Omp25-dependent engagement of SLAMF1 by Brucella abortus in dendritic cells limits acute inflammation and favours bacterial persistence in vivo.

The strategies by which intracellular pathogenic bacteria manipulate innate immunity to establish chronicity are poorly understood. Here, we show that Brucella abortus outer membrane protein Omp25 specifically binds the immune cell receptor SLAMF1 in vitro. The Omp25-dependent engagement of SLAMF1 by B. abortus limits NF-κB translocation in dendritic cells (DCs) with no impact on Brucella intracellular trafficking and replication. This in turn decreases pro-inflammatory cytokine secretion and impairs DC activation. The Omp25-SLAMF1 axis also dampens the immune response without affecting bacterial replication in vivo during the acute phase of Brucella infection in a mouse model. In contrast, at the chronic stage of infection, the Omp25/SLAMF1 engagement is essential for Brucella persistence. Interaction of a specific bacterial protein with an immune cell receptor expressed on the DC surface at the acute stage of infection is thus a powerful mechanism to support microbe settling in its replicative niche and progression to chronicity.

Contribution of mechanosensitive channels to osmoadaptation and ectoine excretion in Halomonas elongata.

For osmoadaptation the halophilic bacterium Halomonas elongata synthesizes as its main compatible solute the aspartate derivative ectoine. H. elongata does not rely entirely on synthesis but can accumulate ectoine by uptake from the surrounding environment with the help of the osmoregulated transporter TeaABC. Disruption of the TeaABC-mediated ectoine uptake creates a strain that is constantly losing ectoine to the medium. However, the efflux mechanism of ectoine in H. elongata is not yet understood. H. elongata possesses four genes encoding mechanosensitive channels all of which belong to the small conductance type (MscS). Analysis by qRT-PCR revealed a reduction in transcription of the mscS genes with increasing salinity. The response of H. elongata to hypo- and hyperosmotic shock never resulted in up-regulation but rather in down-regulation of mscS transcription. Deletion of all four mscS genes created a mutant that was unable to cope with hypoosmotic shock. However, the knockout mutant grew significantly faster than the wildtype at high salinity of 2 M NaCl, and most importantly, still exported 80% of the ectoine compared to the wildtype. We thus conclude that a yet unknown system, which is independent of mechanosensitive channels, is the major export route for ectoine in H. elongata.

Cogan's Syndrome: Clinical Presentations and Update on Treatment.

PURPOSE OF REVIEW: Cogan's syndrome (CS) is a rare systemic vasculitis that can severely affect vision and hearing, which may also have significant systemic effects. Early recognition of this autoimmune disorder and intervention can minimize disabling and irreversible damage. RECENT FINDINGS: This article will review the varying clinical presentations of CS and emerging information of systemic disease associated with CS. We will also review recently published promising treatment outcomes using immune modulating medications. As our framework for recognizing the markers of CS and the associated systemic disorders expands, more effective guidelines and treatment options may emerge.

Orbital Vasculitides-Differential Diagnosis.

PURPOSE OF REVIEW: The orbit is subject to a variety of vascular insults that manifest with both specific and nonspecific patterns of vision compromise. The aim of the following review is to highlight the ophthalmic clinical features of systemic vasculitides that most frequently involve the orbit and differentiate them from the most common non-vasculitic orbital disorders. RECENT FINDINGS: New studies continue to explore the autoimmune nature of vasculitic disease and seek to determine optimal use of newer therapies such as biologic agents. The pattern of ocular involvement in the context of clinical history allows the knowledgeable physician to distill a differential diagnosis into a specific or likely cause. Establishing a diagnosis in a timely fashion allows for a custom-tailored approach to therapy.

Depletion of Complement Enhances the Clearance of Brucella abortus in Mice.

Brucellosis is a bacterial disease of animals and humans. Brucella abortus barely activates the innate immune system at the onset of infection, and this bacterium is resistant to the microbicidal action of complement. Since complement stands as the first line of defense during bacterial invasions, we explored the role of complement in B. abortus infections. Brucella abortus-infected mice depleted of complement with cobra venom factor (CVF) showed the same survival rate as mice in the control group. The complement-depleted mice readily eliminated B. abortus from the spleen and did so more efficiently than the infected controls after 7 days of infection. The levels of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-6 (IL-6) remained within background levels in complement-depleted B. abortus-infected mice. In contrast, the levels of the immune activator cytokine gamma interferon and the regulatory cytokine IL-10 were significantly increased. No significant histopathological changes in the liver and spleen were observed between the complement-depleted B. abortus-infected mice and the corresponding controls. The action exerted by Brucella on the immune system in the absence of complement may correspond to a broader phenomenon that involves several components of innate immunity.

Online Ratings of ASOPRS Surgeons: What Do Your Patients Really Think of You?

PURPOSE: To characterize patient evaluations of American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) surgeons on a popular online physician rating website in an effort to determine which factors play a role in determining the likelihood of a patient recommending an ASOPRS surgeon to family and friends. METHODS: After obtaining approval and access from Healthgrades.com, the website database was searched for 612 U.S.-based ASOPRS members using their name as published on http://www.asoprs.org/ as of May 2015. For each surgeon, the total number of ratings and average ratings were recorded under each category. The evaluator recommendation, defined as the response to the questions of "likelihood of recommending Dr. X to family and friends," constituted the main outcome measure. Variables from each surgeon were compared using unpaired t tests, with statistical significance set at p < 0.05. Correlations were analyzed using Spearman correlation (rs), with coefficients of greater than or equal to 0.40 or less than or equal to -0.40 considered significant. RESULTS: Five-hundred nineteen members (85%) had at least 1 rating while 222 members (36%) had 10 or more ratings. The mean number of ratings for all rated members was 11.4 (range, 1-77; standard deviation [SD] = 11.1) and mean evaluator recommendation score was 4.16 (range, 1-5; SD = 0.79). There was a strong negative correlation between total wait time and evaluator recommendation score (rs = -0.409, p < 0.001). The average number of ratings and rating scores for all categories were not significantly different when comparing male with female members. University-employed members had significantly fewer ratings (8.46; range, 1-52; SD = 9.3) compared with other members (11.9; range, 1-77; SD = 11.3) (p < 0.016). There were no differences in any other rating score when comparing those university-employed members with other members. CONCLUSION: Online patient-reported evaluations of ASOPRS surgeons appear high in many categories. Long wait times correlate strongly with lower recommendation scores. Further study is required to determine how online patient reviews correlate to objective outcome measures, and how these reviews affect surgeon selection by patients.

19-Tungstodiarsenate(III) Functionalized by Organoantimony(III) Groups: Tuning the Structure-Bioactivity Relationship.

A family of three discrete organoantimony(III)-functionalized heteropolyanions-[Na{2-(Me2HN(+)CH2)C6H4Sb(III)}As(III)2W19O67(H2O)](10-) (1), [{2-(Me2HN(+)CH2)C6H4Sb(III)}2As(III)2W19O67(H2O)](8-) (2), and [{2-(Me2HN(+)CH2)C6H4Sb(III)}{WO2(H2O)}{WO(H2O)}2(B-ß-As(III)W8O30)(B-α-As(III)W9O33)2](14-) (3)-have been prepared by one-pot reactions of the 19-tungstodiarsenate(III) precursor [As(III)2W19O67(H2O)](14-) with 2-(Me2NCH2)C6H4SbCl2. The three novel polyanions crystallized as the hydrated mixed-alkali salts Cs3KNa6[Na{2-(Me2HN(+)CH2)C6H4Sb(III)}As(III)2W19O67(H2O)]·43H2O (CsKNa-1), Rb2.5K5.5[{2-(Me2HN(+)CH2)C6H4Sb(III)}2As(III)2W19O67(H2O)]·18H2O·Me2NCH2C6H5 (RbK-2), and Rb2.5K11.5[{2-(Me2HN(+)CH2)C6H4Sb(III)}{WO2(H2O)}{WO(H2O)}2(B-ß-As(III)W8O30)(B-α-As(III)W9O33)2]·52H2O (RbK-3), respectively. The number of incorporated {2-(Me2HN(+)CH2)C6H4Sb(III)} units could be tuned by careful control of the experimental parameters. Polyanions 1 and 2 possess a dimeric sandwich-type topology, whereas 3 features a trimeric, wheel-shaped structure, representing the largest organoantimony-containing polyanion. All three compounds were fully characterized in the solid state via single-crystal X-ray diffraction (XRD), infrared (IR) spectroscopy, and thermogravimetric analysis, and their aqueous solution stability was validated by ultraviolet-visible light (UV-vis) and multinuclear ((1)H, (13)C, and (183)W) nuclear magnetic resonance (NMR) spectroscopy. Effective inhibition against six different types of bacteria was observed for 1 and 2, and we could extract a structure-bioactivity relationship for these polyanions.

Tetra-Antimony(III)-Bridged 18-Tungsto-2-Arsenates(V), [(LSb(III))4(A-α-As(V)W9O34)2](10-) (L = Ph, OH): Turning Bioactivity On and Off by Ligand Substitution.

Two tetra-antimony(III)-bridged, sandwich-type 18-tungsto-2-arsenates(V), [(LSb(III))4(A-α-As(V)W9O34)2](10-) (L = Ph (1), OH (2)), were prepared and fully characterized in the solid state and in solution. Both polyanions are stable in aqueous physiological medium for at least 24 h (at concentrations ≥2.5 × 10(-6) M). Despite the presence of an isostructural tetra-antimony(III) motif in 1 and 2, distinctly different antibacterial activity was observed for both polyanions. The minimum inhibitory concentrations (MIC) of 1 (7.8-62.5 µg/mL) is lower than for any other organoantimony(III)-containing polyoxometalate reported to date.

Brucella canis is an intracellular pathogen that induces a lower proinflammatory response than smooth zoonotic counterparts.

Canine brucellosis caused by Brucella canis is a disease of dogs and a zoonotic risk. B. canis harbors most of the virulence determinants defined for the genus, but its pathogenic strategy remains unclear since it has not been demonstrated that this natural rough bacterium is an intracellular pathogen. Studies of B. canis outbreaks in kennel facilities indicated that infected dogs displaying clinical signs did not present hematological alterations. A virulent B. canis strain isolated from those outbreaks readily replicated in different organs of mice for a protracted period. However, the levels of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-12 in serum were close to background levels. Furthermore, B. canis induced lower levels of gamma interferon, less inflammation of the spleen, and a reduced number of granulomas in the liver in mice than did B. abortus. When the interaction of B. canis with cells was studied ex vivo, two patterns were observed, a predominant scattered cell-associated pattern of nonviable bacteria and an infrequent intracellular replicative pattern of viable bacteria in a perinuclear location. The second pattern, responsible for the increase in intracellular multiplication, was dependent on the type IV secretion system VirB and was seen only if the inoculum used for cell infections was in early exponential phase. Intracellular replicative B. canis followed an intracellular trafficking route undistinguishable from that of B. abortus. Although B. canis induces a lower proinflammatory response and has a stealthier replication cycle, it still displays the pathogenic properties of the genus and the ability to persist in infected organs based on the ability to multiply intracellularly.

Expression of extra-cellular levansucrase in Pseudomonas syringae is controlled by the in planta fitness-promoting metabolic repressor HexR.

BACKGROUND: Pseudomonas syringae pv. glycinea PG4180 causes bacterial blight on soybean plants and enters the leaf tissue through stomata or open wounds, where it encounters a sucrose-rich milieu. Sucrose is utilized by invading bacteria via the secreted enzyme, levansucrase (Lsc), liberating glucose and forming the polyfructan levan. P. syringae PG4180 possesses two functional lsc alleles transcribed at virulence-promoting low temperatures. RESULTS: We hypothesized that transcription of lsc is controlled by the hexose metabolism repressor, HexR, since potential HexR binding sites were identified upstream of both lsc genes. A hexR mutant of PG4180 was significantly growth-impaired when incubated with sucrose or glucose as sole carbon source, but exhibited wild type growth when arabinose was provided. Analyses of lsc expression resulted in higher transcript and protein levels in the hexR mutant as compared to the wild type. The hexR mutant's ability to multiply in planta was reduced. HexR did not seem to impact hrp gene expression as evidenced by the hexR mutant's unaltered hypersensitive response in tobacco and its unmodified protein secretion pattern as compared to the wild type under hrp-inducing conditions. CONCLUSIONS: Our data suggested a co-regulation of genes involved in extra-cellular sugar acquisition with those involved in intra-cellular energy-providing metabolic pathways in P. syringae.

Organoantimony(III)-Containing Tungstoarsenates(III): From Controlled Assembly to Biological Activity.

A family of three sandwich-type, phenylantimony(III)-containing tungstoarsenates(III), [(PhSb(III) ){Na(H2 O)}As(III) 2 W19 O67 (H2 O)](11-) (1), [(PhSb(III) )2 As(III) 2 W19 O67 (H2 O)](10-) (2), and [(PhSb(III) )3 (B-α-As(III) W9 O33 )2 ](12-) (3), have been synthesized by one-pot procedures and isolated as hydrated alkali metal salts, Cs3 K3.5 Na4.5 [(PhSb(III) ){Na(H2 O)}As(III) 2 W19 O67 (H2 O)]⋅41H2 O (CsKNa-1), Cs4.5 K5.5 [(PhSb(III) )2 As(III) 2 W19 O67 (H2 O)]⋅35H2 O (CsK-2), and Cs4.5 Na7.5 [(PhSb(III) )3 (B-α-As(III) W9 O33 )2 ]⋅42H2 O (CsNa-3). The number of incorporated {PhSb(III) } units could be selectively tuned from one to three by careful control of the reaction parameters. The three compounds were characterized in the solid state by single-crystal XRD, IR spectroscopy, and thermogravimetric analysis. The aqueous solution stability of sandwich polyanions 1-3 was also studied by multinuclear ((1) H, (13) C, (183) W) NMR spectroscopy. Effective inhibitory activity against six different kinds of bacteria was identified for all three polyanions, for which the activity increased with the number of incorporated {PhSb(III) } groups.

Cogan's syndrome and other ocular vasculitides.

The clinical presentation of Cogan's syndrome has been classified as typical and atypical. Like other forms of ocular vasculitis, Cogan's syndrome has been found to have autoimmune origins with antibodies against the cornea, inner ear, and endothelial antigens. Antineutrophil cytoplasmic antibody (ANCA) and rheumatoid factor (RF) have been associated with Cogan's syndrome as well as ocular-involving vasculitides not as strongly associated with the audiovestibular manifestations such as granulomatosis with polyangiitis and rheumatoid arthritis. The mainstay of therapy has been corticosteroids although other methods have been described in recalcitrant disease and to prevent development of systemic sequelae.

Marinobacterium mangrovicola sp. nov., a marine nitrogen-fixing bacterium isolated from mangrove roots of Rhizophora mangle.

A nitrogen-fixing marine bacterium, designated strain Gal22(T), was isolated from mangrove roots of Rhizophora mangle. Cells were Gram-stain-negative rods, motile with a single polar flagellum. Growth was observed at 4-42 °C, pH 5.5 to 10 and with 0-18 % (w/v) NaCl. Strain Gal22(T) was positive for catalase and oxidase. Q-8 was the predominant lipoquinone. The DNA G+C content was 57.0 mol%. Based on phylogenetic analysis of 16S rRNA gene, strain Gal22(T) belongs to the genus Marinobacterium. The closely related strains were shown to be Marinobacterium lutimaris DSM 22012(T) and Marinobacterium litorale IMCC1877(T) with 99 % and 96 % 16S rRNA gene sequence similarity, respectively. DNA-DNA relatedness analysis indicated that strain Gal22(T) was different from M. lutimaris DSM 22012(T). On the basis of genotypic, morphological and biochemical characteristics, a novel species, Marinobacterium mangrovicola sp. nov. (type strain, Gal22(T) = DSM 27697(T) = CIP 110653(T)), is proposed.

Predictors of Ophthalmology Resident Performance From Medical Student Application Materials.

OBJECTIVE: To determine whether elements in ophthalmology residency applications are predictors of future resident performance. DESIGN: This multi-institutional, cross-sectional, observational study retrospectively reviewed the residency application materials of ophthalmology residents who graduated from residency from 2006 through 2018. Resident performance was scored by 2 faculty reviewers in 4 domains (clinical, surgical, academic, and global performance). Correlation between specific elements of the residency application and resident performance was assessed by Spearman correlation coefficients (univariate) and linear regression (multivariate) for continuous variables and logistic regression (multivariate) for categorical variables. SETTING: Seven ophthalmology residency programs in the US. PARTICIPANTS: Ophthalmology residents who graduated from their residency program. RESULTS: High-performing residents were a diverse group, in terms of sex, ethnicity, visa status, and educational background. Residents with United States Medical Licensing Examination Step 1 scores higher than the national average for that year had significantly higher scores in all 4 performance domains than those who scored at or below the mean (all domains P < 0.05). Residents who had honors in at least 4 core clerkships and who were members of Alpha Omega Alpha Medical Honor Society also had higher scores in all 4 performance domains (all domains P ≤ 0.04). Step 1 score (ρ=0.26, P < 0.001) and the difference between Step 1 score and the national average for that year (ρ=0.19, P = 0.009) positively correlated with total resident performance scores. Residents who passed the American Board of Ophthalmology Written Qualifying Examination or Oral Examination on their first attempt had significantly higher Step 1/2 scores (P ≤ 0.005), Ophthalmology Knowledge Assessment Program scores (P = 0.001), and resident performance scores (P ≤ 0.004). CONCLUSIONS: In this new landscape of increasing numbers of applicants to residency programs and changing of the Step 1 score to pass/fail, our findings may help guide selection committees as they holistically review applicants to select exceptional future residents in ophthalmology.

Ocular vasculitis.

Vasculitis is the inflammation of blood vessels that leads to loss of perfusion and ischemia with necrosis. When this occurs in the orbit, the consequences are typically very conspicuous and can be devastating with decreased quality of life and loss of vision. Systemic vasculitides are often related to ophthalmic disorders, which can serve as the first diagnostic manifestation of potentially life-threatening disease. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (e.g., granulomatosis with polyangiitis), Behcet's disease, rheumatoid arthritis, sarcoidosis, and systemic lupus erythematosus are a few of the diseases commonly associated with ocular vasculitis. Collaboration between ophthalmologists and rheumatologists is important in the successful diagnosis and treatment of patients with vasculitis.

Virtually Accompanied Eating in the Outpatient Therapy of Anorexia Nervosa.

BACKGROUND: Normalizing the eating pattern and weight recovery are the main objectives in treating anorexia nervosa (AN). Eating accompaniment through shared mealtimes is a common strategy in eating disorder management programs. This study aims to examine the impact on weight gain of an internet-delivered meal support group on patients with AN who were under ambulatory treatment with the Eating Disorders Unit of the UC Christus Health Network, Chile. METHODS: An observational study of 54 female patients with AN diagnosis who participated in Online Meal Support Groups (OMSGs) three times a week was performed. Their weight, BMI and BMI%, was reviewed at the beginning of the sessions and at 45- and 90-day follow-up. RESULTS: Patients showed significant weight gain during follow-up. At the 90-day follow-up, patients had gained 4.41 (SD ± 2.82) kg with an effect size of -1.563. CONCLUSIONS: Statistically significant differences were found between the weight at the beginning of the intervention and at the 45- and 90-day follow-up, meaning that eating support online groups may be an effective intervention for weight gain and maintenance in patients with AN. These findings highlight the viability of developing cost-effective and more accessible interventions for AN and thus help reduce the duration of untreated disease and its consequences.

Community strategies for health promotion and prevention of chronic non-communicable diseases with a focus on physical activity and nutrition: the URO/FOCOS study protocol.

Non-communicable diseases (NCDs) account for 71% of all annual deaths, totaling 41 million people worldwide. The development and progression of these diseases are highly related to the environment and lifestyle choices, among which physical inactivity and excess malnutrition stand out. Currently, in Chile, there is no evidence at the regional and local level on the impact of physical activity and healthy nutrition plans and interventions on health promotion, prevention, and timely treatment of NCDs. The following protocol delineates the URO/FOCOS (Universidad Regional de O'Higgins/FOrtaleciendo COmunidades Saludables- Regional University of O'Higgins/Strengthening Healthy Communities) study, which will assess pilot community intervention strategies using a participatory action research approach by identifying barriers and facilitators on the practice of physical activity and healthy eating habits. In this project, the community from the O'Higgins region will be involved throughout the entire research process to develop strategies that promote regular physical activity and healthy eating practices. We propose three interrelated strategies: (1) Participatory Action Research, (2) Community interventions for promoting physical activity and healthy nutrition practices, and (3) health education. The URO/FOCOS study offers a unique opportunity in the O'Higgins region to develop participatory strategies and interventions based on the community's needs and motivations with regard to physical activity and healthy eating habits. We believe these strategies will help to improve the community's overall health through effective changes in their decision and preferences toward a more active lifestyle and healthier nutrition practices.

CD150-dependent hematopoietic stem cell sensing of Brucella instructs myeloid commitment.

So far, hematopoietic stem cells (HSC) are considered the source of mature immune cells, the latter being the only ones capable of mounting an immune response. Recent evidence shows HSC can also directly sense cytokines released upon infection/inflammation and pathogen-associated molecular pattern interaction while keeping a long-term memory of previously encountered signals. Direct sensing of danger signals by HSC induces early myeloid commitment, increases myeloid effector cell numbers, and contributes to an efficient immune response. Here, by using specific genetic tools on both the host and pathogen sides, we show that HSC can directly sense B. abortus pathogenic bacteria within the bone marrow via the interaction of the cell surface protein CD150 with the bacterial outer membrane protein Omp25, inducing efficient functional commitment of HSC to the myeloid lineage. This is the first demonstration of direct recognition of a live pathogen by HSC via CD150, which attests to a very early contribution of HSC to immune response.