Corneal Manifestations of Systemic Sclerosis

Purpose: Corneal involvement in systemic sclerosis (SSc) is rare, but due to rich collagen composition cornea is especially vulnerable to connective tissue diseases. Therefore, our aim was to evaluate corneal parameters of SSc patients.

Methods: The study included 32 SSc patients and 39 control subjects with no ocular symptoms or ocular surface disorders. All study participants underwent Pentacam evaluation and objective signs of dry eye disease (DED), and clinical parameters were evaluated.

Results: All pachymetric values, most of the corneal front surface, corneal volume, as well as anterior chamber depth measurements were significantly lower in the SSc group than in the control group (p < 0.05). Significant negative correlation was found between corneal parameters and age on the one hand, and disease duration on the other.

Conclusions: Early recognition of corneal impairment, a possible extraintestinal manifestation of SSc, should be included in the check-up of the disease in order to reduce sight-threatening complications.     

Isolation of microsatellite markers from tiger grouper (Mycteroperca tigris) and characterization in yellowfin grouper (Mycteroperca venenosa), coney (Cephalopholis fulva), and red hind (Epinephelus guttatus)

Thirty-six microsatellite markers were isolated from an enriched genomic library of tiger grouper (Mycteroperca tigris) and characterized in 20 individuals each for yellowfin grouper (Mycteroperca venenosa), coney (Cephalopholis fulva), and red hind (Epinephelus guttatus). The microsatellites include 23 dinucleotide repeats, twelve trinucleotide repeats, and one tetranucleotide repeat. The microsatellites characterized in this study will be useful for further evaluation of population-genetic indices in the economically important subfamily Epinephelinae.     

The conjugation of an AQP1-directed immunotoxin in the study of site-directed therapy within the CNS

Purpose  

The water channel, aquaporin (AQP)1, is highly specific to the choroid plexus (CP) epithelium within the brain. It is therefore a potential target through which therapeutic agents could be selectively directed to the CP. Here we describe the conjugation of a monoclonal antibody (mAb), raised against an extra-cellular domain of AQP1, to the A chain of ricin (RCA). This reagent should allow study of a highly specific chemical lesion of the CP.     

Rheologic predictors of the severity of the painful sickle cell crisis

Deformable sickle erythrocytes have been reported by Mohandas and Evans to be more adherent to vascular endothelium than rigid irreversibly sickled cells (ISC). To define the clinical implications of this finding we have determined genetic, hematological, clinical, and rheological characteristics of sickle erythrocytes obtained from 65 patients with sickle cell anemia and fetal hemoglobin (Hb F) levels less than 15%. The alpha-globin gene number had a significant effect on the hematological parameters, the percentage of dense cells, ISC number, and HB A2 levels. The presence or absence of alpha thalassemia, however, had no effect on the frequency and severity of the sickle cell painful crisis (r = 0.06, P greater than .05). RBC deformability, determined by an ektacytometer, showed great heterogeneity among patients with three or four alpha-globin genes. Linear regression analyses of the data showed significant positive correlation of the frequency and severity of the painful crisis with RBC deformability (r = 0.49, P less than .001), and negative correlations with the percentage of dense cells (r = -0.37, P = .002), and the percentage of ISC (r = -0.46, P less than .001). We propose that the more deformable the sickle RBC are, the greater their adherence to vascular endothelium, and the more they cause vaso-occlusive crises, RBC deformability and the percentage of dense cells (or ISC) seem to have a predictive value of the frequency and severity of painful crises in sickle cell anemia.     

Sleep characteristics as predictor variables of stress systems markers in insomnia disorder

This study investigates the extent to which sleep characteristics serve as predictor variables for inflammatory, hypothalamic–pituitary–adrenal and autonomic systems markers. Twenty‐nine participants with a diagnosis of insomnia disorder based on the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition (age 25.3 ± 1.6 years, insomnia duration 6.6 ± 0.8 years) and 19 healthy control sleepers (age 25.4 ± 1.4 years) underwent a 2‐week at‐home evaluation keeping a sleep diary and wearing an actigraph, followed by a visit to the Research Center to measure blood pressure, and collect blood and urine samples. The actigraphy‐ and diary‐based variables of sleep duration, sleep‐onset latency, wake after sleep onset and sleep fragmentation/number of night‐time awakenings were averaged and entered as dependent variables in regression analyses. Composite scores were calculated for the autonomic (blood pressure, norepinephrine), inflammatory (monocyte counts, interleukin‐6, C‐reactive protein) and hypothalamic–pituitary–adrenal systems (cortisol), and used as predictor variables in regression models. Compared with controls, individuals with insomnia had a shorter sleep duration (P < 0.05), and a higher hypothalamic–pituitary–adrenal and inflammatory composite score (P < 0.05). The higher inflammatory score was mainly due to higher circulating monocytes (P < 0.05), rather than differences in interleukin‐6 or C‐reactive protein. In persistent insomnia disorder, cortisol is upregulated and associated with actigraphy‐ and diary‐based wake after sleep onset, suggesting that wake after sleep onset may serve as a marker to identify individuals at increased risks for disorders associated with a hyperactive hypothalamic–pituitary–adrenal system. The absence of autonomic and pro‐inflammatory changes (interleukin‐6, C‐reactive protein), despite a substantial decrease in actigraphic sleep duration, may relate to a higher resilience to the adverse biological consequences of insomnia in this young age group.     

An erythroid-specific chromatin opening element reorganizes beta-globin promoter chromatin structure and augments gene expression.

In erythroid tissues the chromatin structure of the beta-globin gene locus is extensively remodeled. Changes include the formation of DNase I hypersensitive sites (HSs) over the promoters of actively expressed genes. To test the hypothesis that such "opening" of promoter chromatin structure is important for beta-globin gene expression, we placed a 101-bp erythroid-specific hypersensitive-site forming element (HSFE) from the core of LCR HS4 immediately upstream of a minimal beta-globin gene promoter. We then studied the effects of this element alone and in combination with other cis-acting elements on globin gene chromatin structure and gene expression in MEL cells and transgenic mice. Single or tandem HSFEs increased the size of the portion of the promoter accessible to DNase digestion, increased the proportion of promoters in an accessible conformation, and increased gene expression approximately 5-fold. These were equivalent to expression levels attained using a 2.8-kb microLCR construct. Inclusion of the LCR HS2 enhancer did not increase expression further. In transgenic mouse fetal liver cells the HSFE increased average expression 2.5-fold compared to the minimal promoter alone. These results indicate that a small cis-acting element is capable of remodeling local beta-globin promoter chromatin structure and producing expression similar to that seen with a microLCR construct.     

Thrombospondin mediates the cytoadherence of Plasmodium falciparum- infected red cells to vascular endothelium in shear flow conditions

Cerebral malaria is thought to involve specific attachment of Plasmodium falciparum-infected knobby red cells to venular endothelium. The nature of surface ligands on host endothelial cells that may mediate cytoadherence is poorly understood. We have investigated the effects of soluble thrombospondin, rabbit antiserum raised against thrombospondin, and human immune serum on cytoadherence of parasitized erythrocytes in ex vivo mesocecum vasculature. Preincubation of infected red cells with soluble thrombospondin or human immune serum inhibits binding of infected red cells to rat venular endothelium. Infusion of the microcirculatory preparation with rabbit antithrombospondin antibodies before perfusion of parasitized erythrocytes also resulted in decreased cytoadherence. In addition, incubation of infected cells with human immune sera obtained from malaria patients significantly inhibited the observed cytoadherence. Our results indicate that thrombospondin mediates binding of infected red cells to venular endothelium and may thus be involved in the pathogenesis of cerebral malaria.     

Adult Children and the Transition of Aging Parents

Abstract

This study explores the experiences of adult children as they transition their functionally and/or cognitively declining aging parents from independent living to supervised housing. A qualitative grounded theory approach was used to chronicle the experiences of adult children as their caregiving responsibilities intensified and their parents' health declined. Purposive, snowball sampling was used to enlist adult children (n = 16) who were in the process of transitioning an aging parent from an independent living situation to one providing assistance with everyday care and tasks. Semi-structured telephone interviews were conducted and designed to follow a pattern of increased frailty of the parent(s) and escalating involvement of the adult child. Two major themes emerged from the data: Changing places and everlasting love. Adult children began to intervene when cognitive or physical declines compromised the safety and well-being of the older adult and began to assume responsibility for day-to-day needs. As disabilities intensified, adult children relied on siblings, friends, social services, and health care providers to assist in planning and implementing caregiving responsibilities. Deep respect and abiding love of the aging parent(s) sustained the adult child throughout the caregiving experience.     

A Systematic Review of Palliative Care Intervention Outcomes and Outcome Measures in Low-Resource Countries

Context

To meet the growing need for palliative care in low-resource countries, palliative care programs should be evidence based and contextually appropriate. This study was conducted to synthesize the current evidence to guide future programmatic and research efforts.

A volumetric prediction model for postoperative cyst shrinkage

Clinical Oral Investigations - With only limited information available on dimensional changes after jaw cyst surgery, postoperative cyst shrinkage remains largely unpredictable. We aimed to propose...