Isolation and characterization of monoclonal antibodies against human carbonic anhydrase-IX.

The architectural complexity and heterogeneity of the tumor microenvironment (TME) remains a substantial obstacle in the successful treatment of cancer. Hypoxia, caused by insufficient oxygen supply, and acidosis, resulting from the expulsion of acidic metabolites, are prominent features of the TME. To mitigate the consequences of the hostile TME, cancer cells metabolically rewire themselves and express a series of specific transporters and enzymes instrumental to this adaptation. One of these proteins is carbonic anhydrase (CA)IX, a zinc-containing extracellular membrane bound enzyme that has been shown to play a critical role in the maintenance of a neutral intracellular pH (pHi), allowing tumor cells to survive and thrive in these harsh conditions. Although CAIX has been considered a promising cancer target, only two antibody-based therapeutics have been clinically tested so far. To fill this gap, we generated a series of novel monoclonal antibodies (mAbs) that specifically recognize the extracellular domain (ECD) of human CAIX. Here we describe the biophysical and functional properties of a set of antibodies against the CAIX ECD domain and their applicability as: 1) suitable for development as an antibody-drug-conjugate, 2) an inhibitor of CAIX enzyme activity, or 3) an imaging/detection antibody. The results presented here demonstrate the potential of these specific hCAIX mAbs for further development as novel cancer therapeutic and/or diagnostic tools.

Front-line emergency department nurses' and physicians' assessments of processes of elder-friendly care for quality improvement.

INTRODUCTION: Geriatric emergency department (ED) care has gained increasing importance and interest due to increasing visits in seniors. AIM: Among ED front-line nurses and physicians, to assess and compare ratings of elder-friendly care process indicators, variability in ratings, and concurrent validity of ratings. METHODS: Four Quebec EDs' full-time registered nurses and physicians rated their geriatric care using 9 subscales. Nurse and physician subscale scores were compared. Inter-rater variability within disciplines and variability between nurses and physicians were measured. Associations between the subscale scores and perceived overall quality of care were tested. RESULTS: 38 nurses and 36 physicians completed the survey (83% of 89 eligible). Scores differed by discipline for 3 of 9 subscales computed; nurses had higher mean scores on Protocols, Family-Centered Discharge, and Staff Education. Very high variation for Staff Education was found within disciplines. Variations for Family-Centered Discharge differed significantly between nurses and physicians. Almost all subscale scores were significantly positively associated with perceived overall quality of care. CONCLUSIONS: ED nurses and physicians rate geriatric care components similarly except for protocols, discharge processes, and continuing education. The subscales have concurrent validity. Results suggest a need for improvement in continuing educational strategies with a particular attention to discharge processes.

Experiences of an Emergency Department Visit Among Older Adults and Their Families: Qualitative Findings From a Mixed-Methods Study.

BACKGROUND: Emergency department (ED) visits are critical events for older adults, but little is known regarding their experiences, particularly about their physical needs, the involvement of accompanying family members, and the transition back to the community. OBJECTIVE: To explore experiences of an ED visit among patients aged 75 and older. METHODS: In a mixed-methods study, a cohort of patients aged 75 and older (or a family member) discharged from the ED back to the community was recruited from 4 urban EDs. A week following discharge, structured telephone interviews supplemented with open-ended questions were conducted. A subsample (76 patients, 32 family members) was purposefully selected. Verbatim transcripts of responses to the open-ended questions were thematically analyzed. RESULTS: Experiences related to physical needs included comfort, equipment supporting mobility and autonomy, help when needed, and access to drink and food. Family members required opportunities to provide patient support and greater involvement in their care. At discharge, patients/families required adequate discharge education, resolution of their health problem, information on medications, and greater certainty about planned follow-up medical and home care services. CONCLUSIONS: Our findings suggest several areas that could be targeted to improve patient and family perceptions of the care at an ED visit.

How Older Adults Experience an Emergency Department Visit: Development and Validation of Measures.

STUDY OBJECTIVE: This study aims to develop and validate measures of experiences of an emergency department (ED) visit suitable for use by older adults or their family members. METHODS: A cohort of patients aged 75 years and older who were discharged home was recruited at 4 EDs. At 1 week after the visit, patients or family members were interviewed by telephone to assess problems experienced at the visit. Twenty-six questions based on 6 domains of care found in the literature were developed: 16 questions were administered to all patients; 10 questions were administered to bed patients only. Scales were developed with multiple correspondence analysis. Regression analyses were used to validate the scales, using 2 validation criteria: perceived overall quality of care and willingness to return to the same ED. RESULTS: Four hundred twelve patients completed the 1-week interview, 197 ambulatory and 215 bed patients; family members responded for 75 patients. Two scales were developed, assessing personal care and communication (8 questions; α=.63) and waiting times (2 questions; α=.79). Both scales were significantly independently associated with perceived overall quality of care and willingness to return to the same ED. CONCLUSION: Two scales assessing important aspects of ED care experienced by older adults are ready for further evaluation in other settings.

Patient Participation Approach to Reduction of Anterior Shoulder Dislocation: P-R-I-M/O-Y-E-S.

A variety of successful techniques are available for reduction of shoulder dislocation; none have been shown to be clearly superior to another. Analgesic methods vary as well from none to deep sedation-analgesia. The literature hints at the importance of optimal muscle relaxation as a factor of success. Yet, the literature describes only cursorily the means by which muscle relaxation is optimized. Patient-centered participation and relaxation methods have been used in other contexts to reduce pain, anxiety, and muscle tension. This article proposes to integrate a patient-centered participation approach to the reduction of anterior shoulder dislocation as a way to optimize muscular relaxation nonpharmacologically. It can be used in the field in combination with the practitioner's reduction technique of choice. It minimizes risks because it entails no deep pharmacological sedation. The mnemonic P-R-I-M/O-Y-E-S is used to respectively represent the four phases: Preparation, Rehearsal, Intervention, and Mobilization as well as the 4 repeated steps in each phase of the procedure: Observe, Yield control, Explain, and Support. The focus is on (1) securing optimal patient participation within a patient-centered approach and (2) achieving nonpharmacological muscular relaxation through a simple relaxation routine. More studies are needed to identify the factors that determine success and guide the practitioner's choice among available options in shoulder dislocation reductions.

Calcium and magnesium ATPase activities in women with varying BMIs.

OBJECTIVE: Intracellular calcium (Ca) is increased in obese humans, and magnesium (Mg)-ATPase activity is increased in monosodium glutamate-induced obese rats. The aims of this study were to test the hypotheses that Ca-ATPase activity is negatively correlated with BMI, and that Mg-ATPase activity is positively correlated with BMI and Ca-ATPase activity in obese women. RESEARCH METHODS AND PROCEDURES: Thirty healthy adult women, with BMIs of 20 to 40, donated a single sample of whole blood and were interviewed as to medical history and family history of obesity. Erythrocyte membranes were isolated and assayed for Ca-ATPase and Mg-ATPase. Weight and height were self-reported. Regression analysis was used to determine relationship between BMI and enzyme activity. Family history of obesity served as a covariant. RESULTS: Ca-ATPase was negatively correlated with increasing BMI (r = - 0.38, p = 0.02). The relationship between BMI and Ca-ATPase remained valid after controlling for family history of obesity (r = -0.36, p = 0.03). There was a positive correlation between Mg-ATPase activity and Ca-ATPase (r = 0.42, p = 0.024), and this relationship remained valid after controlling for BMI and family history of obesity (r = 0.41, p = 0.03). DISCUSSION: Ca-ATPase activity decreases as BMI increases. Decreased ATPase activity may contribute to increased intracellular calcium, previously reported in obese persons. Further studies are needed to determine whether a drop in Ca-ATPase activity can serve as a marker for the development of obesity.

Should calcium and vitamin D be added to the current enrichment program for cereal-grain products?

Mean dietary intakes of calcium and vitamin D in the US adult population are far below the adequate intake (AI) values recommended by the Food and Nutrition Board, Institute of Medicine of the National Academy of Sciences, and thus substantial segments of the American population have inadequate intakes and elevated risks of osteoporosis and colon cancer. The current Code of Federal Regulations, Title 21, sets standards for the optional addition of moderate amounts of calcium and vitamin D in the enrichment of cereal-grain products, a provision that is essentially not used. We propose that the addition of calcium and vitamin D to currently enriched cereal-grain products be mandated in the United States: this would result in an increase in mean daily dietary intakes in the United States of approximately 400 mg Ca and > or =50 IU (or possibly >200 IU) vitamin D. The benefits would be a significant reduction in the incidences of osteoporosis and colon cancer over time and overall improvement in health, with little risk and a modest financial cost because of the ability to capitalize on existing technology. We suggest a full scientific review of cereal-grain enrichment with calcium and vitamin D.

Nutraceutical/drug/anti-terrorism safety assurance through traceability.

Nutraceuticals are naturally occurring/derived bioactive compounds that are reported to have health benefits. The delivery systems for nutraceuticals are foods (functional foods), supplements, or both. Drugs are designed to have medicinal properties for the prevention and treatment of identified diseases or signs and symptoms of disease. Counterfeit drugs contain either placebo, materials not identified in the labeling or substandard or impure materials, which may produce untoward pharmacological or toxicological effects. In addition, the consumer has the right to microbiological safety and prevention from adverse exposure to hazardous chemical(s), and other adverse compounds. Nutraceutical/drug delivery systems are viewed as approaches to (1) enhanced consumer health, (2) decreased healthcare costs, and (3) enhanced economic development. Therefore, the nutra/pharma/ceutical industry is reliant upon a strong underpinning of diversified research that addresses safety and assures chemical and biological efficacy. Significant safety through traceability can be assured by the coupling of the technologies of (a) global positioning (GPS); (b) bar/chip coding; and (c) hazard analysis critical control point (HACCP) management, coupled to rapid nanotechnology marker assays now under development.

Antioxidative phenolic compounds isolated from almond skins (Prunus amygdalus Batsch).

Nine phenolic compounds were isolated from the ethyl acetate and n-butanol fractions of almond (Prunus amygdalus) skins. On the basis of NMR data, MS data, and comparison with the literature, these compounds were identified as 3'-O-methylquercetin 3-O-beta-D-glucopyranoside (1); 3'-O-methylquercetin 3-O-beta-D-galactopyranoside (2); 3'-O-methylquercetin 3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3); kaempferol 3-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (4); naringenin 7-O-beta-D-glucopyranoside (5); catechin (6); protocatechuic acid (7); vanillic acid (8); and p-hydroxybenzoic acid (9). All of these compounds have been isolated from almond skins for the first time. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activities for compounds 1-9 were determined. Compounds 6 and 7 show very strong DPPH radical scavenging activity. Compounds 1-3, 5, 8, and 9 show strong activity, whereas compound 4 has very weak activity.