Dorsalization of the neural tube by the non-neural ectoderm

The patterning of cell types along the dorsoventral axis of the spinal cord requires a complex set of inductive signals. While the chordamesoderm is a well-known source of ventralizing signals, relatively little is known about the cues that induce dorsal cell types, including neural crest. Here, we demonstrate that juxtaposition of the non-neural and neural ectoderm is sufficient to induce the expression of dorsal markers, Wnt-1, Wnt-3a and Slug, as well as the formation of neural crest cells. In addition, the competence of neural plate to express Wnt-1 and Wnt-3a appears to be stage dependent, occurring only when neural tissue is taken from stage 8–10 embryos but not from stage 4 embryos, regardless of the age of the non-neural ectoderm. In contrast to the induction of Wnt gene expression, neural crest cell formation and Slug expression can be induced when either stage 4 or stage 8–10 neural plates are placed in contact with the non-neural ectoderm. These data suggest that the non-neural ectoderm provides a signal (or signals) that specifies dorsal cell types within the neural tube, and that the response is dependent on the competence of the neural tissue

Our Parents, Ourselves: Health Care for an Aging Population; A Report of the Dartmouth Atlas Project

The new Dartmouth Atlas, funded by The John A. Hartford Foundation, is a report card that analyzes Medicare data to show us where the United States is making progress in patient-centered, evidence-based care for Medicare beneficiaries and where improvement is still needed. It also offers insight into regional variations in care.Filling in the gaps in our knowledge about the state of care across the country will help health care providers, health systems, and patients and families work together to improve care for all older adults.This Dartmouth Atlas report looks at a number of measures from Medicare data, including:The number of days older adults spend in contact with the health care system;Use of high-risk medications;Cancer screening rates (and how they compare with recommendations);30-day hospital readmission rates;Annual Wellness Visit (AWV) rates;Late hospice referral; andThe number of days spent in intensive care.The report also offers a historical look at key practices, comparing data from 2003-05 and 2012

Sickle haemoglobin, haemoglobin C and malaria mortality feedbacks.

BACKGROUND: Sickle haemoglobin (HbS) and haemoglobin C (HbC) are both caused by point mutations in the beta globin gene, and both offer substantial malaria protection. Despite the fact that the blood disorder caused by homozygosity for HbC is much less severe than that caused by homozygosity for HbS (sickle cell anaemia), it is the sickle mutation which has come to dominate many old-world malarious regions, whilst HbC is highly restricted in its geographical distribution. It has been suggested that this discrepancy may be due to sickle cell heterozygotes enjoying a higher level of malaria protection than heterozygotes for HbC. A higher fitness of sickle cell heterozygotes relative to HbC heterozygotes could certainly have allowed the sickle cell allele to spread more rapidly. However, observations that carrying either HbC or HbS enhances an individual's capacity to transmit malaria parasites to mosquitoes could also shed light on this conundrum. METHODS: A population genetic model was used to investigate the evolutionary consequences of the strength of malaria selection being correlated with either HbS frequency or HbC frequency. RESULTS: If the selection pressure from malaria is positively correlated with the frequency of either HbS or HbC, it is easier for HbS to succeed in the competitive interaction between the two alleles. CONCLUSIONS: A feedback process whereby the presence of variant haemoglobins increases the level of malaria selection in a population could have contributed to the global success of HbS relative to HbC, despite the former's higher blood disorder cost

Corneal Plasticity: Characterization of the Multipotentiality of Human Keratocytes

Purpose: To determine the cell properties of adult human corneal keratocytes when challenged in the chick embryonic environment. Methods: Cultured human keratocytes were injected along cranial neural crest migratory pathways in chick embryos. Human keratocytes were also cultured under various conditions and differentiated into either fibroblasts or myofibroblasts, then transplanted into the chick embryo. Migration of the injected cells was determined by immunohistochemistry using human cell-specific markers and markers of crest derivatives. Results: Injected human keratocytes proliferated and migrated ventrally adjacent to host neural crest cells. They contributed to numerous neural crest-derived tissues including cranial blood vessels, ocular tissues, musculature of the mandibular process, and cardiac cushion tissue. Conclusions: Adult human corneal keratocytes that have undergone terminal differentiation can be induced to form cranial neural crest derivatives when grafted into an embryonic environment

Stem-Cell Properties of Human Corneal Keratocytes

Purpose: To determine the stem cell properties of human corneal stromal keratocytes when challenged in the chick embryonic environment. Methods: Stromal keratocytes isolated from human corneas were injected along cranial neural crest migratory pathways and in the periocular mesenchyme in chick embryos. Localization Migration of the injected cells stromal keratocytes was determined at various stages of development by immunohistochemistry using human cell-specific markers. Differentiation of the human keratocytes into other neural crest-derived tissues was determined by immunohistochemistry with tissue cell-specific markers. Results: Human keratocytes injected along cranial neural crest pathways proliferated and migrated ventrally adjacent to host neural crest cells. They contributed to numerous neural crest-derived tissues including cranial blood vessels, ocular tissues, and cardiac cushion tissue mesenchyme. Keratocytes injected into the periocular mesenchyme region contributed to the corneal stroma and endothelial layers. Conclusions: Adult human corneal stromal keratocytes exhibit stem cell characteristics. They can be induced to form cranial neural crest derivatives, including other anterior ocular structures, when grafted into an embryonic environment

Risk factors for Barrett’s esophagus among patients with gastroesophageal reflux disease: A community clinic-based case-control study

Objective: To measure the relative risks of Barrett’s esophagus (BE) associated with demographic factors, measures of adiposity and smoking among patients with gastroesophageal reflux disease (GERD). Methods: Patients newly diagnosed with specialized intestinal metaplasia (SIM) (n=197) were compared to patients with GERD (n= 418) in a community clinic-based case-control study. Case sub-groups included those with any visible columnar epithelium (VBE) (n=97), and those with a long segment (=2cm) of columnar epithelium (LSBE) (n=54). Results: Risks increased with older age (adjusted odds ratio (aOR) per decade for SIM=1.3, 95% confidence interval (CI)= 1.1-1.5; VBE aOR=1.4 ,CI=1.1-1.6; LSBE aOR=1.5, CI=1.2-1.9), male gender (SIM aOR=1.5, CI=1.1-2.2; VBE aOR=2.7, CI=1.6-4.5; LSBE aOR=3.9, CI=1.9- 8.1) and possibly Asian race. Increased risk of BE in particular was observed with high waist-tohip ratio (WHR, male high: =0.9, female high: =0.8) (SIM aOR=1.3, CI=0.9-2.1; VBE aOR=1.9, CI=1.0-3.5; LSBE aOR=4.1, CI=1.5-11.4). These associations were independent of body mass index (BMI) for the VBE and LSBE case groups but not for SIM which was the only case group in which BMI was a significant risk factor. Ever smoking cigarettes increased risk similarly for all case groups (SIM aOR=1.8, CI=1.2-2.6; VBE aOR=1.6, CI=1.0-2.6; LSBE aOR=2.6, CI=1.3- 4.9), although dose response relationship was not detected for duration or intensity of smoking. Conclusions: Older age, male gender and history of smoking increased risk of SIM and BE among GERD patients independent of other risk factors for BE. Central adiposity was most strongly related to risk of VBE and LSBE. These results may be useful in development of risk profiles for screening GERD patients