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يوضح هذا الكتاب لقادة المؤسسات الاجتماعية كيفية اجتياز التحديات الصعبة التي تواجههم عند إدارة مؤسساتهم، كما يوضح لهم كيفية استغلال الفرص الرائعة التي تقدمها هذه المؤسسات، كل هذا من خلال استعراضه لعشرة متناقضات الرئيسية تواجه قادة المؤسسات الاجتماعية. فهو زاخر بمعلومات وثيقة الصلة بإدارة المؤسسات الاجتماعية. فهو مفيدة ليس فقط لحديثي العهد بمجال إدارة المؤسسات الاجتماعية، ولكن أيضا للمتمرسين وأصحاب الخبرة في هذا المجال.

BackgroundTertiary lymphoid structures (TLSs) are immune aggregates in peripheral tissues that may support adaptive immune responses. Their presence has been associated with clinical response to checkpoint blockade therapy (CBT), but it is unknown whether TLS have prognostic significance independent of CBT in melanoma. We hypothesized that TLS in melanoma metastases would be associated with increased intratumoral lymphocyte infiltration, but that the intra-TLS immunological milieu would be distinct from the intratumoral immunological milieu. We also hypothesized that the presence of TLS would be associated with improved survival, and that TLS maturation or intra-TLS lymphocyte activity would also correlate with survival.MethodsCutaneous melanoma metastases (CMM) from 64 patients were evaluated by multiplex immunofluorescence for the presence and maturation status of TLS. Intra-TLS lymphocyte density, proliferation and B-cell Ig somatic hypermutation (AID+) were analyzed, as were markers of T-cell exhaustion and Th1/Tc1 differentiation. Associations between TLS maturation and intra-TLS immunologic activity were assessed, as well as associations with intratumoral immune cell infiltration. Independent associations with overall survival (OS) were assessed using log-rank tests and Cox proportional hazards models.ResultsTLS were identified in 30 (47%) of 64 CMM (TLS+) and were associated with increased intratumoral lymphocyte infiltration. However, proliferation of intra-TLS lymphocytes did not correlate with intratumoral lymphocyte proliferation. Most were early TLS; however, subsets of primary or secondary follicle-like TLS were also present. TLS+ lesions were associated with lower risk of tumor recurrence after metastasectomy and with improved OS in multivariate analyses (HR 0.51, p=0.04). OS was longer for TLS with low fractions of CD21+ B-cells (HR 0.29, p=0.02) and shorter for those with low AID+ fraction of B-cells (HR 2.74, p=0.03).ConclusionsThe presence of TLS in CMMs is associated with improved OS in patients treated with surgery before CBT, but TLS vary widely in maturation state, in proportions of proliferating T and B cells, and in markers of B cell function, including AID and CD21. Importantly, these features have additional prognostic significance, which suggest that some TLS may have regulatory function, while others functioning to support antigen-driven immune responses, depending on the cellular composition and activation status.

The 2021 Surviving Sepsis Campaign Guidelines recommend administration of antimicrobials within the first hour of recognition of sepsis. Over the last decade, several studies have demonstrated improved time-to-antibiotic administration and antibiotic appropriateness when a pharmacist was involved in the care of patients with sepsis. To our knowledge, no studies evaluating the appropriate use of antibiotics in sepsis driven entirely by an Emergency Medicine (EM) Clinical Pharmacist Practitioner (CPP) have been published. The purpose of this study is to evaluate the impact of an EM CPP-driven protocol on antimicrobial interventions in patients with sepsis in the emergency department (ED). This was a retrospective comparison of patients with sepsis for whom antimicrobials were ordered in the ED without pharmacist intervention to patients whose antimicrobials were ordered by an EM CPP via a sepsis consult to pharmacy. An EM CPP reviewed individual patient profiles for pertinent historical admissions, culture data, and allergy profiles to guide antimicrobial selection for the suspected source of infection and entered orders under their scope of practice with formal documentation in the electronic medical record (EMR). The primary objective of this study was to compare the rates of appropriate empiric antibiotic utilization in septic patients admitted from the ED pre- and post-protocol implementation. Secondary endpoints included the following, broadening of ED-initiated empiric antibiotics on hospital admission, time-to-antibiotic administration, in-hospital mortality, Rapid Emergency Medicine Score (REMS) association with in-hospital mortality, and hospital length of stay. A total of 144 patients were included: 80 patients prescribed antibiotics without pharmacist intervention and 64 prescribed antibiotics by an EM CPP. Appropriate empiric antibiotic selection in the ED improved from 57.5% (46/80) to 86% (55/64) with EM CPP intervention (difference 28.5%; p < 0.01). Time-to-first antibiotic administration decreased by 64 min (p < 0.01). Administration of antibiotics within 60 min, broadening of antibiotics on admission, hospital length of stay, and in-hospital mortality did not significantly differ across groups. In this small, single-center study, an EM Clinical Pharmacist Practitioner-driven protocol for patients with sepsis in the emergency department improved the rate of appropriate empiric antimicrobial selection and time-to-antibiotic administration. •Timely and appropriate antibiotic administration improves outcomes of septic patients.•A CPP-driven protocol improves the rate of appropriate empiric antimicrobials for sepsis in the ED.•A CPP-driven protocol improves time-to-antibiotic administration in the ED.

Endothelial cells play significant roles in conditioning tissues after injury by the production and secretion of angiocrine factors. At least two distinct subsets of monocytes, CD45 ⁺CD11b ⁺Gr1 ⁺Ly6C ⁺ inflammatory and CD45 ⁺CD11b ⁺Gr1 ⁻Ly6C ⁻ anti-inflammatory monocytes, respond differentially to these angiocrine factors and promote pathogen/debris clearance and arteriogenesis/tissue regeneration, respectively. We demonstrate here that local sphingosine 1-phosphate receptor 3 (S1P ₃) agonism recruits anti-inflammatory monocytes to remodeling vessels. Poly(lactic-co-glycolic acid) thin films were used to deliver FTY720, an S1P ₁/₃ agonist, to inflamed and ischemic tissues, which resulted in a reduction in proinflammatory cytokine secretion and an increase in regenerative cytokine secretion. The altered balance of cytokine secretion results in preferential recruitment of anti-inflammatory monocytes from circulation. The chemotaxis of these cells, which express more S1P ₃ than inflammatory monocytes, toward SDF-1α was also enhanced with FTY720 treatment, but not in S1P ₃ knockout cells. FTY720 delivery enhanced arteriolar diameter expansion and increased length density of the local vasculature. This work establishes a role for S1P receptor signaling in the local conditioning of tissues by angiocrine factors that preferentially recruit regenerative monocytes that can enhance healing outcomes, tissue regeneration, and biomaterial implant functionality.

Background Human-human (HH) interaction mediated by machines (e.g., robots or passive sensorized devices), which we call human-machine-human (HMH) interaction, has been studied with increasing interest in the last decade. The use of machines allows the implementation of different forms of audiovisual and/or physical interaction in dyadic tasks. HMH interaction between two partners can improve the dyad’s ability to accomplish a joint motor task ( task performance ) beyond either partner’s ability to perform the task solo. It can also be used to more efficiently train an individual to improve their solo task performance ( individual motor learning ). We review recent research on the impact of HMH interaction on task performance and individual motor learning in the context of motor control and rehabilitation, and we propose future research directions in this area. Methods A systematic search was performed on the Scopus, IEEE Xplore, and PubMed databases. The search query was designed to find studies that involve HMH interaction in motor control and rehabilitation settings. Studies that do not investigate the effect of changing the interaction conditions were filtered out. Thirty-one studies met our inclusion criteria and were used in the qualitative synthesis. Results Studies are analyzed based on their results related to the effects of interaction type (e.g., audiovisual communication and/or physical interaction), interaction mode (collaborative, cooperative, co-active, and competitive), and partner characteristics. Visuo-physical interaction generally results in better dyadic task performance than visual interaction alone. In cases where the physical interaction between humans is described by a spring, there are conflicting results as to the effect of the stiffness of the spring. In terms of partner characteristics, having a more skilled partner improves dyadic task performance more than having a less skilled partner. However, conflicting results were observed in terms of individual motor learning. Conclusions Although it is difficult to draw clear conclusions as to which interaction type, mode, or partner characteristic may lead to optimal task performance or individual motor learning, these results show the possibility for improved outcomes through HMH interaction. Future work that focuses on selecting the optimal personalized interaction conditions and exploring their impact on rehabilitation settings may facilitate the transition of HMH training protocols to clinical implementations.

Tissue-specific stem cells are found throughout the body and, with proper intervention and environmental cues, these stem cells exercise their capabilities for differentiation into several lineages to form cartilage, bone, muscle, and adipose tissue in vitro and in vivo. Interestingly, it has been widely demonstrated that they do not differentiate with the same efficacy during lineage-specific differentiation studies, as the tissue-specific stem cells are generally more effective when differentiating toward the tissues from which they were derived. This review focuses on four mesodermal lineages for tissue-specific stem cell differentiation: adipogenesis, chondrogenesis, myogenesis, and osteogenesis. It is intended to give insight into current multilineage differentiation and comparative research, highlight and contrast known trends regarding differentiation, and introduce supporting evidence which demonstrates particular tissue-specific stem cells' superiority in lineage-specific differentiation, along with their resident tissue origins and natural roles. In addition, some epigenetic and transcriptomic differences between stem cells which may explain the observed trends are discussed.

In a prior study, topiramate reduced heavy drinking among individuals who sought to reduce their drinking, with the effect moderated by a single nucleotide polymorphism (SNP; rs2832407) in GRIK1, which encodes the kainate GluK1 receptor subunit (Kranzler et al. 2014). The present study sought to replicate prospectively the effect of topiramate and rs2832407 in patients with DSM-5 alcohol use disorder (AUD) who sought to reduce or stop their drinking. We stratified the randomization on genotype (rs2832407*C-allele homozygotes vs. A-allele carriers) and assigned 170 European-American participants (71.2% male) to receive 12 weeks of treatment with topiramate (N  = 85), at a maximal daily dosage of 200 mg, or matching placebo (N = 85). At each of nine treatment visits participants received brief counseling to reduce drinking and increase abstinent days. We hypothesized that topiramate-treated patients with the rs2832407*CC genotype would reduce heavy drinking days (HDDs) more than the other three groups. The rate of treatment completion was 91.8% in both groups. The mean number of HDDs per week in the placebo group was 1.67 (95% CI = (1.29, 2.16), p = 0.0001) times greater than in the topiramate group, which was confirmed by the topiramate group’s significantly greater reduction in the concentration of the liver enzyme γ-glutamyltransferase and lower alcohol-related problems score. There was no significant difference in topiramate’s effect on HDDs between genotype groups. Although consistent with other studies showing a reduction in heavy drinking with topiramate treatment, the prior finding of a moderating effect of rs2832407 genotype was not replicated in this prospective trial.

Lysophosphatidic acid (LPA) is a bioactive lipid that enhances ovarian cancer cell proliferation, migration and invasion in vitro and stimulates peritoneal metastasis in vivo. LPA is generated through the action of autotaxin or phospholipases, and degradation begins with lipid phosphate phosphohydrolase (LPP)-dependent removal of the phosphate. While the effects of LPA on ovarian cancer progression are clear, the effects of LPA metabolism within the tumor microenvironment on peritoneal metastasis have not been reported. We examined the contribution of lipid phosphatase activity to ovarian cancer peritoneal metastasis using mice deficient in LPP1 expression. Homozygous deletion of LPP1 (LPP1 KO) results in elevated levels and decreased turnover of LPA in vivo. Within 2 weeks of intraperitoneal injection of syngeneic mouse ovarian cancer cells, we observed enhanced tumor seeding in the LPP1 KO mice compared to wild type. However, tumor growth plateaued in the LPP1 KO mice by 3 weeks while tumors continued to grow in wild type mice. The decreased tumor burden was accompanied by increased apoptosis and no change in proliferation or angiogenesis. Tumor growth was restored and apoptosis reversed with exogenous administration of LPA. Together, these observations demonstrate that the elevated levels of LPA per se in LPP1 KO mice do not inhibit tumor growth. Rather, the data support the notion that either elevated LPA concentration or altered LPA metabolism affects other growth-promoting contributions of the tumor microenvironment.

[...]the retrospective nature provides opportunity for bias, and led to lack of documentation for some endpoints. [...]patients were not followed once they left the emergency department, and clinical outcomes were not assessed as part of this study. Larger studies that assess pharmacist-driven sedation protocols in the emergency department and associated clinical outcomes, such as ICU length of stay, and ventilator-free days, are still needed to assess the impact of the clinical pharmacist on sedation practices.Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Acknowledgement The authors have no conflicts of interest or anything to disclose.