Novel Phage Lysin Capable of Killing the Multidrug-Resistant Gram-Negative Bacterium Acinetobacter baumannii in a Mouse Bacteremia Model

Acinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is now recognized as one of the more common nosocomial pathogens. Because most clinical isolates are found to be multidrug resistant, alternative therapies need to be developed to control this pathogen. We constructed a bacteriophage genomic library based on prophages induced from 13 A. baumannii strains and screened it for genes encoding bacteriolytic activity. Using this approach, we identified 21 distinct lysins with different activities and sequence diversity that were capable of killing A. baumannii. The lysin (PlyF307) displaying the greatest activity was further characterized and was shown to efficiently kill (>5-log-unit decrease) all tested A. baumannii clinical isolates. Treatment with PlyF307 was able to significantly reduce planktonic and biofilm A. baumannii both in vitro and in vivo. Finally, PlyF307 rescued mice from lethal A. baumannii bacteremia and as such represents the first highly active therapeutic lysin specific for Gram-negative organisms in an array of native lysins found in Acinetobacter phage.     

Parathyroid hormone has an important role in blood pressure regulation in vitamin D–insufficient individuals

ObjectiveThe aim of the present study was to evaluate whether vitamin D status is related to blood pressure (BP) in adults.MethodsWe evaluated the relationship between vitamin D status, intact parathyroid hormone (iPTH) and BP in 332 adults. Anthropometric measurements, BP, and a fasting blood sample was obtained. Participants were stratified into the following BP categories: 1) normal BP; 2) high BP; 3) normal BP through medication. Vitamin D insufficiency was defined as 25-hydroxvitamin D ≤ 75 nmol/L; high iPTH as > 65 pg/mL. The relationships between vitamin D status, iPTH and BP were adjusted for body mass index, waist circumference, blood lipids, physical activity, and sunscreen use.ResultsNo differences in prevalences of vitamin D insufficiency and high iPTH were observed among BP groups. No significant association was observed between BP and vitamin D status. Positive correlations were observed between iPTH and systolic BP (r = 0.168; P = 0.002) and between iPTH and diastolic BP (r = 0.168; P = 0.002). iPTH remained correlated with BP even with adjustments.ConclusionsThe present study contributes to the understanding of calcemic hormones and BP regulation.     

Physical fitness in people with posttraumatic stress disorder: a systematic review

Purpose: People with posttraumatic stress disorder (PTSD) have an increased risk of cardiovascular diseases (CVD). Physical fitness is a key modifiable risk factor for CVD and associated mortality. We reviewed the evidence-base regarding physical fitness in people with PTSD.

Methods: Two independent reviewers searched PubMed, CINAHL, PsycARTICLES, PEDro, and SPORTDiscus from inception until May 2016 using the key words “fitness” OR “exercise” AND “posttraumatic stress disorder” OR “PTSD”.

Results: In total, 5 studies involving 192 (44 female) individuals with PTSD met the inclusion criteria. Lower baseline physical fitness are associated with greater reductions in avoidance and hyperarousal symptoms, as well as with total, physical, and social symptoms of anxiety sensitivity. Rigorous data comparing physical fitness with age- and gender matched general population controls are currently lacking.

Conclusions: The research field regarding physical fitness in people with PTSD is still in its infancy. Given the established relationships between physical fitness, morbidity and mortality in the general population and the current gaps in the PTSD literature, targets for future research include exploring: (a) whether people with PTSD are at risk of low physical fitness and therefore in need of intensified assessment, treatment and follow-up, (b) the relationships among physical fitness, overall health status, chronic disease risk reduction, disability, and mortality in individuals PTSD, (c) psychometric properties of submaximal physical fitness tests in PTSD, (d) physical fitness changes following physical activity in PTSD, and (e) optimal methods of integrating physical activity programs within current treatment models for PTSD.

• Implications for Rehabilitation

• People with PTSD should aim to achieve 150?minutes of moderate or 75?minutes vigorous physical activity per week while also engaging in resistance training exercises at least twice a week.

• Health care professionals should assist people with PTSD to overcome barriers to physical activity such as physical pain, loss of energy, lack of interest and motivation, generalized fatigue and feelings of hyperarousal.

     

Efficacy of further attempts to mobilize CD34+ peripheral stem cells with alternative procedures after primary failure

19 patients who failed the target collection of at least 2.5 x 10(6) CD34+ cells/kg underwent further mobilization procedures either with granulocyte-colony-stimulating factor (G-CSF) alone after failure to chemotherapy plus G-CSF (group 1), or with chemotherapy plus G-CSF (group 2), or with high-dose G-CSF (24 microg/kg) alone (group 3) after failure to respond to standard dose of G-CSF (10 microg/kg) alone. In all groups, an increase in median CD34+ cell yield could be observed following alternative procedures (1.1- to 1.9 x 10(6) kg; p = 0.02). The highest increase in CD34+ cell harvest was achieved in group 1 (0.85 to 2.2 x 10(6) kg), followed by group 2 (1. 2 to 1.7) and group 3 (1.0 to 1.4), but without statistically significant difference between the mobilization technologies. All patients with more than 1.0 x 10(6) CD34+ cells/kg in the first apheresis procedure reached the overall target of 2.5 x 10(6) CD34+ cells/kg after a second or subsequent mobilization procedure. In contrast, only 3 of 8 patients (37%) with less than 1.0 x 10(6) CD34+ cells in the first harvest could reach the target of 2.5 x 10(6) CD34+ cells after further mobilization attempts.     

Rapid transient induction of phenylalanine ammonia-lyase mRNA in elicitor-treated bean cells

DNAs complementary to a size-selected fraction of poly(A)⁺ RNA present in elicitor-treated cells of bean (Phaseolus vulgaris L.) were inserted into pAT153 and used to transform Escherichia coli strain C600. Five clones were identified by hybrid-selected translation and cross-hybridization that contained sequences complementary to mRNA encoding phenylalanine ammonia-lyase (EC 4.3.1.5), which catalyzes the first reaction of phenylpropanoid biosynthesis. The longest insert contained a single open reading frame of 1520 base pairs together with 223 base pairs of 3′ untranslated sequence. RNA blot hybridization showed that elicitor caused a rapid, marked but transient increase in phenylalanine ammonia-lyase mRNA that was closely correlated with changes in translatable mRNA activity in vitro and enzyme synthesis in vivo. Blot hybridization of newly synthesized mRNA purified by organomercurial affinity chromatography following in vivo pulse-labeling with 4-thiouridine indicates that elicitor caused a rapid stimulation of phenylalanine ammonia-lyase mRNA synthesis as an early in the defense response leading to accumulation of phenylpropanoid-derived phytoalexins.     

Pancreatic tumor growth is regulated by the balance between positive and negative modulators of angiogenesis

There is increasing evidence for the implication of tumor-derived angiogenic and anti-angiogenic factors in controlling tumor growth in vivo. In this study, we documented the production of inhibitors of angiogenesis by pancreatic cancer cells and examined how changes in the balance between pro- and anti-angiogenic factors regulate tumor growth in vivo. The human pancreatic cancer cell line Hs-776T (HS-W) produces slow-growing tumors in SCID mice. Cells of a variant form (HS-R) of Hs-776T produced faster-growing tumors compared to HS-W. Characterization of HS-W and HS-R cells in vitro showed similar proliferation rates and production of the angiogenic factors vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Analyzes of anti-angiogenic factors showed comparable levels of angiostatin and thrombospondin 1 and 2, but endostatin was only detected in conditioned media of HS-W cells and was absent in HS-R. Cell proliferation was similar in both tumor types in vivo, whereas HS-W tumors demonstrated increased apoptosis with a high percentage of apoptotic endothelial cells (EC). Subsequently, VEGF was over-expressed in Hs-776T cells (HS-VF), resulting in rapidly growing tumors and lowering tumor and EC apoptosis. Collectively, our study confirms that tumor growth is dependent on its ability to increase the angiogenic stimulus or to reduce the amounts of endogenous anti-angiogenic factors.