Solvation mechanisms of nedocromil sodium from activation energy and reaction enthalpy measurements of dehydration and dealcoholation

Two independent athermal methods of analysis have been used to determine the activation energies associated with the dehydration of nedocromil sodium hydrates. For the highest temperature reaction, monohydrate to the anhydrate, the differences in the measured activation energies indicate a three-dimensional nucleation mechanism in the bulk of the crystal with subsequent three-dimensional anhydrate crystal growth. The number of critical nuclei varies inversely with heating rate. Measured enthalpy values for successive removal of water molecules at 31.7 +/- 1.0, 91.3 +/- 0.8, and 193 +/- 0.6 degrees C are the same, within experimental error, at 21.6 +/- 2.6 kJ (mol H(2)O)(-1), as determined from differential thermal analysis traces. This result implies that an earlier concept of "strong" and "weak" water binding is not relevant and temperatures at which H(2)O molecules are removed is related to nucleation effects and not bond energies. The low temperature shoulder on the 91.3 degrees C peak is identified as an effect arising from open pan analysis conditions. The appearance of "transient" peaks in the conditioning stage of nedocromil sodium trihydrate thermal analysis experiments have been investigated and an explanation based on the presence of alcoholates [(NS)(4) small middle dot 5CH(3)OH, (NS)(5) small middle dot 9C(2)H(5)OH, and (NS)(2) small middle dot C(3)H(7)OH] in the preparations is proposed.     

The role of turmerones on curcumin transportation and P-glycoprotein activities in intestinal Caco-2 cells

The rhizome of Curcuma longa (turmeric) is often used in Asia as a spice and as a medicine. Its most well-studied component, curcumin, has been shown to exhibit poor bioavailability in animal studies and clinical trials. We hypothesized that the presence of lipophilic components (e.g., turmerones) in turmeric extract would affect the absorption of curcumin. The effects of turmerones on curcumin transport were evaluated in human intestinal epithelial Caco-2 cells. The roles of turmerones on P-glycoprotein (P-gp) activities and mRNA expression were also evaluated. Results showed that in the presence of α- and aromatic turmerones, the amount of curcumin transported into the Caco-2 cells in 2 hours was significantly increased. α-Turmerone and verapamil (a P-gp inhibitor) significantly inhibited the efflux of rhodamine-123 and digoxin (i.e., inhibited the activity of P-gp). It is interesting that aromatic turmerone significantly increased the rhodamine-123 efflux and P-gp (MDR1 gene) mRNA expression levels. The effects of α- and aromatic turmerones on curcumin transport as well as P-gp activities were shown here for the first time. The presence of turmerones did affect the absorption of curcumin in vitro. These findings suggest the potential use of turmeric extract (including curcumin and turmerones), rather than curcumin alone, for treating diseases.     

Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome

The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.The oldest Gaelic literature describes the origins of the Irish people as a series of ancient invasions, and the archaeological record in Ireland, as elsewhere in Europe, exhibits several horizons where major cultural shifts are apparent (1). The two most transformative are the arrival of agriculture (∼3750 BC) followed by the onset of metallurgy (∼2300 BC). The Neolithic package characterized by animal husbandry, cereal crops, ceramics, and timber houses reached the shores of Ireland some 5,000 years after its beginnings in the Near East. The second great wave of change starts with the appearance of copper mines, associated with Bell Beaker pottery, which are quickly followed by Bronze tool-making, weaponry, and gold-working, with distinct Food Vessel pottery succeeding from the earlier beakers (2). This period coincides with the end of the large passage graves of Neolithic Ireland in favor of single burials and smaller wedge tombs.Twentieth-century archaeology was dominated by two non-mutually-exclusive paradigms for how such large scale social change occurs (3). The first, demic diffusion, linked archaeological change with the displacement and disruption of local populations by inward migrations. However, from the 1960s onwards, this assertion was challenged by a paradigm of cultural diffusion whereby social change happened largely through indigenous processes.High-throughput sequencing has opened the possibility for genome-wide comparisons of genetic variation in ancient populations, which may be informatively set in the context of extensive modern data (4–10). In Europe, these clearly show population replacement by migrating farmers from southwest Asia at the onset of the Neolithic with some retrenchment of the earlier Mesolithic genome at later stages (5–9, 11, 12). Three longitudinal genome studies have also shown later genome-wide shifts around the beginnings of the Bronze Age in central Europe with substantial introgression originating with the Yamnaya steppe herders (7, 9, 10). However, replacement coupled to archaeological horizons is unlikely to be a universal phenomenon, and whether the islands of Britain and Ireland, residing at the temporal and geographical edges of both the Neolithic and steppe migrations, were subject to successive substantial population influxes remains an open and debated question. For example, a recent survey of archaeological opinion on the origins of agriculture in Ireland showed an even split between adoption and colonization as explanatory processes (13). Recent archaeological literature is also divided on the origins of the insular Bronze Age, with most opinion favoring incursion of only small numbers of technical specialists (1, 2, 14, 15).To address this controversy, we present here the first, to our knowledge, genome-wide data from four ancient Irish individuals, a Neolithic woman (3343–3020 cal BC) from Ballynahatty, Co. Down, found in the context of an early megalithic passage-like grave, and three Early Bronze Age men from a cist burial in Rathlin Island, Co. Antrim (2026–1534 cal BC) with associated Food Vessel pottery (16) (SI Appendix, Section S1).     

Evaluation of the Xpert™ MRSA/SA Blood Culture assay for the detection of Staphylococcus aureus including strains with reduced vancomycin susceptibility from blood culture specimens

The Xpert MRSA/SA Blood Culture (BC) assay (Cepheid, Sunnyvale, CA) was prospectively compared to culture and found to have excellent specificity for both Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in BC specimens with a sensitivity of 75% (3/4) and 100% (17/17), respectively. Among 28 heterogeneous vancomycin-intermediate S. aureus (hVISA)/VISA spiked BCs, the assay correctly identified 84.6% VISA and 80% hVISA isolates as MRSA.     

Resectability and operative morbidity after chemotherapy in neuroblastoma patients with encasement of major visceral arteries

Background/Purpose

Image-defined vessel encasement is a significant risk factor for surgical complications and incomplete resection for intermediate-risk tumors. We sought to examine the impact of vessel encasement on complications or resectability in intermediate-risk or high-risk patients after neoadjuvant chemotherapy.

Methods

We retrospectively reviewed 207 consecutive patients with circumferential encasement of the renal vessels, celiac axis, and/or superior mesenteric artery (SMA) who underwent resection between 1991 and 2009. Specifically, we evaluated resection rates, complications, and outcome.

Results

Median age at diagnosis was 3.0 years, and 79% of patients had stage 4 disease. Of known MYCN status, 23.4% had MYCN amplification. Vessel encasement included renal vessels, celiac axis, or SMA alone in 107, 7, and 4 patients, respectively. Both the renal vessels and celiac axis were encased in 5 patients, renal vessels and SMA in 7 patients, and celiac axis and SMA in 14 patients. Sixty-three patients had all 3 vessels encased. The gross total resection (GTR) rate was 94%. No operative or postoperative deaths occurred. The overall complication rate was 34.8% (n = 72). Overall 5-year survival (±SEM) was 67.4% (±7.4%).

Conclusion

Encasement of major visceral arteries in patients with neuroblastoma who have received chemotherapy does not preclude gross total resection.     

Hodgkin lymphoma presenting with chest wall involvement: a case series

Chest wall tumors in the pediatric population can have a variety of etiologies, malignancy being the most worrisome. Hodgkin lymphoma (HL) rarely presents as a chest wall mass in the pediatric population. In this report, we describe 3 male pediatric patients, all of whom had chest wall masses present at the initial diagnosis of HL. We also discuss the literature on this topic. We conclude that malignancy and, more specifically, HL should always be considered when evaluating a pediatric patient who presents with a chest wall mass.     

The prevalence of tongue lesions in Malaysian dental outpatients from the Klang Valley area

Oral Diseases (2011) 17 , 210–216 Objectives: To determine the prevalence of tongue lesions in Malaysian dental outpatients from the Klang Valley area. Subjects and Methods: A cross sectional study was conducted on 600 Malaysian outpatients (257 men, 343 women, mean age, 37.7 years) attending the Primary Dental Care Unit at the Faculty of Dentistry, University of Malaya. Demographic and medical data were recorded for all respondents. Results: One hundred eighty‐one patients (30.2%) (81 men, 100 women, mean age 42.0 years) were diagnosed with at least one tongue lesion (n = 207) at the time of examination. Of these, 24 patients (4%) had two or more tongue lesions present synchronously. Seven different lesions were diagnosed: fissured tongue (13.8%), crenated tongue (7.8%), pigmented tongue (6.2%), geographic tongue (2.2%), ankyloglossia (1.7%), hairy tongue (1.0%) and median rhomboid glossitis (0.2%). Their racial prevalences were Malays (n = 65, 10.8%), Indians (n = 62, 10.3%), Chinese (n = 53, 8.8%) and other race (n = 1, 0.2%). A significant relationship was observed between crenated tongue and race; between four types of tongue lesions (fissured tongue, geographic tongue, crenated tongue and pigmented tongue) and age; and between fissured tongue and gender (P < 0.05). Conclusions: Distribution characteristics of tongue lesions in Malaysians are important as local reference data in the daily clinical practice.