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People have known that El Niño events are associated with low rainfall in Southern Africa for a century, and seasonal rainfall forecasts are now available in agricultural advisories for farmers. While there is abundant theory as to how farmers might (or should) use seasonal rainfall information on their farms, little is known about whether this information has been widely used or has had widespread benefit. In this study, we use subnational data on cropping area and yield to see if we can detect any macro-level patterns in agricultural choices or outcomes that are related to knowledge of the El Niño Southern Oscillation or seasonal forecast information in Southern Africa. We find that in Lesotho and parts of South Africa, planted area of maize and sorghum is reduced when there is a dry start to the season and an El Niño event is apparent at the time of planting. Similarly, we find that in both Lesotho and most provinces of South Africa, drought years associated with El Niño have worse yields than drought years that are not associated with El Niño (controlling for rainfall). This association could indicate that people are discouraged during El Niño years by the potential for drought, and they might be reducing cropping area, reducing agricultural investments, or turning to other income-generating activities. We are unable to detect a relationship between yields and the accuracy of seasonal rainfall forecasts, therefore we are unable to observe any additional yield benefit when more accurate seasonal forecast information is available., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erin Coughlan de Perez reports financial support was provided by USAID. Erin Coughlan de Perez reports financial support was provided by National Institute of Environmental Health Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Despite advancements in mechanical circulatory support (MCS) technology, persistent critical complications related to blood contact remain unresolved. To provide a safer alternative therapy, CorInnova is developing a non-blood contacting direct cardiac compression (DCC) device for MCS. To support product development toward clinical trials, a simulation platform has been developed to predict clinical outcomes under patient-specific conditions, guiding patient selection for clinical trials. The Harvi simulation was validated using preclinical in vivo data from experimental studies with the CorInnova device, with n = 28 hemodynamic samples simulated from animal data (n = 4 ovine). After confirming validation, further simulation was performed to predict additional hemodynamic outcomes not captured in animal studies. The simulated effects of CorInnova device therapy were not significantly different from animal data for cardiac output, systemic arterial blood pressure, mean pulmonary artery pressure, central venous pressure, or left ventricular pressure (p > 0.050). Harvi accurately predicts the effects of the CorInnova device in heart failure conditions and can be used in preparation for future clinical trials., Competing Interests: Disclosure: E.C.P. (Hord) was a graduate student at Texas A&M University and a research and development engineering intern with CorInnova, Inc. when this scientific work was conducted. Presently, E.C.P. and C.M.B. are salaried employees of CorInnova, Inc. D.B. is a consultant to Harvi Dynamics, Inc. G.V.L. is a consultant to CorInnova, Inc. J.C.C. is a cofounder of CorInnova, Inc., equity holder, board member, and receives consulting fees as the Chief Technology Officer for CorInnova, Inc. R.M.T. has no conflicts of interest to report., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the ASAIO.)

Background: Encephalitozoon cuniculi is an opportunistic intracellular pathogen that establishes a balanced relationship with immunocompetent individuals depending on the activity of their CD8 + T cells lymphocytes. However, lower resistance to experimental infection with E. cuniculi was found in B-1 deficient mice (Xid), besides increased the number of CD8 T lymphocytes. Here, we evaluated the profile of CD8 + T lymphocytes from Balb/c wild-type (WT) or Balb/c Xid mice (with B-1 cell deficiency) on the microbicidal activity of macrophages challenged with E. cuniculi., Methods: Naïve CD8 T lymphocytes from WT or Xid mice uninfected and primed CD8 T lymphocytes from WT or Xid mice infected with E cuniculi were co-cultured with macrophages previously challenged with E. cuniculi. We evaluated macrophages viability and microbicidal activity, and CD8 T lymphocytes viability and presence of activating molecules (CD62L, CD69, and CD107a)., Results: Macrophages co-cultured with naïve CD8 T lymphocytes from WT demonstrated high microbicidal activity. Naïve CD8 T lymphocytes obtained from WT mice had a higher expression of CD69 and LAMP-1-activating molecules compared to Xid CD8 + T lymphocytes. Primed CD8 T lymphocytes from Xid mice proliferated more than those from WT mice, however, when the expression of the activating molecule CD69 associated with the expression of CD62L was kept low. In conclusion, naïve CD8 + T lymphocytes from Xid mice, deficient in B-1 cells, they had reduced expression of activation molecules and cytotoxic activity., 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 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Introduction: The use of packed red blood cells (pRBCs) for resuscitation is limited by the red blood cell storage lesion, a series of biochemical and physiological changes that occur during the storage and aging of blood. Microvesicles (MVs) shed from pRBCs during this process are one component of the red blood cell storage lesion and lead to acute lung injury and pulmonary vascular microthrombi. We hypothesized that MVs from stored pRBCs lead to the release of P-selectin and von Willebrand factor (vWF) from endothelial cells and that this mechanism is mediated via activation of protein kinase C (PKC) or protein kinase A (PKA)., Methods: Leukoreduced, platelet-poor murine pRBCs were isolated from C57BL/6 8-12 week-old male mice via cardiac puncture, prepared via centrifugation using a Ficoll gradient, and stored for up to 14 days, the equivalent of 42 days of storage in humans. MVs were isolated from the stored pRBC units via sequential high-speed centrifugation. Murine lung endothelial cells (MLECs) were cultured and grown to confluence, then treated with MVs and either calphostin C, a PKC inhibitor (10 μg/mL), or PKI 14-22 amide, a PKA inhibitor (10 μM). The supernatant was collected after 1 h. P-selectin and vWF A2 concentrations were quantified via ELISA. Immunofluorescent staining for vWF was performed on MLECs. Statistical analysis was performed via unpaired t-test or ANOVA as indicated and reported as mean ± SD. Concentration is reported as pg/mL., Results: MLECs treated with MVs isolated from stored pRBCs demonstrated increased release of P-selectin and vWF A2 in a dose-dependent fashion. MLECs treated with MVs prepared from stored as compared to fresh pRBCs demonstrated increased release of P-selectin (3751 ± 726 vs 359 ± 64 pg/mL, p < 0.0001) and vWF A2 (3141 ± 355 vs 977 ± 75 pg/mL, p < 0.0001) with increasing duration of storage. The treatment of MVs with calphostin C decreased the amount of P-selectin (1471 ± 444 vs 3751 ± 726 pg/mL, p < 0.0001) and VWF A2 (2401 ± 289 vs 3141 ± 355 pg/mL, p = 0.0017) released into the supernatant by MLECs compared to MVs alone. The treatment of MVs with PKI 14-22 increased the amount of P-selectin released compared to MVs alone (1999 ± 67 vs 1601 ± 135 pg/mL, p = 0.0018)., Conclusions: MVs from stored pRBCs stimulate the release of P-selectin and VWF A2 from endothelial cells. The effect of MVs increases with both dose of MVs and age of stored pRBCs from which they are formed. This mechanism is dependent on activation of PKC and inhibition of this enzyme represents a potentially significant strategy to modulate the inflammatory response to resuscitation with stored pRBCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest related to this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Pneumonia remains a common complication in trauma patients. Sirtuin 1 (SIRT1) is an anti-inflammatory NAD + -dependent deacetylase that has been shown to reduce the severity of ARDS in polymicrobial sepsis. The impact of SIRT1 in acute pneumonia, however, remains unknown. We hypothesized that SIRT1 deletion in pneumonia would worsen the inflammatory response and clinical severity, and that increased SIRT1 expression would be protective., Methods: Ten- to 14-week-old male and female SIRT1 knockout (S1KO) mice, SIRT1 overexpressor (S1OE) mice, and their wildtype (WT) littermates underwent intra-tracheal inoculation with Pseudomonas aeruginosa . Rectal temperature was recorded, SIRT1 lung protein was quantified by western blotting, Sirt1 mRNA was measured by qPCR, and lung leukocyte subpopulations were analyzed by flow cytometry. Data were analyzed by one-way ANOVA using Prism software., Results: Pneumonia created a functional SIRT1 knockdown in the lungs of WT mice by 4 hours, resulting in comparable SIRT1 levels and temperatures to the S1KO mice by 12 hours. Pneumonia also partially reduced SIRT1expression in S1OE mice, but S1OE mice still had improved thermoregulation 12 hours after pneumonia. In all groups, Sirt1 mRNA expression was not affected by infection. Sirtuin 1 deletion was associated with decreased neutrophil infiltration in the lung, as well as a shift toward a more immature neutrophil phenotype. SIRT1 deletion was also associated with decreased myeloperoxidase-positive neutrophils in the lungs following pneumonia, indicating decreased neutrophil activity. S1OE mice had no change in lung leukocyte subpopulations when compared to WT., Conclusion: Pneumonia creates a functional SIRT1 knockdown in mice. SIRT1 deletion altered the early inflammatory cell response to pneumonia, resulting in a neutrophil response that would be less favorable for bacterial clearance. Despite overexpression of SIRT1, S1OE mice also developed low SIRT1 levels and exhibited only minimal improvement. This suggests increasing SIRT1 transcription is not sufficient to overcome pneumonia-induced downregulation and has implications for future treatment options. Targeting SIRT1 through increasing protein stability may promote a more efficient inflammatory cell response to pneumonia, thereby preventing subsequent lung injury., (Copyright © 2023 American Association for the Surgery of Trauma.)

Introduction: Aspirin is one of the most commonly used drugs worldwide. It is known to present antipyretic, anti-inflammatory and anti-thrombotic actions, making it extremely useful in a wide range of clinical contexts. Interestingly, homeopathically prepared Aspirin 15cH has been found to have a pro-thrombotic effect in rats, raising the hypothesis that Aspirin 15cH could also modulate the activity of inflammatory cells in different pathological processes., Objective: Our objective was to assess what effect Aspirin 15cH has on RAW 264.7 macrophages in vitro ., Methods: The effects of Aspirin 15cH on biochemical and morphological activities of lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages were evaluated. These effects were compared with unchallenged macrophages (negative control), untreated LPS-stimulated macrophages, macrophages treated with succussed water (vehicle control), or aspirin 200 µg/mL (pharmacological inhibitor of LPS activity). Cell morphology (adhered cell area and cytoskeleton arrangements), cell viability, toll-like receptor-4 (TLR-4) expression, and the production of nitric oxide, cytokines and intracellular reactive oxygen species were assessed., Results: Aspirin 15cH reduced the number of cells expressing TLR-4 on the surface ( p  = 0.03) and induced a "columnar" morphology of macrophage pseudopods, indicating changes in cytoskeleton arrangement. When cells were treated with both Aspirin 15cH and LPS, cell morphology became heterogeneous, suggesting that sub-populations of cells had differing sensitivities to LPS or Aspirin 15cH. Exposure of the cells to LPS alone, succussed water or aspirin 200 µg/mL produced effects consistent with the literature., Conclusion: Aspirin 15cH, aspirin 200 µg/mL, LPS and succussed water appear to act as independent stimuli able to induce different patterns of macrophage response. Aspirin 15cH induced changes suggestive of M2 polarization of the macrophages (i.e., toward a wound healing or tissue repair, rather than inflammatory, phenotype). These preliminary findings need to be confirmed in further specific studies., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Exercise is known to promote efficient function of stress circuitry. The developing brain is malleable and thus exercise during adolescence could potentially exert lasting beneficial effects on the stress response that would be detectable in adulthood. The current study determined whether adolescent wheel running was associated with reduced stress response in adulthood, 6 weeks after cessation of exercise. Male and female adolescent rats voluntarily ran for 6 weeks and then were sedentary for 6 weeks prior to 10 days of chronic restraint stress in adulthood. Fecal corticosterone levels were measured during stress, and escape from the restraint tube was assessed on the final day as a proxy for depressive-like behavior. Anxiety-like behavior was measured 24 h later with the elevated plus maze and locomotor behaviors with the open field. Brain and body measurements were taken immediately following behavioral testing. Developmental exercise and adulthood stress both exerted independent effects on physiological and behavioral outcomes in adulthood. Exercise history increased the odds ratio of escape from restraint stress in males, but did not influence other stress-induced behaviors. In summary, exercise early in life exerted lasting effects, but did not substantially alter the adulthood response to restraint stress., (© 2023 Wiley Periodicals LLC.)

Encephalitozoon cuniculi is a unicellular, spore-forming, obligate intracellular eukaryote belonging to the phylum Microsporidia. It is known to infect mainly immunocompromised and immunocompetent mammals, including humans. The parasite-host relationship has been evaluated using both in vitro cell culturing and animal models. For example, Balb/c and C57BL/6 mouse strains have been used interchangeably, although the latter has been considered more susceptible due to the higher fungal load observed after infection. In the present study, we identified the characteristics of the immune response of C57BL/6 mice treated or not with the immunosuppressant cyclophosphamide (Cy) and challenged with E. cuniculi by intraperitoneal route. After 14 days of infection, serum was collected to analyze Th1, Th2, and Th17 cytokine levels. In addition, peritoneal washes were performed, and the spleen sample was collected for immune cell phenotyping, whereas liver, spleen, kidney, lung, intestine, and central nervous system (CNS) samples were collected for histopathological analysis. Although infected mice displayed a reduced absolute number of macrophages, they showed an M1 profile, an elevated number of CD4 + T, CD8 + T, B-1, and B-2 lymphocytes, with a predominance of Th1 inflammatory cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, and interleukin [IL]-2) and Th17. Furthermore, Cy-Infected mice showed a reduced absolute number of macrophages with an M1 profile but a reduced number of CD4 + T, CD8 + T, B-1, and B-2 lymphocytes, with a predominance of Th1 inflammatory cytokines (IFN-γ, TNF-α, and IL-2) and Th2 (IL-4). This group displayed a higher fungal burden as well and developed more severe encephalitozoonosis, which was associated with a reduced number of T and B lymphocytes and a mixed profile of Th1 and Th2 cytokines., Competing Interests: Declaration of competing interest The authors Amanda Miyuki Hidifira; Anuska Marcelino Alvares-Saraiva; Elizabeth Christina Perez; Diva Denelle Spadacci-Morena; Ronalda Silva de Araujo; Maria Anete declare no Competing interests in papers publication “Increased susceptibility to encephalitozoonosis associated with mixed Th1/Th2 profile and M1/M2 profile in mice immunosuppressed with cyclophosphamide”., (Copyright © 2023. Published by Elsevier Inc.)

Encephalitozoon cuniculi, an intracellular pathogen, lives in a balanced relationship with immunocompetent individuals based on the activity of T lymphocytes. We previously highlighted the greater susceptibility of B-1 cell-deficient mice (XID mice) to encephalitozoonosis. This study aimed to develop a model of disseminated and severe encephalitozoonosis in mice with combined immunodeficiency to elucidate the role of B cells. To address this objective, cyclophosphamide (Cy)-treated BALB/c and XID mice were inoculated with E. cuniculi, followed by the evaluation of the immune response and histopathological lesions. Immunosuppressed BALB/c mice manifested no clinical signs with an increase in the populations of T lymphocytes and macrophages in the spleen. Immunosuppressed and infected XID mice revealed elevated T cells, macrophages populations, and pro-inflammatory cytokines levels (IFN-γ, TNF-α, and IL-6) with the presence of abdominal effusion and lesions in multiple organs. These clinical characteristics are associated with extensive and severe encephalitozoonosis. The symptoms and lesion size were reduced, whereas B-2 and CD4 + T cells populations were increased in the spleen by transferring B-2 cells adoptive to XID mice. Moreover, B-1 cells adoptive transfer upregulated the peritoneal populations of B-2 cells and macrophages but not T lymphocytes and decreased the symptoms. Herein, we speculated the consistency in the development of severe and disseminated encephalitozoonosis in mice with genetic deficiency of Bruton's tyrosine kinase (Btk) associated with Cy immunosuppression develop with that of the models with T cell deficiency. Taken together, these data emphasized the crucial role of B cells in the protective immune response against encephalitozoonosis., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: Compared with photon cranial radiation therapy (X-CRT), proton cranial radiation therapy (P-CRT) offers potential advantages in limiting radiation-induced sequalae in the treatment of pediatric brain tumors. This study aims to identify cognitive, functional magnetic resonance and positron emission tomography imaging markers and molecular differences between the radiation modalities., Methods and Materials: Juvenile rats received a single faction of 10 Gy (relative biological effectiveness-weighted dose) delivered with 6 MV X-CRT or at the midspread out Bragg peak of a 100 MeV P-CRT beam. At 3, 6, and 12 months post-CRT, executive function was measured using 5-choice serial reaction time task. At ∼12 months post-CRT, animals were imaged with 18 F-Flurodeoxy-glucose positron emission tomography imaging followed by functional ex vivo magnetic resonance imaging and stained for markers of neuroinflammation., Results: Irradiated animals had cognitive impairment with a higher number of omissions and lower incorrect and premature responses compared with sham (P ≤ .05). The accuracy of the animals' X-CRT was less than that of sham (P ≤ .001). No significant difference in rates of cognitive change were found between the radiation modalities. At 12 months post-CRT, glucose metabolism was significantly higher than sham in X-CRT (P = .04) but not P-CRT. Using diffusion tensor imaging, P-CRT brains were found to have higher white matter volume and fiber lengths compared with sham (P < .03). Only X-CRT animals had higher apparent diffusion coefficient values compared with sham (P = .04). P-CRT animals had more connectomic changes compared with X-CRT. Correlative analysis identified several imaging features with cognitive performance. Furthermore, microgliosis (P < .05), astrogliosis (P < .01), and myelin thinning (P <.05) were observed in both radiation modalities, with X-CRT showing slightly more inflammation., Conclusions: Both P-CRT and X-CRT lead to neurocognitive changes compared with sham. Although no significant difference was observed in neuroinflammation between the irradiated groups, differences were found in late-term glucose metabolism and brain connectome. Our results indicate that despite relative biological effectiveness weighting of the proton dose there are still differential effects which warrants further investigation., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper presents evidence relating to a forecast-based cash and non-food item distribution among vulnerable herder households during the 2017-18 dzud (extreme winter) season in Mongolia, and analyses the results of a quasi-experimental study evaluating its impacts. An innovative approach in disaster risk reduction, forecast-based financing (FbF) can have short- and long-term benefits to vulnerable households but remains understudied. The paper contributes information on a multimodal FbF programme offering one-off cash grants and in-kind veterinary kits. The data found significant effects of reduced mortality and increased offspring survival in some types of livestock, and that the timing of FbF assistance is crucial, as reported early assistance correlated to positive outcomes in terms of reduced animal mortality. These findings can be used to design more effective FbF interventions, to understand better the appropriateness of FbF designs, and to use early warnings and early actions to help people prepare and withstand disasters such as dzuds., (© 2020 The Authors Disasters © 2020 Overseas Development Institute.)

Depending on Leishmania species and the presence/absence of virulence factors, Leishmania extracellular vesicles (EVs) can differently stimulate host immune cells. This work is aimed at characterizing and evaluating the protective role of EVs released by Leishmania amazonensis promastigotes under different maintenance conditions. Initially, using a control strain, we standardized 26°C as the best release temperature to obtain EVs with a potential protective role in the experimental leishmaniasis model. Then, long-term (LT-P) promastigotes of L. amazonensis were obtained after long-term in vitro culture (100 in vitro passages). In vivo -derived (IVD-P) promastigotes of L. amazonensis were selected after 3 consecutive experimental infections in BALB/c mice. Those strains developed similar lesion sizes except for IVD-P at 8 weeks post infection. No differences in EV production were detected in both strains. However, the presence of LPG between LT-P and IVD-P EVs was different. Groups of mice immunized with EVs emulsified in the adjuvant and challenged with IVD-P parasites showed decreased lesion size and parasitic load compared with the nonimmunized groups. The immunization regimen with two doses showed high IFN- γ and IgG2a titers in challenged mice with either IVD-P or LT-P EVs. IL-4 and IL-10 were detected in immunized mice, suggesting a mixed Th1/Th2 profile. EVs released by either IVD-P or LT-P induced a partial protective effect in an immunization model. Thus, our results uncover a potential protective role of EVs from L. amazonensis for cutaneous leishmaniasis. Moreover, long-term maintenance under in vitro conditions did not seem to affect EV release and their immunization properties in mice., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Talita Vieira Dupin et al.)

Background: Since 2014, the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) algorithm for the management of knee osteoarthritis (OA) is available worldwide., Aim: Based on this document, a Southeast Asia Working Group (SEAWG) wished to see how the new ESCEO algorithm developed in 2019 was perceived by Southeast Asian experts and how it was integrated into their clinical practice., Methods: A SEAWG was set up between members of the international ESCEO task force and a group of Southeast Asian experts., Results: Non-pharmacological management should always be combined with pharmacological management. In step 1, symptomatic slow-acting drugs for osteoarthritis are the main background therapy, for which high-quality evidence is available only for the formulations of patented crystalline glucosamine sulfate and chondroitin sulfate. In step 2, oral NSAIDs are a useful option, considering the cardiovascular/renal/gastrointestinal profiles of the individual patient. Intra-articular hyaluronic acid and corticosteroids are a possible alternative to oral NSAIDs, but limited evidence is available. If steps 1 and 2 do not give adequate relief of symptoms, tramadol can be used, but its safety is debated. In general, the indications of the ESCEO algorithm are important in Southeast Asian countries, but the reimbursement criteria of local health systems are an important aspect for adherence to the ESCEO algorithm., Conclusion: This guidance provides evidence-based and easy-to-follow advice on how to establish a treatment algorithm in knee OA, for practical implementation in clinical practice in Southeast Asian countries.

Microsporidia are recognized as opportunistic pathogens in individuals with immunodeficiencies, especially related to T cells. Although the activity of CD8+ T lymphocytes is essential to eliminate these pathogens, earlier studies have shown significant participation of macrophages at the beginning of the infection. Macrophages and other innate immunity cells play a critical role in activating the acquired immunity. After programmed cell death, the cell fragments or apoptotic bodies are cleared by phagocytic cells, a phenomenon known as efferocytosis. This process has been recognized as a way of evading immunity by intracellular pathogens. The present study evaluated the impact of efferocytosis of apoptotic cells either infected or not on macrophages and subsequently challenged with Encephalitozoon cuniculi microsporidia. Macrophages were obtained from the bone marrow monocytes from C57BL mice, pre-incubated with apoptotic Jurkat cells (ACs), and were further challenged with E. cuniculi spores. The same procedures were performed using the previously infected Jurkat cells (IACs) and challenged with E. cuniculi spores before macrophage pre-incubation. The average number of spores internalized by macrophages in phagocytosis was counted. Macrophage expression of CD40, CD206, CD80, CD86, and MHCII, as well as the cytokines released in the culture supernatants, was measured by flow cytometry. The ultrastructural study was performed to analyze the multiplication types of pathogens. Macrophages pre-incubated with ACs and challenged with E. cuniculi showed a higher percentage of phagocytosis and an average number of internalized spores. Moreover, the presence of stages of multiplication of the pathogen inside the macrophages, particularly after efferocytosis of infected apoptotic bodies, was observed. In addition, pre-incubation with ACs or IACs and/or challenge with the pathogen decreased the viability of macrophages, reflected as high percentages of apoptosis. The marked expression of CD206 and the release of large amounts of IL-10 and IL-6 indicated the polarization of macrophages to an M2 profile, compatible with efferocytosis and favorable for pathogen development. We concluded that the pathogen favored efferocytosis and polarized the macrophages to an M2 profile, allowing the survival and multiplication of E. cuniculi inside the macrophages and explaining the possibility of macrophages acting as Trojan horses in microsporidiosis., Competing Interests: The authors have declared that no competing interests exist.

Background:  The homeopathic medicines Silicea terra ( Sil ) and Zincum metallicum ( Zinc ) modulate macrophage activity and were assessed in an experimental study in-vitro for their effects on macrophage-BCG (Bacillus Calmette-Guérin) interaction., Methods:  RAW 264.7 macrophages were infected with BCG, treated with different potencies of Sil and Zinc (6cH, 30cH and 200cH) or vehicle, and assessed 24 and 48 h later for bacilli internalization, hydrogen peroxide (H 2 O 2 ) and cytokine production, and lysosomal activity., Results:  Treatment with vehicle was associated with non-specific inhibition of H 2 O 2 production to the levels exhibited by uninfected macrophages. Sil 200cH induced significant reduction of H 2 O 2 production ( p  < 0.001) compared with the vehicle and all other treatments, as well as higher lysosomal activity ( p  ≤ 0.001) and increased IL-10 production ( p  ≤ 0.05). Such effects were considered specific for this remedy and potency. The number of internalized bacilli was inversely proportional to Zinc potencies, with statistically significant interaction between dilution and treatment ( p  = 0.003). Such linear-like behavior was not observed for Sil dilutions: peak internalization occurred with the 30cH dilution, accompanied by cellular degeneration, and IL-6 and IL-10 increased ( p  ≤ 0.05) only in the cells treated with Sil 6cH., Conclusion:   Sil and Zinc presented different patterns of potency-dependent effect on macrophage activity. Bacterial digestion and a balanced IL-6/IL-10 production were related to Sil 6cH, though reduced oxidative stress with increased lysosomal activity was related to Sil 200cH. Degenerative effects were exclusively related to Sil 30cH, and potency-dependent phagocytosis was related only to Zinc ., Competing Interests: Dr. Bonamin reports grants from UNIP., (Faculty of Homeopathy. This article is published by Thieme.)

People affected by conflict are particularly vulnerable to climate shocks and climate change, yet little is known about climate change adaptation in fragile contexts. While climate events are one of the many contributing drivers of conflict, feedback from conflict increases vulnerability, thereby creating conditions for a vicious cycle of conflict. In this study, we carry out a systematic review of peer-reviewed literature, taking from the Global Adaptation Mapping Initiative (GAMI) dataset to documenting climate change adaptation occurring in 15 conflict-affected countries and compare the findings with records of climate adaptation finance flows and climate-related disasters in each country. Academic literature is sparse for most conflict-affected countries, and available studies tend to have a narrow focus, particularly on agriculture-related adaptation in rural contexts and adaptation by low-income actors. In contrast, multilateral and bilateral funding for climate change adaptation addresses a greater diversity of adaptation needs, including water systems, humanitarian programming, and urban areas. Even among the conflict-affected countries selected, we find disparity, with several countries being the focus of substantial research and funding, and others seeing little to none. Results indicate that people in conflict-affected contexts are adapting to climate change, but there is a pressing need for diverse scholarship across various sectors that documents a broader range of adaptation types and their results., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2021.)

Autophagy is a natural regulatory mechanism of the cell that eliminates unnecessary and dysfunctional cellular components to maintain homeostasis. Several authors have demonstrated that this mechanism can be induced by pathological conditions as cancer. However, their role in tumor development is still a controversial issue in cancer research. Here, we discussed the most relevant findings concerning autophagy in tumor development. In this critical review performed with studies published between 2002 and 2018, we found that the main pathway involved in the autophagy process is the PI3K/AKT/mTOR intracellular signaling pathway. Regarding their role in cancer development, breast cancer is the main study target, followed by lung, prostate and colon cancer. In these issues, 46% of the works consulted suggesting that autophagy inhibits tumor progression by favor a better antitumor response, 4% suggest that favors growth and tumor progression and, 50% of the authors failed to establish whether autophagy inhibits or favors tumor development. Herein, we concluded that depending on the study model, autophagy may favor or inhibits growth and cancer progression.

One major limitation hindering the translation of in vitro osteoarthritis research into clinical disease-modifying therapies is that chondrocytes rapidly spread and dedifferentiate under standard monolayer conditions. Current strategies to maintain rounded morphologies of chondrocytes in culture either unnaturally restrict adhesion and place chondrocytes in an excessively stiff mechanical environment or are impractical for use in many applications. To address the limitations of current techniques, we have developed a unique composite thin-film cell culture platform, the CellWell, to model articular cartilage that utilizes micropatterned hemispheroidal wells, precisely sized to fit individual cells (12-18 μm diameters), to promote physiologically spheroidal chondrocyte morphologies while maintaining compatibility with standard cell culture and analytical techniques. CellWells were constructed of 15-μm-thick 5% agarose films embedded with electrospun poly(vinyl alcohol) (PVA) nanofibers. Transmission electron microscope (TEM) images of PVA nanofibers revealed a mean diameter of 60.9 ± 24 nm, closely matching the observed 53.8 ± 29 nm mean diameter of human ankle collagen II fibers. Using AFM nanoindentation, CellWells were found to have compressive moduli of 158 ± 0.60 kPa at 15 μm/s indentation, closely matching published stiffness values of the native pericellular matrix. Primary human articular chondrocytes taken from ankle cartilage were seeded in CellWells and assessed at 24 h. Chondrocytes maintained their rounded morphology in CellWells (mean aspect ratio of 0.87 ± 0.1 vs three-dimensional (3D) control [0.86 ± 0.1]) more effectively than those seeded under standard conditions (0.65 ± 0.3), with average viability of >85%. The CellWell's design, with open, hemispheroidal wells in a thin film substrate of physiological stiffness, combines the practical advantages of two-dimensional (2D) culture systems with the physiological advantages of 3D systems. Through its ease of use and ability to maintain the physiological morphology of chondrocytes, we expect that the CellWell will enhance the clinical translatability of future studies conducted using this culture platform.

Avoidance of novelty, termed neophobia, protects animals from potential dangers but can also impair their adaptation to novel environments or food resources. This behaviour is particularly well described in birds but the neurobiological correlates remain unexplored. Here, we measured neuronal activity in the amygdala and the striatum, two brain regions believed to be involved in novelty detection, by labelling the early gene c-fos following chicks exposure to a novel food (NF), a novel object (NO) or a familiar food (FF). NF and NO chicks showed significantly longer latencies to touch the food, less time eating and emitted more fear-vocalizations than control chicks. Latency to touch the food was also longer for NO than for NF chicks. Significantly higher densities of c-fos positive cells were present in all the nuclei of the arcopallium/amygdala of NF and NO chicks compared to FF chicks. Also, NO chicks showed higher positive cell densities than NF chicks in the posterior amygdaloid, the intermediate and the medial arcopallium. Exposure to novel food or object induced a similar increase in c-fos expression in the nucleus accumbens and the medial striatum. Our data provide evidence activation of the arcopallium/amygdala is specific of the type of novelty. The activation of striatum may be more related to novelty seeking., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In many species, vocal communication is essential for coordinating social behaviors including courtship, mating, parenting, rivalry, and alarm signaling. Effective communication requires accurate production, detection, and classification of signals, as well as selection of socially appropriate responses. Understanding how signals are generated and how acoustic signals are perceived is key to understanding the neurobiology of social behaviors. Here we review our long-standing research program focused on Xenopus , a frog genus which has provided valuable insights into the mechanisms and evolution of vertebrate social behaviors. In Xenopus laevis , vocal signals differ between the sexes, through development, and across the genus, reflecting evolutionary divergence in sensory and motor circuits that can be interrogated mechanistically. Using two ex vivo preparations, the isolated brain and vocal organ, we have identified essential components of the vocal production system: the sexually differentiated larynx at the periphery, and the hindbrain vocal central pattern generator (CPG) centrally, that produce sex- and species-characteristic sound pulse frequencies and temporal patterns, respectively. Within the hindbrain, we have described how intrinsic membrane properties of neurons in the vocal CPG generate species-specific vocal patterns, how vocal nuclei are connected to generate vocal patterns, as well as the roles of neurotransmitters and neuromodulators in activating the circuit. For sensorimotor integration, we identified a key forebrain node that links auditory and vocal production circuits to match socially appropriate vocal responses to acoustic features of male and female calls. The availability of a well supported phylogeny as well as reference genomes from several species now support analysis of the genetic architecture and the evolutionary divergence of neural circuits for vocal communication. Xenopus thus provides a vertebrate model in which to study vocal communication at many levels, from physiology, to behavior, and from development to evolution. As one of the most comprehensively studied phylogenetic groups within vertebrate vocal communication systems, Xenopus provides insights that can inform social communication across phyla., (Copyright © 2020 the authors.)

Exercise is known to produce a myriad of positive effects on the brain, including increased glia, neurons, blood vessels, white matter and dendritic complexity. Such effects are associated with enhanced cognition and stress resilience in humans and animal models. As such, exercise represents a positive experience with tremendous potential to influence brain development and shape an adult brain capable of responding to life's challenges. Although substantial evidence attests to the benefits of exercise for cognition in children and adolescents, the vast majority of existing studies examine acute effects. Nonetheless, there is emerging evidence indicating that exercise during development has positive cognitive and neural effects that last to adulthood. There is, therefore, a compelling need for studies designed to determine the extent to which plasticity driven by developmental exercise translates into enhanced brain health and function in adulthood and the underlying mechanisms. Such studies are particularly important given that modern Western society is increasingly characterized by sedentary behavior, and we know little about how this impacts the brain's developmental trajectory. This review synthesizes current literature and outlines significant knowledge gaps that must be filled in order to elucidate what exercise (or lack of exercise) during development contributes to the health and function of the adult brain., (Copyright © 2019 ISDN. Published by Elsevier Ltd. All rights reserved.)

Here, we have investigated the possible effect of B-1 cells on the activity of peritoneal macrophages in E. cuniculi infection. In the presence of B-1 cells, peritoneal macrophages had an M1 profile with showed increased phagocytic capacity and index, associated with the intense microbicidal activity and a higher percentage of apoptotic death. The absence of B-1 cells was associated with a predominance of the M2 macrophages, reduced phagocytic capacity and index and microbicidal activity, increased pro-inflammatory and anti-inflammatory cytokines production, and higher percentual of necrosis death. In addition, in the M2 macrophages, spore of phagocytic E. cuniculi with polar tubular extrusion was observed, which is an important mechanism of evasion of the immune response. The results showed the importance of B-1 cells in the modulation of macrophage function against E. cuniculi infection, increasing microbicidal activity, and reducing the fungal mechanisms involved in the evasion of the immune response., Competing Interests: The authors have declared that no competing interests exist.

Background: Although it has been previously demonstrated that acute inflammation can promote the tumor growth of a sub-tumorigenic dose of melanoma cells through of 5-lipoxygenase inflammatory pathway and its product leukotriene B 4, and also that the peritumoral treatment with eicosapentaenoic acid and its product, leukotriene B 5 , reduces the tumor development, the effect of the treatment by gavage with omega-3 and omega-6 in the tumor microenvironment favorable to melanoma growth associated with acute inflammation has never been studied., Methods: C57BL/6 mice were coinjected with 1 × 10 6 apoptotic cells plus 1 × 10 3 viable melanoma cells into the subcutaneous tissue and treated by gavage with omega-3-rich fish oil or omega-6-rich soybean oil or a mixture of these oils (1:1 ratio) during five consecutive days., Results: The treatment by gavage with a mixture of fish and soybean oils (1:1 ratio) both reduced the melanoma growth and the levels of leukotriene B 4 (LTB 4 ), prostaglandin E 2 (PGE 2 ), PGE 2 /prostaglandin E 3 (PGE 3 ) ratio, and CXC ligand 1 (CXCL1) and increased the levels of interleukin 10 (IL-10) to IL-10/CXCL1 ratio in the melanoma microenvironment., Conclusion: The oral administration of a 1:1 mixture of fish oil and soybean oil was able to alter the release of inflammatory mediators that are essential for a microenvironment favorable to the melanoma growth in mice, whereas fish oil or soybean oil alone was ineffective.

Background: Although Lactobacillus casei Shirota (LcS) can benefit the immune status, the effects of LcS in the immune/inflammatory responses of marathon runners has never been evaluated. Therefore, here we evaluated the effect of daily ingestion of fermented milk containing or not LcS in the systemic and upper airway immune/inflammatory responses before and after a marathon., Methods: Forty-two male marathon runners ingested a fermented milk containing 40 billion of LcS/day (LcS group, n = 20) or placebo (unfermented milk, n = 22) during 30 days pre-marathon. Immune/inflammatory parameters in nasal mucosa and serum, as well as concentrations of secretory IgA (SIgA) and antimicrobial peptides in saliva, were evaluated before and after fermented milk ingestion, immediately, 72 h, and 14 d post-marathon., Results: Higher proinflammatory cytokine levels in serum and nasal mucosa, and also lower salivary levels of SIgA and antimicrobial peptides, were found immediately post-marathon in the placebo group compared to other time points and to LcS group. In opposite, higher anti-inflammatory levels and reduced neutrophil infiltration on nasal mucosa were found in the LcS group compared to other time points and to the placebo group., Conclusion: For the first time, it is shown that LcS is able to modulate the systemic and airways immune responses post-marathon.

Vocal recognition is central to the coordination and organization of behavior in pair-bonding species such as zebra finches. Zebra finches' vocalizations are individualized and support acoustic discrimination processes. Physiological states - such as the ones involved in emotional stress - can modify vocal production and consequently the structure of vocalizations. These modifications might signal the state of the caller but also impair individual recognition processes. This may represent a signaling trade-off, especially in contexts where both pieces of information can be critically important, for example when mates use calls to reunite after social isolation. Here we study the impact of a stress on the individual vocal signature in both female and male zebra finch distance calls. We built a manually curated database of distance calls of several individuals (both females and males) recorded in control and stress conditions. The stress was induced either by social isolation of the bird or using exogenous corticosterone. We developed a machine learning approach to assess the impact of stress on the individual characterization of calls. We show that while calls' spectral structure is significantly modified by stress, it still allows for the correct classification of calls to the caller. Moreover, we also show that the stress-induced modification of calls' structure is not a 'general feature signal' that can be detected as a 'stress' signal regardless of identity. Thus, female and male zebra finch calls' structure show stress-induced flexibility that stays within the range of individual vocal signatures., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The peritoneal cavity has a microenvironment capable of promoting proliferation, differentiation, and activation of the resident cells and recruitment of blood cells through the capillary network involved in the peritoneum. Among the cells found in the peritoneal cavity, B-1 cells are a particular cell type that contains features that are not very well defined. These cells differ from conventional B lymphocytes (B-2) by phenotypic, functional, and molecular characteristics. B-1 cells can produce natural antibodies, migrate to the inflammatory focus, and have the ability to phagocytose pathogens. However, the role of B-1 cells in immunity against parasites is still not completely understood. Several experimental models have demonstrated that B-1 cells can affect the susceptibility or resistance to parasite infections depending on the model and species. Here, we review the literature to provide information on the peculiarities of B-1 lymphocytes as well as their interaction with parasites.

Although an effective treatment for pediatric brain tumors, cranial radiation therapy (CRT) damages surrounding healthy tissue, thereby disrupting brain development. Animal models of pediatric CRT have primarily relied on visual tasks to assess cognitive impairment. Moreover, there has been a lack of sex comparisons as most research on the cognitive effects of pediatric CRT does not include females. Therefore, we utilized olfaction, an ethologically relevant sensory modality, to assess cognitive impairment in an animal model of CRT that included both male and female mice. Specifically, we used the novel odor recognition (NOdorR) task with social odors to test recognition memory, a cognitive parameter that has been associated with olfactory neurogenesis, a form of cellular plasticity damaged by CRT. In addition to odor recognition memory, olfactory ability or discrimination of non-social and social odors were assessed both acutely and 3 months after CRT. Magnetic resonance imaging (MRI) and histology were performed after behavioral testing to assess long-term damage by CRT. Long-term but not acute radiation-induced impairment in odor recognition memory was observed, consistent with delayed onset of cognitive impairment in human patients. Males showed greater exploration of social odors than females, but general exploration was not affected by irradiation. However, irradiated males had impaired odor recognition memory in adulthood, compared to non-irradiated males (or simply male controls). Female olfactory recognition memory, in contrast, was dependent on estrus stage. CRT damage was demonstrated by (1) histological evaluation of olfactory neurogenesis, which suggested a reduction in CRT versus control, and (2) imaging analyses which showed that the majority of brain regions were reduced in volume by CRT. Specifically, two regions involved in social odor processing (amygdala and piriform cortex) were damaged by cranial irradiation in males but not females, paralleling olfactory recognition findings.

Microsporidia are intracellular pathogens that cause severe disease in immunocompromised humans and animals. We recently demonstrated that XID mice are more susceptible to Encephalitozoon cuniculi infection by intraperitoneal route, evidencing the role of B-1 cells in resistance against infection. The present study investigated the resistance and susceptibility against E. cuniculi oral infection, including the role of B-1 cells. BALB/c and BALB/c XID (B-1 cells deficient) mice were orally infected with E. cuniculi spores. No clinical symptoms were observed in infected animals; histopathology showed lymphoplasmocytic enteritis with degeneration of the apexes of the villi in all infected groups. Higher parasite burden was observed in infected BALB/c XID mice. In the spleen and peritoneum, all infected mice showed a decrease of lymphocytes, including CD8 + T cells, mostly in infected BALB/c XID mice. Adoptive transfer of B-1 cells (XID + B-1) was associated with a lower parasite burden. Pro-inflammatory cytokines (IFN-γ, TNF-α and IL-6) increased mostly in infected XID + B1 mice. Together, the present results showed that BALB/c XID mice infected by the oral route were more susceptible to encephalitozoonosis than BALB/c mice, demonstrating the B-1 cells importance in the control of the immune response against oral E. cuniculi infection., (Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

B-1 lymphocytes are known to increase the metastatic potential of B16F10 melanoma cells via the extracellular signal-regulated kinase (ERK) pathway. Since IL-10 is associated with B-1 cells performance, we hypothesized that IL-10 could be implicated in the progression of melanoma. In the present work, we found that the C57BL/6 mice, inoculated with B16F10 cells that were co-cultivated with B-1 lymphocytes from IL-10 knockout mice, developed fewer metastatic nodules than the ones which were injected with the melanoma cells that were cultivated in the presence of wild-type B-1 cells. The impairment of metastatic potential of the B16F10 cells was correlated with low activation of the ERK signaling pathway, supporting the idea that the production of IL-10 by B-1 cells influences the behavior of the tumor. A microarray analysis of the B-1 lymphocytes revealed that IL-10 deficiency is associated with down-regulation of the genes that code for claudin-10, a protein that is involved in cell-to-cell contact and that has been linked to lung adenocarcinoma. In order to determine the impact of claudin-10 in the cross-talk between B-1 lymphocytes and the B16F10 tumor cells, we took advantage of small interfering RNA. The silencing of claudin-10 gene in B-1 lymphocytes inhibited activation of the ERK pathway and abrogated the B-1-induced aggressive behavior of the B16F10 cells. Thus, our findings suggest that the axis IL-10/claudin-10 is a promising target for the development of therapeutic agents against aggressive melanoma.

Microsporidiosis are diseases caused by opportunistic intracellular fungi in immunosuppressed individuals, as well as in transplanted patients, the elderly and children, among others. Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and decreased T cell response, neutrophil function, humoral immunity failure, increasing the susceptibility to infections. Here, we investigated the susceptibility of streptozotocin (STZ)-induced type I diabetic and/or immunosuppressed mice to encephalitozoonosis by Encephalitozoon cuniculi. Microscopically, granulomatous hepatitis, interstitial pneumonia and pielonephritis were observed in all infected groups. STZ treatment induced an immunossupressor effect in the populations of B (B-1 and B2) and CD4+ T lymphocytes. Moreover, infection decreased CD4+ and CD8+ T lymphocytes and macrophages of DM mice. Furthermore, infection induced a significant increase of IL-6 and TNF-α cytokine serum levels in DM mice. IFN-γ, the most important cytokine for the resolution of encephalitozoonosis, increased only in infected mice. In addition to the decreased immune response, DM mice were more susceptible to encephalitozoonosis, associated with increased fungal burden, and symptoms. Additionally, cyclophosphamide immunosuppression in DM mice further increased the susceptibility to encephalitozoonosis. Thus, microsporidiosis should be considered in the differential diagnosis of comorbidities in diabetics.

Background: In previous results mice treated with high dilutions of antimony presented reduction of monocyte migration to the site of infection with increase in B lymphocytes population in the local lymph node., Aims: To know the mechanisms involved, a series of in vitro studies was done, using co-cultures of macrophages (RAW 264.7) and Leishmania (L.) amazonensis treated with different dilutions of antimony (Antimonium crudum or AC), in different times., Methodology: Spreading, phagocytosis, the oxidative activity of macrophages, the viability of free promastigotes and the cytokines/chemokines concentration in the supernatant were evaluated. The assays were performed in quadruplicate., Results: Cells treated with AC 30cH (10 -58 M) and AC 200cH (10 -398 M) presented a temporary reduction of the spreading after 02h of incubation, followed by increase after 48h, being the most significant increase observed after the AC 200cH treatment. However, the percentage of internalized parasites at 48, 96 and 120h of incubation was also higher in cells treated with AC 200cH. It is suggested that the AC 200cH improves the ability of phagocytes to internalize the parasites, but not to digest them. The cytokines-chemokines panel corroborated these results. Both dilutions potentiated the parasite-induced reduction of cytokines production, especially IL-6, IL 12 p40 and γ-IFN, after 48h of incubation. In addition, the production of MIP-1 beta (CCL4), a chemokine involved in chronic inflammation, was also reduced after 120h. A specific effect of AC 30cH was seen by the inhibition of two peaks of CCL2 (MCP-1) observed in infected macrophages, at 24 and 120h. Since this cytokine is an important chemokine for monocytes, it explains the results obtained formerly in vivo. The morphology of macrophages after acridine orange staining revealed that the treatment with AC 30cH reduced substantially the acid vacuoles in the cytoplasm, indicating a certain inability of these cells to digest the parasites. On the other hand, a large peak of VEGF-A, associated with increase of internalized parasites was observed after 120h of treatment with AC 200cH, which could be associated to the regulation of the chronic inflammation events by M1-M2 polarization. There was no statistical difference among groups regarding the production of TNF, NO and H 2 O 2 , showing that the drugs do not alter macrophage cytotoxic activity. A clear quantitative and qualitative variation of the modulatory effects of AC 30cH and 200cH was seen, in function of time., Conclusions: Both dilutions were able to potentiate the decrease of most of cytokines and chemokines induced by the parasite infection in vitro, which explains the clinical improvement seen previously in vivo, however, the mechanisms involved and the epidemiological significance of these findings are still under discussion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Encephalitozoon cuniculi is an opportunist intracellular pathogen of mammals. The adaptive immune response is essential to eliminate E. cuniculi, but evidence is mounting that the response initiated by the innate immune response may ultimately define whether or not the parasite can survive. B-1 cells may act as antigen-presenting cells or differentiate into phagocytes, playing different roles in many infection models. However, the role of these cells in the dynamics of Encephalitozoon sp. infections is still unknown. To investigate the role of B-1 cells in E. cuniculi infection, BALB/c and BALB/c XID (B-1 cells deficient) mice were infected with E. cuniculi spores. Cytometric analyses of peritoneal cells showed that B-1 cells and macrophages increased significantly in infected BALB/c mice compared to uninfected controls. Despite the increase in the number of CD4 + and CD8 + lymphocytes in XID mice, these animals were more susceptible to infection as evidenced histologically with more prominent inflammatory lesions and parasite burden. Pro-inflammatory cytokines increased in both infected BALB/c and BALB/c XID mice. To confirm B-1 cells role in encephalitozoonosis, we adoptively transferred B-1 cells to BALB/c XID mice and this group showed few symptoms and microscopic lesions, associated with an increased in cytokines. Together, these results suggest that B-1 cells may increase the resistance of BALB/c mice to encephalitozoonosis, evidencing for the first time the important role of B-1 lymphocytes in the control of microsporidia infection., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Social stimuli can have rewarding properties and promote learning. In birds, conspecific vocalizations like song can act as a reinforcer, and specific song variants can acquire particular rewarding values during early life exposure. Here we ask if, during adulthood, an acoustic signal simpler and shorter than song can become a reward for a female songbird because of its particular social value. Using an operant choice apparatus, we showed that female zebra finches display a preferential response toward their mate's calls. This reinforcing value of mate's calls could be involved in the maintenance of the monogamous pair-bond of the zebra finch., ((c) 2016 APA, all rights reserved).)

Objective: In patients with rheumatoid arthritis (RA), morning stiffness is linked more to functional disability and pain than disease activity, as assessed by joint counts and markers of inflammation. As part of the Asia Pacific Morning Stiffness in Rheumatoid Arthritis Expert Panel, a group of eight rheumatologists met to formulate consensus points and develop recommendations for the assessment and management of morning stiffness in RA., Methods: On the basis of a systematic literature review and expert opinion, a panel of Asian rheumatologists formulated recommendations for the assessment and medical treatment of RA., Results: The panel agreed upon 10 consensus statements on morning stiffness, its assessment and treatment. Specifically, the panel recommended that morning stiffness, pain and impaired morning function should be routinely assessed in clinical practice. Although there are currently no validated tools for these parameters, they should be assessed as part of the patients' reported outcomes in RA. The panel also agreed on the benefits of low-dose glucocorticoids in RA, particularly for the improvement of morning stiffness., Conclusions: These recommendations serve to guide rheumatologists and other stakeholders on the assessment and management of morning stiffness, and help implement the treat-to-target principle in the management of RA., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Physiological resonance - where the physiological state of a subject generates the same state in a perceiver - has been proposed as a proximate mechanism facilitating pro-social behaviours. While mainly described in mammals, state matching in physiology and behaviour could be a phylogenetically shared trait among social vertebrates. Birds show complex social lives and cognitive abilities, and their monogamous pair-bond is a highly coordinated partnership, therefore we hypothesised that birds express state matching between mates. We show that calls of male zebra finches Taeniopygia guttata produced during corticosterone treatment (after oral administration of exogenous corticosterone and during visual separation from the partner) provoke both an increase in corticosterone concentrations and behavioural changes in their female partner compared to control calls (regular calls emitted by the same male during visual separation from the partner only), whereas calls produced during corticosterone treatment by unfamiliar males have no such effect. Irrespective of the caller status (mate/non-mate), calls' acoustic properties were predictive of female corticosterone concentration after playback, but the identity of mate calls was necessary to fully explain female responses. Female responses were unlikely due to a failure of the call-based mate recognition system: in a discrimination task, females perceive calls produced during corticosterone treatment as being more similar to the control calls of the same male than to control calls of other males, even after taking acoustical differences into account. These results constitute the first evidence of physiological resonance solely on acoustic cues in birds, and support the presence of empathic processes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Autologous vaccination with tumor-primed dendritic cells increases immune response against tumor, which seems to be improved in host absence of CCR5. Because B-1 lymphocytes modulate the activity of different immune cells, we decided to study their influence in the resistance against murine B16F10 melanoma in a CCR5 deprived environment. Adoptive transfer of peritoneal B-1 CCR5(+/+) lymphocytes to CCR5(-/-) animals inhibited the establishment of lung metastasis and melanoma cell growth, in comparison to saline-treated CCR5(-/-) mice. In loco cell analysis demonstrated that the adoptive transfer of B-1 CCR5(+/+) lymphocytes to CCR5 deficient host was associated with a more intense influx of T CD8(+) to tumor site, indicating that the presence of CCR5(+/+) B-1 cells in the tumor environment induces the migration of T CD8 CCR5(-/-) cells to the implantation site. To corroborate this idea, CCR5(-/-) mice were injected with non B-1 peritoneal cells from wild type (WT) mice before B16F10 inoculation. In this regimen, CCR5(-/-) mice were not protected from tumor growth reinforcing the idea that, in host absence of CCR5, B-1 cells are essential to confer tumor resistance. This work indicates that, in the host absence of CCR5, naive B-1 cells may activate CD8T lymphocytes thereby promoting tumor resistance. Our results strongly suggest that autologous vaccination with B-1 lymphocytes in combination with CCR5 antagonists can be an alternative approach to tumor therapy., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

B-1 cells constitute a distinct B cell population with unique phenotypic and functional characteristics. They represent the main B cell population found in mouse peritoneal and pleural cavities. The communication between B-1 cells and peritoneal macrophages has been previously studied, and the effect this interaction has on macrophages has been previously described. Using an in vitro co-culture model, herein we demonstrated that peritoneal macrophages were able to increase survival rates and to stimulate proliferation of B-1 cells. IL-6 was also found to be important in B-1 cell survival; recombinant IL-6 increases the percentage of viable B-1 cells in culture. Furthermore, molecules involved in the IL-6 signaling pathway, such as STAT-3 and Bcl-2, were highly expressed in B-1 cells after co-culture with peritoneal macrophages. IL-6-deficient peritoneal macrophages were not able to increase B-1 cell survival, confirming the importance of this cytokine. Altogether, our results indicate a novel mechanism in which peritoneal macrophages are able to regulate the B-1 population via IL-6 secretion.

B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. The role of both cell populations in cancer progression is still controversial. Previous studies have indicated that direct contact between B-1 cells and B16 melanoma tumor cells (B16) increases the metastatic potential of the tumor cells. However, cellular changes that are induced in B-1 cells during the interaction between these two cell types have not been evaluated. In the present study, it is hypothesized that B-1 cells are modified after their interaction with tumor cells, leading to both increased cell viability and rate of proliferation. Additionally, soluble factors that were secreted by B16 cells were sufficient to augment B-1 cell viability and to modify the production of IL-10 by B-1 cells. Impressively, after direct or indirect contact with the B16 cells, B-1 cells became resistant to radiation-induced cell death. Thus, future studies that assess the importance of concomitant immunity and other conventional therapies in cancer treatment are needed., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

The present study analyzed the immune modulation mechanisms of thymulin 5CH in a granuloma experimental model. Male adult Balb/c mice were inoculated with BCG into the footpad to induce granuloma, which was quantitatively evaluated. The phenotypic characterization of phagocyte, T- and B-lymphocyte populations in the peritoneum, and local lymph node was done by flow cytometry. During all experimental periods, thymulin 5CH and vehicle (control) were given ad libitum to mice, diluted into the drinking water (1.6 × 10(-17) M). After 7 days from inoculation, thymulin-treated mice presented reduction in the number of epithelioid cytokeratine-positive cells (P = 0.0001) in the lesion, in relation to young phagocytes. After 21 days, the differentiation of B1 peritoneal stem cells into phagocytes reached the peak, being higher in thymulin-treated mice (P = 0.0001). Simultaneously, the score of infected phagocytes in the lesion decreased (P = 0.001), and the number of B1-derived phagocytes, CD4+ and CD8+ T lymphocytes in the local lymph node increased in relation to control (P = 0.0001). No difference was seen on the CD25+ Treg cells. The results show that thymulin 5CH treatment is able to improve the granuloma inflammatory process and the infection remission, by modulating local and systemic phagocyte differentiation.

Animal vocalizations convey multiple pieces of information about the sender. Some of them are stable, such as identity or sex, but others are labile like the emotional or motivational state. Only a few studies have examined the acoustic expression of emotional state in non-human animals and related vocal cues to physiological parameters. In this paper, we examined the vocal expression of isolation-induced stress in a songbird, the zebra finch (Taeniopygia guttata). Although songbirds use acoustic communication extensively, nothing is known to date on how they might encode physiological states in their vocalizations. We tested the hypothesis that social isolation in zebra finches induces a rise of plasma corticosterone that modifies the vocal behavior. We monitored plasma corticosterone, as well as call rate and acoustic structure of calls of males in response to the playback of female calls of varied saliences (familiar versus stranger) in two situations: social isolation and social housing. Social isolation induced both a rise in plasma corticosterone, and a range of modifications in males' vocal behavior. Isolated birds showed a lower vocal activity, an abolition of the difference of response between the two stimuli, and evoked calls with longer duration and higher pitch. Because some of these effects were mimicked after oral administration of corticosterone in socially housed subjects, we conclude that corticosterone could be partly responsible for the isolation-related modifications of calls in male zebra finches. To our knowledge, this is the first demonstration of the direct implication of glucocorticoids in the modulation of the structure of vocal sounds., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The consensus statements were developed to assist healthcare practitioners in providing optimal care to postmenopausal individuals at risk for osteoporosis and fragility fractures in the local setting., Methodology: The Technical Review Committee formed by the Osteoporosis Society of the Philippines Foundation Inc. in cooperation with the Philippine Orthopedic Association drafted, retrieved available published evidence, and appraised important issues on osteoporosis and fragility fractures. The Appraisal of Guidelines Research and Evaluation instrument was used to appraise published guidelines while a systematic way of validating the quality of evidence and the level of recommendation was done using the GRADE system. A multidisciplinary panel of experts and stakeholders in an en banc meeting conferred and approved the recommendations., Results and Conclusion: There were five key issues on preventive, seven on diagnostic, nine on therapeutic aspects of osteoporosis with four other surgical concerns on fragility fractures. All were approved by a panel of stakeholders through a majority vote. These statements will best inform the clinicians and the specialists including orthopedic surgeons and general care practitioners on issues of postmenopausal Filipino women at risk for osteoporosis and fragility fractures., (© 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.)

Anesthesia education is highly stressful. Some stress motivates students, but excess stress leads to failure and unhappiness. While stress cannot be eradicated from the practice of anesthesia, it can be managed, especially when its signs are recognized early. The purposes of this study were to determine the perception of students' stress in nurse anesthesia programs and to examine the presence and use of stress management programs and open-door policies existing in nurse anesthesia schools. An author-developed questionnaire assessed the stress management programs and open-door policies of nurse anesthesia programs, Life Event Scale scores of the students, school-related stressors, and student coping strategies. The study, which surveyed all 2,200 of the nation's nurse anesthesia students, with a 68.4% response rate, showed that students experience a significant level of stress. It also demonstrated a need for schools to develop stress management programs.