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Both fatty bone marrow (FBM) and somatic mutations in hematopoietic stem cells (HSCs), also termed clonal hematopoiesis (CH) accumulate with human aging. However it remains unclear whether FBM can modify the evolution of CH. To address this question, we herein present the interaction between CH and FBM in two preclinical male mouse models: after sub-lethal irradiation or after castration. An adipogenesis inhibitor (PPARγ inhibitor) is used in both models as a control. A significant increase in self-renewal can be detected in both human and rodent DNMT3A Mut -HSCs when exposed to FBM. DNMT3A Mut -HSCs derived from older mice interacting with FBM have even higher self-renewal in comparison to DNMT3A Mut -HSCs derived from younger mice. Single cell RNA-sequencing on rodent HSCs after exposing them to FBM reveal a 6-10 fold increase in DNMT3A Mut -HSCs and an activated inflammatory signaling. Cytokine analysis of BM fluid and BM derived adipocytes grown in vitro demonstrates an increased IL-6 levels under FBM conditions. Anti-IL-6 neutralizing antibodies significantly reduce the selective advantage of DNMT3A Mut -HSCs exposed to FBM. Overall, paracrine FBM inflammatory signals promote DNMT3A -driven clonal hematopoiesis, which can be inhibited by blocking the IL-6 pathway. Age related accumulation of adipocytes in the bone marrow could alter normal and leukemic haematopoiesis. Here, in fatty bone marrow (FBM) preclinical models, the authors show that inflammatory cytokines increased in the FBM, such as IL-6, promote DNMT3a driven clonal hematopoiesis.

Background Telehealth has become increasingly widespread across healthcare systems worldwide. However, its integration into Israel's Maternal and Child Health Clinics (MCHCs) remains limited. These national clinics play a crucial role in disease prevention and public health, yet the use of telenursing by nurses during the COVID-19 pandemic and beyond was infrequent. This study aimed to explore the factors predicting nurses’ intention to adopt telenursing in MCHCs, based on the Theory of Planned Behavior. Methods A cross-sectional design was employed. An online anonymous survey was distributed among 279 MCHC nurses from three districts of Israel. A structural equation model was used to test the direct and indirect effects on nurses’ intention to use telenursing. Results Actual use was significantly lower than intention to use telenursing (p < 0.001). Direct associations were observed between digital literacy and attitudes (p < 0.01), subjective norms (p < 0.01), and perceived behavioral control (PBC; p < 0.01). In addition, direct associations were observed between subjective norms and intention (p < 0.01), and between PBC and intention (p < 0.01). Furthermore, indirect associations were observed among digital literacy and intention via subjective norms (p = 0.01), and PBC (p < 0.01). Conclusions Integrating telenursing services into MCHCs requires targeted training for nurses to support technology gaps. Interventions aimed at developing remote health services skills are essential for enhance nurses’ PBC and perception of subjective norm related to telenursing, which in turn will increase their intentions to engage in such service. Implementing remote health services in MCHCs may improve parental adherence and more frequent online follow-ups, ultimately support the health promotion of infants and mothers and benefit public health. Key messages • Nurses’ perceptions and technological skills influence their intentions to use telenursing in MCHCs. • Interventions should strengthen nurses’ digital literacy, thereby increasing their perceived behavioral control and social norms regarding telenursing, to facilitate its integration.

Scholars who support pain-and-suffering damages argue that, from an optimal deterrence perspective, defendants should bear the full social cost of their conduct, which includes pain-and-suffering costs.4 According to this view, pain-and-suffering damages actually compensate for a concrete loss: disfigurement, emotional trauma, extended physical discomfort, and loss of normal life-enhancing capacities.

In this paper, we study contracts with two-sided incomplete information. Prior literature on contract remedies does not formally account for the nonbreaching party's option to not sue for damages upon breach, when her expected payoff from suing is negative, given the contractual terms and her private information about her post-breach loss. With this option incorporated into the analysis, we show that: First, courts should commit to awarding fixed damages, because awarding flexible damages based on ex post information will distort the incentives to breach. This result is not driven by the information-forcing effect of basing damages on ex ante expectations, à la Hadley vs. Baxendale, rather it is driven by the endogenous decision to litigate breach. Second, the option of acquiescing to the breach expands the breach set under specific performance, which can be more efficient than other remedies. Third, the efficiency advantage of ex ante expectation damages over ex post actual damages is further enhanced when we account for the possibility of renegotiation.

We evaluate the effect of tort reform on employer-sponsored health insurance premiums by exploiting state-level variation in the timing of reforms. Using a dataset of health plans representing over 10 million Americans annually between 1998 and 2006, we find that the most common set of tort reforms during this period reduces premiums of employer-sponsored self-insured health plans by 2.1%. Of the four individual reforms comprising this set, caps on noneconomic damages and collateral source reforms have the greatest impact. We do not find reductions in premiums for fully insured plans, which in our sample are almost entirely Health Maintenance Organizations (HMOs). Further analysis reveals that self-insured HMOs are also unresponsive to reforms. Taken together, these findings suggest that HMOs reduce \"defensive medicine,\" even absent reform. The results are the first direct evidence that tort reform reduces healthcare costs in aggregate; prior research has largely focused on particular medical conditions.

Evaluation of potential tropic effects of vascular endothelial growth factor (VEGF) on the incorporation and differentiation of bone-marrow-derived stem cells (BMSCs) in a murine model of anterior ischemic optic neuropathy (AION). In the first approach, small-sized subset of BMCs were isolated from GFP donors mice by counterflow centrifugal elutriation and depleted of hematopoietic lineages (Fr25lin(-)). These cells were injected into a peripheral vein (1 × 10(6) in 0.2 ml) or inoculated intravitreally (2 × 10(5)) to syngeneic mice, with or without intravitreal injection of 5 μg/2μL VEGF, simultaneously with AION induction. In a second approach, hematopoietic cells were substituted by myelablative transplant of syngeseic GFP + bone marrow cells. After 3 months, progenitors were mobilized with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by VEGF inoculation into the vitreous body and AION induction . Engraftment and phenotype were examined by immunohistochemistry and FISH at 4 and 24 weeks post-transplantation, and VEGF receptors were determined by real time PCR. VEGF had no quantitative effect on incorporation of elutriated cells in the injured retina, yet it induced early expression of neuroal markers in cells incorporated in the RGC layer and promoted durable gliosis, most prominent perivascular astrocytes. These effects were mediated by VEGF-R1/Flt-1, which is constitutively expresses in the elutriated fraction of stem cells. Mobilization with GM-CSF limited the differentiation of bone marrow progenitors to microglia, which was also fostered by VEGF. VEGF signaling mediated by Flt-1 induces early neural and sustained astrocytic differentiation of stem cells elutriated from adult bone-marrow, with significant contribution to stabilization retinal architecture following ischemic injury.

This study evaluates tort reform's impact on private health insurance coverage. Tort reform may reduce costly damage awards and defensive medicine. On the other hand, tort reform may increase health care costs by reducing doctors' caretaking or increasing questionable treatments. Reducing health care costs should increase health insurance coverage rates, while cost increases should decrease coverage rates. We find that between 1981 and 2007 damage caps, collateral source reform, and joint-and-several liability reform increased health insurance coverage among price-sensitive groups between one-half and one percentage points each. We conclude that tort reform reduces health care costs, at least for price-sensitive groups.

Scholars have been debating for years the comparative advantage of damages and specific performance. Yet, most work has compared a single remedy contract to another single remedy contract. But contract law provides the non-breaching party with a variety of optional remedies to choose from in case of a breach, and parties themselves regularly write contracts which provide such options. In this article, we start filling this gap by studying multi-remedy contracts. Specifically, we compare a contract that grants the non-breaching party an option to choose between liquidated damages and specific performance with an exclusive remedy contract, which restricts the non-breaching party's remedy to liquidated damages only.