Identification of the Photoreceptor Transcriptional Co-Repressor SAMD11 as Novel Cause of Autosomal Recessive Retinitis Pigmentosa.

Retinitis pigmentosa (RP), the most frequent form of inherited retinal dystrophy is characterized by progressive photoreceptor degeneration. Many genes have been implicated in RP development, but several others remain to be identified. Using a combination of homozygosity mapping, whole-exome and targeted next-generation sequencing, we found a novel homozygous nonsense mutation in SAMD11 in five individuals diagnosed with adult-onset RP from two unrelated consanguineous Spanish families. SAMD11 is ortholog to the mouse major retinal SAM domain (mr-s) protein that is implicated in CRX-mediated transcriptional regulation in the retina. Accordingly, protein-protein network analysis revealed a significant interaction of SAMD11 with CRX. Immunoblotting analysis confirmed strong expression of SAMD11 in human retina. Immunolocalization studies revealed SAMD11 was detected in the three nuclear layers of the human retina and interestingly differential expression between cone and rod photoreceptors was observed. Our study strongly implicates SAMD11 as novel cause of RP playing an important role in the pathogenesis of human degeneration of photoreceptors.

[Effects of education and strength training on functional tests among older people with osteoarthritis]. / Programas de Educación en Salud y Entrenamiento de la Fuerza en adultos mayores con artrosis de cadera leve a moderada.

BACKGROUND: Hip and knee osteoarthritis are important causes of pain and disability among older people. Education and strength training can alleviate symptoms and avoid functional deterioration. AIM: To assess muscle strength, fall risk and quality of life of older people with osteoarthritis and the effects of physiotherapy education and strength training on these variables. MATERIAL AND METHODS: Thirty participants aged 78 ± 5 years (63% women) were randomly assigned to receive physiotherapy (Controls), physiotherapy plus education (Group 1) and physiotherapy plus strength training (group 2). At baseline and after 16 weeks of intervention, patients were evaluated with the Senior Fitness Test, Timed Up and Go and Quality of Life score short form (SF-36). RESULTS: During the intervention period, Senior Fitness Test and Timed Up and Go scores improved in all groups and SF-36 did not change. The improvement in Senior Fitness Test and Timed Up and Go was more marked in Groups 1 and 2 than in the control group. CONCLUSIONS: Education and strength training improve functional tests among older people with osteoarthritis.

Programas de Educación en Salud y Entrenamiento de la Fuerza en adultos mayores con artrosis de cadera leve a moderada / Effects of education and strength training on functional tests among older people with osteoarthritis

Background: Hip and knee osteoarthritis are important causes of pain and disability among older people. Education and strength training can alleviate symptoms and avoid functional deterioration. Aim: To assess muscle strength, fall risk and quality of life of older people with osteoarthritis and the effects of physiotherapy education and strength training on these variables. Material and Methods: Thirty participants aged 78 ± 5 years (63% women) were randomly assigned to receive physiotherapy (Controls), physiotherapy plus education (Group 1) and physiotherapy plus strength training (group 2). At baseline and after 16 weeks of intervention, patients were evaluated with the Senior Fitness Test, Timed Up and Go and Quality of Life score short form (SF-36). Results: During the intervention period, Senior Fitness Test and Timed Up and Go scores improved in all groups and SF-36 did not change. The improvement in Senior Fitness Test and Timed Up and Go was more marked in Groups 1 and 2 than in the control group. Conclusions: Education and strength training improve functional tests among older people with osteoarthritis.

Association of PPARG2 Pro12Ala variant with larger body mass index in Mestizo and Amerindian populations of Mexico.

Previous studies have sought to associate the Pro12Ala variant of the peroxisome proliferator-activated receptor gamma2 (PPARG2) gene with type 2 diabetes, insulin resistance, and obesity, with controversial results. We have determined the Pro12Ala variant frequency in 370 nondiabetic Mexican Mestizo subjects and in five Mexican Amerindian groups and have investigated its possible association with lipid metabolism, insulin serum levels, and obesity in three of these populations. Two independent case-control studies were conducted in 239 nondiabetic individuals: 135 case subjects (BMI > or = 25 kg/m2) and 104 control subjects (BMI < 25 kg/m2). The PPARG2 Ala12 allele frequency was higher in most Amerindian populations (0.17 in Yaquis, 0.16 in Mazahuas, 0.16 in Mayans, and 0.20 in Triquis) than in Asians, African Americans, and Caucasians. The Pro12Ala and Ala12Ala (X12Ala) genotypes were significantly associated with greater BMI in Mexican Mestizos and in two Amerindian groups. X12Ala individuals had a higher risk of overweight or obesity than noncarriers in Mestizos (OR = 3.67; 95% CI, 1.42-9.48; p = 0.007) and in Yaquis plus Mazahuas (OR = 3.21; 95% CI, 1.27-8.11; p = 0.013). Our results provide further support of the association between the PPARG2 Ala12 allele and risk of overweight or obesity in Mestizos and two Amerindian populations from Mexico.

Differential effects of obesity with and without hyperinsulinemia on plasma lipoprotein(a) concentrations in men.

To determine the association of in vivo concentrations of insulin, obesity, and gender with lipoprotein(a) [Lp(a)] levels, we used a cross-sectional population-based survey of a multistage random sample of the Mexico City adult population. We studied 423 normoglycemic, normotensive subjects from an original sample of 825, comprised of 239 men and 189 women with a mean age of 38.6 years (range, 17 to 90). All subjects were divided into 8 groups according to body mass index, fasting insulin, and gender. Lp(a) concentrations (mg/dL) were similar in obese women with and without high insulin levels (19.9 v 18.6), but hyperinsulinemic obese men had significantly lower Lp(a) levels than normoinsulinemic obese men (7.9 v 29.4). In addition, the proportion of obese men with Lp(a) concentrations of > or = 30 mg/dL was significantly higher in the normoinsulinemic than in the hyperinsulinemic (29.2% v 0.0%). The frequency distribution of Lp(a) levels was shifted to a lower range in hyperinsulinemic men compared with normoinsulinemic men. Our results show that in men, hyperinsulinemic obesity is associated with low Lp(a) levels, while obesity with normoinsulinemia is related to increased Lp(a) concentration. These observations were not found in women. These findings may explain the conflicting results reported by several studies.

[Insulin resistance: an etiological factor in essential arterial hypertension and coronary cardiopathy]. / Resistencia a la insulina: factor etiológico de la hipertensión arterial esencial y de la cardiopatía coronaria.

Insulin resistance has been implicated in the pathogenesis of essential hypertension. Studies from other countries discovered insulin resistance; in people with essential hypertension in was also associated with obesity, however, insulin resistance was found in lean people too. In obesity, insulin resistance occurs secondarily to many physiopathological states and circulating factors which adversely affects insulin action. The metabolic abnormality in this action was mainly found in relation to abdominal fat; in other cases, insulin resistance was found to be inherited. Hyperinsulinaemia can actually increase blood pressure and is associated with venous and arterial thrombosis and it also rises lipid levels. It is interesting too that insulin resistance and hyperinsulinaemia are associated with impaired fibrinolysis through high levels of fibrinogen and plasminogen activator inhibitor of endothelial type and in identifying individuals prone to myocardial infarction. Some antihypertensive drugs like beta-blockers, methyl-dopa and diuretics increase insulin resistance, while angiotensin converting enzyme-inhibitors have not shown any adverse metabolic affects. Alfa-1-blocker were beneficial and alfa-2-agonists were neutral, whereas calcium channel-antagonists are still in controversy. Treatment should be designed to improve the metabolic state; physical exercise, a diet rich in fruit, vegetable and rott vegetables, the reduction of abdominal fat and, finally, the use of antihypertensive drugs which decrease insulin resistance would be expected to reverse hyperinsulinaemia. Biguanides like metformin have also been found to reduce insulin resistance.

[The diagnosis of Cushing's disease by the nocturnal dexamethasone administration test]. / Diagnóstico de la enfermedad de Cushing mediante la prueba de administración nocturna de dexametasona.

Prospective study performed at the General Hospital, National Medical Center, XXI Century, Endocrinology Ward, Mexico-City, to compare the diagnostic sensitivity in Cushing's disease of the oral high doses (8 mg) dexametazone suppression test in single doses with nocturnal administration (DXM-N) and the classic doses of two days (DXM-C). Fourteen patients with hypercortisolism were studied; on thirteen the hypophyseal origin was surgical confirmed. Sensitivity of high doses of oral dexametazone test was proved by using serial samples of serum cortisol; the Fisher test was used for analysis of the suppression of serum cortisol after the test was done.