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Community health centers in the United States, first launched as a federal initiative in 1965, were rooted in models from South Africa, the American civil rights struggle, and a national commitment to address poverty. The first 2 centers, one serving a rural population in the Mississippi Delta and another a public housing project in Boston, incorporated such core principles as provision of primary care to a defined area or population; public health interventions addressing social determinants of health; emphasis on community participation; community empowerment leading to control of the new institutions; epidemiologic methods to identify problems and guide decisions; new combinations of clinical and public health personnel; and reduction of disparities in health and healthcare of the poor and minorities. The continuing relevance of these principles in today's greatly expanded health center network is reviewed. [ABSTRACT FROM AUTHOR]

Abstract: Thoracic trauma is a major cause of mortality due to the associated inflammatory acute respiratory distress syndrome and morbidity due to impaired tissue regeneration. Trauma-induced lung inflammation is characterized by the early recruitment of cells with pro- or anti-inflammatory activity to the lung. Therapeutic interventions reducing the level of tissue inflammation may result in decreased tissue damage and improved healing and recovery. Stem cells might be able to improve trauma outcome via immunomodulation or by enhancing tissue regeneration.Here, we describe the migratory dynamics of murine mesenchymal, hematopoietic and endothelial stem and progenitor cells (SPCs) as well as mature inflammatory cells (monocytes, neutrophils, lymphocytes) to peripheral blood (PB) and lung tissue between 0.2 and 48 h post-blunt chest trauma (TXT). We demonstrate that the kinetics of immune cell and SPC distribution upon trauma are both cell-type and tissue-dependent. We identified a transient, early increase in the number of inflammatory cells in PB and lung at 2 h post-TXT and a second wave of infiltrating SPCs in lungs by 48 h after TXT induction, suggesting a role for SPCs in tissue remodeling after the initial inflammatory phase. Cxcl12/Cxcr4 blockade by AMD3100 within the first 6 h after TXT, while inducing a strong and coordinated mobilization of SPCs and leukocytes to PB and lung tissue, did not significantly affect TXT associated inflammation or tissue damage as determined by inflammatory cytokine levels, plasma markers for organ function, lung cell proliferation and survival, and myofibroblast/fibroblast ratio in the lung. Further understanding the dynamics of the distribution of endogenous SPCs and inflammatory cells will therefore be indispensable for stem cell-based or immunomodulation therapies in trauma., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Endogenously mobilized stem and progenitor cells (SPCs) or exogenously provided SPCs are thought to be beneficial for trauma therapy. However, still little is known about the synchronized dynamics of the number of SPCs in blood after severe injury and parameters like cytokine profiles that correlate with these numbers. We determined the number of hematopoietic stem cells, common myeloid progenitors, granulocyte-macrophage progenitors, and mesenchymal stem/stromal cells in peripheral blood (PB) 0 to 3, 8, 24, 48, and 120 h after polytrauma in individual patients (injury severity score ≥ 21). We found that the number of blood SPCs follows on average a synchronous, inverse bell-shaped distribution, with an increase at 0 to 3 h, followed by a strong decrease, with a nadir in SPC numbers in blood at 24 or 48 h. The change in numbers of SPCs in PB between 48 h and 120 h revealed two distinct patterns: Pattern 1 is characterized by an increase in the number of SPCs to a level higher than normal, pattern 2 is characterized by an almost absent increase in the number of SPCs compared to the nadir. Changes in the concentrations of the cytokines CK, MDC, IL-8, G-CSF Gro-α, VEGF, and MCP-1 correlated with changes in the number of SPCs in PB or were closely associated with Pattern 1 or Pattern 2. Our data provide novel rationale for investigations on the role of stem cell mobilization in polytraumatized patients and its likely positive impact on trauma outcome.

The bioavailability of nitric oxide (NO) within the vascular wall is limited by superoxide anions (O2.-). The relevance of extracellular superoxide dismutase (ecSOD) for the detoxification of vascular O2.- is unknown. We determined the involvement of ecSOD in the control of blood pressure and endothelium-dependent responses in angiotensin II-induced hypertension and renovascular hypertension induced by the two-kidney, one-clip model in wild-type mice and mice lacking the ecSOD gene. Blood pressure was identical in sham-operated ecSOD+/+ and ecSOD-/- mice. After 6 days of angiotensin II-treatment and 2 and 4 weeks after renal artery clipping, blood pressure was significantly higher in ecSOD-/- than ecSOD+/+ mice. Recombinant ecSOD selectively decreased blood pressure in hypertensive ecSOD-/- mice, whereas ecSOD had no effect in normotensive and hypertensive ecSOD+/+ mice. Compared with sham-operated ecSOD+/+ mice, sham-operated ecSOD-/- mice exhibited attenuated acetylcholine-induced relaxations. These responses were further depressed in vessels from clipped animals. Vascular O2.-, as measured by lucigenin chemiluminescence, was higher in ecSOD-/- compared with ecSOD+/+ mice and was increased by clipping. The antioxidant tiron normalized relaxations in vessels from sham-operated and clipped ecSOD-/-, as well as from clipped ecSOD+/+ mice. In contrast, in vivo application of ecSOD selectively enhanced endothelium-dependent relaxation in vessels from ecSOD-/- mice. These data reveal that endogenous ecSOD is a major antagonistic principle to vascular O2.-, controlling blood pressure and vascular function in angiotensin II-dependent models of hypertension. ecSOD is expressed in such an abundance that even in situations of high oxidative stress no relative lack of enzyme activity occurs.

We report on a 42-year-old female patient with glycogen storage disease type 1a (von Gierke disease, GSD 1a) who developed hepatic adenomas and finally a hepatocellular carcinoma 10 years after renal transplantation. The tumor was resected; however, the patient died 6 months later as a result of fulminant carcinoma recurrence. In patients who have GSD 1a with terminal renal failure, combined liver and kidney transplantation may be considered at an early stage of the disease.

Background: Expression of proinflammatory molecules by tubular epithelial cells plays an important role in renal allograft rejection and inflammatory kidney diseases. Different studies from patients with acute rejection point to the involvement of distal tubular segments. At present no in vitro system for the human distal tubule is established., Methods: Human distal tubular cells were isolated immunomagnetically. Cultured cells were stimulated with cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-1beta, or a cytokine mix). Secretion of RANTES (regulated upon activation, normal T-cell expressed and secreted) was evaluated with an enzyme-linked immunoassay. Expression of HLA-DR and intercellular adhesion molecule (ICAM)-1 was assessed by flow cytometric analysis and immunofluorescence studies., Results: Our data clearly indicate that distal tubular cells express RANTES, HLA-DR, and ICAM-1 in response to a mixture of specific cytokines. Dexamethasone inhibited the induced expression of RANTES and HLA-DR significantly, but not that of ICAM-1., Conclusions: We demonstrate an appropriate in vitro system for the human distal tubule. The present study proves the involvement of the distal tubular segment during inflammatory kidney diseases.

Objective: To determine the practice patterns of anesthesiologist intensivists (with the special certificate of competence in critical care medicine from the American Board of Anesthesiology) in the use of neuromuscular blocking drugs, in the ICU setting., Design: A survey., Participants: All anesthesiologists with the special certificate of competence in critical care (n = 374) were selected for this study. Of the 339 who could be contacted and who were still actively practicing, 185 (55%) completed the survey., Results: In the ICU setting, anesthesiologist intensivists most commonly used vecuronium (52%) administered by bolus injection, bolus injection followed by infusion, or by continuous infusion. The most frequent indication for muscle relaxation was facilitation of mechanical ventilation (89%). Neuromuscular blockade was most commonly monitored clinically (55%), with only 34% of respondents using a peripheral nerve stimulator. All respondents indicated the concomitant use of sedatives or narcotics with muscle relaxants., Conclusions: This study was created to address the dearth of information regarding actual usage of muscle relaxants in the ICU setting. The survey population was chosen as one with great familiarity in the use of muscle relaxants. The 55% response rate was significantly greater than the expected response rate for a single mailing survey. In the ICU setting, neuromuscular blocking drugs are most frequently used to facilitate mechanical ventilation. The prevalence of vecuronium use is of interest in light of recent case reports of prolonged neuromuscular blockade after long-term vecuronium administration. The low frequency of peripheral nerve stimulator monitoring during muscle relaxation may contribute, in part, to the problem of prolonged blockade after drug withdrawal. Muscle relaxants are not used in the absence of sedation and/or analgesia by this practitioner population.

The influence of adrenalectomy and mineralocorticoid and glucocorticoid treatment on atrial natriuretic peptide (ANP) concentration of 18 microdissected rat brain nuclei was investigated. Adrenalectomy increased ANP levels highly in those brain areas that control water intake (the subfornical organ and supraoptic nucleus) and in the drinking center (the perifornical nucleus and the lateral hypothalamus). In all of these brain regions, aldosterone elevated ANP levels in intact animals. Adrenalectomy decreased ANP levels markedly in the OVLT and preoptic periventricular nucleus, which constitute the so-called AV3V region. The ANP level of these two brain areas was nearly restored to baseline levels both after administration of sodium chloride and after replacement of aldosterone, whereas dexamethasone treatment failed to have any effect.