Subcutaneous immunization with a novel immunogenic candidate (urease) confers protection against Brucella abortus and Brucella melitensis infections

Brucellosis is a world prevalent endemic illness that is transmitted from domestic animals to humans. Brucella spp. exploits urease for survival in the harsh conditions of stomach during the gastrointestinal infection. In this study, we examined the immune response and the protection elicited by using recombinant Brucella urease (rUrease) vaccination in BALB/c mice. The urease gene was cloned in pET28a and the resulting recombinant protein was employed as subunit vaccine. Recombinant protein was administered subcutaneously and intraperitoneally. Dosage reduction was observed with subcutaneous (SC) vaccination when compared with intraperitoneal (IP) vaccination. rUrease induced mixed Th1–Th2 immune responses with high titers of specific IgG1 and IgG2a. In lymphocyte proliferation assay, splenocytes from IP and SC‐vaccinated mice displayed a strong recall proliferative response with high amounts of IL‐4, IL‐12 and IFN‐γ production. Vaccinated mice were challenged with virulent Brucella melitensis, B. abortus and B. suis. The SC vaccination route exhibited a higher degree of protection than IP vaccination (p value ≤ 0.05). Altogether, our results indicated that rUrease could be a useful antigen candidate for the development of subunit vaccines against brucellosis.     

Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone

We have studied a 50-year-old white man with chronic urticaria and angioedema who has responded to treatment with cimetidine alone for over 2 yr. In a double-blind, placebo-controlled study, cimetidine alone was at least as effective as chlorpheniramine in relief of urticaria and angioedema. Additionally, cimetidine significantly inhibited (p less than 0.01) the wheal response to histamine when it was compared to placebo. The inhibition of wheal response to histamine by cimetidine was significantly higher (p less than 0.05) than chlorpheniramine. The presence of predominantly H2- rather than H1-histamine receptors in the cutaneous blood vessels may be responsible for the therapeutic effects of cimetidine in this patient.     

Detailed monitoring of the effects of mannitol following experimental head injury.

The experimental model of a cerebral missile injury developed by Crockard was used in three groups of Rhesus monkeys treated with mannitol. One group received mannitol 15 minutes after being injured with a BB pellet at 90 m/sec impact. Another group was wounded identically, but mannitol treatment was delayed until 1 hour after injury. The last group was wounded with the missile traveling at 180 m/sec, and mannitol was started 15 minutes after trauma. The data were contrasted with the results from the original model. After receiving mannitol, all groups showed marked improvement in mean blood pressure, cerebral perfusion pressure, cerebral blood flow, and cerebral metabolic rate of oxygen consumption out of proportion to the degree of reduction in intracranial pressure (ICP). The authors conclude that the therapeutic value of mannitol may, in some injuries, be directly related to its effects on blood flow and metabolism, as well as to its better known effects upon ICP.     

A Contemporary 20-Year Cleveland Clinic Experience of Nonbacterial Thrombotic Endocarditis: Etiology,Echocardiographic Imaging,Management, and Outcomes

BackgroundNonbacterial thrombotic endocarditis, or marantic endocarditis, is rare. Contemporary data on the etiology, echocardiographic evaluation, and management of nonbacterial thrombotic endocarditis are limited.MethodsA single-center retrospective cohort study was performed. Electronic medical records and echocardiographic records were searched for patients ages ≥18 years with a confirmed diagnosis of nonbacterial thrombotic endocarditis between January 1999 and November 2019. Demographic, echocardiographic, and management data were collected.ResultsOf 600,577 transthoracic echocardiograms (TTEs) and 89,264 transesophageal echocardiograms (TEEs), 42 patients had nonbacterial thrombotic endocarditis (mean age: 54 ± 14.5 years; 66.7% were female). The median duration of follow-up was 8.2 (interquartile range 3.3-24.4) months. Seventeen patients (40.5%) had malignancy, 33.3% had systemic lupus erythematosus, and 35.7% had antiphospholipid antibody syndrome. Stroke was the most common presentation (59.5%).TTE enabled the diagnosis in 19 cases (45.2%), compared with TEE, which identified the condition in 33 of 34 (97.1%) cases in which it was utilized. Three-dimensional echocardiography was performed in 17 TEEs. The most common valves involved were mitral (61.9%), and aortic (23.8%) valves. Thirty-two patients were managed with anticoagulation. Ten patients underwent surgery. Sixteen (38.1%) patients died, most of whom had a diagnosis of advanced malignancy.ConclusionIn a contemporary 20-year cohort, TTE and TEE played important roles in diagnosis, with superior diagnostic performance of TEE for nonbacterial thrombotic endocarditis. Mortality was high, and advanced malignancy portended a worse prognosis. Management in most cases was therapeutic anticoagulation. In select cases, surgery provided favorable outcomes.     

Pattern of in-hospital pediatric mortality over a 3-year period at University teaching hospitals in Iran

Introduction:

Causes of death are different and very important for policy makers in different regions. This study was designed to analyze the data for our in-patient children mortality.

Materials and Methods:

In this cross-sectional study from March 2011 to March 2013, all patients from 2 months to 18 years who died in pediatric intensive care unit, emergency room or medical pediatric wards in the teaching hospitals were studied.

Results:

From a total of 18,915 admissions during a 2-year-period, 256 deaths occurred with a mean age of 4.3 ± 5 years and mortality 1.35%. An underlying disease was present in 70.7% of the patients and in 88.5% of them the leading causes of death were related to the underlying diseases. The most common underlying diseases were congenital heart disease and cardiomyopathy in 50 (27.6%). The four main causes of deaths were sepsis (14.8%), pneumonia (14.5%), congestive heart failure (9.8%), and hepatic encephalopathy (9.8%).

Conclusion:

We may conclude that after sepsis and pneumonia, congestive heart failure, and hepatic encephalopathy are the leading causes of death. Most patients who died had underlying diseases including malignancies, heart and liver diseases as the most common causes.     

Prevalence of Mental Health Problems in Children and Its Associated Socio-Familial Factors in Urban Population of Semnan,Iran (2012)

Background:

The World Health Organization (WHO) defines mental health as “a state of well-being in which every individual realizes own potential, can cope with the normal pressures of life, is able to work effectively, and can make a contribution to community”.

Objectives:

Mental Health Problems (MHP) is a great concern for all societies in terms of its burden and impact. This survey screened MHP and its impact in an Iranian urban population aged 6 - 12 years old, and explored its associated socio-familial factors.

Patients and Methods:

The survey was conducted in the elementary schools of Semnan, using random cluster sampling. Collection and analysis of data was performed using the parent version of the “Strengths and Difficulties Questionnaire (SDQ)” and survey commands of Stata-nine, taking into account cluster effect and population weights. Associations were assessed by fitting simple and multiple logistic regression models. P < 0.05 was considered significant.

Results:

With regard to the SDQ total score, 19.3% (95% CI: 8.6, 30.1) scored above the normal threshold (9.6% abnormal, 9.7% borderline). The frequency of problems ranged between 16.1% (peer problems) and 8.4% (emotional symptoms), and in all subscales boys were affected more than girls. The impact score was abnormal in 68.4% of all children, and was greater in girls than in boys. “A previously diagnosed mental health disorder” (OR = 11.11, 95% CI: 5.55, 25.00), “male gender” (OR = 1.43, 95% CI: 1.10, 1.87 and “less time spent with the child by father” (OR = 1.61, 95% CI: 1.20, 2.17) were significantly associated with an abnormal SDQ.

Conclusions:

The high rate of MHP in 6 - 12 year-old children and the lack of any significant correlation with their age, underpins the importance of early screening for MHP in schools, with particular focus on high risk groups.     

Platelet dynamics following allergen challenge in allergic asthmatics

BACKGROUND: There is evidence that platelet activation occurs in allergic inflammation and asthma, but little is known about the role platelets play in airway inflammation associated with asthma. Objectives: In the present study, we have investigated the kinetics of platelet activation following allergen provocation of allergic asthmatics to determine the dynamics of platelet activation relative to changes in lung function and changes in airway inflammation. METHODS: Changes in platelet count and haematocrit from baseline were measured during the early asthmatic response (EAR), late asthmatic response (LAR; or at corresponding time points) and at 24 h were compared between allergen- and saline-challenged groups. A subgroup of allergen-challenged asthmatics, a group of 7 challenged asthmatics and 7 controls were bronchoscoped, and BAL fluid was collected and analysed for levels of histamine and eosinophil cationic protein. RESULTS: There was a fall in circulating platelet count, but not haematocrit after allergen challenge when compared with saline during the LAR or at 24 h. At 24 h FEV(1) had returned to within 20% of baseline in all subjects, although the thrombocytopaenia and airway inflammation persisted. CONCLUSIONS: Our results suggest that persistent thrombocytopaenia accompanies allergen exposure and persists beyond changes in airway obstruction at a time when airway inflammation is present. Our results provide further evidence that platelets may be involved in allergic disease.     

Implementing Goals-of-Care Conversations: Lessons From High- and Low-Performing Sites From a VA National Initiative

ContextThe Veterans Health Administration (VA) National Center for Ethics in Healthcare implemented the Life-Sustaining Treatment Decisions Initiative, including policy and practice standards, clinician communication training, a documentation template, and central implementation support to foster advance care planning via goals-of-care conversations for seriously ill veterans in 2014, spreading nationally to other Veterans Health Affairs (VA) sites in 2017.ObjectivesOur goal was to describe the range of early implementation experiences among the pilot sites, and compare them with spread sites that implemented LSTDI about two years later, identifying cross-site best practices and pitfalls.MethodsWe conducted semistructured interviews with 32 key stakeholders from 12 sites to identify cross-site best practices and pitfalls related to implementation.ResultsThree primary implementation themes emerged: organizational readiness for transformation, importance of champions, and time and resources needed to achieve implementation. Each theme's barriers and facilitators highlighted variability in success based on complexity in terms of vertical hierarchy and horizontal cross-role/cross-clinic relationships.ConclusionLearning health care systems need multilevel interdisciplinary implementation approaches to support communication about serious illness, from broad-based system-level training and education to build communication skills, to focusing on characteristics of successful individual champions who listen to critics and are tenacious in addressing concerns.