The association between endothelial function and autoimmune thyroiditis induced by iodine excess.

BACKGROUND: Iodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. METHODS: A total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. RESULTS: Here, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. CONCLUSION: Collectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines.

BDNF and cAMP are neuroprotective in a porcine model of traumatic optic neuropathy.

Traumatic optic neuropathy (TON) is a devastating condition that can occur after blunt or penetrating trauma to the head, leading to visual impairment or blindness. Despite these debilitating effects, no clinically available therapeutic targets neuroprotection or promotes axon regeneration in this or any optic neuropathy. Limited data in large-animal models are a major obstacle to advancing treatments toward clinical therapeutics. To address this issue, we refined a surgical model of TON in Yucatan minipigs. First, we validated the model by demonstrating visual impairment by flash visual-evoked potential and retinal ganglion cell degeneration and death. Next, we developed and optimized a delivery method and nontoxic dosing of intravitreal brain-derived neurotrophic factor (BDNF) and cAMP. Finally, we showed that intravitreal injection of BDNF and cAMP rescued visual function and protected against retinal ganglion cell death and optic nerve axon degeneration. Together these data in a preclinical large-animal model advance our understanding of and ability to model TON and further identify and develop candidate clinical therapeutics.

Single-cell transcriptomic analysis of corneal organoids during development.

Corneal organoids are useful tools for disease modeling and tissue transplantation; however, they have not yet been well studied during maturation. We characterized human iPSC-derived corneal organoids at 1, 2, 3, and 4 months of development using single-cell RNA sequencing to determine the cellular heterogeneity at each stage. We found pluripotent cell clusters committed to epithelial cell lineage at 1 month; early corneal epithelial, endothelial, and stromal cell markers at 2 months; keratocytes as the largest cell population at 3 months; and a large epithelial cell population at 4 months. We compared organoid to fetal corneal development at different stages and found that 4-month organoids closely resemble the corneal cellular complexity of the fetal (16 post conception week) and adult cornea. Using RNA velocity trajectory analysis, we found that less differentiated cells appear to give rise to corneal epithelial cells during development.

The whole blood DNA methylation of RAB8A and RAP1A in autoimmune thyroiditis: evidence and validation of iodine exposure in a population from different water iodine areas.

Our study aimed to identify and verify G protein-related methylated genes in AIT patients, while also investigate those genes in AIT patients exposed to iodine in different water iodine areas. Different areas were classified by median water iodine (MWI) concentrations: Iodine-Fortified Areas (IFA, MWI<10µg/L), Iodine-Adequate Areas (IAA, 40≤MWI≤100 µg/L), and Iodine-Excessive Areas (IEA, MWI>100 µg/L). We studied 176 AIT cases and 176 controls, with 89, 40, and 47 pairs in IFA, IAA, and IEA, respectively. Using the Illumina Human Methylation 850k BeadChip, we identified candidate methylated genes. MethylTargetTM and QRT-PCR validated DNA methylation and mRNA expression. Results showed hypomethylation and high expression of RAB8A and RAP1A in all 176 AIT cases. RAB8A's CpG sites were mainly hypomethylated in IFA and IEA, while RAP1A's sites were primarily hypomethylated in IEA. This study underscores how water iodine exposure may influence RAB8A and RAP1A methylation in AIT.

A study of programmed death-1/programmed death ligand and iodine-induced autoimmune thyroiditis in NOD.H-2h4 mice.

Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death-1 (PD-1)/programmed death ligand (PD-L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD-1/PD-L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD-L1) antibody was administered intraperitoneally to NOD.H-2h4 mice. The relevant indicators were determined by flow cytometry, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic-cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN-γ)/tumor necrosis factor (TNF-α)/interleukin (IL-2)/IL-17, and the relative expression of PD-1/PD-L1/programmed death-2 (PD-L2) increased with the intervention of excess iodine. After the intervention of the PD-L1 antibody, the expression of PD-1/PD-L1/PD-L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN-γ/TNF-α/ IL-2/IL-17 did not decrease. Collectively, although PD-1/PD-L participates in the occurrence of SAT and induces inflammation, administration of the PD-L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD-1/PD-L intervention can treat autoimmune thyroid disease.

Effects of different iodine levels on the DNA methylation of intrinsic apoptosis-associated genes and analysis of gene-environment interactions in patients with autoimmune thyroiditis.

Iodine is an essential nutrient that may change the occurrence of autoimmune thyroiditis (AIT). Apoptosis and DNA methylation participate in the pathogenesis and destructive mechanism of AIT. We detected the methylation and the expression of mRNA of intrinsic apoptosis-associated genes (YWHAG, ING4, BRSK2 and GJA1) to identify the potential interactions between the levels of methylation in these genes and different levels of iodine. 176 adult patients with AIT in Shandong Province, China, were included. The MethylTargetTM assay was used to verify the levels of methylation. We used PCR to detect the mRNA levels of the candidate genes. Interactions between methylation levels of the candidate genes and iodine levels were evaluated with multiplicative and addictive interaction models and GMDR. In the AIT group, YWHAG_1 and six CpG sites and BRSK2_1 and eight CpG sites were hypermethylated, whereas ING4_1 and one CpG site were hypomethylated. A negative correlation was found between methylation levels of YWHAG and mRNA expression. The combination of iodine fortification, YWHAG_1 hypermethylation and BRSK2_1 hypermethylation was significantly associated with elevated AIT risk. A four-locus model (YWHAG_1 × ING4_1 × BRSK2_1 × iodine level) was found to be the best model of the gene-environment interactions. We identified abnormal changes in the methylation status of YWHAG, ING4 and BRSK2 in patients with AIT in different iodine levels. Iodine fortification not only affected the methylation levels of YWHAG and BRSK2 but also interacted with the methylation levels of these genes and may ultimately increase the risk of AIT.

The effect and mechanism of excessive iodine on the endothelial function of human umbilical vein endothelial cells.

Iodine excess (IE) can cause thyroid dysfunction, thyroid diseases can adversely affect cardiovascular function. Accordingly, this study was to explore the direct and indirect effects of IE on endothelial function. Nthy-ori 3-1 and HUVECs cells were treated with potassium iodide (KI). CCK-8, LDH leakage, Elisa, RT-PCR and Western blotting were used to detect relevant indicators. Results showed that a certain level of KI can directly and indirectly reduce the viability of HUVECs and increase cytotoxicity. KI decreased the expression of ET-1 and VWF in HUVECs, inhibited the secretion of ET-1 in culture medium, and increased the expression of IL-6 and TNFα in HUVECs or Nthy-ori 3-1 cells alone. In the co-culture system, KI decreased the expression of ET-1 and THBD and increased the expression of TNFα and IL-6. Collectively, IE can directly and indirectly inhibit endothelial function of endothelial cells, which may be related to its induced inflammatory response.

The Thyroid Condition and Residual Clinical Signs in 31 Existing Endemic Neurological Cretins After 42 Years of Iodine Supplementation in China.

Backgroud: Endemic cretinism is the most severe manifestation among the iodine deficiency-related disorders. The clinical status of the cretins may be modified subsequently by the duration and severity of the disease. We aimed to reassess the clinical status and thyroid function of 31 surviving "neurological cretins" after 42 years of iodine supplementation in a historically severely iodine deficiency area of China. Methods: It was a cross-sectional study in design and we investigated all 31 surviving neurological cretins and 85 controls. A detailed neurological examination was conducted on each patients. All the participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum levels of thyroid hormones, thyroid antibodies, serum iodine concentration (SIC) and urine iodine concentration (UIC) were measured. Results: The neurological cretins had shorter stature than that of the control. Neurological damage is still present in patients with cretinism. The prevalence of subclinical hypothyroidism and thyroid nodule in the cretins was significantly higher (χ2 =4.766, P=0.029 and χ2 =17.077, P<0.0001, respectively) compared with the control. After adjusting for confounding factors, endemic neurocretinism was found to be an independent risk factor for subclinical hypothyroidism (OR=4.412; 95% CI: 1.358-14.334; P=0.014) and thyroid nodule (OR=6.433; 95% CI: 2.323-17.816; P<0.0001). Conclusions: Iodine supplementation after birth does not reverse the neurological damage that results from maternal/foetal hypothyroidism in utero and is subsequently manifested as neurological cretinism. There is a cross-sectional association between endemic neurocretinism and subclinical hypothyroidism and thyroid nodule.

Relationships between the serum TPOAb and TGAb antibody distributions and water iodine concentrations, thyroid hormones and thyroid diseases: a cross-sectional study of 2503 adults in China.

The aim of this study was to explore the status of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in three areas with differing water iodine concentrations; and to discuss the relationships between these two thyroid antibodies and thyroid diseases in the three areas. We investigated 2503 adults from three areas. Urinary iodine concentrations, thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), TPOAb, TGAb and thyroid volume (TV) were measured, and thyroid ultrasonography was performed. The positivity rates of TGAb(+), TPOAb(+) and TGAb(+) and TPOAb(+) or TGAb(+) were significantly higher in iodine fortification (IF) areas than iodine adequate (IA) areas (all P < 0·05). In IF and iodine excess areas, the positivity rates of TPOAb(+), TGAb(+) and TPOAb(+) or TGAb(+) significantly increased with age (all P for trend < 0·05). The levels of TSH, TV and the prevalence of overt hypothyroidism, subclinical hypothyroidism and goitre were significantly elevated in the thyroid antibody-positive groups in the three areas, but the FT3 was diminished (all P < 0·010). Positivity for TPOAb and TGAb was associated with an increased risk of subclinical hypothyroidism in the three areas. In areas with different median water iodine, positivity for both TPOAb and TGAb was associated with elevated TSH values. Notably, with the increased levels of TPOAb, the frequency of abnormally elevated TSH increased dramatically in the three areas.

The Use of Panitumumab-IRDye800CW in a Novel Murine Model for Conjunctival Squamous Cell Carcinoma.

Purpose: Conjunctival squamous cell carcinoma (SCC) is a sight-threatening ocular surface malignancy with the primary treatment modality being surgical resection. To evaluate surgical imaging modalities to improve surgical resection, we established a novel murine model for conjunctival SCC to demonstrate the utility of panitumumab-IRDye800, a fluorescently labeled anti-epidermal growth factor receptor (EGFR) antibody. Methods: NOD-scid IL2Rgammanull (NSG) mice received subconjunctival injection of UM-SCC-1 or SCC-9, head and neck SCC cell lines. On tumor growth, mice were injected with Panitumumab-IRDye800CW, and imaged with a small animal imaging system and optical coherence tomography (OCT). Immunohistochemistry for SCC markers were used to confirm tumor origin. Results: Seventy-five percent (N = 4) of the UM-SCC-1 group developed aggressive, rapidly growing tumors that were P40 and EGFR positive within two weeks of inoculation. The SCC-9 tumors failed to demonstrate any growth (N = 4). Ocular tumors demonstrated high fluorescence levels with a tumor to background ratio of 3.8. Conclusions: Subconjunctival injections are an appropriate technique to create in vivo models for assessing treatment modalities and novel therapies in conjunctival SCC. Translational Relevance: This model demonstrates Panitumumab-IRDye800CW's utility in the ophthalmic setting and suggests that clinical trials may be warranted.

Fibroblast growth factor 21, a stress regulator, inhibits Drp1 activation to alleviate skeletal muscle ischemia/reperfusion injury.

Abnormal Drp1 activation and subsequent excessive mitochondrial fission play a critical role in ischemia-reperfusion injury (I/RI). Although fibroblast growth factor 21 (FGF21) protects organs against I/RI and regulates metabolism, which indicates that FGF21 is involved in mitochondria homeostasis, the detailed mechanism remains unclear. Herein, we investigated whether FGF21 had an effect on Drp1 activation during skeletal muscle I/RI. Drp1 phosphorylation and its translocation to mitochondria, as regulated by FGF21, was examined in mouse and C2C12 cell I/RI models. Mice overexpressing FGF21 displayed alleviation of serum index, histological lesions and apoptosis levels. Moreover, FGF21 markedly decreased cyclin-dependent kinase 1 (CDK1) and Drp1 phosphorylation at Ser616, accompanied by reduced accumulation in mitochondria. In parallel in vitro studies, cells with FGF21 knockdown displayed enhanced Drp1 activation, and the reverse effect was found when FGF21 was added. More importantly, FGF21 attenuated mitochondrial fission with linear mitochondria rather than fragmented mitochondria. Furthermore, a CDK1 inhibitor reduced Drp1 activation and mitochondrial fission due to FGF21 knockdown. This study shows that FGF21 inhibits Drp1 activation to protect mitochondria from fission, thereby rescuing cells from I/RI-induced apoptosis. Our findings may provide a new therapeutic approach to ameliorate skeletal muscle I/RI.

PNP Hydrogel Prevents Formation of Symblephara in Mice After Ocular Alkali Injury.

PURPOSE: To create an alkali injury symblephara mouse model to study conjunctival fibrosis pathophysiology and test polymer nanoparticle (PNP) hydrogel as a preventative therapeutic. METHODS: Mice were injured using NaOH-soaked filter paper to determine the optimal NaOH concentration to induce the formation of symblephara. Injured mice were observed for 7 days to detect the formation of symblephara. Forniceal shortening observed on hematoxylin and eosin (H&E)-stained tissue sections was used as a symblephara marker. Alpha-smooth muscle actin (α-SMA) expression, Masson's trichrome assay, and periodic acid-Schiff (PAS) staining were used to determine myofibroblast expression, collagen deposition, and goblet cell integrity. PNP hydrogel, with multivalent, noncovalent interactions between modified biopolymers and nanoparticles, was applied immediately after alkali injury to determine its ability to prevent the formation of symblephara. RESULTS: Forniceal shortening was observed in H&E images with 1N NaOH for 2 minutes after 7 days without globe destruction. PNP hydrogel prevented forniceal shortening after alkali injury as observed by H&E histology. α-SMA expression and collagen deposition in eye tissue sections were increased in the fornix after injury with 1N NaOH compared with uninjured controls. PNP hydrogel treatment immediately after injury reduced α-SMA expression and collagen deposition in the forniceal region. Mucin-secreting goblet cells stained with PAS were significantly lower in alkali-injured and PNP hydrogel-treated conjunctivas than in uninjured control conjunctivas. CONCLUSIONS: We observed that 1N NaOH for 2 minutes induced maximal forniceal shortening and symblephara in mice. PNP hydrogel prevented forniceal shortening and conjunctival fibrosis after injury. This first murine model for symblephara will be useful to study fibrosis pathophysiology after conjunctival injury and to determine therapeutic targets for cicatrizing diseases. TRANSLATIONAL RELEVANCE: This mouse model of symblephara can be useful for studying conjunctival scarring disease pathophysiology and preventative therapeutics. We tested PNP hydrogel, which prevented the formation of symblephara after injury.

Development of pH-responsive absorbent pad based on polyvinyl alcohol/agarose/anthocyanins for meat packaging and freshness indication.

Absorbent pads with antioxidant and pH-responsive color changing functions have been developed based on polyvinyl alcohol (PVA), agarose (AG), and purple sweet potato anthocyanins (PSPA), aiming for fresh keeping and freshness indication of meat. The effects of PSPA content on the structure, physical properties, and colorimetric response towards pH changing of pads were evaluated. The results showed that PSPA interacted with PVA and AG and influenced the crystallinity, thermal stability and micro-morphology of pads. The increase of the PSPA content from 3% to 12% improved the strength and DPPH radical scavenging activity of the pads, but reduced the swelling ratio. Significant color change of the pads was observed when pH increased from 3 to 10, and the pad containing 9% PSPA presented the most distinguishable color change with the change of pH. When applied as an absorbent pad for minced meat packaging, the pad indicated the real-time spoilage of the meat through obvious color change, and also extended the shelf life by at least 24 h. Therefore, the dual-functional pad shows great potential to be applied as a smart and active packaging for fresh meat, which would play an important role in ensuring food safety and improving food storage quality.

A Meta-Analysis of the Effect of Iodine Excess on the Intellectual Development of Children in Areas with High Iodine Levels in their Drinking Water.

The purpose of this meta-analysis is to comprehensively investigate the effect of iodine excess on children's intellectual development in areas with high iodine levels in their drinking water. We systematically searched the electronic databases and identified 17 publications (16 in Chinese and 1 in English) on the effect of iodine excess on children's intelligence published between January 31, 1985, and January 31, 2020. This meta-analysis included 14,794 children from 28 studies. The results showed that compared with the control group, the intelligence level of children in the high iodine group reduced significantly by 1.64 points (WMD=-1.64; 95% CI (-3.225, -0.049), Z=2.02, P<0.05). Subgroup analyses were performed according to the water iodine concentration, water iodine concentration of the control group, the intelligence test method, and regions of China (i.e., north and south). We noted that when the water iodine concentration was <300µg/L, 301-600µg/L, 600.1-900µg/L, and >900µg/L, the intelligence level of the high iodine groups decreased by varying degrees, although not statistically significant (all P>0.05). The water iodine concentration of the control group was divided into two groups (<150 µg/L and <100 µg/L) and the heterogeneity analysis showed that the heterogeneity of the control group decreased significantly when the concentration of water iodine was <150 µg/L, I2 = 67.3%, P<0.001, which indicated a potential source of heterogeneity. The analyses by test method showed that among the studies which used the China Joint Raven's test, the intelligence level of children in the high iodine group was 0.86 points lower than in the control group (P>0.05). Conversely, we observed that among the studies which used the China Binet intelligence test and the binaphthalene intelligence test of Tanzhida in Japan to evaluate children's intelligence level, the intelligence level of children in the high iodine groups was significantly lower (3.65 points and 8.0 points, respectively) compared with the control groups (P<0.05). The analysis of the regions of China demonstrated that whereas the reduction in children's intelligence level from excess iodine in the north of China was not statistically significant (WMD=-0.16, 95% CI (-2.18, 1.85), P>0.05), the association was statistically significant in the southern part of China (WMD=-1.86, 95% CI (-3.57, -0.09), P<0.05). This study found that high iodine concentration was statistically significantly associated with a decline in intelligence level in children. Comparatively, the intelligence level of children who were exposed to high iodine concentrations reduced significantly by 1.64 points. These findings have public health implications.

Efficient absorptive removal of Cd(â ¡) in aqueous solution by biochar derived from sewage sludge and calcium sulfate.

Biochar derived from co-pyrolysis of sewage sludge and calcium sulfate was used to remove Cd(II) from aqueous solution. The results showed that the Cd(Ⅱ) adsorption better followed Freundlich model, and the maximum adsorption capacities were 109.0 mg/g (288 K), 127.9 mg/g (298 K) and 145.4 mg/g (308 K). The Cd(Ⅱ) removal was a multi-layer adsorption process dominated by chemisorption, which was also a spontaneous and endothermic process. The contribution of physisorption gradually increased as the Cd(Ⅱ) initial concentration. The Cd(Ⅱ) removal process which better followed pseudo-second-order kinetic model, was divided into three stages. The first (0-0.3 h) and second stages (0.3-2 h) were separately controlled by liquid film diffusion/intraparticle diffusion/chemical reaction and liquid film diffusion/chemical reaction, while the third stage (0.3-24 h) was the dynamic equilibrium process. The speciation distribution of Cd on biochar surface was mainly CdCO3/CdOOC and CdO/CdSiO3, indicating coprecipitation, ion exchange and complexation contributed more to the Cd(Ⅱ) removal.

Investigation of correlation between bony pelvis dimensions and pelvic organ prolapse in different compartments.

OBJECTIVE: To investigate the association between bony pelvis dimensions and anterior, apical, and posterior compartment pelvic organ prolapse (POP) and explore the mechanism of different types of POP from an anatomical point of view. STUDY DESIGN: A total of 253 patients with POP were selected as the experimental group (138 patients with anterior compartment defect, 86 with apical compartment defect, and 29 with posterior compartment defect); 253 patients with uterine myoma constituted the control group. Their demographics were recorded, and anteroposterior diameters of the pelvic inlet, intertuberous diameter, and interspinous diameter were measured. One-way analysis of variance, least significant difference t-test, and Student's t-test were used to evaluate the pelvic measurements among the four groups. RESULTS: The anteroposterior diameter of the pelvic inlet in the apical compartment POP group was smaller than that in the other groups (P < 0.05). Interspinous diameters in the anterior and apical groups were larger than those in the posterior POP and control groups (P < 0.05). Intertuberous diameter in the control group was smaller than that in the anterior and apical POP groups and larger than that in the posterior POP group (P < 0.05). CONCLUSION: Women with apical compartment POP are more likely to have a smaller anteroposterior diameter. Larger interspinous and intertuberous diameters were associated with anterior and apical POP, and smaller intertuberous diameter was associated with posterior POP.

Pyrolysis molecule of Torreya grandis bark for potential biomedicine.

Torreya grandis is a unique tree species in China. Although full use has been made of the timber, the processing and utilization of the bark has not been effective. In order to explore a new way to utilize the bark of Torreya grandis, a powder of T. grandis bark was prepared and analyzed qualitatively and quantitatively. Differential scanning calorimetry (TG) and pyrolysis gas chromatography-mass spectrometry (PY-GC/MS) revealed many bioactive components in the bark of T. grandis, such as acetic acid, 2-methoxy-4-vinyl phenol, D-mannose, and furfural. These substances have potential broad applications in the chemical industry, biomedicine, and food additives. The chemical constituents of the bark of T. grandis suggest a theoretical basis for the future development and utilization of the bark of T. grandis.

Investigation of correlation between diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction.

OBJECTIVE: To investigate correlation between key diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction (FPFD). STUDY DESIGN: Correlation with incidence of FPFD was analyzed by measuring the two diameters of pelvic inlet and outlet planes (i.e. anteroposterior diameter of pelvic inlet and transverse diameter of pelvic outlet) in 298 patients with FPFD and 508 patients in control group taking into account of other relevant factors. RESULTS: The transverse diameter of pelvic outlet was significantly larger in experimental group than in control group (9.55cm vs. 8.50cm, P<0.01); while the difference in anteroposterior diameter of pelvic inlet between the two groups was not statistically significant (11.63cm vs. 11.26cm, P=0.205>0.01); Binary logistic regression analysis indicated that the anteroposterior diameter of pelvic inlet was not correlated with incidence of FPFD, but the transverse diameter of pelvic outlet was one of the influencing factor for FPFD. CONCLUSIONS: The transverse diameter of pelvic outlet is closely correlated with incidence of FPFD and represents one of the risk factors for FPFD; a transverse diameter of pelvic outlet greater than 9.5cm is the threshold for onset of FPFD and can be used as an early predictive index for FPFD.

Trend towards varying combinatorial centromere association in morphologically identical clusters in Purkinje neurons.

Neurons with similar morphology and neurotransmitter content located at a specific brain region may be part of the same or functionally separate networks. To address the question whether morphologically similar neurons have similar structural architecture at the chromosomal level, we studied Purkinje neurons in the cerebellum. Previous studies have shown that in Purkinje neurons centromeres of several chromosomes form clusters and that the number and size of these clusters remain stable in the adult brain. We examined whether the same set of centromeres form clusters in all the Purkinje neurons. Fluorescent in situ hybridization (FISH) with chromosome-specific para-centromeric probes provided an indirect evidence for a trend towards varying contributions from different chromosomes forming the centromeric clusters in adjacent Purkinje neurons. The results of the study indicate that the individual Purkinje neurons are likely unique in inter-chromosomal spatial associations.

Cell-type specific proximity of centromeric domains of one homologue each of chromosomes 2 and 11 in nuclei of cerebellar Purkinje neurons.

In Purkinje neurons of the mouse cerebellum, the centromeres of several chromosomes are placed in close proximity to form a distinct pattern of clusters and exhibit reproducible spatial redistributions during development. In granule neurons, an adjacent cell type in the cerebellum, the pattern, size, and number of centromeric aggregations are different from those of Purkinje neurons. The present work was undertaken to test the hypothesis that the same chromosomes form part of one aggregate in a cell-type-specific manner. Fluorescence in situ hybridization (FISH) with chromosome-specific paracentromeric probes was used to identify centromeric regions of individual chromosomes in cerebellar Purkinje and granule neurons of the adult mouse. When pairs of centromeric probes were used in two-color FISH, one homologue each of chromosomes 2 and 11 were routinely found close to each other in Purkinje neurons but not in granule neurons. This finding of specific proximity was limited to the pair 2 and 11, out of the ten chromosome pairs that were randomly selected and studied. Our results indicate that, in adult Purkinje neurons, a cell-type-specific spatial proximity is present between centromeric domains of one homologue each of chromosomes 2 and 11.