MicroRNAs enriched in hematopoietic stem cells differentially regulate long-term hematopoietic output

The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output.     

Effect of improved home ventilation on asthma control and house dust mite allergen levels

Background:  The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates.
Methods:  We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus . All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months.
Results:  At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: −2.6 to 29.8, P  = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9–40.1, P  = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline.
Conclusions:  The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.     

Prenatal diagnosis of autosomal dominant microcephaly and postnatal evaluation with magnetic resonance imaging

A case of fetal autosomal dominant microcephaly was prenatally diagnosed with ultrasonography in a woman with previously undiagnosed microcephaly. At the time of initial ultrasonographic assessment, the mother was identified to have a markedly small cranium, consistent with maternal microcephaly. The ultrasonographic examination showed the fetal head size to be four standard deviations below the mean for gestational age. Gestational dating from the other biometric parameters and from the last menstrual period was consistent with 31 weeks' gestation. Neurosonographic evaluation of the fetus revealed no obvious structural abnormalities. Serial ultrasonographic examinations at 35 and 38 weeks' gestation showed no changes in the fetal head size. A 2.64 kg male fetus was delivered at term. Neonatal assessment showed the fetal head circumference to be less than the second percentile for gestational age. Neurologic assessment of the neonate with magnetic resonance imaging showed abnormal development of the brain, with small cerebellar and cerebral hemispheres, and pachygyria. These images are compared with the magnetic resonance images of the mother. Our findings of maternal and fetal microcephaly are consistent with autosomal dominant microcephaly. To our knowledge, this is the first report of the prenatal diagnosis of autosomal dominant microcephaly.     

Altered maternal thyroid function: fetal and neonatal myocardial metabolism

The influence of the maternal thyroid status on the fetal and neonatal myocardial protein, carbohydrate and lipid metabolism was studied in rats. The neonates born of hypothyroid mothers could not survive beyond 8 days after birth. The offsprings born of hypothyroid mothers showed growth retardation, decreased level of heart mitochondrial protein, reduced myocardial free fatty acid (FFA) oxidation at birth and afterwards, low glucose oxidation by the heart at later fetal stages, and afterwards, despite low heart glycogen reserve, glucose oxidation was high. The offsprings born of hyperthyroid mothers showed stimulation in overall growth, increased myocardial FFA oxidation and increased 14C-glucose incorporation into glycogen as well as increased myocardial glucose oxidation during fetal stages. Results indicate that maternal thyroid hormones play an important role in the metabolic control of fetuses and neonates.     

Lateral rectus split in the management of Duane's Retraction Syndrome

This case reports Type I Duane's Retraction Syndrome with marked upshoot of the globe in adduction. An 18-year-old patient presented with complaints of not being able to move his left eye outwards since childhood. A 'Y' split of the lateral rectus muscle was performed in the affected eye. There was marked cosmetic and functional improvement in the patient which was stable after 6 months of follow-up. Y splitting of the lateral rectus muscle is a simple technique that can be used effectively in the treatment of marked upshoot or downshoot in Duane's Retraction Syndrome.     

Viscoexpression of anterior chamber cysticercus cellulosae

We report a case of anterior chamber Cysticercus cellulosae that was removed by viscoexpression.     

Use of the dopamine agonist cabergoline in the treatment of movement disorders

Cabergoline is an ergot-derived dopamine agonist used in the treatment of Parkinson's disease (PD). Both ergot and non-ergot-derived dopamine agonists directly stimulate dopamine receptors, unlike levodopa, which must undergo presynaptic breakdown to dopamine beforehand. Cabergoline has the longest half-life of the dopamine agonists currently available and is effective when given once-daily. It has been proposed that therapy with cabergoline may mimic physiological dopaminergic stimulation in PD by providing striatal intrasynaptic dopamine replacement. Its long half-life is likely to result in sustained rather than pulsatile dopaminergic stimulation, the preferred manner of treating PD. Placebo-controlled trials using cabergoline as an adjunctive therapy in PD have shown that it significantly reduces 'off' time, improves motor function and reduces levodopa requirements. Cabergoline has been shown to be as effective as other dopamine agonists in improving motor function as monotherapy in early PD, and a 5-year levodopa-controlled study indicates the superiority of cabergoline over levodopa in reducing dyskinesias. The efficacy of cabergoline in PD patients with nocturnal disabilities, restless leg syndrome and augmentation has also been demonstrated. Audits of the clinical efficacy of cabergoline indicate that it is well-tolerated and has an acceptable side effect profile.