Alterations in erythrocyte Na+,K+-cotransport in normal and hypertensive human pregnancy

Many physiological variables known or thought to affect erythrocyte Na+,K+-cotransport are altered in pregnancy. The interrelationships of Na+,K+-cotransport and pregnancy were therefore examined. Values were elevated by more than 30% in both second and third trimesters with a return towards non-pregnant levels in the postpartum period. Although pregnancy was also associated with elevated plasma cholesterol, renin activity and aldosterone, there was no significant relationship within the pregnant group between Na+,K+-cotransport and any of these factors. No change could be demonstrated in Na+,K+-cotransport values after 7 days of either high (greater than 250 mmol/day) or low (less than 50 mmol/day) sodium intake and values for those who developed pregnancy-associated hypertension (PAH, pre-eclampsia) were not significantly different from those in continuously normotensive women in either the second or the third trimesters of pregnancy.     

Assessment of tolerance to immunosuppressive activity of delta 9-tetrahydrocannabinol in rats

Immunosuppression evoked by delta 9-tetrahydrocannabinol (delta 9-THC) has been a consistent finding in rats but the development of tolerance to this phenomenon has not been explored. Therefore, Fischer rats of both sexes were orally given delta 9-THC at 6 or 12 mg/kg or sesame oil as vehicle control for 5-26 days before and after I.P. antigenic stimulation with sheep red blood cells (SRBC). delta 9-THC doses were relevant to those of man and produced mild CNS-inhibition followed by CNS-stimulation, tolerance developing to both behavioral phases. The primary immune response was evaluated by determining splenic antibody-forming cells (AFC), hemagglutinin (HT) and/or hemolysin (HS) titers. Simultaneous administration of delta 9-THC and SE induced dose-related splenic atrophy and reduced AFC proliferation as well as HT and HS responses. These changes were not elicited by sesame oil. Tolerance did not develop to immunosuppression during 26 days of cannabinoid treatment. delta 9-THC given 3 days post SRBC inoculation induced immunosuppression at 12 but not 6 mg/kg. Immunosuppression was directly related to delta 9-THC rather than to non-specific debilitating factors since body weights are stable. The inductive phase of the primary immune response was most sensitive to impairment although the reproductive phase was also affected at the high dose level.     

Immunological Deficiency Associated With Cigarette Smoke Inhalation by Mice

Inhalation of cigarette whole smoke (CWS) or its vapor phase (CVP) significantly impaired immune response capability in mice. Significant immunosuppressive effects on the humoral antibody response to a single antigenic stimulus were evident in animals exposed to smoke for seven days before or two days after administration of antigen. Impairment of the immunological response capability appeared to be temporary, with recovery about 14 days after exposure. Different lengths of exposure prior to antigenic stimulation neither produced an additive impairment of the immunological response nor rendered the experimental animals more tolerant to CWS or CVP. The immunological deficiency was specific to CWS and CVP inhalation rather than to nonspecific debilitating stress factors. The inductive phase was the period of the primary and secondary immune response most sensitive to impairment by exposure to CWS or CVP.     

How Might Immunization Rates Change if Cost Sharing Is Eliminated?

Objectives

There is a debate regarding the effect of cost sharing on immunization, particularly as the Affordable Care Act will eliminate cost sharing for recommended vaccines. This study estimates changes in immunization rates and spending associated with extending first-dollar coverage to privately insured children for four childhood vaccines.

Methods

We used the 2008 National Immunization Survey and peer-reviewed literature to generate estimates of immunization status for each vaccine by age group and insurance type. We used the Truven Health Analytics 2006 MarketScan Commercial Claims and Encounters Database of line-item medical claims to estimate changes in immunization rates that would result from eliminating cost sharing, and we used the Kaiser Family Foundation/Health Research and Educational Trust Employer Health Benefits Survey to determine the prevalence of coverage for patients with first-dollar coverage, patients who face office visit cost sharing, and patients who face cost sharing for all vaccine cost components. We assumed that once cost sharing is removed, coverage rates in plans that impose cost sharing will rise to the level of plans that do not.

Results

We estimate that immunization rates would increase modestly and result in additional direct spending of $26.0 million to insurers/employers. Further, these payers would have an additional $11.0 million in spending associated with eliminating cost sharing for children already receiving immunizations.

Conclusions

The effects of eliminating cost sharing for vaccines vary by vaccine. Overall, immunization rates will rise modestly given high insurance coverage for vaccinations, and these increases would be more substantial for those currently facing cost sharing. However, in addition to the removal of cost sharing for immunizations, these findings suggest other strategies to consider to further increase immunization rates.Immunization of children against potentially life-threatening illnesses has proved one of the greatest public health successes and one of the most cost-effective medical interventions of the 20th century.^1,2 One barrier to immunization is financial: enrollees seeking immunizations may be confronted with cost sharing (i.e., the contribution consumers make toward the cost of their health care as defined by their health insurance policy) that they are unable or unwilling to pay.^1–8 Approximately 7% of enrollees with private insurance face cost sharing for the administration of immunizations.⁹This barrier will be lowered as part of the Patient Protection and Affordable Care Act (hereafter, ACA), also referred to as the Health Reform Act.¹⁰ Subpart II Section 2713 of the Act, which was enacted in September 2010, requires first-dollar coverage for vaccines recommended by the Advisory Committee on Immunization Practices (ACIP).¹¹ First-dollar coverage means that cost sharing in the form of copays, co-insurance, or deductibles will not apply for ACIP-recommended vaccines. The policy intent was to provide financial relief to patients who were previously deterred by financial barriers, encouraging them to obtain vaccinations once these financial barriers were removed.We examined immunization patterns among privately insured children and adolescents under different levels of cost sharing to estimate the effects of removing cost sharing for both the vaccine dose and administration. Children who are uninsured, underinsured for vaccines, or Medicaid eligible qualify for the Vaccines for Children (VFC) program, which offers vaccines at no cost, and were excluded from this analysis. With the passage of the ACA, children will primarily receive vaccines under private insurance or qualify through expanded Medicaid eligibility to receive vaccines through the VFC program. It is estimated that 89% of the population will have private health insurance coverage when health reform is fully implemented in 2022.^12,13 In 2010, 90% of children had health insurance coverage (public or private) at least some time during the year, of which 60% were covered by private insurance.¹⁴Our analysis focused on four vaccines: (1) measles, mumps, and rubella (MMR); (2) heptavalent pneumococcal conjugate (PCV7); (3) human papillomavirus (HPV); and (4) meningococcal conjugate (MCV4). These vaccines present different challenges to uptake based on age recommendation, cost, and integration in the immunization delivery system (15^–19 MMR is also less expensive than newer vaccines. PCV7, which was recommended by ACIP in 2000, is an example of a vaccine that signaled a new era of more expensive vaccines, though it is also integrated into well-child visits. In 2010, a next-generation PCV13 vaccine replaced PCV7, adding six serotypes to the vaccine. Finally, HPV vaccine, recommended for use in 2006, and MCV4, recommended by ACIP in 2005, highlight the challenges of vaccinating adolescents who sporadically access preventive health care.²⁰ HPV vaccine also highlights the challenges of introducing new vaccines that are not only more expensive but also raise questions about social norms and stigma.²¹

Table 1.

Vaccine product characteristics in the U.S. by licensure, indication, school requirement, and recent coverage levelsOpen in a separate window^aU.S. Food and Drug Administration licensure dates of selected vaccines^bCenters for Disease Control and Prevention (US). 2011 National Immunization Survey [cited 2013 Sep 19]. Available from: URL: http://www.cdc.gov/vaccines/stats-surv/nis/nis-2011-released.htm^cCoverage estimates are for PCV13 (surrogate for coverage, as PCV13 is a replacement product to PCV7 licensed in 2010).MMR = measles, mumps, and rubellaPCV7 = heptavalent pneumococcal conjugateMCV4 = meningococcal conjugateHPV = human papillomavirusPCV13 = 13-valent pneumococcal conjugateTo understand the role of cost sharing and its impact on vaccine coverage, we modeled the effects of eliminating cost sharing for select immunizations routinely recommended for children and adolescents and discuss other factors that may be important impediments to immunization.     

The basolateral amygdala is necessary for negative prediction errors to enhance cue salience,but not to produce conditioned inhibition

Behavioral evidence shows that prediction errors (PEs) not only drive associative learning, but also enhance the salience of predictive cues, making them better able to capture attention when they are next encountered. Research from our laboratory suggests that this latter consequence of PEs depends on a neural circuit that includes the amygdala. Lesions of the basolateral complex of the amygdala (BLA), for instance, selectively disrupt enhancements in cue processing that are normally induced by positive PEs without compromising simple excitatory learning. This result is consistent with electrophysiological evidence showing that BLA neurons track positive PEs. Interestingly, the same neurons also seem to track negative PEs, suggesting the possibility that the BLA might also use these errors to drive enhancements in cue processing. Here, we examined the role of the BLA in the processing (Experiment 1) and utilization (Experiment 2) of negative PEs in increasing cue salience in an unblocking procedure. Using FOS expression as an index of neural activity, Experiment 1 confirmed that BLA neurons track negative PEs with reinforcement downshifts. This tracking was evident both when these errors were generated by decreasing the concentration of a sucrose reinforcer (which encourages the development of conditioned inhibition) and when they were generated by decreasing the number of sucrose reinforcers (which encourages excitatory learning – unblocking – and allows the detection of enhancements in cue processing). Experiment 2 demonstrated that BLA lesions abolished enhancements in cue processing while sparing inhibitory learning. These results suggest a general role of the BLA in utilizing PEs, whatever their sign, for boosting cue processing.     

Weight gain during the dolutegravir transition in the African Cohort Study

IntroductionDolutegravir (DTG) has become a preferred component of first‐line antiretroviral therapy (ART) in many settings but may be associated with excess weight gain. We evaluated changes in weight and body mass index (BMI) after switch to single‐tablet tenofovir/lamivudine/dolutegravir (TLD) by people living with HIV (PLWH) in four African countries.MethodsThe African Cohort Study (AFRICOS) prospectively follows adults with and without HIV in Kenya, Uganda, Tanzania and Nigeria. Demographics, ART regimen, weight, BMI and waist‐to‐hip ratio were collected every 6 months. Multivariable Cox proportional hazards modelling was used to estimate hazard ratios and 95% confidence intervals (CIs) for factors associated with developing a BMI ≥25 kg/m². Linear mixed effects models with random effects were used to examine the average change in BMI, weight and waist‐to‐hip ratio.ResultsFrom 23 January 2013 to 1 December 2020, 2950 PLWH were enrolled in AFRICOS and 1474 transitioned to TLD. In adjusted models, PLWH on TLD had 1.77 times the hazard of developing a high BMI (95% CI: 1.22–2.55) compared to PLWH on non‐TLD ART. Examining change in weight among all PLWH on ART, participants on TLD gained an average of 0.68 kg (95% CI: 0.32–1.04) more than PLWH on other regimens after adjusting for duration on ART, sex, age, study site and CD4 nadir. Among participants who switched to TLD, the average change in weight prior to TLD switch was 0.35 kg/year (95% CI: 0.25–0.46) and average change in weight was 1.46 kg/year (95% CI: 1.18–1.75) in the year following transition to TLD after adjustment for confounders.ConclusionsElevated BMI and weight gain among PLWH on TLD are concerning safety signals. Implications for the development of metabolic comorbidities should be monitored, particularly if annual weight gain persists during continued follow‐up after transitioning to TLD.     

Feeding, artificial sucking habits, and malocclusions in 3-year-old girls in different regions of the world

PURPOSE: The way babies and young children are reared is important to their health and development. Extensive breast-feeding has also been shown to reduce the development of artificial sucking habits like digit or pacifier-sucking. The aim of this study was to determine feeding methods, artificial sucking habits, and the presence of malocclusions in 3-year-old girls living in different regions of the world. METHODS: Children from the following countries were involved in the present study: (1) Brazil (Porto Alegre); (2) Japan (Niigata); (3) Mexico (Mexico City); (4) Norway (Oslo); (5) Sweden (Falk?ping); (6) Turkey (Istanbul); (7) and the United States (Iowa City, Iowa). During the interview and examination, the following variables were evaluated and registered: (1) breastfeeding and bottle-feeding; (2) duration and frequency; (3) sucking habits; (4) posterior and anterior crossbites; and (5) other malocclusions/normal occlusion. RESULTS: The prevalence of breast-feeding was very high in all groups, ranging between 78% and 98%. The prevalence of bottle-feeding in the different areas was also high. Except for Iowa City, the prevalence of digit-sucking was relatively low. Pacifier-sucking is fairly popular in most areas, with the exception of Niigata. The prevalence of normal occlusion in different cities ranged from 38% to 98%. CONCLUSIONS: There are considerable differences in feeding, as well as artificial sucking habits, in different areas of the world and at different periods.     

Surface membrane determinants on childhood acute lymphocytic leukemia cells: immunoglobulin, Fc and C3 receptors.

Most reports have now described two populations of childhood ALL patients: those with thymic (T) cell receptors and those lacking receptors on their neoplastic cells. Assays for the surface receptors of the T and thymic-independent (B) system were used to study forty-seven patients with ALL whose bone marrow contained a mean of 85% leukaemic cells. Two patients had T-cell disease and thirty-six were non-T and non-B. nine patients were identified whose leukaemic cells had membrane properties associated with the B-cell system: surface immunoglobulin, Fc receptors and/or complement receptors. Combined T and B receptors were found in one case. The same surface characteristics were found on leukaemic cells from these patients' bone marrow, blood, pleural and cerebrospinal fluid. Studies showed that the leukaemic cells were not of monocytic or granulocytic origin. Although a remission was obtained in each patient, the relapse rate of the B-cell group was worse than a similarly treated group of thirty-six non-T, non-B ALL patients (P less than 0.001). Initial total leucocyte counts of the B-cell group were greater than the non-T, non-B group (P 0.05), but when the patients in both groups with total leucocyte counts greater than 25,000/mm3 were compared, the relapse rate of the B-cell patients was significantly worse (P less than 0.025). The results show that patients with leukaemic cells possessing B-cell properties comprise a significant proportion of ALL cases, and their presence on leukaemic cells has an ominous significance.