The earliest domestic cat on the Silk Road.

We present the earliest evidence for domestic cat (Felis catus L., 1758) from Kazakhstan, found as a well preserved skeleton with extensive osteological pathologies dating to 775-940 cal CE from the early medieval city of Dzhankent, Kazakhstan. This urban settlement was located on the intersection of the northern Silk Road route which linked the cities of Khorezm in the south to the trading settlements in the Volga region to the north and was known in the tenth century CE as the capital of the nomad Oghuz. The presence of this domestic cat, presented here as an osteobiography using a combination of zooarchaeological, genetic, and isotopic data, provides proxy evidence for a fundamental shift in the nature of human-animal relationships within a previously pastoral region. This illustrates the broader social, cultural, and economic changes occurring within the context of rapid urbanisation during the early medieval period along the Silk Road.

Altered neuronal density and neurotransmitter expression in the ganglionated region of Ednrb null mice: implications for Hirschsprung's disease.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital condition in which enteric ganglia, formed from neural crest cells (NCC), are absent from the terminal bowel. Dysmotility and constipation are common features of HSCR that persist following surgical intervention. This persistence suggests that the portion of the colon that remains postoperatively is not able to support normal bowel function. To elucidate the defects that underlie this condition, we utilized a murine model of HSCR. METHODS: Mice with NCC-specific deletion of Ednrb were used to measure the neuronal density and neurotransmitter expression in ganglia. KEY RESULTS: At the site located proximal to the aganglionic region of P21 Ednrb null mice, the neuronal density is significantly decreased and the expression of neurotransmitters is altered compared with het animals. The ganglia in this colonic region are smaller and more isolated while the size of neuronal cell bodies is increased. The percentage of neurons expressing neuronal nNOS and VIP is significantly increased in Ednrb nulls. Conversely, the percentage of choline acetyltransferase (ChAT) expressing neurons is decreased, while Substance P is unchanged between the two genotypes. These changes are limited to the colon and are not detected in the ileum. CONCLUSIONS & INFERENCES: We demonstrate changes in neuronal density and alterations in the balance of expression of neurotransmitters in the colon proximal to the aganglionic region in Ednrb null mice. The reduced neuronal density and complementary changes in nNOS and ChAT expression may account for the dysmotility seen in HSCR.

Tracing toothache intensity in the brain.

Identification of brain regions that differentially respond to pain intensity may improve our understanding of trigeminally mediated nociception. This report analyzed cortical responses to painless and painful electrical stimulation of a right human maxillary canine tooth. Functional magnetic resonance images were obtained during the application of five graded stimulus strengths, from below, at, and above the individually determined pain thresholds. Study participants reported each stimulus on a visual rating scale with respect to evoked sensation. Based on hemodynamic responses of all pooled stimuli, a cerebral network was identified that largely corresponds to the known lateral and medial nociceptive system. Further analysis of the five graded stimulus strengths revealed positive linear correlations for the anterior insula bilaterally, the contralateral (left) anterior mid-cingulate, as well as contralateral (left) pregenual cingulate cortices. Cerebral toothache intensity coding on a group level can thus be attributed to specific subregions within the cortical pain network.

Evaluation of different fluoridated dentifrice formulations using an in situ erosion remineralization model.

OBJECTIVE: The objective of these three clinical in situ studies was to investigate the relative performance of commercially available and experimental dentifrice formulations, having different fluoride sources and excipient ingredients, at remineralizing a bovine enamel surface previously softened by a dietary acid challenge. METHODS: Each study utilized the same randomized, placebo-controlled, single-blind, crossover design. Subjects undertook single brushings of their natural teeth, with an in situ appliance in place, using different dentifrices in a randomly assigned order. Study A involved 58 subjects with the following dentifrices: Sensodyne Pronamel (1450 ppm F as NaF/5% KNO3); Blend-a-Med Classic (1450 ppm F as NaF); and a matched (Pronamel) placebo control (0 ppm F). Study B involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Crest Cavity Protection (1100 ppm F as NaF); Crest Pro-Health (0.454% SnF2 [1100 ppm F]/sodium hexametaphosphate); and a matched (Pronamel) placebo control (0 ppm F). Study C involved 56 subjects with the following dentifrices: Sensodyne Pronamel (1150 ppm F as NaF/5% KNO3); Sensodyne Pronamel Gentle Whitening (1150 ppm F as NaF/5% KNO3); Colgate Sensitive Multi Protection (1000 ppm F as NaMFP/5.53% potassium citrate/2% zinc citrate); and a matched (Pronamel) placebo control (0 ppm F). Subjects wore their palatal appliances holding eight bovine enamel blocks, previously exposed for 25 minutes to an in vitro erosive challenge with grapefruit juice, for the duration of the experiment. Five minutes after appliance insertion, subjects undertook a supervised, 90-second brush/rinse regimen with their assigned dentifrice. Surface microhardness (SMH) of the specimens was determined prior to the erosive challenge (baseline), after the in vitro erosive challenge, and were remeasured after four hours in situ remineralization following the tooth brushing event. Finally, SMH values were determined after a second in vitro erosive challenge at the end of the in situ remineralization period. Statistical analyses included ANOVA and pair-wise comparisons between treatments, testing at a 5% significance level. RESULTS: All three studies demonstrated significantly greater percent surface microhardness recovery (% SMHr) and percent relative erosion resistance (% RER) for dentifrices containing sodium fluoride compared to placebo controls. Overall, significantly greater % SMHr (p < 0.0001) was observed for Sensodyne Pronamel compared to Blend-a-Med Classic, Crest Pro-Health, and Colgate Sensitive Multi Protection dentifrices. Similarly, Sensodyne Pronamel delivered directionally better % RER vs. Blend-a-Med Classic (p = 0.0731), and significantly higher % RER vs. Crest Pro-Health (p = 0.0074) and Colgate Sensitive Multi Protection (p <0.0001). Crest Cavity Protection demonstrated significantly better % RER (p = 0.031) than Crest Pro-Health, which in turn demonstrated significantly better % RER than the placebo control (p < 0.0001). No other statistically significant between-product comparisons were observed. CONCLUSION: The results of these in situ studies support the effectiveness of dentifrices containing sodium fluoride to reharden enamel previously softened with an erosive challenge. Furthermore, these studies demonstrate the protective effects conferred to enamel, from erosion following the remineralization process in the presence of "ionic" fluoride. Under clinically relevant conditions, Sensodyne Pronamel and Sensodyne Pronamel Gentle Whitening offered superior anti-erosion performance compared to currently marketed dentifrice controls. These studies reinforce previous research indicating the importance of formulation effects on the relative remineralization performance of dentifrices under erosive conditions.

Effect of massage of the hamstring muscles on selected electromyographic characteristics of biceps femoris during sub-maximal isometric contraction.

The aim of this study was to investigate whether a single massage of the hamstring muscles would alter selected electromyographic characteristics of biceps femoris during a sub-maximal isometric contraction. Eleven healthy young males participated in this crossover study. They were randomly assigned to two groups, receiving either a 15-minute hamstring muscle massage or a 15-minute prone rest. One week later they returned to receive the alternate intervention. Immediately pre- and post-intervention, participants were instructed to contract their muscles just sufficiently to maintain right knee flexion (5 degrees from full extension) for 30 seconds. Simultaneous to this contraction, surface electromyography (EMG) was used to record the electrical activity of right biceps femoris. Electromyograms were analyzed by calculating the averaged/integrated EMG (aEMG) and median frequency (MF) for each of 14 one-second windows, sampled every two seconds throughout the 30-second contractions per participant. Mean values of aEMG and MF were calculated per participant (aEMGmean and MFmean), pre- and post-massage or rest intervention. Group means (n = 11) of aEMGmean and MFmean were then calculated and compared using a repeated measures analysis of variance (ANOVA) procedure (p < 0.05). Rates of change of aEMG and MF throughout each 30-second contraction were represented by their respective gradients as functions of time. These gradients were similarly compared pre- to post-intervention using repeated measures ANOVA (p < 0.05). For the young healthy males considered in this study, a single massage of the hamstring muscles had no statistically significant effects on selected electromyographic characteristics of biceps femoris during sub-maximal isometric contractions (p > 0.05).

Evaluation of a desensitizing test dentifrice using an in situ erosion remineralization model.

OBJECTIVE: To evaluate, in an in situ remineralization model, the ability of a low abrasion fluoride dentifrice containing potassium nitrate to enhance the remineralization of enamel that was previously subjected to an in vitro dietary erosion challenge. METHODOLOGY: Thirteen subjects completed a single-blind (to specimen analyst) crossover design study with four randomly assigned dentifrice treatments: placebo dentifrice (0 ppm F; PD); dose response control dentifrice (250 ppm F; DD); clinically tested fluoride dentifrice (1100 ppm F; FD); and test dentifrice (1150 ppm F + 5% KNO3; TD). Each subject wore a palatal appliance holding eight bovine enamel blocks that were previously exposed for 25 minutes to an in vitro erosive challenge with grapefruit juice. Surface microhardness (SMH) was determined prior to the erosive challenge (baseline), after the in vitro erosive challenge, after in situ remineralization, and after a second in vitro erosive challenge. Statistical analyses included ANOVA and pair-wise comparisons between treatments, testing at a 5% significance level. RESULTS: The mean percent SMH recovery (SD) was 20.4 (7.7)a for PD; 27.4 (5.9)b for DD; 29.5 (8.9)bc for FD; 33.4 (6.7)c for TD. The mean percent net erosion resistance (SD) was -57.7 (10.8)a for PD; -41.3 (11.6)b for DD; -28.7 (9.7)c for FD; -23.6 (7.3)c for TD. Different superscript letters following the means imply statistically significant differences between groups for each response. CONCLUSION: The test dentifrice was shown to significantly enhance the remineralization of enamel previously subjected to an erosion challenge.

Effect of massage of the hamstring muscle group on performance of the sit and reach test.

OBJECTIVE: To investigate if a single massage of the hamstring muscle group would alter the performance of the sit and reach test. METHODS: Before treatment, each of 11 male subjects performed the sit and reach test. The treatment consisted of either massage of the hamstring muscle group (both legs, total time about 15 minutes) or supine rest with no massage. Performance of the sit and reach test was repeated after treatment. Each subject returned the subsequent week to perform the tests again, receiving the alternative treatment relative to their initial visit. Mean percentage changes in sit and reach scores after treatment were calculated for the massage and no massage treatments, and analysed using Student's t tests. RESULTS: Mean (SD) percentage changes in sit and reach scores after massage and no massage were small (6.0 (4.3)% and 4.6 (4.8)% respectively) and not significantly different for subjects with relatively high (15 cm and above) values before treatment. Mean percentage changes in sit and reach scores for subjects with relatively low values before treatment (below 15 cm) were large (18.2 (8.2)% and 15.5 (16.2)% respectively), but no significant differences were found between the massage and no massage groups. CONCLUSIONS: A single massage of the hamstring muscle group was not associated with any significant increase in sit and reach performance immediately after treatment in physically active young men.

dSIR2 and dHDAC6: two novel, inhibitor-resistant deacetylases in Drosophila melanogaster.

We have identified new members of the histone deacetylase enzyme family in Drosophila melanogaster. dHDAC6 is a class II deacetylase with two active sites, and dSIR2 is an NAD-dependent histone deacetylase. These proteins, together with two class I histone deacetylases, dHDAC1 and dHDAC3, have been expressed and characterized as epitope-tagged recombinant proteins in Schneider SL2 cells. All these proteins have in vitro deacetylase activity and are able to deacetylate core histone H4 at all four acetylatable lysine residues (5, 8, 12, and 16). Recombinant dHDAC6 and dSIR2 are both insensitive to TSA and HC toxin and resistant, relative to dHDAC1 and dHDAC3, to inhibition by sodium butyrate. Indirect immunofluorescence microscopy of stably transfected SL2 lines reveals that dHDAC1 and dSIR2 are nuclear, dHDAC6 is cytosolic, and dHDAC3 is detectable in both cytosol and nucleus. dHDAC6 and dSIR2 elute from Superose 6 columns with apparent molecular weights of 90 and 200 kDa, respectively. In contrast, dHDAC1 and dHDAC3elute at 800 and 700 kDa, respectively, suggesting that they are components of multiprotein complexes. Consistent with this, recombinant dHDAC1 coimmunoprecipitates with components of the Drosophila NuRD complex and dHDAC3 with an as yet unknown 45-kDa protein.

Molecular cloning of Drosophila melanogaster cDNAs that encode a novel histone deacetylase dHDAC3.

The steady-state level of histone acetylation in eukaryotes is established and maintained by multiple histone acetyltransferases (HATs) and histone deacetylases (HDACs) and affects both the structure and the function of chromatin. Histone deacetylases play a key role in the regulation of transcription, and form a highly conserved protein family in many eukaryotic species. Here we describe the cloning, sequencing and genetic mapping of two histone deacetylase genes in Drosophila melanogaster: dHDAC1 is essentially identical to the previously cloned D. melanogaster d-Rpd3 gene and dHDAC3, a novel gene, is orthologous to the human and the chicken (Gallus gallus) HDAC3 genes. The predicted amino acid sequence (438 aa) of dHDAC3 shows 58.1% identity with dHDAC1/d-Rpd3, the only previously known member of the HDAC family in this organism. The map positions on polytene chromosomes for dHDAC1 and dHDAC3 were determined as 64C1-6 and 83A3-4 respectively. A search for other dHDAC3-like genes failed to find other potential paralogues in D. melanogaster, but identified significant homologies with bacterial and fungal genes encoding enzymes that metabolise acetyl groups, and with genes for other hydrolyases such as carboxypeptidase. In addition, histone deacetylase activity in D. melanogaster nuclear extracts can be inhibited by high concentrations of zinc and activated by low concentrations, which is identical to the properties of bovine carboxypeptidase A. On the basis of sequence and functional similarities, we suggest that histone deacetylases are metal-substituted enzymes.

Colonoscopic follow-up after resection for colorectal cancer: a selective policy.

A policy of selective colonoscopy after resection for colorectal cancer was evaluated to assess the benefit of detecting missed synchronous and metachronous tumours in patients under 70 years of age with a good prognosis, and the possible risk of missing such lesions in those not screened. With preoperative barium enema and palpation at laparotomy, synchronous cancers and adenomas were found in 2 and 28 per cent, respectively, of 275 consecutive patients undergoing resection. Eighty-five patients were selected for postoperative colonoscopy, which was repeated at least once in 32, there being a total of 60 repeat examinations. Adenomas, but no cancers, were found in 19 patients (22 per cent) on first screening, but on repeat colonoscopy early metachronous cancers were detected in three patients (9 per cent) and adenomas on 21 examinations (35 per cent). Only one of the patients followed by clinical examination developed a symptomatic tumour. This suggests that postoperative colonoscopy is unlikely to benefit the majority but may be extremely important for young fit patients with continuing polyp formation who are at high risk of developing metachronous cancer.

Barrett's oesophagus: effect of antireflux surgery on symptom control and development of complications.

Forty-five patients with histologically proven Barrett's columnar-lined oesophagus (CLO) were treated in one unit over a 9-year period. Patients were studied prospectively as part of a surveillance programme; all initially received standard conservative treatment including high-dose H2-receptor antagonists. A satisfactory initial response was seen in 21 patients, but in 24 the symptoms were unchanged or progressed; 19 patients in the latter group were considered suitable for antireflux surgery and underwent fundoplication. Symptoms of heartburn or dysphagia persisted or recurred in 88 per cent of patients receiving medical treatment alone and complications developed in 38 per cent, including nine strictures and one adenocarcinoma. In patients undergoing antireflux surgery, symptoms persisted or recurred in 21 per cent and complications developed in 16 per cent (P < 0.01). Complete regression of Barrett's CLO occurred in two patients (11 per cent) after antireflux surgery. The results of this study suggest the superiority of antireflux surgery over pharmacological acid suppression in the control of symptoms and prevention of complications in patients with Barrett's CLO.

Imipramine inhibiton of ragweed allergic conjunctivitis.

Twenty-seven patients sensitive to ragweed pollen were treated with topical imipramine 0.05% in one eye and vehicle in the other in a double-masked fashion. The eyes treated with imipramine showed significantly less redness, tearing, and discomfort after exposure to pollen extract. Imipramine, a tricyclic antidepressant, appears to be an effective antihistamine in the eye.

Safflower oil emulsion: single and multiple infusions with or without added heparin in normal human volunteers.

Intravenous hyperalimentation in chronically ill patients has become increasingly common in hospitalized patients. Total parenteral nutrition includes supply of carbohydrates, amino acids, and lipids. The safety of a new emulsion of safflower oil (Liposyn 10%) infused by peripheral vein was evaluated in 15 normal male volunteers. All subjects tolerated Liposyn infusion, with a low incidence of side effects, when given either as a single infusion or multiple daily infusions to provide 4% of daily caloric requirements in the form of linoleic acid for 5 consecutive days. In large doses, the lipid infusion was accompanied by a decrease in Lee-White clotting time in most subjects, and 1.5 to 2 U/ml of heparin added to the emulsion reversed this effect. Such mini doses of heparin also accelerated the breakdown and disappearance of triglycerides, with a resultant increase in serum free fatty acids and cholesterol. These data suggest that safflower oil emulsion can be used as a source of essential fatty acids for intravenous alimentation. It is also suggested that patients receiving lipid infusion should receive heparin to minimize risks associated with hypercoagulability of blood.

Changes in the cell surface of the dimorphic forms of Candida albicans by treatment with hydrolytic enzymes.

The release of acid phosphatase and polysaccharide-peptide complexes by hydrolytic enzymes from the surface of the blastospore and mycelial forms of Candida albicans has been examined in cells from 4 h and 18 h cultures and the results correlated with the appearance of the treated cells in the electron microscope. Treatment with dithiothreitol was necessary for the degradative action of the enzymes to occur. Material released by all the treatments used had a similar qualitative composition, but the proportions of mannan, glucan, peptide and acid phosphatase varied with different treatments and with the type of cell examined. I,3-beta-Glucanase was required for major changes in the cell wall to be effected, but a significant amount of material was released with a chitinase preparation containing some protease activity. Protoplasts were obtained from all types of cell using Cytophaga lytic enzyme L1 which had I,3-beta-glucanase and protease activity, but the purified I,3-beta-glucanase and protease prepared from Streptomyces violaceus cultures required the presence of a chitinase before protoplasts were released. The bonding association between the major components which comprise the cell wall, and the spatial distribution of these macromolecules, varies appreciably between the two dimorphic forms and with the age of the culture.