Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report.

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828

The Woman Question in Revolutionary Cuba: Is Marxism Really Working for Women?

Since the 1959 revolution, there has been substantial advancement towards women’s equality in Cuba. But the progress is incomplete. Though Marxists argue that this indicates that the revolution’s work is not yet complete, I take a different stance: the fact that the problem is not solved means that a targeted attack on women’s oppression is needed. Cuba has adopted a traditional Marxist or Marxist feminist approach to women’s equality, which helped produce some positive changes for women. However, the limitations of the theory – namely, the ideas that women’s equality should be subsumed to a larger Marxist revolution and that patriarchy is a historically specific situation that would dissolve with the change to a communist mode of production – mean that Cuba cannot adequately address gender inequality. Because Cuban leadership prioritizes the revolution and does not believe that patriarchy needs to be directly attacked, women’s oppression to continues. Even though they acknowledge that the progress is incomplete for women in Cuba, leaders stand by Marxist theory – the only way for the “remnants” of past societies to disappear is to keep the revolution pressing forward. Contrary to the position of the Cuban state, I argue that more revolution alone will not generate full women’s equality. I present evidence in the areas of health, work, and politics that illustrate that patriarchy persists. Rather than dissolving with a change in the material base, Cuba’s patriarchy has evolved into Marxist machismo. Women’s equality cannot be a secondary goal of the Cuban revolution: in order to achieve full equality in Cuba, a women’s movement that directly attacks women’s oppression as women is imperative

Cytosol Mg2+ modulates Ca2+ ionophore induced secretion from rabbit neutrophils

AbstractThe influence of extracellular Mg2+ on Ca2+ ionophore (A23187 and ionomycin) induced secretion and changes in the cytosol pH of rabbit neutrophils suspended in Ca2+-free buffer has been investigated. While extracellular Ca2+ is obligatory for ionomycin induced secretion, we have defined conditions under which A23187 can induce secretion in Ca2+-free media. The different behaviour of these two Ca2+ ionophores is discussed on the basis of their different counter cation specificities

Two G-proteins act in series to control stimulus-secretion coupling in mast cells: use of neomycin to distinguish between G-proteins controlling polyphosphoinositide phosphodiesterase and exocytosis

Provision of GTP (or other nucleotides capable of acting as ligands for activation of G-proteins) together with Ca2+ (at micromolar concentrations) is both necessary and sufficient to stimulate exocytotic secretion from mast cells permeabilized with streptolysin-O. GTP and its analogues, through their interactions with Gp, also activate polyphosphoinositide-phosphodiesterase (PPI-pde generating inositol 1,4,5-trisphosphate and diglyceride [DG]). We have used mast cells labeled with [3H]inositol to test whether the requirement for GTP in exocytosis is an expression of Gp activity through the generation of DG and consequent activation of protein kinase C, or whether GTP is required at a later stage in the stimulus secretion sequence. Neomycin (0.3 mM) inhibits activation of PPI-pde, but maximal secretion due to optimal concentrations of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) can still be evoked in its presence. When ATP is also provided the concentration requirement for GTP-gamma-S in support of exocytosis is reduced. This sparing effect of ATP is nullified when the PPI-pde reaction is inhibited by neomycin. We argue that the sparing effect of ATP occurs as a result of enhancement of DG production and through its action as a phosphoryl donor in the reactions catalyzed by protein kinase C

Von Willebrand's disease in the Bantu

No Abstrac

VTA neurons coordinate with the hippocampal reactivation of spatial experience

Spatial learning requires the hippocampus, and the replay of spatial sequences during hippocampal sharp wave-ripple (SPW-R) events of quiet wakefulness and sleep is believed to play a crucial role. To test whether the coordination of VTA reward prediction error signals with these replayed spatial sequences could contribute to this process, we recorded from neuronal ensembles of the hippocampus and VTA as rats performed appetitive spatial tasks and subsequently slept. We found that many reward responsive (RR) VTA neurons coordinated with quiet wakefulnessassociated hippocampal SPW-R events that replayed recent experience. In contrast, coordination between RR neurons and SPW-R events in subsequent slow wave sleep was diminished. Together, these results indicate distinct contributions of VTA reinforcement activity associated with hippocampal spatial replay to the processing of wake and SWS-associated spatial memory.National Institutes of Health (U.S.) (Grant R01-MH061976)United States. Office of Naval Research (Grant N00014-10-1-0936)National Institutes of Health (U.S.) (Grant K08-MH-81207-01A1

VTA neurons coordinate with the hippocampal reactivation of spatial experience

Spatial learning requires the hippocampus, and the replay of spatial sequences during hippocampal sharp wave-ripple (SPW-R) events of quiet wakefulness and sleep is believed to play a crucial role. To test whether the coordination of VTA reward prediction error signals with these replayed spatial sequences could contribute to this process, we recorded from neuronal ensembles of the hippocampus and VTA as rats performed appetitive spatial tasks and subsequently slept. We found that many reward responsive (RR) VTA neurons coordinated with quiet wakefulness-associated hippocampal SPW-R events that replayed recent experience. In contrast, coordination between RR neurons and SPW-R events in subsequent slow wave sleep was diminished. Together, these results indicate distinct contributions of VTA reinforcement activity associated with hippocampal spatial replay to the processing of wake and SWS-associated spatial memory.National Institutes of Health (U.S.) (Grant R01-MH061976)United States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant N00014-10-1-0936)National Institutes of Health (U.S.) (Mentored Grant K08-MH-81207-01A1

Task Shifting in the provision of medical abortion

Introduction: Unsafe abortion is one of the main causes of maternal mortality. Each year, approximately 21.6 million women worldwide still undergo an unsafe abortion resulting in an estimated 47000 deaths. Currently 39% of the population lives in countries with highly restrictive abortion laws. However also in countries where abortion is legal, obstructive administrative procedures and insufficient services or providers reduce access to safe abortion services. Medical abortion is one of the safest medical procedures, with minimal morbidity and a negligible risk of death. Task shifting may result in increased access to and availability of medical abortion services while maintaining the same quality of care. While task shifting can be done to other healthcare professionals, it can also be done to women themselves with the use of telemedicine. Material, methods and results: Study 1 describes the outcome of medical abortions provided via Women on Web, a telemedical abortion service for women with an unwanted pregnancy up to 9 weeks living in countries without safe abortion care. This retrospective study analyzed interactive web-based questionnaires, follow-up forms, emails, and telephone calls from 484 women who received a medical abortion at their home addresses. Sixteen of the 265 (6.0%) women who provided follow-up information reported that they did not use the medication. Of the remaining 249 women who did the medical abortion at home, 13.6% reported having a surgical intervention afterwards and 1.6% reported a continuing pregnancy. After the follow up rate increased from 54.8% to 77.6% of the cases, 12.6% of the women reported they did not take the medication and only 6.8% of the women having the medical abortion at home underwent a surgical intervention afterwards. Study 2 explored the factors that influence the surgical intervention rate after home medical abortion provided through Women on Web to women with a pregnancy up to 9 weeks. Of the 2323 women who did the medical abortion, 289 (12.4%) received a surgical intervention. High rates were found in Eastern Europe (14.8%), Latin America (14.4%) and Asia/Oceania (11.0%) and low rates in Western Europe (5.8%), the Middle East (4.7%) and Africa (6.1%; ii p=0.000). More interventions were carried out when women had a longer gestational age (p=0.000). Women without a surgical intervention reported satisfaction with the treatment more frequently (p=0.000). Study 3 evaluated the need for and outcome of self-administered medical abortion in Brazil, provided through telemedicine. Of the 370 women used the medicines, 307 women provided follow-up information about the outcome of the medical abortion. Of this group, 207 (67.4%) of the women were up to 9 weeks pregnant, 71 (23.1%) were 10, 11 or 12 weeks pregnant, and 29 (9.5%) of the women were at least 13 weeks pregnant. There was a significant difference in surgical intervention rates after the medical abortion at the different gestations (19.3% at 13 weeks, p=0.06). However, 42.2% of the women who had received a surgical intervention afterwards did not have any symptoms of a complication. Study 4 assessed the efficacy, safety and acceptability of midlevel provision of medical abortion in a clinical high resource setting. In total 1180 women eligible for inclusion were recruited and randomized to either a nurse midwife or a gynecologist for counseling, examination including ultrasound and treatment. The provision of medical abortion by midlevel providers proved to be as effective and safe as the medical abortion provided by physicians. The risk difference for efficacy was 1.6%, which falls within the 5% margin that was set for equivalence (p=0.027). Women were significantly more likely to prefer a midwife for the consultation (p<0,001). Conclusion: The research shows that medical abortion can be safely and effectively provided by midlevel health care providers as well as women themselves through telemedicine. The acceptability and outcome of medical abortion up to 9 weeks of pregnancy is similar when provided by doctors, nurse midwives or administered by women themselves via telemedicine. Surgical intervention rates after the medical abortion provided via telemedicine reflect local medical practices. The risk of surgical intervention and ongoing pregnancy after home medical abortion only tends to increase after 12 weeks of pregnancy

Ethnocultural transference and countertransference in psychodynamic psychotherapy in the Netherlands

In recent years, members of non-Western ethnic minorities in the Netherlands have increasingly received psychodynamic psychotherapy, up to now usually from native Dutch therapists. All the ordinary mental problems and common components of psychodynamic therapy can then acquire somewhat different contents and significance. This article is on ethnocultural transference and countertransference in the therapeutic relationship between second-generation post-migration patients with a non-Western background and native Dutch therapists

Magic number 7 ±\pm 2 in networks of threshold dynamics

Information processing by random feed-forward networks consisting of units with sigmoidal input-output response is studied by focusing on the dependence of its outputs on the number of parallel paths M. It is found that the system leads to a combination of on/off outputs when $M \lesssim 7$, while for $M \gtrsim 7$, chaotic dynamics arises, resulting in a continuous distribution of outputs. This universality of the critical number $M \sim 7$ is explained by combinatorial explosion, i.e., dominance of factorial over exponential increase. Relevance of the result to the psychological magic number $7 \pm 2$ is briefly discussed.Comment: 6 pages, 5 figure