Sleep disorders and the eye

During the past decade, associations between sleep disorders and certain ophthalmologic disorders have been increasingly recognized. To review the literature on these important associations, we conducted a PubMed search using combinations of the following terms: sleep disorders, sleep apnea, circadian rhythm disorder, continuous positive airway pressure, eye disease, floppy eyelid syndrome, glaucoma, ischemic optic neuropathy, papilledema, nocturnal lagophthalmos, and vision loss. We limited our search to articles published in English that involved human participants. All available dates were included. One of the most common sleep disorders, obstructive sleep apnea, has been associated with a variety of eye diseases, including glaucoma, nonarteritic anterior ischemic optic neuropathy, floppy eyelid syndrome, papilledema, and continuous positive airway pressure-associated eye complications. Nocturnal lagophthalmos manifests during sleep and is defined as the failure to fully close the eyelids at night. Finally, blindness is associated with increased risk of circadian rhythm disorders. On the basis of the existing published literature, we discuss these rarely recognized associations, potential pathophysiologic mechanisms, and the effect these associations have on the clinical management of patients. The knowledge of these associations is important for the primary care physician, ophthalmologist, and sleep physician so that underlying sleep disorders or ophthalmologic disorders can be detected.     

Coping simultaneously with 2 stressors: immigrants with ovarian cancer

The dual adjustment to being a cancer patient and an immigrant involves major changes in life and might be a severe experience. This study set out to describe the experience of women who have come to Israel from the former Soviet Union and are coping with ovarian cancer. It focused on illness narratives as presented by 8 patients with cancer at stage III. Our findings indicated that the dual process might have different implications according to the meaning attributed by the patient to the illness situation. Viewing the illness as one more burden among other difficulties, such as language barrier, was a prism through which patients experienced their vulnerability in coping with the illness. Alongside a helplessness pattern, we found indications of interviewees' perceiving advantages in their status as immigrant cancer patients, by dealing with that problem alongside other difficulties. They showed a "fighting spirit" in coping with the illness. Immigration can have a moderating effect on patients' experiences, and the 2 stressors do not necessarily accumulate. Our findings indicate that patients' meaning to the illness experience was a "litmus test," which indicated the way patients would describe their coping stages. This may have potential as a clinical marker of psychological vulnerability.     

The relationship between physicians' self-reported target fasting blood glucose levels and metabolic control in type 2 diabetes. The QuED Study Group--quality of care and outcomes in type 2 diabetes

OBJECTIVE: To investigate the relationship between beliefs of physicians relative to intensive metabolic control in type 2 diabetes and levels of HbA1c obtained in a sample of their patients. RESEARCH DESIGN AND METHODS: Physicians' beliefs were investigated through a questionnaire sent to a sample of self-selected clinicians participating in a nationwide initiative aimed at assessing the relationship between the quality of care delivered to patients with type 2 diabetes and their outcomes. At the same time, physicians were asked to collect clinical data on a random sample of their patients, stratified by age (<65 vs. > or = 65 years). Mean HbA1c levels in the study population were thus evaluated according to target fasting blood glucose (FBG) used by their physicians. RESULTS: Of 456 physicians, 342 (75%) returned the questionnaire. Among the responders, 200 diabetologists and 99 general practitioners (GPs) recruited 3,297 patients; 2,003 of whom were always followed by the same physician and 1,294 of whom were seen by different physicians in the same structure on different occasions. Only 14% of the respondents used target FBG levels < or = 6.1 mmol/l, whereas 38% pursued values >7.8 mmol/l, with no statistically significant difference between diabetologists and GPs. The analysis of the relationship between FBG targets and metabolic control, restricted to those patients always seen by the same physician, showed a strong linear association, with mean HbA1c values of 7.0 +/- 1.6 for patients in the charge of physicians pursuing FBG levels < or = 6.1 mmol/l and 7.8 +/- 1.8 for those followed by physicians who used target values >7.8 mmol/l. After adjusting for patients' and physicians' characteristics, the risk of having HbA1c values > 7.0% was highly correlated with physicians' beliefs. Patients followed by different physicians in the same unit showed a risk of inadequate metabolic control similar to that of patients followed by physicians adopting a nonaggressive policy. CONCLUSIONS: Doctors adopt extremely heterogeneous target FBG levels in patients with type 2 diabetes, which in turn represent an important independent predictor of metabolic control. To improve patient outcomes, physicians-centered educational activities aimed at increasing the awareness of the potential benefits of a tight metabolic control in patients with type 2 diabetes are urgently needed.     

A new era for fibrodysplasia ossificans progressiva: a druggable target for the second skeleton

Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic condition that leads to the formation of a second (heterotopic) skeleton, and is the most catastrophic disorder of heterotopic ossification in humans. Throughout childhood and early adult life, FOP progressively immobilizes all of the joints of the normotopic skeleton, rendering movement impossible. At present, there is no effective prevention or treatment. Recently, a recurrent mutation in the glycine-serine activation domain of the activin receptor IA/activin-like kinase-2, a bone morphogenetic protein type I receptor, was reported in all sporadic and familial cases of classic FOP, making this one of the most highly specific disease-causing mutations in the human genome. The discovery of the FOP gene establishes a critical milestone in understanding FOP, reveals a highly conserved druggable target in the TGF-beta/bone morphogenetic protein signaling pathway and compels therapeutic approaches for the development of small molecule signal transduction inhibitors for activin-like kinase-2. Effective therapies for FOP, and possibly for a vast array of more common conditions of heterotopic ossification, will be based on blocking activin-like kinase-2, a critical node in the BMP signaling pathway.     

Multi‐modal imaging for assessment of tissue‐engineered bone in a critical‐sized calvarial defect mouse model

Tissue‐engineered bone (TEB) analysis in vivo relies heavily on tissue histological and end‐point evaluations requiring the sacrifice of animals at specific time points. Due to differences in animal response to implanted tissues, the conventional analytical methods to evaluate TEB can introduce data inconsistencies. Additionally, the conventional methods increase the number of animals required to provide an acceptable statistical power for hypothesis testing. Alternatively, our non‐invasive optical imaging allows for the longitudinal analysis of regenerating tissue, where each animal acts as its own control, thus reducing overall animal numbers. In our 6 month feasibility study, TEB, consisting of a silk protein scaffold with or without differentiated mesenchymal stem cells, was implanted in a critical‐sized calvarial defect mouse model. Osteogenesis of the TEB was monitored through signal variation, using magnetic resonance imaging (MRI) and near‐infrared (NIR) optical imaging with IRDye® 800CW BoneTag^TM (800CW BT, a bone‐specific marker used to label osteogenically differentiated mesenchymal stem cells and mineralization). Histological endpoint measurements and computed tomography (CT) were used to confirm imaging findings. Anatomical MRI revealed decreased signal intensity, indicating mineralization, in the TEB compared to the control (i.e. silk scaffold only) at various growth stages. NIR optical imaging results demonstrated a signal intensity increase of the TEB compared to control. Interpretation of the imaging results were confirmed by histological analysis. Specifically, haematoxylin and eosin staining revealing de novo bone in TEB showed that 80% of the defect was covered by TEB, while only 40% was covered for the control. Taken together, these results demonstrate the potential of multi‐modal non‐invasive imaging to visualize and quantify TEB for the assessment of regenerative medicine strategies. Copyright © 2015 John Wiley & Sons, Ltd.     

Pinealectomy exaggerates and melatonin treatment suppresses neuroma formation of transected sciatic nerve in rats: gross morphological, histological and stereological analysis

At present, an intensive effort for prevention of neuroma formation following peripheral nerve section continues. It has been recently suggested that surgical pinealectomy (Px) induces elevation of the collagen content in the granulation tissue of a wound, while melatonin application after Px suppresses elevation of the collagen accumulation in the tissue. The aim of the present study was to assess whether melatonin had the ability to suppress collagen production and neuroma formation following peripheral nerve transection. A total of 40 male rats (four groups of 10) were left intact (intact controls) or sham operated (sham group), were Px, or were Px and given melatonin (Px + melatonin group). All animals underwent a surgical intervention consisting of right sciatic nerve neurectomy. After 4 wk, the animals were killed following intracardiac perfusion. Gross morphology of neuroma formation in the proximal nerve segment was examined and proximal neuroma evaluated. Macroscopic and microscopic findings revealed that Px caused a proliferation of connective tissue and large neuroma formation at the proximal ends of transected nerves. Stereological analysis showed that there was a statistically significant reduction in connective tissue content of the same region in Px animals treated with melatonin (P < 0.005). The results achieved in a rodent model of sciatic nerve neuroma formation showed that there was a positive correlation between macroscopic and microscopic observations, and that melatonin enhanced axonal regeneration presumably due to its inhibitory effect on neuroma formation.     

The effect of 3-year treatment with 0.25 mg/day of micronized 17beta-estradiol on cognitive function in older postmenopausal women

OBJECTIVES: To evaluate the effect of ultra-low-dose (0.25 mg/d) micronized 17beta-estradiol on cognitive function in older postmenopausal women. DESIGN: Randomized, placebo-controlled trial conducted for 3 years. SETTING: Academic health center in greater Hartford, Connecticut. PARTICIPANTS: Fifty-seven healthy, community-dwelling, older postmenopausal women. INTERVENTION: Women received 0.25 mg/d of micronized 17beta-estradiol (estrogen therapy (ET), n=32) or placebo (n=25); all women who had not had a hysterectomy received 100 mg/d of oral micronized progesterone for 2-week periods every 6 months. MEASUREMENTS: Neuropsychological measures of memory, language, mood, and executive function were collected at baseline, 3 months, and 36 months. Measures of executive function included the Controlled Oral Word Association Test, the Trail Making Test, and the Wisconsin Card Sorting Test. The Boston Naming Test was used to measure language skills. The Symbol Digit Modalities Test was used as a measure of sustained attention. Measures of memory included the Complex Figure Test, Fuld Object Memory Test, and a selected subtest from the Wechsler Memory Scale. Scores from the Geriatric Depression Scale and the Beck Anxiety Inventory were used to assess symptoms of depression. RESULTS: No differences were found between ET and placebo on any of the neurocognitive measures or depression instruments, nor were there any differences when the groups were stratified according to age. CONCLUSION: This small study, which had adequate power to detect change in some but not all domains of cognition tested, revealed that low-dose estrogen neither benefits nor harms cognitive function in older women after 3 years of treatment, but confirmation is needed from larger trials.