scholarly journals Antibiotic Susceptibility of Bartonella Grown in Different Culture Conditions

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 718
Author(s):  
Shiva Kumar Goud Gadila ◽  
Monica E. Embers
Keyword(s):  
Antibiotic Susceptibility ◽  
Acute Infection ◽  
Standard Of Care ◽  
Growth Conditions ◽  
Culture Conditions ◽  
Intracellular Growth ◽  
Current Standard ◽  
Life Threatening Illness ◽  
Life Threatening ◽  
The Impact

Bartonellosis is caused by a Gram-negative intracellular bacterium with a zoonotic transmission. The disease, caused by any of several genospecies of Bartonella can range from a benign, self-limited condition to a highly morbid and life-threatening illness. The current standard of care antibiotics are generally effective in acute infection; these include azithromycin or erythromycin, doxycycline, gentamicin, rifampin, and ciprofloxacin. However, treatment of chronic infection remains problematic. We tested six different antibiotics for their ability to stop the growth of Bartonella sp. in the standard insect media and in an enrichment media. All antibiotics (ceftriaxone, doxycycline, gentamycin, azithromycin, ampicillin, and azlocillin) had minimum inhibitory concentrations (MICs) below 0.5 µg/mL in the BAPGM enrichment media but were ineffective at inhibiting growth when the standard insect media was used. Azlocillin was the most potent, with a MIC of 0.01 µg/mL. When Bartonella was tested under intracellular growth conditions, none of the antibiotics were efficacious singly. However, growth inhibition was observed when azlocillin and azithromycin were combined. These studies illustrate the impact of growth medium and intracellular environment on antibiotic susceptibility testing and indicate that azlocillin combined with azithromycin may be an effective drug combination for the treatment of Bartonellosis.

scholarly journals The Impact of Parkinson’s Disease on Social Communication: An Exploratory Questionnaire Study

2021 ◽  
Author(s):  
Saryu Sharma ◽  
Kimberly Fleck ◽  
Sherri Winslow ◽  
Kathrin Rothermich
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Emotional Expression ◽  
Social Communication ◽  
Standard Of Care ◽  
Pragmatic Language ◽  
Current Standard ◽  
Comprehensive Management ◽  
Pragmatic Skills ◽  
The Impact

Individuals with Parkinson’s Disease (PD) often show breakdown in the interpretation of pragmatic language meaning. However, there is no current standard of care for evaluating social communication dysfunction in PD which affects the persons with PD and their caregivers. Thus, we developed a questionnaire for individuals with PD to evaluate social communication difficulties. Objective: The aim of this study was to develop a questionnaire to demonstrate a need for comprehensive management guidelines for individuals with PD regarding social communication skills. This questionnaire will highlight the areas of deficit for the individuals with PD. Methods: Fifty-one people with self-reported Parkinson’s Disease answered 28 survey questions. These questions pertained to emotional expression and perception, social communication, sarcasm/humor, and pragmatic skills. Exploratory factor analysis and reliability analysis were performed to identify which items loaded onto the desired factor and to check the internal consistency of the items. Results: Persons with PD reported changes in emotional expression and perception, social communication, sarcasm and humor, and pragmatic skills domains post PD diagnosis. No correlations were found between age/time since diagnosis and emotional expression, social communication, sarcasm, and humor.Conclusion: The current study provides evidence that persons with PD experience social communication challenges. Therefore, it is crucial to increase awareness of these deficits in PD to recognize the impact of the disease on social communication.

Role for Thrombin Receptor Antagonism With Vorapaxar in Secondary Prevention of Atherothrombotic Events: From Bench to Bedside

2017 ◽  
Vol 23 (1) ◽  
pp. 23-37 ◽  
Author(s):  
Jae Youn Moon ◽  
Francesco Franchi ◽  
Fabiana Rollini ◽  
Dominick J. Angiolillo
Keyword(s):  
Platelet Activation ◽  
Standard Of Care ◽  
Current Standard ◽  
Recurrence Rates ◽  
Risk Patients ◽  
Thrombotic Complications ◽  
Artery Disease ◽  
Activation Pathways ◽  
The Impact ◽  
Ischemic Events

In spite of treatment with the current standard of care antiplatelet regimens including dual antiplatelet therapy, recurrence rates of ischemic events remain elevated for high-risk patients with atherosclerotic disease. This may be in part attributed to the fact that other key platelet activation pathways remain uninhibited and can thus continue to trigger platelet activation and lead to thrombotic complications. Thrombin is a powerful inducer of platelet activation and mediates its effects directly on platelets through protease activator receptors (PARs), particularly the PAR-1 subtype, making PAR-1 inhibition an attractive approach for reducing atherothrombotic events. These observations have led to the development of several PAR-1 antagonists. Vorapaxar is a direct inhibitor of PAR-1 and the only agent of this class approved for the prevention of recurrent ischemic events in patients with prior myocardial infarction or peripheral artery disease. In the present manuscript, we present a review of the pathophysiologic role of thrombin on thrombotic complications, the impact of vorapaxar on outcomes, including the most recent updates deriving from clinical trials, as well as future perspectives in the field.

Randomized phase II 8-arm factorial study of adjuvant dose-dense (dd) temozolomide (TMZ) with permutations of thalidomide (Thal), isotretinoin (CRA), and/or celecoxib (Cel) for newly diagnosed glioblastoma (GBM).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2003-2003
Author(s):  
Mark R. Gilbert ◽  
Kenneth R. Hess ◽  
Lore Lagrone ◽  
Morris D. Groves ◽  
Victor A. Levin ◽  
...  
Keyword(s):  
Factorial Design ◽  
Phase Ii ◽  
Standard Of Care ◽  
Hepatic Function ◽  
Newly Diagnosed ◽  
Cytostatic Agents ◽  
Current Standard ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
The Impact

2003 Background: Concurrent radiation and TMZ followed by 6-12 months of adjuvant TMZ (d 1-5 of a 28d cycle) is the current standard of care for patients with newly diagnosed GBM. The addition of cytostatic or signal transduction agents may enhance efficacy without a significant increase in toxicity. A phase I trial (Neuro-oncology 2009) established the safety of ddTMZ with 2 or 3 of the cytostatic agents. Methods: This randomized phase II study was conducted by the Brain Tumor Trials Collaborative (BTTC) and the MDACC CCOP. The primary objectives: determine if specific cytostatic agents added to ddTMZ alters outcomes (PFS, OS) and compare triplet with doublet therapy. Eligibility criteria: centrally confirmed newly diagnosed GBM, age ≥18, KPS≥60, stable or improved after chemoradiation (pseudoprogression allowed), adequate hematologic, renal and hepatic function. Pts were randomly assigned to 12 treatment cycles (28 d/cycle) in 8 arms: ddTMZ alone (150 mg/m2/day, 7-d on, 7-d off) or TMZ-containing doublet, triplet and quadruplet combinations with Thal, CRA, or Cel. Results: The study enrolled 155 eligible patients from 11/2005 to 9/2010 to the 8 arms of the factorial design. Median age was 53 (18-84) and median KPS, 90 (60-100). Compared with TMZ alone, the TMZ+CRA doublet had worse PFS (10.5, 6.5 mo; p=0.043) and OS (21.2, 11.7 mo; p=0.037). Trends were also seen for worse outcome (PFS, OS) for CRA-containing regimens, improved OS for Cel containing arms and no impact of Thal. A strong trend for OS improvement was seen for triplet compared with doublet regimens (20.1, 17.0 mo; p=0.15), but no difference for PFS. Treatment was well tolerated with expected high rates of grade 3/4 lymphopenia, and overall a modest toxicity rate. Conclusions: The results indicate that the addition of CRA to ddTMZ may be detrimental in patients with newly diagnosed GBM. This study demonstrated the utility of the factorial design in efficiently testing drug combinations, the impact of individual agents in these combinations as well as doublet vs. triplet regimens and supports its utility in testing combinations of targeted agents.

scholarly journals Impact of Engineered Expression of Mitochondrial Association Factor 1b on Toxoplasma gondii Infection and the Host Response in a Mouse Model

mSphere ◽  
2018 ◽  
Vol 3 (5) ◽  
Author(s):  
Elizabeth D. English ◽  
Jon P. Boyle
Keyword(s):  
Toxoplasma Gondii ◽  
Chronic Infection ◽  
Acute Infection ◽  
Chronic Phase ◽  
Parasite Burden ◽  
Cytokine Signaling ◽  
Parasite Protein ◽  
Content Type ◽  
Life Threatening ◽  
The Impact

ABSTRACT The opportunistic intracellular parasite Toxoplasma gondii causes a lifelong chronic infection capable of reactivating in immunocompromised individuals, which can lead to life-threatening complications. Following invasion of the host cell, host mitochondria associate with the parasitophorous vacuole membrane. This phenotype is T. gondii strain specific and is mediated by expression of a host mitochondrial association-competent (HMA+) paralog of the parasite protein mitochondrial association factor 1 (MAF1b). Previous work demonstrated that expression of MAF1b in strains that do not normally associate with host mitochondria increases their fitness during acute infection in vivo. However, the impact of MAF1b expression during chronic T. gondii infection is unclear. In this study, we assess the impact of MAF1b expression on cyst formation and cytokine production in mice. Despite generally low numbers of cysts generated by the in vitro culture-adapted strains used in this study, we find that parasites expressing MAF1b have higher numbers of cysts in the brains of chronically infected mice and that MAF1b+ cyst burden significantly increases during the course of chronic infection. Consistent with this, mice infected with MAF1b+ parasites have higher levels of the serum cytokines RANTES and VEGF (vascular endothelial growth factor) at day 57 postinfection, although this could be due to higher parasite burden at this time point rather than direct manipulation of these cytokines by MAF1b. Overall these data indicate that MAF1b expression may also be important in determining infection outcome during the chronic phase, either by directly altering the cytokine/signaling environment or by increasing proliferation during the acute and/or chronic phase. IMPORTANCE The parasite Toxoplasma gondii currently infects approximately one-third of the world’s population and causes life-threatening toxoplasmosis in individuals with undeveloped or weakened immune systems. Current treatments are unable to cure T. gondii infection, leaving infected individuals with slow-growing tissue cysts for the remainder of their lives. Previous work has shown that expression of the parasite protein mitochondrial association factor 1 (MAF1b) is responsible for the association of T. gondii parasites with host mitochondria and provides a selective advantage during acute infection. Here we examine the impact of MAF1b expression during chronic T. gondii infection. We find that mice infected with MAF1b-expressing parasites have higher cyst burden and cytokine levels than their wild-type counterparts. A better understanding of the genes involved in establishing and maintaining chronic infection will aid in discovering effective therapeutics for chronically infected individuals.

Partner interdependence and coping with life-threatening illness: The impact on dyadic adjustment.

2013 ◽  
Vol 27 (5) ◽  
pp. 702-711 ◽  
Author(s):  
Betsy L. Fife ◽  
Michael T. Weaver ◽  
William L. Cook ◽  
Timothy T. Stump
Keyword(s):  
Dyadic Adjustment ◽  
Life Threatening Illness ◽  
Life Threatening ◽  
And Coping ◽  
The Impact

Surviving childhood cancer: A descriptive approach to understanding the impact of life-threatening illness

1992 ◽  
Vol 1 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Ross E. Gray ◽  
Brian D. Doan ◽  
Peter Shermer ◽  
Annette Vatter Fitzgerald ◽  
Martin P. Berry ◽  
...  
Keyword(s):  
Childhood Cancer ◽  
Life Threatening Illness ◽  
Life Threatening ◽  
Descriptive Approach ◽  
The Impact

scholarly journals Over 2000-fold increased production of the leaderless bacteriocin garvicin KS by genetic engineering and optimization of culture conditions

2018 ◽  
Author(s):  
Amar A. Telke ◽  
Kirill V. Ovchinnikov ◽  
Kiira S. Vuoristo ◽  
Geir Mathiesen ◽  
Tage Thorstensen ◽  
...  
Keyword(s):  
Growth Conditions ◽  
Culture Conditions ◽  
Research Field ◽  
Bacteriocin Production ◽  
Gene Dose ◽  
Constant Ph ◽  
Wide Range ◽  
Bottle Neck ◽  
High Production ◽  
The Impact

AbstractThe leaderless bacteriocin Garvicin KS (GarKS) is a potent antimicrobial, being active against a wide range of important pathogens. GarKS production by the native producerLactococcus garvieaeKS1546 was however relatively low (80 BU/ml) under standard laboratory growth conditions (batch culture in GM17 at 30°C). To improve the production of GarKS, we systematically evaluated the impact of different media and media components on bacteriocin production. Based on the outcomes a new medium formulation was made to greatly improve bacteriocin production. The new medium composed of pasteurized milk and tryptone (PM-T), increased GarKS production about 60-fold compared to that achieved in GM17. GarKS production was increased further 4-fold (i.e., to 20,000 BU/ml) by increasing gene dose of the bacteriocin gene cluster (gak) in the native producer. Finally, a combination of the newly composed medium (PM-T), an increased gene dose and a cultivation at a constant pH 6 and a 50-60% dissolved oxygen level in growth medium, gave rise to a GarKS production of 164,000 BU/ml. This high production, which is about 2000-fold higher compared to that initially achieved in GM17, corresponds to a GarKS production of 1.2 g/L. To our knowledge, this is one of the highest bacteriocin production reported hitherto.ImportanceLow bacteriocin production is a well-known bottle-neck in developing bacteriocins into large-scaled and useful applications. The present study shows different approaches that significantly improve bacteriocin production. This is an important research field to better exploit the antimicrobial potential of bacteriocins, especially with regard to the decreasing effect of antibiotics in infection treatments due to the global emergence of antibiotic resistance.

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