patients undergoing renal replacement therapy. DESIGN AND SETTING: Cross-sectional study in Belo Horizonte, Brazil. METHODS: Patients' depression and anxiety levels were assessed using the Beck Inventory. The independent variables were the 36-Item Short-Form Health Survey (SF-36), Charlson Comorbidity Index and Global Subjective Assessment, along with sociodemographic and clinical characteristics. RESULTS: 205 patients were included. Depression and anxiety symptoms were detected in 41.7% and 32.3% of dialysis patients and 13.3% and 20.3% of transplantation patients, respectively. Lower SF-36 mental summary scores were associated with depression among transplantation patients (odds ratio, OR: 0.923; 95% confidence interval, CI: 0.85-0.99; P = 0.03) and dialysis patients (OR: 0.882; 95% CI: 0.83-0.93; P ≤ 0.001). Physical component summary was associated with depression among dialysis patients (OR: 0.906; 95% CI: 0.85-0.96; P = 0.001). Loss of vascular access (OR: 3.672; 95% CI: 1.05-12.78; P = 0.04), comorbidities (OR: 1.578; 95% CI: 1.09-2.27; P = 0.01) and poorer SF-36 mental (OR: 0.928; 95% CI: 0.88-0.97; P = 0.002) and physical (OR: 0.943; 95% CI: 0.89-0.99; P = 0.03) summary scores were associated with anxiety among -dialysis patients. CONCLUSIONS: Depression and anxiety symptoms occurred more frequently among patients undergoing dialysis. Quality of life, comorbidities and loss of vascular access were associated factors.

The Need to Consider Context in the Evaluation of Anti-infectious and Immunomodulatory Effects of Vitamin A and its Derivatives.

Vitamin A and its derivatives (retinoids) act as potent regulators in many aspects of mammalian reproduction, development, repair, and maintenance of differentiated tissue functioning. Unlike other vitamins, Vitamin A and retinoids, which have hormonal actions, present significant toxicity, which plays roles in clinically relevant situations, such as hypervitaminosis A and retinoic acid ("differentiation") syndrome. Although clinical presentation is conspicuous in states of insufficient or excessive Vitamin A and retinoid concentration, equally relevant effects on host resistance to specific infectious agents, and in the general maintenance of immune homeostasis, may go unnoticed, because their expression requires either pathogen exposure or the presence of inflammatory co-morbidities. There is a vast literature on the roles played by retinoids in the maintenance of a tolerogenic, noninflammatory environment in the gut mucosa, which is considered by many investigators representative of a general role played by retinoids as anti-inflammatory hormones elsewhere. However, in the gut mucosa itself, as well as in the bone marrow and inflammatory sites, context determines whether one observes an anti-inflammatory or proinflammatory action of retinoids. Both interactions between specialized cell populations, and interactions between retinoids and other classes of mediators/regulators, such as cytokines and glucocorticoid hormones, must be considered as important factors contributing to this overall context. We review evidence from recent studies on mucosal immunity, granulocyte biology and respiratory allergy models, highlighting the relevance of these variables as well as their possible contributions to the observed outcomes.