Adiponectin levels are high in children with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

Objective: It has been shown that adiponectin serves as an insulin-sensitizing adipokine. Serum concentrations of adiponectin are low in children with obesity, and increase with fat mass loss, indicating that adiponectin can serve as a biomarker. Since the prevalence of overweight and obesity is increased in children with congenital adrenal hyperplasia (CAH), our study aimed to evaluate serum levels of adiponectin in a cohort of CAH children and adolescents, and their associations with clinical parameters such as chronological age (CA), body mass index (BMI), Tanner stage (TS), medication and metabolic control.
Patients and methods: We studied 51 patients, aged between 5.6 and 19.6 years (median 11.8; 30 females, 21 males), cross-sectionally. All patients had genetically confirmed CAH and received standard steroid substitution therapy. Adiponectin was measured by an enzyme linked immunoassay. Since BMI SDS of the CAH cohort were significantly higher compared to the reference population, we built matched pairs with healthy Caucasian subjects from a normal representative cohort for sex, Tanner stage, chronologic age and BMI.
Results: Adiponectin concentrations were significantly higher in CAH patients (median 11 μg/L) compared to the matched controls (6.7 μg/L, p < 0.0001). Correlation analyses in CAH patients revealed a significant inverse relationship between adiponectin and CA, TS, BMI, serum DHEAS and serum testosterone, but no correlation with hydrocortisone and fludrocortisone dosage.
Conclusion: Currently, the importance of the elevated adiponectin concentrations in CAH children for risk assessment is not clear. However, our data imply that besides adequate metabolic control of glucocorticoid substitution, a long-term follow-up of other metabolic markers of insulin resistance should be conducted in CAH patients.     

Identification and characteristics of vaccine refusers

Background  

This study evaluated the utility of immunization registries in identifying vaccine refusals among children. Among refusers, we studied their socioeconomic characteristics and health care utilization patterns.     

Not all non-drinkers with HIV are equal: demographic and clinical comparisons among current non-drinkers with and without a history of prior alcohol use disorders*

Studies of persons living with HIV (PLWH) have compared current non-drinkers to at-risk drinkers without differentiating whether current non-drinkers had a prior alcohol use disorder (AUD). The purpose of this study was to compare current non-drinkers with and without a prior AUD on demographic and clinical characteristics to understand the impact of combining them. We included data from six sites across the US from 1/2013 to 3/2015. Patients completed tablet-based clinical assessments at routine clinic appointments using the most recent assessment. Current non-drinkers were identified by AUDIT-C scores of 0. We identified a prior probable AUD by a prior AUD diagnosis in the electronic medical record (EMR) or a report of attendance at alcohol treatment in the clinical assessment. We used multivariate logistic regression to examine factors associated with prior AUD. Among 2235 PLWH who were current non-drinkers, 36% had a prior AUD with more patients with an AUD identified by the clinical assessment than the EMR. Higher proportions with a prior AUD were male, depressed, and reported current drug use compared to non-drinkers without a prior AUD. Former cocaine/crack (70% vs. 25%), methamphetamine/crystal (49% vs. 16%), and opioid/heroin use (35% vs. 7%) were more commonly reported by those with a prior AUD. In adjusted analyses, male sex, past methamphetamine/crystal use, past marijuana use, past opioid/heroin use, past and current cocaine/crack use, and cigarette use were associated with a prior AUD. In conclusion, this study found that among non-drinking PLWH in routine clinical care, 36% had a prior AUD. We found key differences between those with and without prior AUD in demographic and clinical characteristics, including drug use and depression. These results suggest that non-drinkers are heterogeneous and need further differentiation in studies and that prior alcohol misuse (including alcohol treatment) should be included in behavioural health assessments as part of clinical care.     

Human Visual and Vestibular Heading Perception in the Vertical Planes

Heading estimation has not previously been reported in the vertical planes. This is a potentially interesting issue because although distribution of neuronal direction sensitivities is near uniform for vertical headings, there is an overrepresentation of otolith organs sensitive to motion in the horizontal relative to the vertical plane. Furthermore, thresholds of horizontal motion perception are considerably lower than those of vertical motion which has the potential to bias heading perception. The current data from 14 human subjects (age 19 to 67) measured heading estimation in response to vestibular motion of 14 cm (28 cm/s) over a 360 ° of headings at 5 ° intervals. An analogous visual motion was tested in separate trials. In this study, earth and head vertical/horizontal were always aligned. Results demonstrated that the horizontal component of heading was overestimated relative to the vertical component for vestibular heading stimuli in the coronal (skew) and sagittal (elevation) planes. For visual headings, the bias was much smaller and in the opposite direction such that the vertical component of heading was overestimated. Subjects older than 50 had significantly worse precision and larger biases relative to that of younger subjects for the vestibular conditions, although visual heading estimates were similar. A vector addition model was fit to the data which explains the observed heading biases by the known distribution of otolith organs in humans. The greatly decreased precision with age is explained by the model with decreases in end organ numbers, and relatively greater loss of otoliths that are sensitive to vertical motion.     

Hemisphere-scale differences in conifer evolutionary dynamics

Fundamental differences in the distribution of oceans and landmasses in the Northern and Southern Hemispheres potentially impact patterns of biological diversity in the two areas. The evolutionary history of conifers provides an opportunity to explore these dynamics, because the majority of extant conifer species belong to lineages that have been broadly confined to the Northern or Southern Hemisphere during the Cenozoic. Incorporating genetic information with a critical review of fossil evidence, we developed an age-calibrated phylogeny sampling ∼80% of living conifer species. Most extant conifer species diverged recently during the Neogene within clades that generally were established during the later Mesozoic, but lineages that diversified mainly in the Southern Hemisphere show a significantly older distribution of divergence ages than their counterparts in the Northern Hemisphere. Our tree topology and divergence times also are best fit by diversification models in which Northern Hemisphere conifer lineages have higher rates of species turnover than Southern Hemisphere lineages. The abundance of recent divergences in northern clades may reflect complex patterns of migration and range shifts during climatic cycles over the later Neogene leading to elevated rates of speciation and extinction, whereas the scattered persistence of mild, wetter habitats in the Southern Hemisphere may have favored the survival of older lineages.     

Hyaline‐vascular type Castleman’s disease of the pararenal retroperitoneum: Multidetector CT findings

We describe the case of a 40‐year‐old woman who presented with a pararenal hyaline‐vascular type Castleman’s disease that had an arterial supply from the renal artery and a draining vein as showed by multidetector CT. Identification of the renal artery relationship to the feeding vessel of the mass is critical to prevent potential surgical complications.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.     

Bacteriology of sinusitis in human immunodeficiency virus-positive patients: Implications for management

The bacteriology of sinusitis in human immunodeficiency virus (HIV)-infected patients has been only sporadically reported. In this study, we report the results of cultures taken from 12 HIV patients with refractory chronic sinusitis who underwent surgery. Nine of the 12 patients had positive cultures with 16 isolates and 5 patients having multiple isolates. Five of the 12 patients grew out atypical or opportunistic infections not responsive to standard medical therapy, including 3 patients with cytomegalovirus, 1 with Aspergillus fumigatus, and 1 with Mycobacterium kansasii. These results suggest the need for aggressive medical care for HIV-infected patients with sinusitis and early intervention for tissue cultures in patients who do not respond to standard antibiotic regimens.     

Comparison of in vitro and in vivo methods to study stability of PLGA microencapsulated tetanus toxoid vaccines

The purpose of this study was to investigate the utility of various in vitro and in vivo methods to assess the stability of experimental vaccines containing tetanus toxoid (TT) within PLGA microspheres. In vitro, the breakdown of the encapsulating polymers into their acid components led to changes in the structure of TT, as determined by the physico-chemical methods, rendering it undetectable by capture ELISA and altering its structural integrity. The changes in TT were directly related to increasing acidity of the vaccine supernate. Purified toxoid (not encapsulated) exposed to low pH (2.5) underwent similar changes but re-neutralisation of buffer containing free toxoid, even after one week at pH 2.5 led to some re-folding of protein as determined by fluorescence spectroscopy and gel filtration chromatography. The microencapsulated vaccines were still able to generate an antibody response in mice even after prolonged pre-incubation at 37 degrees C and the apparent absence of detectable toxoid in the vaccine supernate. Electron microscopy demonstrated differences in the amount of degradation between different formulations of microspheres. Vaccines that had retained their spherical morphology after incubation in vitro for up to 28 days were able to induce protective antibodies response equal to that of freshly prepared vaccines, which indicates that the toxoid within intact microspheres remained immunogenic. Immunochemical and physico-chemical detection methods, performed on antigen released from PLGA vaccines in vitro, are valuable in providing information on product characteristics but may not be able to predict effectiveness and should be used with in vivo methods to evaluate the stability of such formulations.     

Improved leukocyte tracking in mouse retinal and choroidal circulation

The purpose of this study is to develop a new method with which to visualize leukocyte dynamics in murine choroidal and retinal circulation. Both pigmented (B10.RIII) and non-pigmented (BALB/c) mice were used in this study. One hundred microl of 0.05% sodium fluorescein was injected via the mice tail vein to outline the vessel, followed by 150 microl (10(7) cells) C-AM labelled leukocytes. Fundus images were obtained with a confocal scanning laser ophthalmoscope. The dynamic image sequences were recorded simultaneously on videotape (S-VHS) and digitally at 25 frames per sec. The digital images were later analysed with a custom-made personal computer-based image analysis system. Both the choroidal and retinal circulation can be visualized in non-pigmented mice in the first few seconds of fluorescein angiography. However, the view of the choroidal and the retinal capillary circulation is soon blurred due to the rapid fluorescein leakage in the choroid. In contrast, in pigmented mice, retinal circulation is clear against the dark background of the choroid, while choroidal circulation is masked behind the pigment epithelial layer and cannot be seen at all. C-AM labelled leukocytes were clearly seen in the retinal circulation of all experimental mice and in the choroidal circulation of non-pigmented mice for as long as 30 min. The number of labelled circulating cells decreased as time clasped. Cells moved rapidly in the retinal arteries, slowing down or even stopping for a few seconds in the capillary system, and then moved slightly faster again through the postcapillary venules and veins. In non-pigmented mice, significant number of cells were seen to have arrested in the choroidal circulation. There was no difference between B10.RIII mice and BALB/c mice in vessel diameters, leukocyte velocities and shear stresses. This method allows the visualization of leukocytes and provides data on their behavior as they move through the choroidal and retinal circulation of non-pigmented mice, and in the retinal circulation of pigmented mice. It provides a valuable new tool for the investigation of real time leukocyte dynamics in murine retinal and choroidal microcirculations both under physiological conditions and during the development of ocular disease.