Can vergence training improve reading in dyslexics?

Background: Dyslexia affects 5%–8% of the population of the Western world. While reading, different eye movements are required. Compared to other persons, dyslexics have more and longer fixations, shorter saccade amplitude, a higher percentage of regression, and more fixation disparity when reading. In non-reading situations, dyslexics do not have more binocular problems than others. The aim of the present study was to investigate whether computerized orthoptic vergence training could improve reading ability for dyslexic children.

Methods: The study was conducted at Ängkärrskolan, Solna, an elementary school exclusively for dyslexic children. Twelve subjects, aged 13–14 years, were trained with RetCorr, a computerized vergence training program. Reading speed was assessed before and after treatment. The results were compared with an age-matched control group.

Results: The dyslexic subjects conducted on average 11.75 sessions (±2.53 SD) of orthoptic training over a 5-week period. On average, the number of words read per minute before training were 87.83 (±16.80 SD) and after training 95.58 words (±18.08 SD). The difference was statistically significant (p?=?0.0066). In the control group, the change was from 85.00 (±19.68 SD) words to 89.37 words (±19.71 SD) over the same time period. This difference was not significant (p?=?0.1235).

Discussion: Most scientists agree that dyslexia is mainly a phonological impairment. Nevertheless, the results show that vergence treatment might help dyslexics. Larger studies are required to provide guidance in this area.     

Overexpression of pro-inflammatory genes and down-regulation of SOCS-1 in human PTC and in hypoxic BCPAP cells

Hypoxia-inducible factor-1α (HIF-1α) is frequently overexpressed and activated in many cancer types. However, its regulation and function in thyroid carcinomas are only partially known. Aim of our study was to demonstrate that adaptation to the hypoxic micro-environment by human papillary thyroid carcinoma (PTC) cells, in the absence of leukocyte infiltrate, induces a “molecular inflammation” process characterized by the expression of a large set of genes normally involved in inflammation. To address this, tumor, peritumor or normal host tissue from eleven human PTC surgical samples, were separated by laser capture microdissection (LCMD) and studied by real-time quantitative PCR and Western blot. In such condition, we observed an increased expression and activation of HIF-1α, NF-kB and pro-inflammatory genes only in tumor tissues. Importantly, an anti-inflammatory gene such as SOCS-1 was markedly down-regulated in tumor tissue compared to surrounding normal host tissue. Similar results were found in fine-needle aspiration biopsy (FNAB)-derived specimens from PTC and in hypoxic human papillary thyroid tumor cell line, BCPAP. Moreover, we also detected an elevated expression of metalloproteinase-9 (MMP9) both in solid tumor and in hypoxic-treated BCPAP cells. Our findings reveal that, in human PTC tumor, hypoxic conditions are accompanied by up-regulation of pro-inflammatory genes, down-regulation of anti-inflammatory genes and increased expression of MMP9. We propose that a better understanding of the pro- and anti-inflammatory pathways involved in the “molecular inflammation” process even in the absence of leukocyte, may help to clarify progression toward malignancy and may prove useful for new anti-tumor strategy.     

Progression of phosphorylated α‐synuclein in Macaca fuscata

Prion‐like spreading of abnormal proteins is proposed to occur in neurodegenerative diseases, and the progression of α‐synuclein (α‐syn) deposits has been reported in the brains of animal models injected with synthetic α‐syn fibrils or pathological α‐syn prepared from patients with Parkinson''s disease (PD) and dementia with Lewy bodies (DLB). However, α‐syn transmission in nonhuman primates, which are more similar to humans, has not been fully clarified. Here, we injected synthetic human α‐syn fibrils into the left striatum of a macaque monkey (Macaca fuscata). At 3 months after the injection, we examined neurodegeneration and α‐syn pathology in the brain using α‐syn epitope‐specific antibodies, antiphosphorylated α‐syn antibodies (pSyn#64 and pSer129), anti‐ubiquitin antibodies, and anti‐p62 antibodies. Immunohistochemical examination with pSyn#64, pSer129, and α‐syn epitope‐specific antibodies revealed Lewy bodies, massive α‐syn‐positive neuronal intracytoplasmic inclusions (NCIs), and neurites in the left putamen. These inclusions were also positive for ubiquitin and p62. LB509, a human‐specific α‐syn antibody targeting amino acid residues 115–122, showed limited immunoreactivity around the injection site. The left substantia nigra (SN) and the bilateral frontal cortex also contained some NCIs and neurites. The left hemisphere, including parietal/temporal cortex presented sparse α‐syn pathology, and no immunoreactivity was seen in olfactory nerves, amygdala, hippocampus, or right parietal/temporal cortex. Neuronal loss and gliosis in regions with α‐syn pathology were mild, except for the left striatum and SN. Our results indicate that abnormal α‐syn fibrils propagate throughout the brain of M. fuscata via projection, association, and commissural fibers, though the progression of α‐syn pathology is limited.     

Clinical and cytogenetic characterization of 13 Dutch patients with deletion 9p syndrome: Delineation of the critical region for a consensus phenotype

The deletion 9p syndrome is caused by a constitutional monosomy of part of the short arm of chromosome 9. It is clinically characterized by dysmorphic facial features (trigonocephaly, midface hypoplasia, and long philtrum), hypotonia and mental retardation. Deletion 9p is known to be heterogeneous and exhibits variable deletion sizes. The critical region for a consensus phenotype has been reported to be located within a approximately 4-6 Mb interval on 9p22. In the present study, deletion breakpoints were determined in 13 Dutch patients by applying fluorescence in situ hybridization (FISH) and in some specific cases by array-based comparative genomic hybridization (array CGH). No clear genotype-phenotype correlation could be established for various developmental features. However, we were able to narrow down the critical region for deletion 9p syndrome to approximately 300 kb. A functional candidate gene for trigonocephaly, the CER1 gene, appeared to be located just outside this region. Sequence analysis of this gene in nine additional patients with isolated trigonocephaly did not reveal any pathogenic mutations.     

Laurin-Sandrow syndrome: review and redefinition

We report on a newborn infant with characteristics of Laurin-Sandrow syndrome (LSS). She had hypertelorism, flat nose with grooved collumella, "V" shaped mouth with thin lips, 7 well-recognized and fused digits and 1 additional postaxial bilateral appendix on each hand. The right and left feet had 12 and 11 toes, respectively, the 4 external ones were recognizable, and the rest were fused in a uniform mass but with independent nails. There was also a 2.3 cm-long digitiform appendix in the internal part of both feet. Radiographs showed seven metacarpals and seven metatarsals with similar morphology; both hands lacking thumbs. The four lateral-most toes had regular shaped phalanges and the rest were irregular. The left digitiform appendix had three bones and the right only two. Tibiae were shorter than fibulae. Central Nervous System examination showed an abnormally shaped olivary nucleus, cerebellar cortical heterotopias, gray matter ectopias in both spinal cord and hemispheric white matter, marked ventricular dilatation, and moderate diffuse white matter gliosis. Karyotype was 46XX. A complete necropsy study is presented and all reported cases are reviewed focusing on their phenotypic differences and their nosologic classification. We propose the entity LSS only in cases with symmetric tetrameric polysyndactyly, especially cup-shaped hands and mirror feet, in association with nasal anomalies.     

Persistence of apoptosis-resistant T cell-activating dendritic cells promotes T helper type-2 response and IgE antibody production

Antigen-specific T cell-mediated apoptosis of dendritic cells (DCs) represents a unique down-regulatory mechanism that prevents the continuous activation of T cells by antigen-loaded DCs; this regulatory mechanism is impaired in allergy and as a consequence a large proportion of DCs tends to escape apoptosis following cognate interaction with CD4(+) T cells. However, the biological relevance of greater numbers of apoptosis-resistant DCs to the development of allergic IgE-mediated reactions remained to be determined. Here, we sought to investigate the in vitro and in vivo regulatory features of apoptosis-resistant DCs and to assess their role in host sensitization. Freshly isolated CD11c(+/hi)B220(-)DCs from ovalbumin (OVA)-sensitized, OVA-immunized and na?ve Balb/c mice were cultured with OVA-specific T cells and levels of T cell-mediated DCs apoptosis assessed by flow cytometry. Surviving apoptosis-resistant DCs were then recovered and subsequently co-cultured with OVA-specific CD62L(hi)CD44(low) na?ve T cells or passively transferred into naive syngenic recipients. In vitro profile of DC and T cell lymphokine production, chemokine receptors expression and in vivo, post-adoptive DC transfer T helper (T(H)) and IgE responses were assessed. Apoptosis-resistant DCs showed differential regulatory properties compared to their freshly isolated counterpart independent of the sensitization status of the donor. When co-cultured with na?ve OVA-specific T cells, apoptosis-resistant DCs from either sensitized or immunized mice induced T cells that produced increased levels of IL-4 and reduced levels of IFN-gamma and showed increased expression of T(H)-2 related CCR4 and CCR8 chemokine receptors. Finally, adoptive transfer of apoptosis-resistant DCs, induced higher levels of OVA-specific IgE responses in absence of antigen challenge in syngenic recipients compared to freshly isolated DCs from both sensitized and immunized mice. These data would suggest that sensitization-associated increased numbers of apoptosis-resistant T cell-activating DCs contribute to the generation/maintenance of IgE-mediated allergic reactions.     

Transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation: a clinicopathologic study of 5 cases and review of the literature

To date, only 16 cases of transitional cell carcinoma of the endometrium and endometrial carcinoma with transitional cell differentiation have been reported in the literature. We reviewed the clinicopathologic features of 5 cases of endometrial carcinoma with transitional cell differentiation. The mean age was 68 years, and all patients presented with postmenopausal bleeding. Macroscopically, the tumors were intracavitary and friable. Microscopically, the tumors were composed of tightly packed papillary structures with thin fibrovascular cores, resembling a transitional cell carcinoma of the urinary tract. One tumor showed exclusively transitional cell differentiation, whereas the remaining 4 neoplasms showed that the transitional cell carcinoma was admixed with a variable proportions of endometrioid adenocarcinoma. Four cases were in FIGO stage IB, whereas the remaining tumor infiltrated the uterine cervix (FIGO stage IIB). Immunoreactivity was typical of müllerian derivatives (cytokeratin 7 positive, cytokeratin 20 negative). p16 protein was positive in all cases, but human papillomavirus DNA was not detected in any of the tumors. None of the patients developed local recurrence or distant metastases, even though there are too few cases of transitional cell carcinoma of the endometrium reported to make any statistically valid conclusions about response to therapy and prognosis. Transitional cell carcinoma is an unusual variant of endometrial carcinoma, with distinctive histologic and immunophenotypic features. Identification of this variant broadens the morphological spectrum of epithelial neoplasms of the endometrium.