LC/MS/MS structure elucidation of reaction intermediates formed during the TiO2 photocatalysis of microcystin-LR

Microcystin-LR (MC-LR), a cyanotoxin and emerging drinking water contaminant, was treated with TiO₂ photocatalysts immobilized on stainless steel plates as an alternative to nanoparticles in slurry. The reaction intermediates of MC-LR were identified with mass spectrometry (MS) at pH of Milli-Q water (pH_sq=5.7). Eleven new [M+H]⁺ were observed in the liquid chromatography mass spectrometry (LC/MS) chromatogram with some of them giving multiple peaks. Most of these reaction intermediates have not been reported from previous studies employing TiO₂ nanoparticles at acidic conditions (pH=4.0). Investigating the effects of pH (for 3.02 photocatalytic films showed that acidic conditions are preferable for the degradation. Combined with the limited surface area of the films and the absence of additional oxidants (i.e., H₂O₂) the degradation was slower and more intermediate steps were identified. Possible structures of the intermediates (formed at neutral pH) after analyzing the corresponding MS/MS spectra are reported. The collision-induced dissociation of the [M+H]⁺ of MC-LR and the intermediates 1011.5 and 1029.5 are discussed and possible fragmentation pathways and mechanisms are also proposed. Analysis of the MS/MS spectra indicates that the fragmentation of some amino acids is less favorable because of internal interaction with free groups of adjacent amino acids. The MS/MS spectra assisted in determining hydroxylation sites, by the formation or alteration of specific product ions such as m/z 599.     

Reduced shear stress and disturbed flow may lead to coronary aneurysm and thrombus formations

BACKGROUND: With Kawasaki disease it is important to clarify the mechanisms of coronary artery aneurysm and thrombus to avoid acute myocardial infarction. The authors tested the hypothesis that shear stress is reduced at coronary branching sites and in coronary artery aneurysms, and that this reduction of shear stress can promote formation of coronary artery aneurysms and thrombus. METHODS: The subjects were 111 children with Kawasaki disease with left coronary artery aneurysms, classified into three groups: giant coronary artery aneurysm (n= 28, diameter of coronary artery >8 mm), aneurysm (n= 44, diameter of coronary artery =8 mm), and normal-appearing coronary (n= 39). Averaged peak flow velocity (APV), flow patterns and shear stress were measured and calculated at normal-appearing coronary vessels, left coronary artery branching sites and intra-coronary aneurysm using flow wire, and coronary angiography. Also, presence and appearance of thrombus were detected by intravascular ultrasonography. RESULTS: The authors found that 90.3% of the coronary artery aneurysms occurred at major left coronary branching sites. APV and shear stress were significantly decreased in giant coronary artery aneurysms (APV, 7.1 +/- 2.1 cm/s; shear stress, 3.8 +/- 2.1 dyne/cm(2)) and at the left coronary artery branching site (APV, 9.1 +/- 1.2; shear stress, 1+/-+/-.2 3.0). In total, 20 of 24 thrombi were detected only in giant aneurysm, and all patients exhibited disturbed flow pattern in their giant coronary artery aneurysms. CONCLUSIONS: Reduced shear stress and disturbed flow pattern may lead to coronary artery aneurysm and thrombus formation.     

Community Health Workers: Examining the Helper Therapy Principle

A community approach to the integration of health and social services for low-income pregnant women is being addressed through Community Integrated Service System (CISS) initiatives of the Maternal Child Health Bureau. This particular CISS program model was designed to enable low-income mothers to function in a Community Health Worker (CHW) role providing social support for at-risk pregnant women. Using Riessman's notion of "helper therapy," the model was also developed to enhance the potential for CHWs to gain helper benefits. The purpose of this exploratory study was to describe perceived helper benefits and stressors associated with the CHW role and to examine the usefulness of an instrument developed to assess benefits and stressors. The study findings revealed that the majority of CHWs perceived helper benefits that included positive feelings about self, a sense of belonging, valuable work experience, and access to health information and skills through training or contact with program staff. Stressors such as feeling inadequate to help, however, were associated with the helper role for some CHWs. Preliminary analysis of the Helper's Perception Measure indicated that it may be an effective measure and should be tested with a larger sample of CHWs.     

Clinical determinants of survival from postoperative renal failure.

In a series of 114 consecutive patients with acute renal failure, the over-all mortality rate was 60 per cent; 62 per cent of the patients had a documented episode of hypotension just prior to the development of acute renal failure. In 11 patients, a second episode of renal failure developed following recovery from the initial episode of acute renal failure; all of these patients died. The urine output rate during the course of acute renal failure was inversely related to the mortality rate in the series as a whole. The mean duration of acute renal failure in survivors of the present series was 11.0 plus or minus 1.4 days. Complications of renal failure in the order of their frequency included hemorrhagic hypotension, sepsis, sepsis with hypotension and consumption coagulopathies; only 12 per cent had no complications. Only six of 51 patients whose clinical course was complicated by sepsis with or without an episode of hypotension survived. By contrast, 30 of 53 patients who had hemorrhagic hypotension without sepsis survived. The date suggest that although acute renal failure has a high mortality rate, it is a benign disease that is potentially reversible. Regardless of age and sex, renal functional recovery will take place if the patient is maintained in good physiologic condition long enough without a continued stress, such as sepsis, hypotension or hypovolemia, all of which prolong renal ischemia. During the course of renal failure, extreme care is essential to maintain adequate circulating volume without extracellular fluid overload; a second hemodynamic insult may result in serious damage to the regenerating renal tubules. We conclude that early recognition of acute renal failure, aggressive management of sepsis, careful titration of fluid and electrolyte therapy, meticulous monitoring, maintenance of the circulation and judicious utilization of dialysis will aid in reduction of mortality in these critically ill patients.     

The efficacy of central venous and pulmonary artery catheters and therapy based upon them in reducing mortality and morbidity

The purpose of this study was to (1) evaluate the relative cost effectiveness of the central venous pressure and flow-directed pulmonary artery catheters used to maintain normal hemodynamic values as therapeutic goals in the control groups vs supranormal values empirically observed in critically ill postoperative survivors in the protocol groups, and (2) to evaluate tissue perfusion and oxygenation in relationship to organ failure and mortality. In two prospective clinical trials there were no significant differences in outcome between the central venous pressure and pulmonary artery control groups that used normal values as therapeutic goals. However, there were marked and significant reductions in morbidity and mortality of the protocol groups using the supranormal cardiac index, oxygen delivery, and oxygen consumption values as goals. The cumulative oxygen debt was less and organ failures were fewer and less severe in the protocol groups than in the control groups.     

Potential for therapeutic targeting of tumor stem cells

Recent developments in isolation and characterization of tumor stem cells (TSCs) have opened new possibilities for developing TSC-targeted therapies. Extensive efforts have been made to ascertain markers of TSCs, including cell surface, enzymatic, gene expression profile, and functional markers. These markers and the technologies used to identify and isolate TSCs are discussed in this review. TSC characteristics, such as quiescence, multidrug resistance, enhanced DNA repair ability, and anti-apoptotic mechanisms, and various features of the in vivo niche, which may make them resistant to conventional therapy, are also discussed here. The increasing understanding of aberrantly expressed molecules and signaling pathways in TSCs may provide the foundation for design of therapeutic strategies for TSC ablation. ( Cancer Sci 2009)     

Primary Ewing sarcoma: follow-up with Ga-67 scintigraphy

While avid accumulation of gallium-67 citrate and technetium-99m methylene diphosphonate (MDP) occurs initially in most cases of primary Ewing sarcoma, uptake after therapy is less well defined. Thirty patients with Ewing sarcoma who underwent Ga-67 and bone scintigraphy at diagnosis, at completion of therapy, and at relapse from 1978 to 1988 were evaluated. All 30 patients showed less primary site Ga-67 activity following therapy. Twenty-three of 28 patients who underwent corresponding bone scintigraphy showed less uptake, but residual activity was usually more intense than with Ga-67. Avid reaccumulation of Ga-67 occurred in four of five patients with primary site relapse, while patients who underwent bone scintigraphy showed less change. It was concluded that a greater decrease in Ga-67 than in Tc-99m MDP uptake often occurs in patients successfully treated for primary Ewing sarcoma. Information obtained at Ga-67 scintigraphy is most likely to be helpful if results of bone scintigraphy remain abnormal or if occult relapse is suspected.     

Evaluation of a comprehensive algorithm for blunt and penetrating thoracic and abdominal trauma.

The objective was to develop a single branched-chain decision tree for both blunt and penetrating thoracic and abdominal trauma and to test its feasibility to track clinical decisions. The algorithm consisted of 14 specific patient management loops and 31 decision nodes. During a 4-month period, the management decisions and clinical course of 434 trauma patients were prospectively observed. Thirty-four patients had no signs of life on arrival to the emergency department (ED) and were excluded from the statistical evaluation; the remaining 400 patients constituted the study group. The mean Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Trauma Score (TS) scores in the series were 21 +/- 10, 34 +/- 12, and 13 +/- 3. The overall patient mortality of the study group was 17 per cent; it was 61 per cent in those patients with major deviations from the algorithm and 6 per cent in patients who complied with the algorithm. The ISS, PATI, and TS scores were 29 +/- 9, 32 +/- 12, and 13 +/- 2 in patients with deviations and 20 +/- 10, 37 +/- 12, and 14 +/- 2 in patients who complied with the algorithm. Of the 37 patients who died with major deviations from the algorithm, the deviation was directly contributory to death in 21 cases (57%) and probably contributory in another 14 cases (38%). There were 108 patients with ISS scores between 20 and 50. In this group, mortality was 55 per cent when a major deviation occurred and 5 per cent without major deviations from the algorithm. The authors conclude that the survival of trauma patients may be improved by following the specific management criteria outlined by the algorithm.