In 2010, 30.6% of respondents reported that they treated patients fewer than 30 hours per week compared to 30% in 2007. The percent of respondents who treated patients for 30 to 39 hours per week declined from 54.9% in 2007 to 45.8% in 2010. Respondents reported an average of 34.6 hours in the practice and 30.0 hours in the practice treating patients. On average, prosthodontists spent (in 2010) about 4.6 hours in the office per week conducting activities other than treatment of patients, including administration, supervision, lab work, meetings, research, and other office activities. The survey was also used to determine how prosthodontists spend their treatment time. Prosthodontists were asked

to report the percent of their treatment time spent in providing various dental procedures and the percent RG7420 concentration of billings received by type of procedure rendered (Fig 5). The data shown in Figure 5 are the average

percent of time spent by prosthodontists in the procedure categories shown and the average percent of billings associated IDH assay with each procedure. The percent of time rendering a procedure and the percent of billings are closely related (Fig 5). Prosthodontist respondents reported that they spend about 21% of their time rendering fixed prosthodontics services, which were about 23% of their billings. About 80% of a prosthodontist’s time and billings is for six services including fixed prosthodontics, implant restoration, complete dentures, operative care, diagnostic care, and removable dentures. Figure 6 Enzalutamide manufacturer contains results comparing the percent of time rendering selected prosthodontic

services in 2007 and 2010. The average percent of time rendering fixed prosthodontics (excluding implants) has declined over the 3-year period, from 24.1% of the time in 2007 to 21.2% in 2010. Percent of time in implant restoration increased slightly, and implant placement declined over the 3-year period from 2007 to 2010. Percent of time in complete dentures declined from 12.5% in 2007 to 11.7% in 2010. Expenses of the practice were another economic activity reviewed by the survey. The nominal mean total practice expense per prosthodontist was $538,230 in 2010 compared to $518,255 in 2007. Expenses per prosthodontist are calculated by dividing the expenses reported for the practice by the total number of prosthodontists treating patients in the practice (full-time [FT] or part-time [PT], owners or nonowners). While mean overall expenses per prosthodontist increased, not all expense categories increased (Fig 7). Relative increases occurred in practice supply expense and employee taxes. Decreases in expenses per prosthodontist occurred for staff salaries, commercial lab charges, in-house lab charges, and officer salaries. The nominal mean salaries of officers declined by 34% over the period 2007 to 2010. Average nominal expenses per prosthodontist declined 86% for in-house lab, declined 29% for commercial lab, and declined 11% for staff salaries (Fig 7).

To test this hypothesis,

we first showed that CD3− infiltrating cells (non-T cells) expressed negligible levels of IFN-γ (not shown), and tumor-infiltrating T cells expressed high levels of IFN-γ (Fig. 1D). Proteasomal inhibitors The levels of IFN-γ+ T cells were higher in HCC tissues compared to adjacent tissues (Fig. 1D). Thus, tumor-infiltrating T cells are the major source of IFN-γ in HCC. Then we examined the potential effect of tumor-infiltrating T-cell-derived IFN-γ on KC galectin-9 expression. We cocultured normal blood CD14+ monocytes with T cells from HCC tissue or adjacent tissue. Tumor-infiltrating T cells were superior at inducing galectin-9 expression on monocytes as compared to adjacent T cells (Fig. 1E). The induction was blocked by neutralizing antibody against IFN-γ (Fig. 1E). To further support the stimulatory role of IFN-γ, we showed that recombinant IFN-γ induced galectin-9 expression on monocytes (Fig. 1E). Additionally, we isolated KCs from relatively normal liver tissues in patients with hepatic hemangiomas, performed similar experiments, and confirmed the stimulatory effects of IFN-γ derived from HCC-associated T cells on the expression of KC galectin-9

(Fig. 1F). The results demonstrate that tumor-infiltrating T-cell-derived IFN-γ contributes to the increased galectin-9 expression on KCs in the HCC microenvironment. Galectin-9 is the ligand for Tim-3. After determining the expression and regulation of galectin-9 in the HCC microenvironment, we further studied the expression of Tim-3. Flow cytometry R788 research buy analysis showed that Tim-3 was expressed on Urocanase tumor-infiltrating CD4+ and CD8+ T cells. In HBV-positive patients, the levels of Tim-3+CD4+ T cells were higher than that of CD8+ T cells (Fig. 2A,B). Furthermore, Tim-3+ T cells were largely found in HCC tissues, not in the adjacent tissues (Fig. 2A,B). In

HBV-negative patients, the percentages of Tim-3+ T cells were less than 3% in both HCC and adjacent tissues (Fig. 2A). In line with this, multiple-color fluorescent staining demonstrated that there were higher numbers of Tim-3+CD4+ cells in snap-frozen HCC tissues than adjacent tissues (15 ± 3% versus 4 ± 2%) (Fig. 2C). As Tim-3+ T cells were basically detected in HBV-associated HCC, we extended our studies further to include large numbers of paraffin-fixed HBV-associated HCC tissues with conventional immunohistochemistry staining (Fig. 2D). In line with flow analysis and multiple-color fluorescent staining, there were higher numbers of Tim-3+ cells in HCC tissues than adjacent tissues (12 ± 8 versus 2 ± 2) (Fig. 2D). These results indicate that Tim-3 expression is increased on T cells infiltrating the HCC microenvironment. We further evaluated the pathological relevance of Tim-3 expression in HBV-associated HCC. Based on conventional immunohistochemistry staining in paraffin-fixed HCC tissues (Fig.

To test this hypothesis,

we first showed that CD3− infiltrating cells (non-T cells) expressed negligible levels of IFN-γ (not shown), and tumor-infiltrating T cells expressed high levels of IFN-γ (Fig. 1D). PLX-4720 concentration The levels of IFN-γ+ T cells were higher in HCC tissues compared to adjacent tissues (Fig. 1D). Thus, tumor-infiltrating T cells are the major source of IFN-γ in HCC. Then we examined the potential effect of tumor-infiltrating T-cell-derived IFN-γ on KC galectin-9 expression. We cocultured normal blood CD14+ monocytes with T cells from HCC tissue or adjacent tissue. Tumor-infiltrating T cells were superior at inducing galectin-9 expression on monocytes as compared to adjacent T cells (Fig. 1E). The induction was blocked by neutralizing antibody against IFN-γ (Fig. 1E). To further support the stimulatory role of IFN-γ, we showed that recombinant IFN-γ induced galectin-9 expression on monocytes (Fig. 1E). Additionally, we isolated KCs from relatively normal liver tissues in patients with hepatic hemangiomas, performed similar experiments, and confirmed the stimulatory effects of IFN-γ derived from HCC-associated T cells on the expression of KC galectin-9

(Fig. 1F). The results demonstrate that tumor-infiltrating T-cell-derived IFN-γ contributes to the increased galectin-9 expression on KCs in the HCC microenvironment. Galectin-9 is the ligand for Tim-3. After determining the expression and regulation of galectin-9 in the HCC microenvironment, we further studied the expression of Tim-3. Flow cytometry this website analysis showed that Tim-3 was expressed on Thalidomide tumor-infiltrating CD4+ and CD8+ T cells. In HBV-positive patients, the levels of Tim-3+CD4+ T cells were higher than that of CD8+ T cells (Fig. 2A,B). Furthermore, Tim-3+ T cells were largely found in HCC tissues, not in the adjacent tissues (Fig. 2A,B). In

HBV-negative patients, the percentages of Tim-3+ T cells were less than 3% in both HCC and adjacent tissues (Fig. 2A). In line with this, multiple-color fluorescent staining demonstrated that there were higher numbers of Tim-3+CD4+ cells in snap-frozen HCC tissues than adjacent tissues (15 ± 3% versus 4 ± 2%) (Fig. 2C). As Tim-3+ T cells were basically detected in HBV-associated HCC, we extended our studies further to include large numbers of paraffin-fixed HBV-associated HCC tissues with conventional immunohistochemistry staining (Fig. 2D). In line with flow analysis and multiple-color fluorescent staining, there were higher numbers of Tim-3+ cells in HCC tissues than adjacent tissues (12 ± 8 versus 2 ± 2) (Fig. 2D). These results indicate that Tim-3 expression is increased on T cells infiltrating the HCC microenvironment. We further evaluated the pathological relevance of Tim-3 expression in HBV-associated HCC. Based on conventional immunohistochemistry staining in paraffin-fixed HCC tissues (Fig.

4a),[77] demonstrating the infectivity of HEV in click here pig liver that was for sale for human consumption. Taken together, although there is currently no direct evidence to prove HEV infection from pigs to humans, it is beyond doubt that pigs are the most important animal reservoir for HEV infection in humans in Japan, especially in Hokkaido, where the highest number of patients with

hepatitis E have been reported, most likely due to the consumption of pig meat/viscera (Table 4). Wild boars (Sus scrofa) are indigenous to many countries worldwide, including Japan, posing ecological and infectious disease concerns. In some countries including Japan, recreational hunting of wild boars and the consumption of boar meat provides an increased risk for the transmission of various pathogens, such as HEV, from wild boars to humans. The prevalence of HEV infection among wild boars in Japan has been investigated by many researchers, and the findings are summarized

in Table 5.[32, 79-84] The HEV seropositivity in wild boars varied from 4.5% to 34.3%, and the HEV RNA detection rate ranged 1.1–13.3% in wild boars from different geographical regions in Japan. In 2003, Matsuda et al.[18] reported, for the first time, two patients who developed a severe HEV infection after consuming raw liver from a wild boar. Later, Shimizu et al.[85] described four cases of acute hepatitis E in Aichi prefecture that occurred after the ingestion of boar meat. The HEV strains isolated from these patients that belonged to genotype 4, formed a single cluster, and were 98.8–99.7% identical to those recovered from wild boars captured in the same prefecture. PI3K Inhibitor Library ic50 Zoonotic food-borne transmission of HEV from wild boars to humans has been demonstrated by analyzing a case of hepatitis E caused by ingestion of boar meat, with the HEV strain sharing 99.95% nucleotide sequence identity with that in the leftover boar meat the patient had eaten.[19] Upon inoculation of A549 or PLC/PRF/5 cells with HEV in liver homogenates at 9.8 × 105 copies Phosphoprotein phosphatase per well or more (six-well plate), the boar HEV multiplied efficiently (Fig. 4b) and produced infectious

progeny viruses.[77] These findings indicate that wild boars are another important reservoir for HEV in humans. Most strains of HEV recovered from wild boars worldwide belong to genotype 3.[30] However, in Japan, boar HEV strains of not only genotype 3, but also genotype 4, have been detected. In addition, two novel HEV strains (JBOAR135-Shiz09 and wbJOY_06) belonging to unrecognized genotypes (provisionally designated as genotypes 5 and 6, respectively) have been recovered from wild boars in Japan.[86-88] It remains unknown whether these novel HEV strains can be transmitted to humans, and are also part of the reservoir for HEV. In 2003, Tei et al.[17] reported four patients who became infected with HEV after eating venison.

11 Disease concordance rate in monozygotic twin pairs (the proportion of affected pairs concordant for the disease) is another powerful tool to estimate the impact of genetic factors in susceptibility to complex disorders, including autoimmune disorders.11 In the past, PBC concordance rate has been limited to two reports,24, 25 one in a concordant and one in a discordant pair of twins, but monozygosity was not genetically proven. Thanks to a worldwide effort, we were able to identify eight monozygotic and eight dizygotic twin pairs in which at least one subject was affected by PBC and to find

a concordance rate of 63%, the highest among autoimmune diseases.7 In the general attempt to dissect the effects of different exposure to environmental factors, we also explored classical epigenetic factors in sets of PBC-affected twins, but excluded their major role in PBC development.26 Belnacasan cell line A role for genetics in PBC is also suggested by animal models of human PBC.27 Most of them are indeed spontaneous murine models due to selleck compound a number of different genetic changes. The genetically determined models of PBC include the interleukin-2 (IL-2) receptor alpha deleted (IL-2Rα−/−), transforming growth factor beta (TGF-β) receptor II dominant-negative (dnTGF-betaRII), scurfy, nonobese diabetic (NOD) c3c4, and AE2 gene-disrupted (AE2a,b−/−) mice. For one

of these models (the IL-2 receptor alpha deleted), there has been a corresponding PBC-like disease reported in a child with IL-2 receptor alpha (CD25) deficiency.28 The literature PAK6 on PBC contains many publications that have attempted to identify genes with a role in disease susceptibility and progression by evaluating small numbers of variants in one or a few specific candidate genes by means of case–control study designs. Of course, most of these genes code for immune-related molecules and were already implicated in other autoimmune disorders, including

tumor necrosis factor (TNF), cytotoxic T lymphocyte antigen-4 (CTLA-4), Toll-like receptors, caspase-8, vitamin D receptor, interleukins IL-1, IL-2, and IL-10, and numerous cytokine and chemokine receptors. However, such approaches have led to very few insights into the genetic basis of PBC, mainly for lack of robust replication. A paradigmatic example is that related to CTLA-4 gene association studies. Although two earlier studies from the UK29 and China30 found a single-nucleotide polymorphism (SNP) associated with PBC, more recent data from Brazil,31 Italy,32 Germany,33 the UK,34 and the US35 failed to confirm it. In addition, the follow-up study by the UK group34 failed to replicate their original positive finding,29 whereas the follow-up study by the US group36 found a novel SNP association in contrast with their original negative finding.35 Accordingly, caution is suggested when interpreting these findings.

Results: Compared to wild type mice, ASMase-/- mice were resistant to alcohol induced steatosis, exhibiting 70%ndash;90% lower trigliceride levels and oil red staining.

Consistent with these findings, alcohol-induced ER stress (Chop, Pdi) and liver injury (3%ndash;4 fold increase in ALT) were observed in wild type but not in ASMase null mice. Interestingly, increase ICG-001 manufacturer in plasma Hcy levels was similar in wild type and ASMase null mice (5%ndash;7 fold). Wild type but not ASMase null mice exhibitied increased StARD1 overexpression and mitochondrial cholesterol trafficking by alcohol feeding. Moreover, evidence for Kupffer cell M1 /M2 polarization was similar for wild type and ASMase mice. Lysosomal permeabilization examined by NAG activation in the cytosol was lower in ASMase null mice compared to wild type

mice. Conclusion: ASMase null mice are resistant to intragastric alcohol-induced ER stress, steatosis, and liver injury despite severe Hcy, implying that the ability of Hcy to induce ER stress in response to alcohol is dependent on ASMase. Disclosures: Hidekazu Tsukamoto – Consulting: Shionogi & Co., S.P. Pharmaceutics; Grant/Research Support: The Toray Co. Neil Kaplowitz – Consulting: GlaxoSmithKline, Gefitinib JNJ, Merck, Novartis, Hepregen, Takeda, Otsuka; Independent Contractor: Acetaminophen Litigation The following people have nothing to disclose: Anna Baulies, Laura Martinez, Carmen Garcia-Ruiz, Jose Fernandez-Checa Backgrounds: The Wnt/β-catenin pathway is important for the regulation of liver growth, repair, and regeneration. It has been previously shown that chronic ethanol consumption blunts normal liver regenerative responses, in particular by inhibiting insulin/IGF signaling. Treatment with PPARδ agonist restored hepatic insulin responsiveness and normalized liver histology. Accordingly, we hypothesized whether these effects are associated with improvements in Wnt signaling. In this study, we investigated the effects

of chronic ethanol exposure Parvulin and subsequent treatment with PPARδ agonist on the expression of Wnt pathway genes during a post-partial hepatectomy (PH) time course. Methods: Adult male Long Evans rats were fed with isocaloric liquid diets containing 0 or 37% ethanol for 8 weeks followed by 2/3 PH. During the last three weeks, a portion of rats was fed with PPARδ agonist. All animals were sacrificed at 0, 18, 24, 30, 48, 72 hour, and one week time points after PH. Total RNA was extracted from liver tissue. The expression of 19 genes involved in the Wnt pathway was quantified by reporter signal amplification using the Quantigene 2.0 Multiplex Assay (Affymetrix). Results: Chronic ethanol consumption led to expression changes in the 19 genes tested, demonstrating an inhibition of Wnt/β-catenin signaling.

17, 18 Taura et al. do not examine the issue of cholangiocyte EMT. Members of their group, however, reported in abstract format at the 2009 American Association for the Study of Liver Diseases Annual Meeting that mouse cholangiocytes, analyzed by robust lineage-tracing techniques with the cytokeratin-19 promoter, show no evidence of EMT in bile duct ligation or CCl4 fibrosis models.21 Our group has obtained similarly negative results in alpha-fetoprotein–Cre; Rosa26–yellow fluorescent protein mice, in which both hepatocytes and cholangiocytes are tagged. These studies now require the screen of peer review, but the coincident results are hard to ignore, and it

appears that lineage tracing may debunk the concept of cholangiocyte EMT in PXD101 the same way hepatocyte EMT was addressed in the article by Taura et Daporinad research buy al.12 For cholangiocytes, however, it is hard to dismiss the observation that bile duct basement membranes undergo degradation in fibrosis, and that cholangiocytes assume fibroblast-like, noncuboidal shapes. How can these convincing findings from histological analyses be reconciled with the negative data from lineage-tracing experiments? As detailed above, most of the initial data in favor of hepatocyte EMT were derived from animal models, which makes these models an appropriate

way to study this phenomenon. Evidence in favor of cholangiocyte EMT, however, is for the most part derived from human samples. There are significant differences between human diseases and the bile duct ligation and CCl4 rodent models, in particular, in the extent of progenitor cell activation and the ductular reaction.22 It is therefore critical to identify reliable surrogate markers of EMT for use in human tissue staining, regardless of the organ under study. Some progress in this area may come with the development of panels of specific markers next based on recently described global regulators of EMT programs.23 The existence of reliable biomarkers might have called hepatocyte (and renal epithelial) EMT into question earlier. These will be essential to investigating EMT in cholangiocytes,

other cells of the liver, and other organs as the study of fibrosis moves forward. “
“The high prevalence of non-alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases.

17, 18 Taura et al. do not examine the issue of cholangiocyte EMT. Members of their group, however, reported in abstract format at the 2009 American Association for the Study of Liver Diseases Annual Meeting that mouse cholangiocytes, analyzed by robust lineage-tracing techniques with the cytokeratin-19 promoter, show no evidence of EMT in bile duct ligation or CCl4 fibrosis models.21 Our group has obtained similarly negative results in alpha-fetoprotein–Cre; Rosa26–yellow fluorescent protein mice, in which both hepatocytes and cholangiocytes are tagged. These studies now require the screen of peer review, but the coincident results are hard to ignore, and it

appears that lineage tracing may debunk the concept of cholangiocyte EMT in PR171 the same way hepatocyte EMT was addressed in the article by Taura et Wnt activation al.12 For cholangiocytes, however, it is hard to dismiss the observation that bile duct basement membranes undergo degradation in fibrosis, and that cholangiocytes assume fibroblast-like, noncuboidal shapes. How can these convincing findings from histological analyses be reconciled with the negative data from lineage-tracing experiments? As detailed above, most of the initial data in favor of hepatocyte EMT were derived from animal models, which makes these models an appropriate

way to study this phenomenon. Evidence in favor of cholangiocyte EMT, however, is for the most part derived from human samples. There are significant differences between human diseases and the bile duct ligation and CCl4 rodent models, in particular, in the extent of progenitor cell activation and the ductular reaction.22 It is therefore critical to identify reliable surrogate markers of EMT for use in human tissue staining, regardless of the organ under study. Some progress in this area may come with the development of panels of specific markers Thiamet G based on recently described global regulators of EMT programs.23 The existence of reliable biomarkers might have called hepatocyte (and renal epithelial) EMT into question earlier. These will be essential to investigating EMT in cholangiocytes,

other cells of the liver, and other organs as the study of fibrosis moves forward. “
“The high prevalence of non-alcoholic fatty liver disease (NAFLD) has made the condition an important public health issue. Two clinical entities are manifestations of NAFLD, namely, non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). The former tends to be benign and non-progressive while the latter can progress to cirrhosis, which in rare cases gives rise to hepatocellular carcinoma. The diagnosis of NAFLD is based on: (i) a history of no or limited daily alcohol intake (<20 g for women and <30 g for men); (ii) presence of hepatic steatosis by imaging or by histology; and (iii) exclusion of other liver diseases.

Results: The aptamers could be clustered into 4 subgroups, and the correlation coefficients between aptamers were from 0.009 to 0.707, indicating that most of these aptamers have different targets in PHC serum. The results of aptamer assay were significantly correlated with some clinical Cabozantinib and laboratory parameters, such as 8 aptamers with liver cirrhosis background, 7 aptamers with liver function, 7 aptamers with international normalized rate (INR), 6 aptamers with tumor size, 6 aptamers with blood platelet count, 4 aptamers with total bilirubin. The patients could be clustered into 2-4 subgroups

with the results of aptamer assay. Some clinical and laboratory parameters were significantly different between or among subgroups (P < 0.05∼0.01). This is the first attempt of molecular classification by aptamer assay. Conclusion: Primary hepatic carcinoma could be clustered into subgroups with the results of aptamer assay, suggesting that aptamer-based molecular classification of PHC has feasibility and clinical value. Key Word(s): 1. Aptamer; 2. classification; 3. Correlation; 4. hepatoma; Presenting Author: SHIFTEH ABEDIAN Additional Authors: MEHDISABERI FIROOZI, REZA MALEKZADEH Corresponding Author: SHIFTEH ABEDIAN, MEHDISABERI FIROOZI Affiliations: TUMS(DDRI) Objective: Hepatocellular Carcinoma Doxorubicin molecular weight (HCC) is the sixth common cancer in world. In order to define the characteristics of HCC in our country we studied

the cases that have been admitted in a large referral gastroenterology ward during 2000-2011. Methods: The discharge sheets of 7000 patients had been admitted in Shariati hospital GI ward during this period were reviewed. We defined and coded the final diagnosis on the basis of ICD-10 and then extracted the etiologic causes-outcome and other demographic data of HCC from discharge notes. The not diagnosis of HCC was done according to liver biopsy or typical imaging studies according to international guidelines. Results: 7000 patients admitted during this time in GI

Ward that 3.4% of them had HCC. 74% of these patients were men (age 55.81 ± 4.91 years) and 26% were women (age 53.61 ± 17.30 years). The mortality rate in this group was 17.2%. In women the common etiologies were related to: cryptogenic (47.36%), Hepatitis B virus (HBV) (39.48%), cholestatic liver disease in 7.89% and hepatitis C virus (HCV) in 5.57%. In men 62.03% of HCC was related to HBV, 22.22% to cryptogenic, 10.19% to HCV. The most common presentations in these patients were ascites and spontaneous bacterial peritonitis (48.8%), hepatic encephalopathy (24%), variceal bleeding (12%) and hepatorenal syndrome (2.5%). The most common presentations of patients who died were hepatic encephalopathy (41.8%), variceal bleeding (31.5%), ascites and/or spontaneous bacterial peritonitis (15%), and hepatorenal syndrome (5.2%). Conclusion: More than half of HCC is related to viral hepatitis and especially to HBV.

Her sense of humor, practicality, and calm demeanor—actually knitting during board meetings—reduced the angst level of the proceedings. She mentored fellows and graduate students at Yale and in Memphis, was a frequent reviewer of articles, and a popular invitée to lecture in Europe, South America, South Africa, and Australia, as well as in North America. Caroline’s effervescent personality, her sense of humor, and adventurous bent paralleled her intense kindness,

compassion, and good works, both civic and personal. In his terminal years, she made frequent trips home ATM inhibitor to be with her ailing father. When my wife and I were temporarily “homeless” in New Haven, because our house purchase fell through, unsolicited she unhesitatingly offered us (and our dog) refuge in her famous 1870s “pink” house that she had tastefully renovated.

Renovating old homes was another of her hobbies. Caroline was the most disarmingly color-, age-, race-, ethnicity-, religion-, and lifestyle-blind human being whom I have ever met. She could move effortlessly from a party at the mansion of the President of the University to an evening of movies and pizza with the house staff and the fellows—and Aloxistatin cell line frequently did so. She was an inveterate traveler of the US and the world with her friends, including her annual winter trip to Virgin Gorda in the Caribbean, and summer escapes to Lake Squam in New Hampshire. Caroline never met a beach that she could not swim. While not as athletic as

her tennis champion mother, she learned scuba in the Yale Gymnasium swimming pool, and no matter the depth, the wildness of the waves, or the threatening rocks, she always had to see what was beneath the surface. Her compassion encompassed humans and animals alike, including making a single-handed attempt (until help arrived), while dressed in all her finery and signature raccoon coat, to transport her wheelchair-bound stroke victim friend to the symphony. She would drive one of her beloved but Addisonian dachshunds across state lines to a Immune system distant and expensive animal hospital for therapy. How tragic that she ended her days totally disabled, wheelchair-bound herself, and unable to think or communicate. How sad that she, who bonded with her patients to put them at ease, no matter their lifestyle or behavior, was herself all “locked in” and “shut out” at the end. Caroline Riely considered the following extract from a sermon preached by Henry Scott Holland (1847-1918), Regius Professor of Divinity at the University of Oxford, at St. Paul’s Cathedral, London, in May 1910, to be a wonderfully composed meditation on life. It was read at her memorial ceremony held in Richmond, 69 years after her birth. Death is nothing at all. It does not count. Nothing has happened. Everything remains exactly as it was. I am I, and you are you, and the old life that we lived so fondly together is untouched, unchanged. Whatever we were to each other, that we are still.