Microplastics (MP) have been reported in Southern Ocean (SO), where they are likely to encounter Antarctic zooplankton and enter pelagic food webs. Here we assess the presence of MP within Antarctic ...krill (
) and salps (
) and quantify their abundance and type by micro-Fourier transform infrared microscopy. MP were found in both species, with fibres being more abundant than fragments (krill: 56.25% and salps: 22.32% of the total MP). Polymer identification indicated MP originated from both local and distant sources. Our findings prove how
MP ingestion from these organisms is a real and ongoing process in the SO. MP amount was higher in krill (2.13 ± 0.26 MP ind
) than salps (1.38 ± 0.42 MP ind
), while MP size extracted from krill (130 ± 30 µm) was significantly lower than MP size from salps (330 ± 50 µm). We suggest that differences between abundance and size of MP ingested by these two species may be related to their food strategies, their ability to fragment MP as well as different human pressures within the collection areas of the study region. First comparative field-based evidence of MP in both krill and salps, two emblematic zooplankton species of the SO marine ecosystems, underlines that Antarctic marine ecosystems may be particularly sensitive to plastic pollution.
Animal shape and size is controlled with amazing precision during development. External factors such as nutrient availability and crowding can alter overall animal size, but individual body parts ...scale reproducibly to match the body even with challenges from a changing environment. How is such precision achieved? Here, we review selected research from the last few years in Drosophila--arguably the premier genetic model for the study of animal growth--that sheds light on how body and tissue size are regulated by forces intrinsic to individual organs. We focus on two topics currently under intense study: the influence of pattern regulators on organ and tissue growth and the role of local competitive interactions between cells in tissue homeostasis and final size.
Generation of an organ of appropriate size and shape requires mechanisms that coordinate growth and patterning, but how this is achieved is not understood. Here we examine the role of the growth ...regulator dMyc in this process during Drosophila wing imaginal disc development. We find that dMyc is expressed in a dynamic pattern that correlates with fate specification of different regions of the wing disc, leading us to hypothesize that dMyc expression in each region directs its growth. Consistent with this view, clonal analysis of growth in each region demonstrated distinct temporal requirements for dMyc that match its expression. Surprisingly, however, experiments in which dMyc expression is manipulated reveal that the endogenous pattern has only a minor influence on wing shape. Indeed, when dMyc function is completely lacking in the wing disc over most of its development, the discs grow slowly and are small in size but appear morphologically normal. Our experiments indicate, therefore, that rather than directly influence differential growth in the wing disc, the pattern of dMyc expression augments growth directed by other regulators. Overall, however, an appropriate level of dMyc expression in the wing disc is necessary for each region to achieve a proportionately correct size.
We evaluated 79 patients with multiple myeloma (MM) ≥70 years referred to our blood and marrow transplant clinic, within 1 year of diagnosis from 2010 to 2019, for consideration of autologous stem ...cell transplant (ASCT). Thirty-eight (48%) of 79 patients underwent ASCT. ASCT was not pursued in 41 (52%) patients due to: patient or physician preference in 80% (n = 33) or ineligibility in 20% (n = 8). Baseline characteristics of patients in the two groups were similar. Median PFS from treatment start amongst patients undergoing ASCT (n = 38) vs. not (n = 41) was 41 months vs. 33 months, p = 0.03. There was no difference in OS, with estimated 5-year OS of 73% vs. 83%, respectively (p = 0.86). Day +100 transplant-related mortality (TRM) was 0%. ASCT was an independent favorable prognostic factor for PFS in multivariate analysis, after accounting for HCT-CI score, performance status, hematologic response, and maintenance. Finally, patients ≥70 years undergoing ASCT had similar PFS compared to a contemporaneous institutional cohort of patients <70 years (n = 631) (median PFS from transplant: 36 vs. 47 months, p = 0.25). In this retrospective analysis, ASCT was associated with low TRM and better PFS in fit older adults with MM compared to non-transplant therapy, with comparable benefits as seen in younger patients.
Background
Ex vivo lung perfusion (EVLP) is used to assess and preserve lungs prior to transplantation. However, its inherent immunomodulatory effects are not completely understood. We examine ...perfusate and tissue compartments to determine the change in immune cell composition in human lungs maintained on EVLP.
Methods
Six human lungs unsuitable for transplantation underwent EVLP. Tissue and perfusate samples were obtained during cold storage and at 1‐, 3‐ and 6‐h during perfusion. Flow cytometry, immunohistochemistry, and bead‐based immunoassays were used to measure leukocyte composition and cytokines. Mean values between baseline and time points were compared by Student's t test.
Results
During the 1st hour of perfusion, perfusate neutrophils increased (+22.2 ± 13.5%, p < 0.05), monocytes decreased (−77.5 ± 8.6%, p < 0.01) and NK cells decreased (−61.5 ± 22.6%, p < 0.01) compared to cold storage. In contrast, tissue neutrophils decreased (−22.1 ± 12.2%, p < 0.05) with no change in monocytes and NK cells. By 6 h, perfusate neutrophils, NK cells, and tissue neutrophils were similar to baseline. Perfusate monocytes remained decreased, while tissue monocytes remained unchanged. There was no significant change in B cells or T cell subsets. Pro‐inflammatory cytokines (IL‐1b, G‐CSF, IFN‐gamma, CXCL2, CXCL1 granzyme A, and granzyme B) and lymphocyte activating cytokines (IL‐2, IL‐4, IL‐6, IL‐8) increased during perfusion.
Conclusions
Early mobilization of innate immune cells occurs in both perfusate and tissue compartments during EVLP, with neutrophils and NK cells returning to baseline and monocytes remaining depleted after 6 h. The immunomodulatory effect of EVLP may provide a therapeutic window to decrease the immunogenicity of lungs prior to transplantation.
Delirium is a very common, but refractory clinical state, notably present in intensive care and in the growing aging community. It is characterized by fluctuating disturbances in a number of key ...behavioral features, namely cognition, mood, attention, arousal, and self-awareness. Histamine is arguably the most pleotropic neurotransmitter in the human brain, and this review provides a rationale, and proposes that this neuroactive amine plays a role in modulating the characteristic features of delirium. While centrally permeable H
and H
histamine receptor antagonists have pro-delirium potential, we propose that centrally permeable H
histamine receptor antagonists may provide an exciting new strategy to combat delirium. The Histamine H
receptor may also have an indirect inflammatory neuroglial role which requires further exploration.
A psychiatric assistance dog (PAD) is a service dog that is trained to assist its handler (owner) who has been diagnosed with a mental health condition such as post-traumatic stress disorder (PTSD), ...schizophrenia, depression, anxiety, or bipolar disorder. Literature searches reveal that little is known about the population of people who own PADs, the types of dogs used or the functions they provide. One third (
= 199) of PAD owners in Australia registered with the charity "mindDog" participated in an online survey designed to better understand the person and dog team. Participants learned about PADs through the internet (37%), health care practitioners (32%), or family/friends (30%). The dogs in the sample were of varying age, gender and breed. The most common reasons for people to choose a dog to be a PAD were temperament (60%) and size/weight (48%). Just under half (48%) of the dogs had been acquired by the owner specifically to be trained as a PAD, and the rest were existing pets. All the dogs were trained by the owner or a combination of the owner and a qualified trainer; none were trained exclusively by assistance/service dog provider organizations. The median age of the participants at the time of data collection was 47 years, ranging from 10 to 75 years. Most (77%) identified as female. Depression (84%), anxiety (social 61%; generalized 60%), PTSD (62%), and panic attacks (57%) were the most reported mental health diagnoses. Tasks the dogs performed for their owners included: reduction of anxiety through tactile stimulation (94%); nudging/pawing to bring back to the present (71%); interrupting undesirable behavior (51%); constant body contact (50%); deep pressure stimulation (45%) and blocking contact from other people (42%). PAD usage decreased (46%), increased (30%) or did not change (24%) participants' use of psychiatric or other health care services. Decrease in service use was mainly due to reduced suicide attempts, and less requirement for hospitalization and medication; increased use was mainly due to enhanced ability to attend appointments. Results of this study show that PAD owners have differing mental health diagnoses, and their dogs perform different tasks to support them in daily life. Every participant described the relationship with his/her PAD as positive, suggesting that a successful working partnership does not require the dog to have been bred or raised specifically for the role. A better understanding of this population and the person-dog relationship will inform the appropriate choice, training and use of PADs for people living with mental health problems.
Initial therapy of chronic graft-
-host disease is prednisone ± a calcineurin-inhibitor, but most patients respond inadequately. In a randomized, adaptive, phase II/III, multicenter trial we studied ...whether prednisone/sirolimus or prednisone/sirolimus/photopheresis was more effective than prednisone/sirolimus/calcineurin-inhibitor for treating chronic graft-
-host disease in treatment-naïve or early inadequate responders. Primary endpoints of this study were proportions of subjects alive without relapse or secondary therapy with 6-month complete or partial response in phase II, or with 2-year complete response in phase III. The prednisone/sirolimus/photopheresis arm closed prematurely because of slow accrual and the remaining two-drug
three-drug study ended in phase II due to statistical futility with 138 evaluable subjects. The two-drug and three-drug arms did not differ in rates of 6-month complete or partial response (48.6%
50.0%,
=0.87), or 2-year complete response (14.7%
15.5%,
=0.90). Serum creatinine values >1.5 times baseline were less frequent in the calcineurin-inhibitor-free arm at 2 months (1.5%
11.7%,
=0.025) and 6 months (7.8%
24.0%,
=0.016). Higher adjusted Short Form-36 Physical Component Summary and Physical Functioning scores were seen in the two-drug arm at both 2 months (
=0.02 and
=0.04, respectively) and 6 months (
=0.007 and
=0.001, respectively). Failure-free survival and overall survival rates at 2 years were similar for patients in the the two-drug and three-drug arms (48.6%
46.2%,
=0.78; 81.5%
74%,
=0.28). Based on similar long-term outcomes, prednisone/sirolimus is a therapeutic alternative to prednisone/sirolimus/calcineurin-inhibitor for chronic graft-
-host disease, being easier to administer and better tolerated.
A hematopoietic cell transplantation regimen was adapted from a preclinical model that used reduced-intensity conditioning (RIC) and protected against graft-versus-host disease (GVHD) by skewing ...residual host T-cell subsets to favor regulatory natural killer T cells. One hundred eleven patients with lymphoid (64) and myeloid (47) malignancies received RIC using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) followed by the infusion of granulocyte colony-stimulating factor-mobilized grafts. Included were 34 patients at least 60 years of age, 32 patients at high risk of lymphoma relapse after disease recurrence following prior autologous transplantation, and 51 patients at high risk of developing GVHD due to lack of a fully human leukocyte antigen (HLA)–matched related donor. Durable chimerism was achieved in 97% of patients. Cumulative probabilities of acute GVHD (grades II-IV) were 2 and 10% of patients receiving related and unrelated donor grafts. Nonrelapse mortality (NRM) at 1 year was less than 4%. Cumulative incidence of chronic GVHD was 27%. The 36-month probability of overall and event-free survival was 60% and 40%, respectively. Disease status at start of conditioning and the level of chimerism achieved after transplantation significantly impacted clinical outcome. The high incidence of sustained remission among patients with active disease at time of transplantation suggests retained graft-versus-tumor reactions. Active trial registration currently at clinicaltrials.gov under IDs of NCT00185640 and NCT00186615.
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