Transgender identity in young people and adults recorded in UK primary care electronic patient records: retrospective, dynamic, cohort study.

Objectives: To quantify the change in proportion of young people and adults identified as transgender in UK primary care records and to explore whether rates differ by age and socioeconomic deprivation. Design: Retrospective, dynamic, cohort study. Setting: IQVIA Medical Research Data, a database of electronic primary care records capturing data from 649 primary care practices in the UK between 1 January 2000 and 31 December 2018. Participants: 7 064 829 individuals aged 10-99 years, in all four UK countries. Main outcome measures: Diagnostic codes indicative of transgender identity were used. Sex assigned at birth was estimated by use of masculinising or feminising medication and procedural/diagnostic codes. Results: 2462 (0.03%) individuals had a record code indicating a transgender identity. Direction of transition could be estimated for 1340 (54%) people, of which 923 were assigned male at birth, and 417 were assigned female at birth. Rates of recording in age groups diverged substantially after 2010. Rates of the first recording of codes were highest in ages 16-17 years (between 2010 and 2018: 24.51/100 000 person years (95% confidence interval 20.95 to 28.50)). Transgender codes were associated with deprivation: the rate of the first recording was 1.59 (95% confidence interval 1.31 to 1.92) in the most deprived group in comparison with the least deprived group. Additionally, the rate ratio of the proportion of people who identified as transgender was 2.45 (95% confidence interval 2.28 to 2.65) in the most deprived group compared with the least deprived group. Substantial increases were noted in newly recorded transgender codes over time in all age groups (1.45/100 000 person years in 2000 (95% confidence interval 0.96 to 2.10) to 7.81/100 000 person years in 2018 (6.57 to 9.22)). In 2018, the proportion of people with transgender identity codes was highest in the age groups 16-17 years (16.23 per 10 000 (95% confidence interval 12.60 to 20.57)) and 18-29 years (12.42 per 10 000 (11.06 to 13.90)). Conclusion: The rate of transgender identity recorded in primary care records has increased fivefold from 2000 to 2018 and is highest in the 16-17 and 18-29 age groups. Transgender diagnostic coding is associated with socioeconomic deprivation and further work should investigate this association. Primary and specialist care should be commissioned accordingly to provide for the gender specific and general health needs of transgender people.

Reclaiming Placemaking for an Alternative Politics of Legitimacy and Community in Homelessness.

This study is about the struggle for legitimacy in place among a group of people often assumed to have neither. It examines the roll of informal placemaking and community building in struggles for settlement among people experiencing homelessness. It does so through ethnographic observation, photo-documentation, and participatory action research at three sites in Oakland, California, on which unhoused people (and some housed members of the surrounding community) have demonstrated bold forms of grassroots placemaking on public land. The first site, which came to be known as Housing and Dignity Village, was a small intentionally organized community of unhoused women and families that existed for 41 politically charged days in a low-income residential neighborhood before being cleared by authorities in 2018. The second, a highly visible piece of desirable city-owned land, has been occupied by unhoused people to varying degrees since 2016 while being considered for various housing development proposals. The third is the Wood Street Encampment, Oakland's largest encampment and one of its longest standing, which has survived numerous partial evictions and a web of jurisdictional authority to become home to an extensive and innovative informal community-building effort. Despite their differences, each offers a powerful case of place-based bottom-up community organizing among unhoused people, in which placemaking becomes part of a subtle politics of visibility, being, and legitimacy. The study argues that these instances and others not only demonstrate a different sort of placemaking, but demand that we reconsider and reclaim the concept itself.

A comparison of the breathing apparatus deadspace associated with a supraglottic airway and endotracheal tube using volumetric capnography in young children.

BACKGROUND: Supraglottic airway (SGA) devices including the air-Q® are being used with increasing frequency for anesthesia in infants and younger pediatric patients. To date, there is minimal research documenting the potentially significant airway deadspace these devices may contribute to the ventilation circuit when compared to an endotracheal tube (ETT). The aim of this study was to evaluate the airway apparatus deadspace associated with an air-Q® versus an ETT in young children. METHODS: In a prospective cohort study, 59 patients between 3 months and 6 years of age, weighing between 5 and 20 kg, scheduled for outpatient urologic or general surgery procedures were recruited. An air-Q® or ETT was inserted at the discretion of the attending anesthesiologist, and tidal volume, positive end expiratory pressure, respiratory rate, and end-tidal CO2 were controlled according to protocol. Airway deadspace was recorded using volumetric capnography every 2 min for 10 min. RESULTS: Groups were similar in demographics. There was a significant difference in weight-adjusted deadspace volume between the air-Q® and ETT groups, 4.1 ± 0.8 ml/kg versus 3.0 ± 0.7 ml/kg, respectively (P < 0.001). Weight-adjusted deadspace volume (ml/kg) increased significantly with decreasing weight for both the air-Q® and ETT groups. CONCLUSIONS: In healthy children undergoing positive pressure ventilation for elective surgery, the air-Q® SGA introduces significantly greater airway deadspace than an ETT. Additionally, airway deadspace, and minute ventilation required to maintain normocarbia, appear to increase with decreasing patient weight irrespective of whether a SGA or ETT is used.

A comparison of the breathing apparatus deadspace associated with a supraglottic airway and endotracheal tube using volumetric capnography in young children / 대한마취과학회지

Background@#Supraglottic airway (SGA) devices including the air-Q® are being used with increasing frequency for anesthesia in infants and younger pediatric patients. To date, there is minimal research documenting the potentially significant airway deadspace these devices may contribute to the ventilation circuit when compared to an endotracheal tube (ETT). The aim of this study was to evaluate the airway apparatus deadspace associated with an air-Q® versus an ETT in young children. @*Methods@#In a prospective cohort study, 59 patients between 3 months and 6 years of age, weighing between 5 and 20 kg, scheduled for outpatient urologic or general surgery procedures were recruited. An air-Q® or ETT was inserted at the discretion of the attending anesthesiologist, and tidal volume, positive end expiratory pressure, respiratory rate, and end-tidal CO2 were controlled according to protocol. Airway deadspace was recorded using volumetric capnography every 2 min for 10 min. @*Results@#Groups were similar in demographics. There was a significant difference in weight-adjusted deadspace volume between the air-Q® and ETT groups, 4.1 ± 0.8 ml/kg versus 3.0 ± 0.7 ml/kg, respectively (P < 0.001). Weight-adjusted deadspace volume (ml/kg) increased significantly with decreasing weight for both the air-Q® and ETT groups. @*Conclusions@#In healthy children undergoing positive pressure ventilation for elective surgery, the air-Q® SGA introduces significantly greater airway deadspace than an ETT. Additionally, airway deadspace, and minute ventilation required to maintain normocarbia, appear to increase with decreasing patient weight irrespective of whether a SGA or ETT is used.

A comparison of the breathing apparatus deadspace associated with a supraglottic airway and endotracheal tube using volumetric capnography in young children / 대한마취과학회지

Background@#Supraglottic airway (SGA) devices including the air-Q® are being used with increasing frequency for anesthesia in infants and younger pediatric patients. To date, there is minimal research documenting the potentially significant airway deadspace these devices may contribute to the ventilation circuit when compared to an endotracheal tube (ETT). The aim of this study was to evaluate the airway apparatus deadspace associated with an air-Q® versus an ETT in young children. @*Methods@#In a prospective cohort study, 59 patients between 3 months and 6 years of age, weighing between 5 and 20 kg, scheduled for outpatient urologic or general surgery procedures were recruited. An air-Q® or ETT was inserted at the discretion of the attending anesthesiologist, and tidal volume, positive end expiratory pressure, respiratory rate, and end-tidal CO2 were controlled according to protocol. Airway deadspace was recorded using volumetric capnography every 2 min for 10 min. @*Results@#Groups were similar in demographics. There was a significant difference in weight-adjusted deadspace volume between the air-Q® and ETT groups, 4.1 ± 0.8 ml/kg versus 3.0 ± 0.7 ml/kg, respectively (P < 0.001). Weight-adjusted deadspace volume (ml/kg) increased significantly with decreasing weight for both the air-Q® and ETT groups. @*Conclusions@#In healthy children undergoing positive pressure ventilation for elective surgery, the air-Q® SGA introduces significantly greater airway deadspace than an ETT. Additionally, airway deadspace, and minute ventilation required to maintain normocarbia, appear to increase with decreasing patient weight irrespective of whether a SGA or ETT is used.

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases.

The development of new therapeutic approaches to diseases relies on the identification of key molecular targets involved in amplifying disease processes. One such molecule is thioredoxin-interacting protein (TXNIP), also designated thioredoxin-binding protein-2 (TBP-2), a member of the α-arrestin family of proteins and a central regulator of glucose and lipid metabolism, involved in diabetes-associated vascular endothelial dysfunction and inflammation. TXNIP sequesters reduced thioredoxin (TRX), inhibiting its function, resulting in increased oxidative stress. Many different cellular stress factors regulate TXNIP expression, including high glucose, endoplasmic reticulum stress, free radicals, hypoxia, nitric oxide, insulin, and adenosine-containing molecules. TXNIP is also directly involved in inflammatory activation through its interaction with the nucleotide-binding domain, leucine-rich-containing family, and pyrin domain-containing-3 (NLRP3) inflammasome complex. Neurodegenerative diseases such as Alzheimer's disease have significant pathologies associated with increased oxidative stress, inflammation, and vascular dysfunctions. In addition, as dysfunctions in glucose and cellular metabolism have been associated with such brain diseases, a role for TXNIP in neurodegeneration has actively been investigated. In this review, we will focus on the current state of the understanding of possible normal and pathological functions of TXNIP in the central nervous system from studies of in vitro neural cells and the brains of humans and experimental animals with reference to other studies. As TXNIP can be expressed by neurons, microglia, astrocytes, and endothelial cells, a complex pattern of regulation and function in the brain is suggested. We will examine data suggesting TXNIP as a therapeutic target for neurodegenerative diseases where further research is needed.

Novel fluorinated derivative of curcumin negatively regulates thioredoxin-interacting protein expression in retinal pigment epithelial and macrophage cells.

Thioredoxin-interacting protein (TXNIP) has multiple disease-associated functions including inducing oxidative stress by inhibiting the anti-oxidant and thiol reducing activity of thioredoxin (TRX), reducing cellular glucose transport, and is a component of the activated inflammasome complex. Increased expression of TXNIP is encountered in diabetic conditions of high glucose. Curcumin and chemical derivatives have multiple therapeutic properties as anti-inflammatories, anti-oxidants, amyloid aggregation inhibitors and modulate a number of cellular signaling pathways. Using a fluorinated-derivative of curcumin (designated Shiga-Y6), we showed significant inhibition of TXNIP mRNA and protein expression, and induction of TRX mRNA and protein in ARPE-19 retinal pigment epithelial cells and THP-1-derived macrophages, while the non-fluorinated structural equivalent (Shiga-Y52) and native curcumin did not show these same effects. Shiga-Y6 was effective in reducing high glucose, endoplasmic reticulum stress-induced TXNIP in ARPE-19 cells, and reducing lipopolysaccharide and endoplasmic stress-induced proinflammatory gene expression in THP-1 macrophages. Moreover, TXNIP-knockdown experiments showed that the anti-inflammatory effect of Shiga-Y6 in LPS-stimulated THP-1 macrophages was TXNIP-independent.

Compressed 3D and 2D digital images versus standard 3D slide film for the evaluation of glaucomatous optic nerve features.

SYNOPSIS: Clinicians can feel confident compressed three-dimensional digital (3DD) and two-dimensional digital (2DD) imaging evaluating important features of glaucomatous disc damage is comparable to the previous gold standard of stereoscopic slide film photography, supporting the use of digital imaging for teleglaucoma applications. BACKGROUND/AIMS: To compare the sensitivity and specificity of 3DD and 2DD photography with stereo slide film in detecting glaucomatous optic nerve head features. METHODS: This prospective, multireader validation study imaged and compressed glaucomatous, suspicious or normal optic nerves using a ratio of 16:1 into 3DD and 2DD (1024×1280 pixels) and compared both to stereo slide film. The primary outcome was vertical cup-to-disc ratio (VCDR) and secondary outcomes, including disc haemorrhage and notching, were also evaluated. Each format was graded randomly by four glaucoma specialists. A protocol was implemented for harmonising data including consensus-based interpretation as needed. RESULTS: There were 192 eyes imaged with each format. The mean VCDR for slide, 3DD and 2DD was 0.59±0.20, 0.60±0.18 and 0.62±0.17, respectively. The agreement of VCDR for 3DD versus film was κ=0.781 and for 2DD versus film was κ=0.69. Sensitivity (95.2%), specificity (95.2%) and area under the curve (AUC; 0.953) of 3DD imaging to detect notching were better (p=0.03) than for 2DD (90.5%; 88.6%; AUC=0.895). Similarly, sensitivity (77.8%), specificity (98.9%) and AUC (0.883) of 3DD to detect disc haemorrhage were better (p=0.049) than for 2DD (44.4%; 99.5%; AUC=0.72). There was no difference between 3DD and 2DD imaging in detecting disc tilt (p=0.7), peripapillary atrophy (p=0.16), grey crescent (p=0.1) or pallor (p=0.43), although 3D detected sloping better (p=0.013). CONCLUSIONS: Both 3DD and 2DD imaging demonstrates excellent reproducibility in comparison to stereo slide film with experts evaluating VCDR, notching and disc haemorrhage. 3DD in this study was slightly more accurate than 2DD for evaluating disc haemorrhage, notching and sloping.

Antinociception induced by a novel α2A adrenergic receptor agonist in rodents acute and chronic pain models.

The mechanisms and antinociceptive effects of a novel α2A adrenoceptor agonist, 3-(2-chloro-6-fluorobenzil)-imidazolinide-2,4-dione (PT-31) were investigated using animal models of acute and chronic pain. The effects of PT-31 on pain responses were examined using hot plate and formalin tests in mice and spinal nerve ligation (SNL)-induced hyperalgesia in rats. The effects of antagonists acting on α adrenoceptor were assessed to investigate the interaction of these pathways upon PT-31 induced antinociception. PT-31 effects on motor activity/skills and on hemodynamic parameters were also evaluated. PT-31 had dose-dependent antinociception effects on hot-plate and formalin-injection induced pain responses. Thermal hyperalgesia and mechanical allodynia were reduced following a 7 d treatment with PT-31 (1, 5, and 10mg/kg/d, p.o.), and those effects were attenuated by yohimbine (5mg/kg), atropine (2mg/kg), L-nitro arginine methyl ester (L-NAME; 30mg/kg), or naloxone (2mg/kg). In contrast to clonidine, PT-31 did not have locomotor or hemodynamic effects in rats. The present results suggest that PT-31 represents a candidate for pain treatment with advantages over clonidine, namely no locomotor or hemodynamic impairments.

Effect of microcystin-LR on human placental villous trophoblast differentiation in vitro.

Microcystin-LR is a cyanobacterial toxin found in surface and recreational waters that inhibits protein phosphatases and may disrupt the cytoskeleton. Microcystins induce apoptosis in hepatocytes at ≤ 2.0 µM. Nothing is known about the effects of microcystins on human placental trophoblast differentiation and function. The differentiation of villous trophoblasts to form syncytiotrophoblast occurs throughout pregnancy and is essential for normal placental and fetal development. To investigate the effects of microcystin, villous cytotrophoblasts were isolated from term placentas using an established method and exposed to microcystin-LR. Microcystin-LR below the cytotoxic dose of 25 µM did not cause cell rounding or detachment, had no effect on apoptosis, and no effect on the morphological differentiation of mononucleated cytotrophoblasts to multinucleated syncytiotrophoblast. However, secretion of human chorionic gonadotropin (hCG) increased in a microcystin-LR dose-dependent manner. When incubated with l-buthionine sulphoximine (BSO) to deplete glutathione levels, trophoblast morphological differentiation proceeded normally in the presence of microcystin-LR. Microcystin-LR did not disrupt the trophoblast microtubule cytoskeleton, which is known to play a role in trophoblast differentiation. Immunofluorescence studies showed that trophoblasts express organic anion transport protein 1B3 (OATP1B3), a known microcystin transport protein. In comparison to hepatocytes, trophoblasts appear to be more resistant to the toxic effects of microcystin-LR. The physiological implications of increased hCG secretion in response to microcystin-LR exposure remain to be determined.

Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation.

Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2) and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts) and a villous pathway (giving rise to multinucleated syncytiotrophoblast). Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries. We tested the idea that sodium butyrate (an epigenetic modulator) induces trophoblast differentiation in early gestation rhesus monkey trophoblasts through activation of the Wnt/ß-catenin pathway. The results show that syncytiotrophoblast formation was increased by butyrate, accompanied by nuclear accumulation of ß-catenin, and increased expression of EnvV2 and galectin-1 (two factors thought to be involved in trophoblast fusion). Surprisingly, the expression of GCM1 and syncytin-2 was not affected by sodium butyrate. When trophoblasts were incubated with lithium chloride, a GSK3 inhibitor that mimics Wnt activation, nuclear accumulation of ß-catenin also occurred but differentiation into syncytiotrophoblast was not observed. Instead the cells differentiated to mononucleated spindle-shaped cells and showed molecular and behavioral characteristics of endovascular trophoblasts. Another highly specific inhibitor of GSK3, CHIR99021, failed to induce endovascular trophoblast characteristics. These observations suggest that activation of the Wnt/ß-catenin pathway correlates with both trophoblast differentiation pathways, but that additional factors determine specific cell fate decisions. Other experiments suggested that the differential effects of sodium butyrate and lithium chloride might be explained by their effects on TNFα production. The results provide valuable tools to manipulate trophoblast differentiation in vitro and to better understand the differentiation pathways that occur during early gestation.

Early Developmental and Evolutionary Origins of Gene Body DNA Methylation Patterns in Mammalian Placentas.

Over the last 20-80 million years the mammalian placenta has taken on a variety of morphologies through both divergent and convergent evolution. Recently we have shown that the human placenta genome has a unique epigenetic pattern of large partially methylated domains (PMDs) and highly methylated domains (HMDs) with gene body DNA methylation positively correlating with level of gene expression. In order to determine the evolutionary conservation of DNA methylation patterns and transcriptional regulatory programs in the placenta, we performed a genome-wide methylome (MethylC-seq) analysis of human, rhesus macaque, squirrel monkey, mouse, dog, horse, and cow placentas as well as opossum extraembryonic membrane. We found that, similar to human placenta, mammalian placentas and opossum extraembryonic membrane have globally lower levels of methylation compared to somatic tissues. Higher relative gene body methylation was the conserved feature across all mammalian placentas, despite differences in PMD/HMDs and absolute methylation levels. Specifically, higher methylation over the bodies of genes involved in mitosis, vesicle-mediated transport, protein phosphorylation, and chromatin modification was observed compared with the rest of the genome. As in human placenta, higher methylation is associated with higher gene expression and is predictive of genic location across species. Analysis of DNA methylation in oocytes and preimplantation embryos shows a conserved pattern of gene body methylation similar to the placenta. Intriguingly, mouse and cow oocytes and mouse early embryos have PMD/HMDs but their placentas do not, suggesting that PMD/HMDs are a feature of early preimplantation methylation patterns that become lost during placental development in some species and following implantation of the embryo.

Safety and efficacy of Ahmed glaucoma valve implantation in refractory glaucomas in Northern Indian eyes.

PURPOSE: To evaluate the safety and efficacy of Ahmed glaucoma valve (AGV) implantation in refractory glaucoma in Northern Indian eyes. BACKGROUND: The success rate of trabeculectomy remains low in cases of refractory glaucoma even with the use of antifibrotics. Glaucoma drainage devices have proven to be more efficacious in reducing intraocular pressure (IOP) in these glaucomas. METHODS: Retrospective records of 55 consecutive patients who underwent AGV implantation at Dr. Shroff's Charity Eye Hospital, New Delhi, India from January 2003 to December 2012 were reviewed. Pre-operative data included age, gender, eye laterality, specific diagnosis, number of anti-glaucoma medications, number of prior incisional surgeries, visual acuity and IOP on medical treatment. Postoperative data included visual acuity and IOP on day one, 1 week, 1 month, 3 months, 6 months, 1 year and yearly thereafter, number of anti-glaucoma medications, any complication or additional surgical intervention required. Success was defined as IOP >5 and <22 mmHg with or without treatment. RESULTS: Mean IOP decreased from 39.71 ± 8.99 pre-operatively to 17.52 ± 5.72 mmHg at last follow-up (p < 0.001) and number of medications reduced from 3.27 ± 0.84 to 1.25 ± 0.88 (p < 0.001). Visual acuity remained within one Snellen line or improved at last follow-up in 47 cases (85.4%). The cumulative probability of success was 85.45% at 1 year and 79.63% at 3 years. The incidence of post-operative complications was 25.45%. CONCLUSION: AGV implantation has proven to be safe and is effective in controlling IOP in refractory glaucoma in Northern Indian eyes.

MUC1 Is Expressed by Human Skin Fibroblasts and Plays a Role in Cell Adhesion and Migration.

The mucin MUC1 is expressed by normal and cancerous epithelial cells and some nonepithelial cells in which it plays roles in regulating adhesion, migration, and cell signaling. In the present studies we found that MUC1 is expressed by normal human neonatal and adult skin fibroblasts. Fibroblasts are usually considered negative for MUC1 expression. Reverse-transcription polymerase chain reaction and Western blot analyses indicate the presence of full-length MUC1, and immunofluorescence and subcellular fractionation studies show that the protein is expressed on the plasma membrane. Immunohistochemical analyses confirmed the expression of MUC1 by fibroblasts in cryosections of normal human skin. Silencing MUC1 expression in fibroblasts using MUC1 shRNA increased the adhesion of cells to collagen and laminin. Transfection with MUC1 shRNA also increased fibroblast migration on collagen as measured in a wound-healing assay. The expression of α2-integrin was increased in MUC1 shRNA-transfected fibroblasts in which it was localized to membrane ruffles, providing a possible explanation for the increased cell migration on collagen. These results extend the range of expression of MUC1 to skin fibroblasts and suggest a functional role for MUC1 in fibroblast adhesion and motility.

The MUC1 extracellular domain subunit is found in nuclear speckles and associates with spliceosomes.

MUC1 is a large transmembrane glycoprotein and oncogene expressed by epithelial cells and overexpressed and underglycosylated in cancer cells. The MUC1 cytoplasmic subunit (MUC1-C) can translocate to the nucleus and regulate gene expression. It is frequently assumed that the MUC1 extracellular subunit (MUC1-N) does not enter the nucleus. Based on an unexpected observation that MUC1 extracellular domain antibody produced an apparently nucleus-associated staining pattern in trophoblasts, we have tested the hypothesis that MUC1-N is expressed inside the nucleus. Three different antibodies were used to identify MUC1-N in normal epithelial cells and tissues as well as in several cancer cell lines. The results of immunofluorescence and confocal microscopy analyses as well as subcellular fractionation, Western blotting, and siRNA/shRNA studies, confirm that MUC1-N is found within nuclei of all cell types examined. More detailed examination of its intranuclear distribution using a proximity ligation assay, subcellular fractionation, and immunoprecipitation suggests that MUC1-N is located in nuclear speckles (interchromatin granule clusters) and closely associates with the spliceosome protein U2AF65. Nuclear localization of MUC1-N was abolished when cells were treated with RNase A and nuclear localization was altered when cells were incubated with the transcription inhibitor 5,6-dichloro-1-b-d-ribofuranosylbenzimidazole (DRB). While MUC1-N predominantly associated with speckles, MUC1-C was present in the nuclear matrix, nucleoli, and the nuclear periphery. In some nuclei, confocal microscopic analysis suggest that MUC1-C staining is located close to, but only partially overlaps, MUC1-N in speckles. However, only MUC1-N was found in isolated speckles by Western blotting. Also, MUC1-C and MUC1-N distributed differently during mitosis. These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC1-C have dissimilar intranuclear distribution patterns.

Visual field loss morphology in high- and normal-tension glaucoma.

Purpose. To determine whether the patterns of visual field damage between high-tension glaucoma (HTG) and normal-tension glaucoma (NTG) are equivalent. Methods. In this retrospective cross-sectional study, fifty-one NTG and 57 HTG patients were recruited. For each recruited patient only the left eye was chosen. Glaucomatous patients had abnormal visual fields and/or glaucomatous changes at the optic nerve head. They were classified as HTG or NTG on the basis of intraocular pressure (IOP) measurements. Patients' visual fields were analyzed by using Humphrey Field Analyzer (HFA), program 30-2, full threshold. The visual field sensitivity values and the pattern deviation map values of the 72 tested points were considered. Then a pointwise analysis and an area analysis, based on the Glaucoma Hemifield test criteria, were performed, and a comparison between the two subgroups was made by Student's t test. Results. Between NTG and HTG, no significant difference was found pointwise for almost all the visual field points, except for two locations. One was under the blind spot, and the other was in the inferior hemifield around the twenty-degree position. When area analysis was considered, three areas showed a significantly different sensitivity between HTG and NTG. Conclusions. These data suggested that there was no relevant difference in the pointwise analysis between NTG and HTG; however, when visual field areas were compared, no difference in paracentral areas was found between NTG and HTG, but superior nasal step and inferior and superior scotomata showed to be deeper in HTG than in NTG.

Nesprin-3 regulates endothelial cell morphology, perinuclear cytoskeletal architecture, and flow-induced polarization.

Changes in blood flow regulate gene expression and protein synthesis in vascular endothelial cells, and this regulation is involved in the development of atherosclerosis. How mechanical stimuli are transmitted from the endothelial luminal surface to the nucleus is incompletely understood. The linker of nucleus and cytoskeleton (LINC) complexes have been proposed as part of a continuous physical link between the plasma membrane and subnuclear structures. LINC proteins nesprin-1, -2, and -4 have been shown to mediate nuclear positioning via microtubule motors and actin. Although nesprin-3 connects intermediate filaments to the nucleus, no functional consequences of nesprin-3 mutations on cellular processes have been described. Here we show that nesprin-3 is robustly expressed in human aortic endothelial cells (HAECs) and localizes to the nuclear envelope. Nesprin-3 regulates HAEC morpho-logy, with nesprin-3 knockdown inducing prominent cellular elongation. Nesprin-3 also organizes perinuclear cytoskeletal organization and is required to attach the centrosome to the nuclear envelope. Finally, nesprin-3 is required for flow-induced polarization of the centrosome and flow-induced migration in HAECs. These results represent the most complete description to date of nesprin-3 function and suggest that nesprin-3 regulates vascular endothelial cell shape, perinuclear cytoskeletal architecture, and important aspects of flow-mediated mechanotransduction.

Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases.

The receptor for advanced glycation end products (RAGE) has been demonstrated to play a central role in the pathogenic mechanisms of a growing number of important neurological diseases, including Alzheimer's disease (AD) and stroke. Two functional types of RAGE have been associated with neurological diseases: cell membrane-bound (full length) and soluble. In general, ligand binding to full-length RAGE initiates sustained cellular activation and receptor-dependent signaling resulting in inflammation and cellular stress, and is ultimately associated with increased RAGE expression. By comparison, soluble forms of RAGE, generated either by alternative splicing or by proteolysis, can reduce the severity of the consequence of ligand-membrane RAGE interactions by preventing ligands from binding to the full-length RAGE. This can inhibit the neurotoxic or proinflammatory responses involved in disease states. This article reviews the pathobiology of RAGE, with emphasis on soluble forms of RAGE, and discusses its relevance to AD and to other neurological diseases, as well as how manipulation of the different forms of RAGE is becoming a powerful therapeutic strategy.

Trophoblast stem cells: models for investigating trophectoderm differentiation and placental development.

The placenta is an ephemeral organ containing diverse populations of trophoblasts that are all derived from the embryonic trophectoderm but have morphological, functional, and molecular diversity within and across species. In hemochorial placentation, these cells play especially important roles, interfacing with and modifying the cells of the maternal decidua. Within the rapidly growing placenta, it has been shown that there are trophoblast stem cells well characterized in the mouse and postulated but not well understood in primates. This review will discuss the characteristics of candidates for human and nonhuman primate trophoblast stem cells, present the diverse methods of their generation, and propose future prospects for experimental systems in which they can shed light on developmental and pathophysiological processes in human pregnancy.