State paid family leave policies and infant maltreatment.

BACKGROUND: Growing research points to economic policies as protective mechanisms for vulnerable families. Research on pediatric abusive head trauma suggests that paid family leave (PFL) may protect infants in the general population from physical abuse. OBJECTIVE: To examine the association of state-level paid family leave policies with infant (ages 0-1) maltreatment rates. PARTICIPANTS AND SETTING: A state-level panel dataset was constructed from the National Child Abuse and Neglect Data System (2002-2019) data on infant maltreatment investigations among four states with PFL (California, New Jersey, New York, and Rhode Island) and 36 states without PFL. METHODS: A piecewise longitudinal model and a nested model comparison were conducted to estimate the treatment effect of PFL on the population rate of infant maltreatment investigations. Supplementary analyses examined the moderating effect of three covariates. RESULT: PFL reduced the linear rate of change in infant maltreatment rates in the states where it was enacted by a factor of 0.979 for each year post-policy implementation compared to states without such policies, B = -0.021, SE = 0.008, 95 % CI = [-0.036,-0.005]. Examining treatment states only, the slope of infant maltreatment became significantly shallower post-policy implementation, χ2(1) = 3.178, p = .075. Interactions testing the moderating effects of family poverty and adults with less than high school education were significant, B = -0.304, 95 % CI = [-0.564,-0.052]; B = -0.511, 95 % CI = [-0.799,-0.249], respectively. CONCLUSION: Results suggest that PFL has a beneficial effect on infant maltreatment rates and add to growing evidence that policies aimed to support household economic stability could be a vital child maltreatment prevention policy tool.

Minimally invasive approach: is this the future of aortic surgery?

Median sternotomy incision has shown to be a safe and efficacious approach in patients who require thoracic aortic interventions and still represents the gold-standard access. Nevertheless, over the last decade, less invasive techniques have gained wider clinical application in cardiac surgery becoming the first-choice approach to treat heart valve diseases, in experienced centers. The popularization of less invasive techniques coupled with an increased patient demand for less invasive therapies has motivated aortic surgeons to apply minimally invasive approaches to more challenging procedures, such as aortic root replacement and arch repair. However, technical demands and the paucity of available clinical data have still limited the widespread adoption of minimally invasive thoracic aortic interventions. This review aimed to assess and comment on the surgical techniques and the current evidence on mini thoracic aortic surgery. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-021-01258-2.

Treating acute colonic diverticulitis with extraluminal pericolic air: An Acute Care Surgery in the Netherlands (ACCSENT) multicenter retrospective cohort study.

BACKGROUND: Owing to improved quality of computed tomography, a new category of complicated acute diverticulitis, including patients with pericolic air but without abscess formation, can be defined (Hinchey 1a). Recent studies question whether this new category of acute diverticulitis could be treated as uncomplicated cases. The aim of our study is to report on the clinical course of acute diverticulitis Hinchey 1a in current clinical practice. METHODS: For this multicenter retrospective cohort study, patients presenting at the emergency department with Hinchey 1a acute diverticulitis as demonstrated by computed tomography scan, were identified. The primary outcome measure was successful conservative treatment with observation alone, antibiotics, and/or hospital admission. Readmissions, percutaneous drainage of abscesses, and emergency operations were considered as failure. RESULTS: Between October 2016 and October 2018, 1,199 patients were clinically suspected for acute diverticulitis, of whom 101 (8.4%) were radiologically diagnosed to have type 1a acute diverticulitis (average age 57 (±13) years, 45% female) and started with conservative treatment. This was successful in 86 (85%) patients. One of the 15 unsuccessfully treated patients (1%) received percutaneous drainage of an abdominal abscess. Surgery was required in 9 cases (9%) after a median time of 6 days (range, 3 to 69 days). Although a difference in the volume of extraluminal air on computed tomography scan was found, this was not shown to be a risk factor for the clinical course. CONCLUSION: Patients with type 1a acute diverticulitis can be treated successfully by conservative therapy in the majority of cases (85%). More research is required to define predictive factors for successful conservative management.

Coastal flooding will disproportionately impact people on river deltas.

Climate change is intensifying tropical cyclones, accelerating sea-level rise, and increasing coastal flooding. River deltas are especially vulnerable to flooding because of their low elevations and densely populated cities. Yet, we do not know how many people live on deltas and their exposure to flooding. Using a new global dataset, we show that 339 million people lived on river deltas in 2017 and 89% of those people live in the same latitudinal zone as most tropical cyclone activity. We calculate that 41% (31 million) of the global population exposed to tropical cyclone flooding live on deltas, with 92% (28 million) in developing or least developed economies. Furthermore, 80% (25 million) live on sediment-starved deltas, which cannot naturally mitigate flooding through sediment deposition. Given that coastal flooding will only worsen, we must reframe this problem as one that will disproportionately impact people on river deltas, particularly in developing and least-developed economies.

Reframing the Wilderness Concept can Bolster Collaborative Conservation.

Indigenous territories represent ~45% of land categorized as wilderness in the Amazon, but account for <15% of all forest loss on this land. At a time when the Amazon faces unprecedented pressures, overcoming polarization and aligning the goals of wilderness defenders and Indigenous peoples is paramount, to avoid environmental degradation.

Therapeutic Breast Reconstruction Using Gene Therapy-Delivered IFNγ Immunotherapy.

After mastectomy, breast reconstruction is increasingly performed using autologous tissue with the aim of improving quality of life. During this procedure, autologous tissue is excised, relocated, and reattached using microvascular anastomoses at the site of the extirpated breast. The period during which the tissue is ex vivo may allow genetic modification without any systemic exposure to the vector. Could such access permit delivery of therapeutic agents using the tissue flap as a vehicle? Such delivery may be more targeted and oncologically efficient than systemic therapy, and avoid systemic complications. The cytokine IFNγ has antitumor effects, and systemic toxicity could be circumvented by localized delivery of the IFNγ gene via gene therapy to autologous tissue used for breast reconstruction, which then releases IFNγ and exerts antitumor effects. In a rat model of loco-regional recurrence (LRR) with MADB-106-Luc and MAD-MB-231-Luc breast cancer cells, autologous tissue was transduced ex vivo with an adeno-associated viral vector encoding IFNγ. The "Therapeutic Reconstruction" released IFNγ at the LRR site and eliminated cancer cells, significantly decreased tumor burden, and increased survival compared with sham reconstruction (P <0.05). Mechanistically, localized IFNγ immunotherapy stimulated M1 macrophages to target cancer cells within the regional confines of the modified tumor environment. This concept of "Therapeutic Breast Reconstruction" using ex vivo gene therapy of autologous tissue offers a new application for immunotherapy in breast cancer with a dual therapeutic effect of both reconstructing the ablative defect and delivering local adjuvant immunotherapy.

Validation and stability analysis of a modified lactate dehydrogenase (LDH) test method to be employed for an in vitro viable skin model.

In view of increasing numbers of dermatological disorders, transdermal drug delivery along with in vitro research is becoming increasingly popular. Herefore, qualified in vitro skin models are required. The objective of this study was the optimization and validation of a modified lactate dehydrogenase (LDH) release assay during the establishment of an in vitro viable human skin model, employable for a variety of skin associated disorders. Firstly, the most suitable LDH isoform for the study was determined. Subsequently, a stability study was conducted to investigate the best storage conditions of the LDH enzyme. Finally, the test system was validated in terms of linear range, range limits and system suitability. The results indicate LDH-5 as most suitable isoform due to its predominance in skin. The stability samples stored at -20 °C in the presence of polyethylene glycol (PEG) as cryoprotector displayed the targeted recovery of 100% ± 15 % until the end of the four-week study in contrast to other investigated conditions. A six-point calibration without PEG and a seven-point calibration with PEG including evaluation of system suitability and quantification limits were established with both correlation coefficients r2 above 0.99 and all deviations below 15%. Concluding from those results, this method can be considered valid and useful for its employment in viability determination of viable in vitro skin models.

Single-Cell Transcriptomics of Human Mesenchymal Stem Cells Reveal Age-Related Cellular Subpopulation Depletion and Impaired Regenerative Function.

Although bone marrow-derived mesenchymal stem cells (BM-MSCs) are widely recognized as promising therapeutic agents, the age-related impacts on cellular function remain largely uncharacterized. In this study, we found that BM-MSCs from young donors healed wounds in a xenograft model faster compared with their aged counterparts (p < .001). Given this significant healing advantage, we then used single-cell transcriptomic analysis to provide potential molecular insights into these observations. We found that the young cells contained a higher proportion of cells characterized by a higher expression of genes involved in tissue regeneration. In addition, we identified a unique, quiescent subpopulation that was exclusively present in young donor cells. Together, these findings may explain a novel mechanism for the enhanced healing capacity of young stem cells and may have implications for autologous cell therapy in the extremes of age. Stem Cells 2019;37:240-246.

Comparison of the Hydroxylase Inhibitor Dimethyloxalylglycine and the Iron Chelator Deferoxamine in Diabetic and Aged Wound Healing.

BACKGROUND: A hallmark of diabetes mellitus is the breakdown of almost every reparative process in the human body, leading to critical impairments of wound healing. Stabilization and activity of the transcription factor hypoxia-inducible factor (HIF)-1α is impaired in diabetes, leading to deficits in new blood vessel formation in response to injury. In this article, the authors compare the effectiveness of two promising small-molecule therapeutics, the hydroxylase inhibitor dimethyloxalylglycine and the iron chelator deferoxamine, for attenuating diabetes-associated deficits in cutaneous wound healing by enhancing HIF-1α activation. METHODS: HIF-1α stabilization, phosphorylation, and transactivation were measured in murine fibroblasts cultured under normoxic or hypoxic and low-glucose or high-glucose conditions following treatment with deferoxamine or dimethyloxalylglycine. In addition, diabetic wound healing and neovascularization were evaluated in db/db mice treated with topical solutions of either deferoxamine or dimethyloxalylglycine, and the efficacy of these molecules was also compared in aged mice. RESULTS: The authors show that deferoxamine stabilizes HIF-1α expression and improves HIF-1α transactivity in hypoxic and hyperglycemic states in vitro, whereas the effects of dimethyloxalylglycine are significantly blunted under hyperglycemic hypoxic conditions. In vivo, both dimethyloxalylglycine and deferoxamine enhance wound healing and vascularity in aged mice, but only deferoxamine universally augmented wound healing and neovascularization in the setting of both advanced age and diabetes. CONCLUSION: This first direct comparison of deferoxamine and dimethyloxalylglycine in the treatment of impaired wound healing suggests significant therapeutic potential for topical deferoxamine treatment in ischemic and diabetic disease.

Ultrasound-Assisted Liposuction Does Not Compromise the Regenerative Potential of Adipose-Derived Stem Cells.

Human mesenchymal stem cells (MSCs) have recently become a focus of regenerative medicine, both for their multilineage differentiation capacity and their excretion of proregenerative cytokines. Adipose-derived mesenchymal stem cells (ASCs) are of particular interest because of their abundance in fat tissue and the ease of harvest via liposuction. However, little is known about the impact of different liposuction methods on the functionality of ASCs. Here we evaluate the regenerative abilities of ASCs harvested via a third-generation ultrasound-assisted liposuction (UAL) device versus ASCs obtained via standard suction-assisted lipoaspiration (SAL). Lipoaspirates were sorted using fluorescent assisted cell sorting based on an established surface-marker profile (CD34+/CD31-/CD45-), to obtain viable ASCs. Yield and viability were compared and the differentiation capacities of the ASCs were assessed. Finally, the regenerative potential of ASCs was examined using an in vivo model of tissue regeneration. UAL- and SAL-derived samples demonstrated equivalent ASC yield and viability, and UAL ASCs were not impaired in their osteogenic, adipogenic, or chondrogenic differentiation capacity. Equally, quantitative real-time polymerase chain reaction showed comparable expression of most osteogenic, adipogenic, and key regenerative genes between both ASC groups. Cutaneous regeneration and neovascularization were significantly enhanced in mice treated with ASCs obtained by either UAL or SAL compared with controls, but there were no significant differences in healing between cell-therapy groups. We conclude that UAL is a successful method of obtaining fully functional ASCs for regenerative medicine purposes. Cells harvested with this alternative approach to liposuction are suitable for cell therapy and tissue engineering applications. Significance: Adipose-derived mesenchymal stem cells (ASCs) are an appealing source of therapeutic progenitor cells because of their multipotency, diverse cytokine profile, and ease of harvest via liposuction. Alternative approaches to classical suction-assisted liposuction are gaining popularity; however, little evidence exists regarding the impact of different liposuction methods on the regenerative functionality of ASCs. Human ASC characteristics and regenerative capacity were assessed when harvested via ultrasound-assisted (UAL) versus standard suction-assisted liposuction. ASCs obtained via UAL were of equal quality when directly compared with the current gold standard harvest method. UAL is an adjunctive source of fully functional mesenchymal stem cells for applications in basic research and clinical therapy.

Enhanced hematopoietic stem cell function mediates immune regeneration following sex steroid blockade.

Mechanisms underlying age-related defects within lymphoid-lineages remain poorly understood. We previously reported that sex steroid ablation (SSA) induced lymphoid rejuvenation and enhanced recovery from hematopoietic stem cell (HSC) transplantation (HSCT). We herein show that, mechanistically, SSA induces hematopoietic and lymphoid recovery by functionally enhancing both HSC self-renewal and propensity for lymphoid differentiation through intrinsic molecular changes. Our transcriptome analysis revealed further hematopoietic support through rejuvenation of the bone marrow (BM) microenvironment, with upregulation of key hematopoietic factors and master regulatory factors associated with aging such as Foxo1. These studies provide important cellular and molecular insights into understanding how SSA-induced regeneration of the hematopoietic compartment can underpin recovery of the immune system following damaging cytoablative treatments. These findings support a short-term strategy for clinical use of SSA to enhance the production of lymphoid cells and HSC engraftment, leading to improved outcomes in adult patients undergoing HSCT and immune depletion in general.

Embryo vitrification using a novel semi-automated closed system yields in vitro outcomes equivalent to the manual Cryotop method.

STUDY QUESTION: Can the equilibration steps prior to embryo vitrification be automated? SUMMARY ANSWER: We have developed the 'Gavi' system which automatically performs equilibration steps before closed system vitrification on up to four embryos at a time and gives in vitro outcomes equivalent to the manual Cryotop method. WHAT IS KNOWN ALREADY: Embryo cryopreservation is an essential component of a successful assisted reproduction clinic, with vitrification providing excellent embryo survival and pregnancy outcomes. However, vitrification is a manual, labour-intensive and highly skilled procedure, and results can vary between embryologists and clinics. A closed system whereby the embryo does not come in direct contact with liquid nitrogen is preferred by many clinics and is a regulatory requirement in some countries. STUDY DESIGN, SIZE, DURATION: The Gavi system, an automation instrument with a novel closed system device, was used to equilibrate embryos prior to vitrification. Outcomes for embryos automatically processed with the Gavi system were compared with those processed with the manual Cryotop method and with fresh (non-vitrified) controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The efficacy of the Gavi system (Alpha model) was assessed for mouse (Quackenbush Swiss and F1 C57BL/6J x CBA) zygotes, cleavage stage embryos and blastocysts, and for donated human vitrified-warmed blastocysts. The main outcomes assessed included recovery, survival and in vitro embryo development after vitrification-warming. Cooling and warming rates were measured using a thermocouple probe. MAIN RESULTS AND THE ROLE OF CHANCE: Mouse embryos vitrified after processing with the automated Gavi system achieved equivalent in vitro outcomes to that of Cryotop controls. For example, for mouse blastocysts both the Gavi system (n = 176) and manual Cryotop method (n = 172) gave a 99% recovery rate, of which 54 and 50%, respectively, progressed to fully hatched blastocysts 48 h after warming. The outcomes for human blastocysts processed with the Gavi system (n = 23) were also equivalent to Cryotop controls (n = 13) including 100% recovery for both groups, of which 17 and 15%, respectively, progressed to fully hatched blastocysts 48 h after warming. The cooling and warming rates achieved with the Gavi system were 14 136°C/min and 11 239°C/min, respectively. LIMITATIONS, REASONS FOR CAUTION: Testing of the Gavi system described here was limited to in vitro development of embryos from two mouse strains and a limited number of human embryos. Validation of Gavi system advanced production models is now required to confirm the success of semi-automated vitrification, including clinical evaluation of pregnancy outcomes from the transfer of Gavi vitrified-warmed human embryos. WIDER IMPLICATIONS OF THE FINDINGS: The Gavi system has the potential to revolutionize and standardize vitrification of embryos and oocytes. The success of the Gavi system shows that it is possible to semi-automate complicated labour-intensive ART methods and processes, and opens up the possibility for further improvements in clinical outcomes and efficiencies in the ART clinic. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Genea Ltd. S.B., N.M.T., T.T.P., S.J.M., M.C.B. and T.S. are shareholders of Genea Ltd. E.V., C.H., C.L., S.R.L. and S.M.D. are shareholders of Planet Innovation Pty Ltd. The remaining authors are employees of either Genea Ltd. or Planet Innovation Pty Ltd.

Climate warming mediates negative impacts of rapid pond drying for three amphibian species.

Anthropogenic climate change will present both opportunities and challenges for pool-breeding amphibians. Increased water temperature and accelerated drying may directly affect larval growth, development, and survival, yet the combined effects of these processes on larvae with future climate change remain poorly understood. Increased surface temperatures are projected to warm water and decrease water inputs, leading to earlier and faster wetland drying. So it is often assumed that larvae will experience negative synergistic impacts with combined warming and drying. However, an alternative hypothesis is that warming-induced increases in metabolic rate and aquatic resource availability might compensate for faster drying rates, generating antagonistic larval responses. We conducted a mesocosm experiment to test the individual and interactive effects of pool permanency (permanent vs. temporary) and water temperature (ambient vs. (+) -3 degrees C) on three anurans with fast-to-slow larval development rates (Great Basin spadefoot [Spea intermontana], Pacific chorus frog [Pseudacris regilla], and northern red-legged frog [Rana aurora]). We found that although tadpoles in warmed pools reached metamorphosis 15-17 days earlier, they did so with little cost (< 2 mm) to size, likely due to greater periphyton growth in warmed pools easing drying-induced resource competition. Warming and drying combined to act antagonistically on early growth (P = 0.06) and survival (P = 0.06), meaning the combined impact was less than the sum of the individual impacts. Warming and drying acted additively on time to and size at metamorphosis. These nonsynergistic impacts may result from cotolerance of larvae to warming and drying, as well as warming helping to offset negative impacts of drying. Our results indicate that combined pool warming and drying may not always be harmful for larval amphibians. However, they also demonstrate that antagonistic responses are difficult to predict, which poses a challenge to proactive conservation and management. Our study highlights the importance of considering the nature of multiple stressor interactions as amphibians are exposed to an increasing number of anthropogenic threats.

Alveolar macrophages are critical for the inhibition of allergic asthma by mesenchymal stromal cells.

Multipotent mesenchymal stromal cells (MSCs) possess reparative and immunoregulatory properties, making them attractive candidates for cellular therapy. However, the majority of MSCs administered i.v. encounter a pulmonary impasse and soon disappear from the lungs, raising the question of how they induce such durable immunosuppressive effects. Using a mouse model of allergic asthma, we show that administration of MSCs isolated from human bone marrow, umbilical cord, or adipose tissue provoked a pronounced increase in alveolar macrophages and inhibited hallmark features of asthma, including airway hyperresponsiveness, eosinophilic accumulation, and Th2 cytokine production. Importantly, selective depletion of this macrophage compartment reversed the therapeutic benefit of MSC treatment on airway hyperresponsiveness. Our data demonstrate that human MSCs exert cross-species immunosuppressive activity, which is mediated by alveolar macrophages in allergic asthma. As alveolar macrophages are the predominant immune effector cells at the air-tissue interface in the lungs, this study provides a compelling mechanism for durable MSC effects in the absence of sustained engraftment.

Clinical ethics consultation in oncology.

PURPOSE: There is limited empirical research exploring the nature of clinical ethical consultations within the oncology population. Our objective was to review and describe clinical ethics consultations at two National Cancer Institute-designated comprehensive cancer centers to identify opportunities for systems improvement in clinical care and opportunities for staff education. METHODS: This case series is derived from two institutional prospectively maintained clinical ethics consultation databases. All ethics consultations from 2007 through 2011 that related to adult patients with cancer were included. RESULTS: A total of 208 eligible patient cases were identified. The most common primary issues leading to ethics consultation were code status and advance directives (25%), surrogate decision making (17%), and medical futility (13%). Communication lapses were identified in 45% of patient cases, and interpersonal conflict arose in 51%. Before ethics consultation, 26% of patients had do-not-resuscitate orders, which increased to 60% after ethics consultation. Palliative care consultation occurred in 41% of patient cases. CONCLUSION: Ethics consultations among patients with cancer reflect the complexities inherent to their clinical management. Appropriately honoring patients' wishes within the context of overall goals of care is crucial. Thoughtful consideration of the role of and relationship with palliative care experts, communication barriers, sources of interpersonal conflict, symptom control, and end-of-life care is paramount to optimal management strategies in this patient population.

Screening for distress, the 6th vital sign: common problems in cancer outpatients over one year in usual care: associations with marital status, sex, and age.

BACKGROUND: Very few studies examine the longitudinal prevalence of problems and the awareness or use of clinical programs by patients who report these problems. Of the studies that examine age, gender and marital status as predictors of a range of patient outcomes, none examines the interactions between these demographic variables. This study examined the typical trajectory of common practical and psychosocial problems endorsed over 12 months in a usual-care sample of cancer outpatients. Specifically, we examined whether marital status, sex, age, and their interactions predicted these trajectories. We did not actively triage or refer patients in this study in order to examine the natural course of problem reports. METHODS: Patients completed baseline screening (N = 1196 of 1707 approached) and the sample included more men (N = 696) than women (N = 498), average age 61.1 years. The most common diagnoses were gastrointestinal (27.1%), prostate (19.2%), skin (11.1%) and gynecological (9.2%). Among other measures, patients completed a Common Problem Checklist and Psychosocial Resources Use questions at baseline, 3, 6, and 12 months using paper and pencil surveys. RESULTS: Results indicated that patients reported psychosocial problems more often than practical and both decreased significantly over time. Younger single patients reported more practical problems than those in committed relationships. Younger patients and women of all ages reported more psychosocial problems. Among a number of interesting interactions, for practical problems, single older patients improved more; whereas among married people, younger patients improved more. For psychosocial problems we found that older female patients improved more than younger females, but among males, it was younger patients who improved more. Young single men and women reported the most past-and future-use of services. CONCLUSIONS: Younger women are particularly vulnerable to experiencing practical and psychosocial problems when diagnosed with cancer, but being married protects these younger women. Marriage appeared to buffer reports of both practical and psychosocial problems, and led to less awareness and use of services. Unexpectedly, young men reported the highest use of psychosocial services. This study informs clinical program development with information on these risk groups.

Selective endothelial overexpression of arginase II induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice.

BACKGROUND: Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO) bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII) gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions. CONCLUSION: We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.

Arginase II knockout mouse displays a hypertensive phenotype despite a decreased vasoconstrictory profile.

Arginase upregulation is associated with aging and cardiovascular diseases. In this study we report on the cardiovascular phenotype of the arginase II knockout (KO) mouse. We demonstrate that vascular sensitivity and reactivity altered over time in these animals such that no influence on responses to vasoconstrictor activity was observed in 7-week-old KO mice, but dampened responses to norepinephrine and phenylephrine were observed by 10 and 15 weeks with Rho kinase influencing these effects in the 15-week-old animals. Despite these dampened vasoconstrictory responses, KO mice demonstrated increased mean arterial pressure from 8 weeks old. This hypertensive phenotype was associated with an increase in left ventricular weight, left ventricular systolic pressure, and diminished diastolic function. KO mice also show enhanced plasma norepinephrine turnover, suggesting an increased sympathetic outflow. In conclusion, our data suggest that global loss of arginase II activity results in hypertension. We suggest that this strain of mouse warrants further investigation as a potentially novel model of hypertension.

[Haemobilia, the rare case of bleeding into GIT]. / Hemobilie, vzácná prícina krvácení do GIT.

AIM OF THE WORK: Bleeding into GIT is still serious problem with not low lethality. Especially, acute bleeding needs fast diagnostics and treatment. The aim of our work is to present the rare case of bleeding into GIT--haemobilia. GROUP OF THE PATIENTS: There is presented casuistics of the patient who was successfully treated on our department for bleeding from erosion of cystic artery as a consequence of acute cholecystitis. CONCLUSION: Nowadays there is dominantly preferred endoscopic approach in diagnostics and treatment of the bleeding into GIT. But surgical approach is in some cases the only one method in treatment of these complications.

[K-ras mutation as a prognostic factor in colorectal carcinoma]. / K-ras mutace u kolorektálního karcinomu jako prognostický faktor vývoje onemocnení.

INTRODUCTION: Colorectal carcinoma presents a serious problem in the Czech Republic: its incidence is on the increase and--according to some statistics takes first place among developed countries worldwide. Therefore, it is advised to incorporate examinational and the rapeutic algorithms with new modalities that will lead to early diagnostics or to a change in existing therapeutic procedures. CHARACTERIZATION OF K-RAS MUTATION: K-ras mutation belongs to the family of protooncogenes where a gene not having undergone mutation expresses proteins that regulate mitosis. Mutation cancels the regulatory function of these proteins, thus leading to the develop ment of tumors, especially carcinoma of the lungs, pancreas, and colorectum. PROJECT OBJECTIVE: The main objective of the project is to prove K-ras mutation in tumors of the colorectum: to detect tumor cells with K-ras mutation in peripheral blood; to detect K-ras mutation in liver metastases: and to verify the hypothesis claiming that tumors with K-ras mutation have a worse prognosis and often lead to disemination, mainly to the liver. METHODOLOGY AND COLLECTION OF DATA: The whole project is tied to an IGA grant and runs according to the strict rules of the protocol applied at the Surgical Clinic of the Pardubice Hospital, with its diagnostic part--PCR analysis being completed at the Biochemical Diagnostic Institute (UKBD) of the Teaching Hospital in Hradec Králové. RESULTS: The project has been running since June, 2004 to December 2006. 76 patients meeting defined parameters have been included in the file to date. K-ras mutation has been detected in the tumor tissue of 25 patients (33%). K-ras mutation hasn't been detected in the blood. DISCUSSION: Genetically analysis of a specific tumor has not yet become a standard part of the examinational and therapeutic algorithm. If an assumption of a worse course of illness and metastasizing--especially to the liver has been proven, the examination of Kras mutation in patients suffering from colorectal carcinoma should lead to the adjustment of their treatment and postoperative dispensarization, or the administration of chemotherapy and radiotherapy at stages when these modalities are not normally applied.