Genetic screening in patients with ovarian dysfunction

Ovarian dysfunction, including premature ovarian insufficiency and decreased ovarian reserve, affects the ovarian reserve and is one of the leading causes of female infertility. More and more cases of ovarian dysfunction are associated with genetic factors. Here, we identified eight potential variants in five genes (MSH4, HFM1, SYCE1, FSHR, and C14orf39) from six independent families by exome sequencing. The splice-site variants in SYCE1 and MSH4 affected canonical splicing isoforms, leading to missing protein domains or premature termination. Our findings expand the mutational spectrum of ovarian dysfunction and provide potential biomarkers for future genetic counseling and for more personalized treatments. Exome sequencing was shown to be a useful tool to better dissect the genetic basis for ovarian dysfunction and yielded a genetic diagnosis in about 5.0% (6/124) of cases in a cohort of 124 patients with ovarian dysfunction.     

Emmetropic eye growth in East Asians and non-East Asians

Purpose

To compare axial length (AL) growth curves in East Asian (EA) and non-EA emmetropes.

Methods

A meta-regression of 28 studies with emmetrope-specific AL data (measured with optical biometry) was performed. Emmetropia was defined as spherical equivalent refraction (SER) between −0.50 and +1.25 D, determined under cycloplegia if the mean age was ≤20 years. The AL growth curve (mean AL vs. mean age) was first fitted to the full dataset using a weighted nonlinear mixed-effects model, before refitting the model with ethnicity as a two-level grouping variable (EA vs. non-EA). Ethnic differences in growth curve parameters were tested using the Wald test.

Results

A total of 3331 EA and 1071 non-EA emmetropes (mean age: 6.5–23.1 years) were included. There was no evidence of an ethnic difference in either final AL (difference: 0.15 mm, 95% CI: −0.04 to 0.35 mm, p = 0.15) or initial AL, as represented by the amount that the final AL needed to be offset to obtain the y-intercept (difference: −2.77 mm, 95% CI: −10.97 to 5.44, p = 0.51). Likewise, AL growth rate (curve steepness) did not differ between ethnic groups (difference: 0.09, 95% CI: −0.13 to 0.31, p = 0.43). Collectively, AL growth rate decreased from 0.24 mm/year at 6 years of age to around 0.05 mm/year at 11 years of age, after which it dipped below the repeatability of optical biometry (±0.04 mm) and practically plateaued around 16 years of age (final AL: 23.60 mm).

Conclusions

EA and non-EA emmetropes have comparable AL growth curves.     

Coronary heart disease and depression in the elderly--a population- based study

BACKGROUND: Growing interest is nowadays focused on the quality of life of elderly people who survive with chronic diseases. Coronary heart disease (CHD) is one of the most common diseases among the elderly and may have an unfavourable impact on the patient's emotional well-being. OBJECTIVES: We aimed to describe the prevalence of depression and the occurrence of depressive symptoms among elderly CHD patients, with a special emphasis on the relations between depression and the severity of CHD, and to find out the possible association between CHD and depression. METHODS: The study was carried out at the health centre of the municipality of Lieto, in south-west Finland. The study population consisted of 488 community-dwelling men and 708 women, over 64 years old, from among whom the participants with CHD (89 men and 73 women) were selected, and for whom 178 male and 146 female sex- and age- matched controls (free of CHD) were drawn from the population. CHD patients were selected on the basis of the presence of angina pectoris or a past myocardial infarction. Depressive symptoms were measured with the Zung Self-rating Depression Scale. Depression was described in relation to the severity of dyspnoea and chest pain among patients. The associations between depression and age, health, health behaviour, drugs, functional ability and social, psychosocial and environmental factors were analysed by logistic regression analyses. RESULTS: The prevalence of depression was 29% among male patients and 20% among female patients. Depression was significantly more common among male CHD patients than among male controls (P = 0.011). Among women, depression was not associated with CHD. Earlier, depression had gone undiagnosed among many CHD patients and controls, especially male patients. Among male CHD patients, depression was associated with more severe dyspnoea, but no similar association was found among female CHD patients. Among men the occurrence of CHD, physical disability, widowhood or divorce, and among women previous clinical depression, physical disability and the use of angiotensin-converting enzyme (ACE) inhibitors, were associated with depression. CONCLUSION: Depression is common among patients with CHD. It seems that CHD is not an independent factor in the aetiology of depression among the elderly. The association of CHD with depression among men is explained by the acute or chronic psychic stress caused by CHD. It may be that the more complicated the patient's CHD, the more probable is the presence of depression.      

The National Stem Cell Therapy Patient Registry of Malaysia—Measuring Clinical Outcomes of Stem Cell Therapy

Very few registries worldwide focus on clinical outcomes of stem cell therapy (SCT) as the large number of applications and rapid development of the field complicates registry design considerably. The National Stem Cell Therapy Patient Registry of Malaysia aims to accommodate this by using a main protocol which covers the overall design and administration of the registry, and condition-specific sub-protocols which deal with outcome measures. The registry will start with a few sub-protocols covering existing modes of SCT in Malaysia, with new sub-protocols released periodically as the need arises.     

Mechanism of the Specific Neuronal Toxicity of a Type I Ribosome-Inactivating Protein, Trichosanthin

The aim was to study the mechanism of neuronal toxicity, the cellular pathway, and the glial cell reactions induced by trichosanthin (TCS), a type I ribosome-inactivating protein (RIP). Ricin A chain (RTA) was included for comparison. TCS, RTA, and fluorescein isothiocyanate (FITC)-labeled TCS and RTA were separately injected into rat eyes. Saline or pure FITC was used as the control. Electron microscopy, confocal microscopy, and lectin and immunohistochemical staining were used to study the neurotoxic mechanism. TCS mainly induced apoptosis by causing degeneration of the mitochondria. TCS was able to enter the Müller and pigment cells. It caused a change in cell number of the following types of glial cells: a decrease in Müller cells, an increase in astrocytes, and little change in microglia. In contrast, RTA mainly induced necrosis and entered vascular endothelial cells. Astrocyte and microglia reactions were stronger in the RTA-treated retinas than those in the TCS-treated retinas. In conclusion, TCS appears to selectively enter and destroy Müller and pigment epithelia cells, which subsequently induce the death of photoreceptors. Degeneration of mitochondria is involved in the pathways of apoptosis of the photoreceptors caused by TCS. In sharp contrast, RTA can enter vascular endothelial cells and damage the vascular endothelium, resulting in retinitis and necrosis.     

Acute seizure-related hospitalizations in children with newly diagnosed epilepsy

Hospitalizations due to breakthrough seizures were studied in children with newly diagnosed epilepsy to evaluate (1) risk factors associated with such admissions, in particular the withholding of medication and subtherapeutic dose of anticonvulsants, and (2) the impact of the unscheduled hospitalization on subsequent seizure outcome. We recruited patients aged less than 18 years with newly diagnosed epilepsy who presented to the pediatric department in Tuen Mun Hospital between January 2002 and December 2003. Patients with acute seizure-related hospitalization within 1 year after diagnosis were included as cases (n = 36); patients with no such hospitalization were included as controls (n = 86). Treatment effect was analyzed at the last follow-up visit before January 2005. Significant univariate association was observed between seizure-related hospitalization and age at seizure onset (OR = 0.91, 95% CI 0.84, 1), idiopathic epilepsy (OR = 0.35, 95% CI 0.15, 0.81), no antiepileptic drug (OR = 3.67, 95% CI 1.51, 8.18), and subtherapeutic doses of antiepileptic drug (OR = 9.9, 95% CI 2.2, 43.8). Independent risk factors of such hospitalizations were etiology of epilepsy, no antiepileptic drug, subtherapeutic dose of antiepileptic drug, and history of febrile convulsion. Sixty-four percent of the cohort was seizure-free. Acute seizure-related hospitalization was associated with less favorable outcome (OR = 3.79, 95% CI 1.48, 9.26).