Effects of perinatal stress and drug abuse on maternal behavior and sensorimotor development of affected progeny.

Methamphetamine (MA) is an addictive psychostimulant with significant potential for abuse. Previous rat studies have demonstrated that MA use during pregnancy impairs maternal behavior and induced delayed development of affected pups. The offspring of drug-addictive mothers were often neglected and exposed to neonatal stressors. The present study therefore examines the effect of perinatal stressors combined with exposure to prenatal MA on the development of pups and maternal behavior. Dams were divided into three groups according to drug treatment during pregnancy: controls (C); saline (SA, s.c., 1 ml/kg); MA (s.c., 5 mg/ml/kg). Litters were divided into four groups according to postnatal stressors: controls (N); maternal separation (S); maternal cold-water stress (W); maternal separation plus cold-water stress (SW). The pup-retrieval test showed differences among postnatally stressed mothers and non-stressed controls. The righting reflex on a surface revealed delayed development of pups prenatally exposed to MA/SA and postnatal stress. Negative geotaxis and Rotarod results confirmed that the MA group was the most affected. Overall, our data suggests that a combination of perinatal stress and prenatal MA can have a detrimental effect on maternal behavior as well as on the sensorimotor development of pups. However, MA exposure during pregnancy seems to be the decisive factor for impairment.

The effect of neonatal maternal stress on plasma levels of adrenocorticotropic hormone, corticosterone, leptin, and ghrelin in adult male rats exposed to acute heterotypic stressor.

Activation of the hypothalamic-pituitary-adrenal (HPA) axis is important for maintenance of homeostasis during stress. Recent studies have shown a connection between the HPA axis and adipose tissue. The present study investigated the effect of acute heterotypic stress on plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), leptin, and ghrelin in adult male rats with respect to neonatal maternal social and physical stressors. Thirty rat mothers and sixty of their male progeny were used. Pups were divided into three groups: unstressed control (C), stressed by maternal social stressor (S), stressed by maternal social and physical stressors (SW). Levels of hormones were measured in adult male progeny following an acute swimming stress (10 min) or no stress. ELISA immunoassay was used to measured hormones. The ACTH and CORT levels were significantly increased in all groups of adult progeny after acute stress; however, CORT levels were significantly lower in both neonatally stressed groups compared to controls. After acute stress, plasma leptin levels were decreased in the C and SW groups but increased in the S group. The data suggest that long-term neonatal stressors lead to lower sensitivity of ACTH receptors in the adrenal cortex, which could be a sign of stress adaptation in adulthood. Acute stress in adult male rats changes plasma levels of leptin differently relative to social or physical neonatal stressors.

[Outcomes of Trifocal Toric Lens Implantation in Cataract Patients]. / Výsledky implantace trifokální torické cocky u pacientu s kataraktou.

AIM: The aim of our study was to evaluate the outcome of cataract surgeries with implantation of intraocular trifocal toric lens, and to study the accuracy of astigmatism correction, lens rotational stability, and safety of the procedures. PATIENTS AND METHODS: Our study comprised 22 eyes of 16 patients who underwent unilateral or bilateral implantation of AT LISA tri toric 939MP, or its implantation in combination with AT LISA tri 839MP. Mean patient age was 58 ± 11 years (39 to 75 years). Mean follow-up was 5 months. Evaluated parameters were preoperative and postoperative decimal corrected (CDVA) and uncorrected (UDVA) distance visual acuity. Uncorrected near (UNVA) and intermediate (UIVA) visual acuity was obtained with Jaeger optotypes. Furthermore, we studied manifest refraction, amount of corneal astigmatism, implanted lens position, and potential complications. Using two types of questionnaires we surveyed patients on their subjective satisfaction with vision. RESULTS: Spherical equivalent changed from preoperative -1.32 ± 4.05 D (-9.25 to 4.00 D) to postoperative -0.23 ± 0.21 D (-0.75 to 0.00 D). Preoperative corneal astigmatism was -1.97 ± 0.76 D (-4.02 to -1.01 D), manifest astigmatism was -1.70 ± 1.26 D. After the surgery, manifest astigmatism significantly improved to -0.34 ± 0.37 D (p<0.001). Mean monocular UDVA increased from 0.26 ± 0.18 (0.05 to 0.60) to postoperative 0.88 ± 0.13 (0.60 to 1.00) (p<0.001). CDVA also improved significantly, from 0.57 ± 0.24 to a final value of 1.02 ± 0.07 (p<0.001). Mean postoperative monocular UNVA was Jaeger 1-2, UIVA corresponded to Jaeger 3-4.No serious complications were recorded. Based on the outcome of questionnaires, all patients are satisfied with their vision and they are independent of spectacles. CONCLUSION: In the present study we have obtained very good functional outcomes of vision at far, near and intermediate in cataract patients after trifocal AT LISA tri toric lens implantation. Also, total astigmatism in studied eyes was substantially reduced. The treatment led to a high subjective satisfaction of patients and to their independence of spectacles. KEY WORDS: trifocal toric intraocular lens, cataract, astigmatism, refractive outcomes, patient subjective satisfaction.

Molecular genetic analysis in 14 Czech Kabuki syndrome patients is confirming the utility of phenotypic scoring.

Kabuki syndrome (KS) is a dominantly inherited disorder mainly due to de novo pathogenic variation in KMT2D or KDM6A genes. Initially, a representative cohort of 14 Czech cases with clinical features suggestive of KS was analyzed by experienced clinical geneticists in collaboration with other specialties, and observed disease features were evaluated according to the 'MLL2-Kabuki score' defined by Makrythanasis et al. Subsequently, the aforementioned genes were Sanger sequenced and copy number variation analysis was performed by MLPA, followed by genome-wide array CGH testing. Pathogenic variants in KMT2D resulting in protein truncation in 43% (6/14; of which 3 are novel) of all cases were detected, while analysis of KDM6A was negative. MLPA analysis was negative in all instances. One female patient bears a 6.6 Mb duplication of the Xp21.2-Xp21.3 region that is probably disease causing. Subjective KS phenotyping identified predictive clinical features associated with the presence of a pathogenic variant in KMT2D. We provide additional evidence that this scoring approach fosters prioritization of patients prior to KMT2D sequencing. We conclude that KMT2D sequencing followed by array CGH is a diagnostic strategy with the highest diagnostic yield.

Highly preferential association of NonF508del CF mutations with the M470 allele.

BACKGROUND: On the basis of previous findings on random individuals, we hypothesized a preferential association of CF causing mutations with the M allele of the M470V polymorphic site of the CFTR gene. METHODS: We have determined the M/V-CF mutation haplotype in a series of 201 North East Italian and 73 Czech CF patients who were not F508del homozygotes, as F508del was already known to be fully associated with the M allele. RESULTS: Out of 358 not F508del CF genes, 84 carried the V allele and 274 the less common M allele. In the N-E Italian population, MM subjects have a risk of carrying a CF causing mutation 6.9x greater than VV subjects when F508del is excluded and 15.4x when F508del is included. In the Czech population a similar, although less pronounced, association is observed. CONCLUSIONS: Besides the possible biological significance of this association, the possibility of exploiting it for a pilot screening program has been explored in a local North East Italian population for which CF patients were characterized for their CF mutation. General M470V genotyping followed by common CF mutation screening limited to couples in which each partner carries at least one M allele would need testing only 39% of the couples, which contribute 89% of the total risk, with a cost benefit.