Defective yeast opsonisation and functional deficiency of complement in sickle cell disease.

Opsonisation of heat-killed baker''s yeast, functional activity of the total alternative pathway of complement, and factor B detected functionally and immunochemically were significantly reduced in 72 children with sickle cell disease compared with 40 age-matched black control children. There was significant correlation between functional activity of the total alternative pathway and functionally measured factor B, but not between factor B measured functionally and immunochemically. The opsonisation defect could be corrected in vitro by normal serum, and factor B-depleted serum, and was qualitatively similar to that seen in patients with primary yeast opsonisation deficiency. Serial studies showed that these serum defects were persistent. Reduction in the activity of components of the alternative pathway of complement and opsonisation was found in 4 patients who had recovered from pneumococcal meningitis and in one who developed osteomyelitis. Defects of yeast opsonisation and complement which are common in patients with sickle cell disease, may partly explain the children''s increased susceptibility to infection, and might help to identify individuals especially at risk.     

Seeking information about HIV/AIDS: a qualitative study of health literacy among people living with HIV/AIDS in a low prevalence context

People living with HIV/AIDS in rural and low HIV prevalence areas face a number of challenges including stigma, limited access to specialized medical care, lack of an HIV/AIDS specialist and fear which may interfere with their ability to find and use information to manage their health. With a large number of HIV cases located in non-metropolitan and rural areas in the US, more research is needed to better understand the health seeking behaviors of individuals living in this context. This study examined how 16 individuals living with HIV sought out information to meet their health needs. In qualitative semi-structured interviews, we explored participants' primary sources of information, types of information sought, and barriers to accessing information. The sample was comprised of people living with HIV/AIDS (PLWHA) who resided in a predominantly rural area with low HIV prevalence. The majority of participants relied on a combination of sources including their HIV/AIDS physician, the Internet, a Ryan-White caseworker and a staff member of a community-based support organization to meet their informational needs. Information sought focused primarily on drug regimens, drug side effects, or drug research. Participants shared barriers to accessing information including stigma, fear, concern about disclosure, and feelings of futility and anger. Findings point to a need to expand health literacy research and interventions to address broader social and structural barriers to health improvement for PLWHA, especially among those living in rural and low HIV prevalence areas.     

Quantitative evaluation of liver-specific promoters from retroviral vectors after in vivo transduction of hepatocytes

Hepatic gene therapy could be used to treat a number of inherited blood diseases such as hemophilia or thrombophilia. Although liver-directed retroviral transduction can result in long-term gene expression in vivo, the low level of protein production has limited its clinical application. We reasoned that the insertion of liver-specific promoters into retroviral vectors would increase gene expression in vivo. The 347- bp human alpha 1-antitrypsin (hAAT), the 810-bp murine albumin (mAIb), the 490-bp rat phosphoenolpyruvate carboxykinase (rPECK), and the 596- bp rat liver fatty acid binding protein promoters were inserted into a Moloney murine leukemia retroviral backbone containing the hAAT reporter gene. Vectors that produced appropriately sized RNA and hAAT protein in vitro were tested in vivo by transducing regenerating rat livers. Long-term serum expression of the hAAT reporter gene was normalized to retroviral transduction efficiency as determined by using a polymerase chain reaction-based assay of genomic DNA from transduced rat livers. The hAAT, mAIb, and rPEPCK promoters were, respectively, 35- , 8-, and 0.02-fold as strong as the previously studied constitutive Pol-II promoter. We conclude that the hAAT promoter resulted in the highest expression from a retroviral vector and may result in therapeutically significant expression of other clinically significant blood proteins.     

Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

PCV16 Smoking Related Costs in the United States

Smoking is a high-risk behavior that affects the health and economic welfare of society. Thus, it is important to quantify the economic burden smoking places on social institutions in the United States.
OBJECTIVE: The purpose of this review paper is to analyze smoking cost studies and to provide estimates that represent the economic costs of smoking from different perspectives of society, and as a whole.
METHODS: Current Contents (1996–), Health Star (1970–), and Medline (1966–) databases were searched through the use of pertinent subject headings and key words: tobacco use, smoking, cost, and economics. The internet was utilized to identify potential sources of epidemiological and cost information on smoking. Recent cost-of-illness studies using different methodologies: human capital, incidence, and prevalence were chosen for review based on their relevance.
RESULTS: Preliminary results indicate that the published cost studies available underestimate the "true" costs of smoking. The most current articles approximate annual direct medical costs to health care payers of $50 billion (1993); inflating to 1997 equals $59 billion or $1,200 per smoker. Although the latest cost studies do not attempt to estimate indirect costs, past studies have found indirect costs to be 1.5–2 times the direct costs. Therefore, using direct and indirect costs we estimate total smoking costs to be $150 billion (1993); inflating to 1997 equals $176 billion or $3,500 per smoker.
CONCLUSION: Quantifying the cost of smoking is a difficult task due to tobacco use infiltrating many aspects of life and the dependency of cost on perspective. Cost-of-illness studies provide cost estimation data which can be useful in aiding decision-makers who are allocating health care resources.     

COVID-19 Gender Disparities and Mitigation Recommendations: A Narrative Review

The coronavirus disease 2019 (COVID-19) pandemic has rapidly created widespread impacts on global health and the economy. Data suggest that women are less susceptible to severe illness. However, sex-disaggregated data are incomplete, leaving room for misinterpretation, and focusing only on biologic sex underestimates the gendered impact of the pandemic on women. This narrative review summarizes what is known about gender disparities during the COVID-19 pandemic and the economic, domestic, and health burdens along with overlapping vulnerabilities related to the pandemic. In addition, this review outlines recommended strategies that advocacy groups, community leaders, and policymakers should implement to mitigate the widening gender disparities related to COVID-19.     

Anthropometry underestimates body protein depletion in haemodialysis patients

The body composition of 62 haemodialysis patients (41 males) and 63 controls (30 males) was assessed using anthropometry and in vivo neutron activation analysis of body nitrogen. There was no significant difference between patients and controls in body mass index (BMI) and percentage body fat. Arm muscle circumference was significantly reduced in males. Lean body mass was strongly correlated with body nitrogen in controls (r = 0.951) but less so in patients (r = 0.876). The mean standardised body nitrogen index (NI) was reduced in male patients by 13% (95% confidence interval -9 to -17%) and in females by 4% (95% confidence interval +4 to -12%). Of the 16 patients with a NI below the control range, arm muscle circumference was below the control range in only 3 and BMI less than 18 kg/m2 in 2. NI was correlated negatively with the duration of renal replacement therapy, duration of haemodialysis, the number of previous failed transplants and the total dose of steroids received but not with current energy or protein intakes. Steroid dose was the only significant independent variable. Anthropometry underestimates body protein depletion in haemodialysis patients and the degree of protein loss is related to the cumulative dose of corticosteroids previously received.