[Fragile X syndrome: new therapeutic strategies]. / Fragiele-X-syndroom: nieuwe therapeutische strategieën.

BACKGROUND: Fragile X syndrome (fxs) is the most common hereditary cause of intellectual disability and autism spectrum disorders. Targeted treatment is currently lacking. In the past decades an enormous amount of knowledge has been obtained concerning the involved molecular pathways, introducing potential targets for disease modifying therapy.
AIM: To present an overview of the development of targeted treatment for fxs.
METHOD: Several important publications were collected and indexed.
RESULTS: While preclinical animal model studies with targeted interventions are promising, the translation to the clinic has been disappointing.
CONCLUSION: Targeted treatment for fxs is necessary and could be applied in other causes of autism spectrum disorders and intellectual disability. Factors relating to translation, study design and outcome measures are possibly contributing to the disappointing results. The clustering of patient care in a center of expertise is required to clinically implement future therapeutic strategies and to facilitate research. In addition, this improves patient care, one example being the recent medical guideline for children with fxs.

Early prenatal disruption; a foetus with features of severe limb body wall sequence, body stalk anomaly and amniotic bands.

Disruption in early pregnancy can cause severe and multiple congenital anomalies in a foetus. Three sequences, Limb-body wall complex (LBWC), amniotic band sequence (ABS) and body-stalk anomaly (BSA) are thought to be caused by disruption. This case report describes a foetus with severe multiple congenital anomalies, that fit the diagnoses of all three sequences, which might advocate these syndromes are a spectrum of one sequence.

Development of a new grading system to assess the foster performance of lactating sows.

Increasing litter size has created the need for more sophisticated, accurate, and welfare-oriented systems for assessing the foster performance of lactating sows. The estimation of milk yield alone is not sufficient for meeting these requirements. Therefore, the aim of the current study was to develop a grading system for assessing the foster performance of lactating sows that can be easily applied in commercial farm practice. Data were collected in two German conventional farrow-to-feeder farms with a total sample size of 639 sows (4.05 ± 2.86 parities) and 1 728 litters. Besides general performance data, the piglets were weighed individually within the first 24 hours after birth and at the peak of lactation (day 18.22 ± 2.48). Based on these data, we proposed a new score referring to the milk score (MS). This score was compared with the commonly used formula for estimating milk yield (est. MY), which solely involves litter weight gain and litter size. The improvement of the developed MS allowed us to distinguish between the birth and foster performances of the lactating sows through considering cross-fostering, litter size, individual piglet weights, and piglet mortality during lactation. Both scores showed a similar progression across parities. It was found that litter size had a significant impact on the performance of lactating sows. A high est. MY was found to be associated with a significantly higher number of piglets per litter (15.79 ± 2.20), lower weight gain per piglet, and increased piglet mortality during lactation compared with sows with high MS, which showed a smaller litter size (13.51 ± 2.18) (P < 0.05). The focus on smaller litter size indicates a performance limitation, which seems to be related to the average teat number of 13-15 teats per sow. We recommend the consideration of the number of functional teats, because a litter size above it will not result in a sow having higher foster performance. In conclusion, as an extension of the common est. MY calculation, the MS considers cross-fostering as current farm-management practice when dealing with larger litters. Our recommendations emphasise the importance of an MS which indicates smaller litter size, higher piglet weight gain, and lower piglet mortality during lactation; these factors are related to an improvement in animal welfare for sows and piglets. Moreover, the presented MS could be used to develop a management tool for farmers to assess the foster performance of lactating sows, considering individual farm-management practices.

Hypermethylation of the p16 gene in normal oral mucosa of smokers.

The oral cavity is the sixth most common anatomical localization of head and neck carcinoma in men. Detection of oral carcinomas in the early asymptomatic stages improves cure rates and the quality of life. Tobacco smoking and alcohol drinking are the most important known risk factors for the development of head and neck tumors, suggesting that the exposure to these risk factors may increase the predisposition for genetic and epigenetic alterations, such as DNA methylation. The presence of methylated CpG islands in the promoter region of human genes can suppress their expression due to the presence of 5-methylcytosine that interferes with the binding of transcription factors or other DNA-binding proteins repressing transcription activity. Hypermethylation leading to the inactivation of some tumor suppressor genes, such as p16, has been pointed out as an initial event in head and neck cancer. Our aim was to evaluate an early diagnostic method of oral pre-cancerous lesions through the analysis of methylation of the p16 gene. DNA samples from normal oral mucosa and posterior tongue border from 258 smokers, without oral cancer, were investigated for the occurrence of p16 promoter hypermethylation. The methylation status of the p16 gene was analyzed using MS-PCR (methylation-sensitive restriction enzymes and PCR amplification), MSP (Methylation-specific PCR) or direct DNA sequence of bisulfite modified DNA. Hyper-methylation was detected in 9.7% (25/258) of the cases analyzed. These findings provide further evidence that epigenetic alteration, leading to the inactivation of the p16 tumor suppressor gene is an early event that might confer cell growth advantages contributing to the tumorigenic process. Thus, the detection of abnormal p16 methylation pattern may be a valuable tool for early oral cancer detection.

Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy.

Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies.

Relationship of inflammatory markers and pain in patients with head and neck cancer prior to anticancer therapy

Pain is a common symptom in patients with cancer, including those with head and neck cancer (HNC). While studies suggest an association between chronic inflammation and pain, levels of inflammatory cytokines, such as C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α), have not been correlated with pain in HNC patients who are not currently undergoing anticancer treatment. The purpose of this study was to examine the relationship between these inflammatory markers and perceived pain in HNC patients prior to anticancer therapy. The study group consisted of 127 HNC patients and 9 healthy controls. Pain was assessed using the Brief Pain Inventory (BPI), and serum levels of CRP and TNF-α were determined using the particle-enhanced turbidimetric immunoassay (PETIA) and ELISA techniques, respectively. Patients experiencing pain had significantly higher levels of CRP (P<0.01) and TNF-α (P<0.05) compared with controls and with patients reporting no pain. There were significantly positive associations between pain, CRP level, and tumor stage. This is the first study to report a positive association between perceived pain and CRP in HNC patients at the time of diagnosis. The current findings suggest important associations between pain and inflammatory processes in HNC patients, with potential implications for future treatment strategies.