Evaluation of delayed timing of artificial insemination with sex-sorted sperm on pregnancy per artificial insemination in seasonal-calving, pasture-based lactating dairy cows.

The objective was to use ovulation synchronization with timed artificial insemination (TAI) to evaluate the effect of timing of artificial insemination (AI) with frozen sex-sorted sperm on fertility performance in pasture-based compact calving herds. Ejaculates from 3 Holstein-Friesian bulls were split and processed to provide frozen sex-sorted sperm (SS) at 4 × 106 sperm per straw, and frozen conventional sperm at 15 × 106 sperm per straw (CONV). A modified Progesterone-Ovsynch protocol was used for estrous synchronization, with TAI occurring 16 h after the second GnRH injection for cows assigned to CONV, and either 16 h (SS-16) or 22 h (SS-22) for cows assigned to SS. Pregnancy diagnosis was conducted by transrectal ultrasound scanning of the uterus 35 to 40 d after TAI (n = 2,175 records available for analysis). Generalized linear mixed models were used to examine the effects of treatment on pregnancy per artificial insemination (P/AI). Fixed effects included treatment (n = 3), bull (n = 3), treatment by bull interaction, parity (n = 4), days-in-milk category (n = 3), and treatment by days-in-milk category, with herd (n = 24) included as a random effect. Pregnancy per AI was greater for CONV compared with both SS-16 and SS-22 (61.1%, 49.0%, and 51.3%, respectively), and the SS treatments did not differ from each other (relative P/AI for SS-16 and SS-22 vs. CONV were 80.2% and 84.0%, respectively). There were significant bull and treatment by bull interaction effects. Additional analysis was undertaken using a model that included herd as a fixed effect. This analysis identified marked herd-to-herd variation (within-herd relative P/AI for the combined SS treatments vs. CONV ranged from 48-121%). The tertile of herds with the best performance achieved a mean relative P/AI of 100% (range = 91-121%), indicating that P/AI equivalent to CONV is achievable with SS. Conversely, the tertile of herds with the poorest performance achieved a mean relative P/AI of 67% (range = 48-77%). We found that SS resulted in poorer overall P/AI compared with CONV sperm regardless of timing of AI. Marked variation existed between herds; however, one-third of herds achieved P/AI results equal to CONV. Identification of factors responsible for the large herd-to-herd variation in P/AI with SS, and development of strategies to reduce this variation, warrant further research.

Short-term pilot study of the effect of sleeve gastrectomy on food preference.

The effect of vertical sleeve gastrectomy (VSG) on food preference has not been examined in humans, but VSG decreases preference for fat and calorically dense foods in rodents. A validated Food Preference Questionnaire (FPQ) assessed food preference changes before and 6 weeks after VSG in humans. The FPQ was completed before and 43 ± 19 days (Mean ± SD) after VSG. Fifteen subjects (14 females) completed the study. Hedonic ratings decreased for foods high in fat and sugar (p = 0.002) and high in fat and complex carbohydrate (p = 0.007). Fat preference (p = 0.048) decreased, VSG reduced preference for calorically dense foods high in fat, sugar, and complex carbohydrate, and these changes may contribute to the weight loss with VSG.

Racial differences in weight loss, payment method, and complications following Roux-en-Y gastric bypass and sleeve gastrectomy.

OBJECTIVES: Obesity affects approximately one-third of the US adult population. Although more black adults are considered to be obese compared to white adults, black adults are less likely to undergo bariatric surgery for weight loss. Black adults typically lose less weight and are more prone to adverse events following bariatric surgery than white adults. The objectives of this study were to compare weight loss, payment methods, and early postoperative complications between black and white adults. DESIGN: A retrospective chart review of 420 Roux-en-Y gastric bypass (RYGB) patients and 454 sleeve gastrectomy (SG) patients (all female) was conducted. A mixed-model analysis was used to assess statistical significance of differences in weight loss between surgeries and races. A Chi-square test was used to assess racial differences in payment method (insurance or private pay) and postoperative complications by operation. Statistical significance was set as P > 0.05. RESULTS: RYGB patients lost significantly more weight at 26, 52, 78, and 104 weeks postoperatively compared to SG patients. White females (WF) lost significantly more weight than black females (BF) at 26, 52, 78, and 104 weeks postoperatively. WF experienced more minor and major complications in the perioperative period than BF, but BF experienced more minor and overall complications in the postoperative period than WF. A greater percentage of black patients had insurance coverage compared to white patients for both surgeries. CONCLUSION: WF appear to lose more weight than BF regardless of surgery, but both races experience surgical complications. Black patients may be less likely to undergo bariatric surgery without insurance coverage.

Early resolution of type 2 diabetes seen after Roux-en-Y gastric bypass and vertical sleeve gastrectomy.

BACKGROUND: Type 2 diabetes (T2D) accounts for the majority of diagnosed cases of diabetes in adults in the United States. Many of these individuals are also morbidly obese and choose to undergo bariatric surgery to lose weight and gain glycemic control. The Roux-en-Y gastric bypass (RYGB) has been shown to resolve diabetes before substantial weight loss occurs. Several studies suggest that the vertical sleeve gastrectomy (VSG), a newer bariatric operation, may result in comparable weight loss and rapid diabetes control. METHODS: We conducted a retrospective chart review of 262 patients diagnosed with diabetes who underwent either the RYGB or the VSG between 2002 and 2010. Medication usage before and after surgery was recorded. Patients who discontinued all medications postoperatively were considered "resolved" of T2D, and those who reduced the number of medications were considered as "showing improvement" in their T2D. Peri- and postoperative complications were also recorded for each operation. RESULTS: At 8 weeks postoperatively, follow-up data were available for 38 RYGB patients and 71 VSG patients. Approximately 79% of RYGB patients and 83% of VSG patients remained off their diabetes medication. VSG patients experienced a significantly lower incidence of major and minor complications both peri- and postoperatively compared with RYGB patients. CONCLUSIONS: Both operations appear to equally resolve T2D in an obese, adult population; however, the incidence of both major and minor complications is much lower in the VSG patient group. Therefore, the VSG should also be considered as a treatment option for obese individuals with T2D.

An assay to measure angiogenesis in human fat tissue.

BACKGROUND: Inhibition of angiogenesis reverses rodent obesity. A validated assay in human fat tissue is needed to study the role of angiogenesis in human obesity. METHODS: Human fat tissue fragments from surgery were placed in 96-well plates, embedded in fibrin thrombin clot and overlaid with cell culture media containing 20% fetal bovine serum. After 15 days, the clots were examined by histology and electron microscopy. The effect of taxol, cobalt chloride and a heparin-steroid combination was tested in the fat tissue assay and compared to the validated human placental vein angiogenesis model (HPVAM). RESULTS: Blood vessels initiated growth and elongated from the fat tissue fragments over 15 days. Presence of blood vessels was confirmed with histology and electron microscopy. Taxol at 10(-6) and 10(-7) M completely inhibited angiogenesis, while Taxol 10(-8) and 10(-9) M and the heparin-steroid partially inhibited angiogenesis. The response to taxol and heparin-steroid was similar to that of the HPVAM, a validated angiogenesis assay. Cobalt chloride, a stimulator of vascular endothelial growth factor (VEGF) stimulated angiogenesis initiation at 10(-9) M in fat tissue and the HPVAM, but at 10(-10) M blood vessel growth was stimulated only in the fat assay. CONCLUSION: This angiogenesis assay based on human fat tissue uses three-dimensionally intact human tissue. The vessels are derived from quiescient vessels within the fat. These properties allow the angiogenic switch to be evaluated in an in vitro setting. The angiogenic response of fat tissue is not identical to placental tissue. This assay allows exploration of angiogenesis in fat tissue.

Regulation of endogenous gene expression using small molecule-controlled engineered zinc-finger protein transcription factors.

Small-molecule-regulated gene expression offers the promise of titrating the dose and duration of action of DNA-based therapies. To this end, we show that engineered zinc-finger protein transcription factors (ZFP TFs) can be coupled with a drug-inducible regulatory domain to permit small-molecule control of endogenous gene transcription. We constructed a drug-responsive ZFP TF via the fusion of a ZFP DNA-binding domain (DBD) targeting the human VEGF-A gene and an effector domain containing a truncated progesterone receptor ligand-binding domain linked to the NFkappaB p65 activation domain. Introduction of this engineered ZFP TF into human or murine cells allowed expression of the chromosomal VEGF-A gene to be induced upon addition of mifepristone, a synthetic steroid analog. Mifepristone-dependent VEGF-A induction was rapid, dose-dependent and reversible. Moreover, stable lines expressing the drug-responsive ZFP TF could be maintained in a state of continuous induction for at least 30 days without loss of viability. Potent VEGF-A induction was demonstrated using different engineered ZFP DBDs, thus this approach may represent a general solution to small-molecule regulation of targeted endogenous genes.

Cancer chemoprevention: selenium as a prooxidant, not an antioxidant.

Although the average daily dietary selenium (Se) intake in the United States is consistently above the adult RDA of 55 microg Se/day, supranutritional supplements of 200 microg Se/day have been shown to provide chemopreventive benefits against several cancers, particularly prostate cancer. The hypothesis herein contends that selenium compounds with the greatest anticarcinogenic potency are likely to be sodium selenite with Se in the +4 oxidation state and methylseleninic acid. These compounds exert their cancer chemopreventive effects by directly oxidizing critical thiol-containing cellular substrates, and are more effective than the more frequently preferred (used) supplements of selenomethionine and Se-methylselenocysteine that lack oxidation capability. Selenate (+6 Se) the immediate precursor of selenite (+4 Se) can be metabolically reduced, and although less potent than the +4 Se compounds cited above, appears to be a more effective anticarcinogen than organic forms of dietary selenium. Apoptosis, an important, Se-induced anticarcinogenic mechanism, is accomplished by the direct oxidation of vicinal sulfhydryl groups in cysteine clusters within the catalytic domains of cellular enzymes (e.g., protein kinase C), and by the production of CH3Se-, which reacts with O2 to generate superoxide and other reactive oxygen species (ROS). Activated oncogenes "prime" cells for Se-induced prooxidative apoptosis thereby providing the needed margin for "killing" cancer cells while leaving normal, healthy cells unharmed. Selenoethers, such as selenomethionine and Se-methylselenocysteine are not oxidizing agents, and first, must be converted to methylselenol (CH3Se-) that can be directly oxidized to methylseleninic acid. The addition of methioninase, to selenomethionine, or beta-lyase to Se-methylselenocysteine, rapidly produces significant amounts of methylselenol, which may be oxidized to methylseleninic acid or may react with O2 to produce superoxide and ROS, resulting in anticarcinogenic activities comparable to selenite or methylseleninic acid. The relatively large amounts of selenomethionine or Se-methylselenocysteine needed to produce apoptosis in cancer cells compared with selenite or methylseleninic acid are a probable consequence of low tissue levels of the required enzymes. Even though many studies have consistently shown that selenomethionine is an ineffective anticarcinogen at doses corresponding to those currently allowed by the FDA, it has been chosen as the Se intervention agent in the 32,500-man (phase III), NCI-funded SELECT trial, which tests the effectiveness of dietary supplements of dietary supplements of Se and tocopherol, individually or in combination, in the prevention of prostate cancer. In 2013, when the data are in, the value of using Se supplements for cancer chemoprevention is likely to be underestimated.

A decision aid for autologous pre-donation in cardiac surgery--a randomized trial.

OBJECTIVES: The objective of this randomized, controlled study was to determine the usefulness of a decision aid on pre-donation of autologous blood before elective open heart surgery. METHODS: The decision aid (DA) group received a tape and booklet which described the options for peri-operative transfusion in detail. The no decision aid (NDA) group received information usually given to patients about autologous donation. RESULTS: A total of 120 patients were randomized. The DA group rated themselves better prepared for decision making and showed significant improvements in knowledge (p = 0.001) and realistic risk perceptions (p = 0.001). In both groups there was an increase in the proportion of patients choosing allogeneic blood between baseline and follow-up (p = 0.001). Patients in the DA group were significantly more satisfied with the amount of information they received, how they were treated and with the decision they made, than patients in the NDA group. CONCLUSION: The decision aid is useful in preparing patients for decision making. PRACTICE IMPLICATIONS: The next stage is to explore strategies to make it available to all appropriate patients.

The Ottawa patient decision aids.

CONTEXT: Shared decision-making programs, or patient decision aids, have been developed for difficult decisions in which patients need to consider benefits versus risks. PRACTICE PATTERN EXAMINED: Decision aids currently used in practice in Ottawa, Ontario, Canada. DATA SOURCES: Published studies of patients faced with decisions about hormone therapy, prenatal testing, lung cancer treatments, and anticoagulation for atrial fibrillation; administrative data on distribution of decision aids; and a survey mailed to pulmonologists and surgeons. RESULTS: Although most patients considering health care options arrive for counseling with strong predispositions toward a particular option, some are uncertain about their choice and express the need for information, clarification of values, and advice about their options. Decision aids prepare patients for decision making by increasing their knowledge about expected outcomes and personal values. The aids are used in our local centers, and more than 6000 kits have been distributed in Canada, the United States, Europe, and Australia. They primarily affect the decisions of patients who are undecided at baseline and sometimes reduce the proportion of patients who choose more intensive options. CONCLUSION: The Ottawa patient decision aids assist patient decision making, particularly among those who are undecided.

Evaluation of the "Time to Quit" self-help smoking cessation program.

Public health and hospital nurses have widespread contact with smokers; an effective smoking cessation program administered by nurses has tremendous potential. This study evaluated: 1) the effectiveness of the self-help cessation program, "Time to Quit"/"Moi aussi, j'écrase" (TTQ), provided on a one-to-one basis; and 2) a smoking cessation training program for baccalaureate nursing students. Nursing students recruited 307 smokers who were randomly assigned to receive one of two interventions. Control smokers received a list of community smoking cessation resources and experimental subjects received this list plus TTQ. Smoking self-reports and cotinine levels were obtained at baseline, six weeks and nine months. More smokers receiving TTQ had reduced at six weeks post-intervention, while there were no differences in quit or reduction rates at the nine-month follow-up. Students were positive about learning the techniques and their knowledge scores were significantly higher than those of non-participating students.

Discriminant analysis of trace element distribution in normal and malignant human tissues.

Discriminant analysis of 16 trace element levels measured by ultramicro energy dispersive X-ray fluorescence in malignant and histologically normal human breast, colon, and lung tissues is shown to be a potentially valuable methodology for making malignant-normal and tissue-type classifications. Linear composites of trace elements producing optimal malignant-normal discriminations are found to differ with respect to the number and identity of elements included in the composite for breast, colon, and lung tissues. Nine-, 10-, and 11-element discriminant functions produced overall classification accuracies of 98% for breast, 100% for colon, and 100% for lung tissues, respectively. Elements found to be most important in distinguishing between malignant and normal tissues are Ca, Rb, and Zn in breast, Ca, Zn, and Fe in colon, and Fe, Mn, and Cu in lung samples. Three-group discriminations between breast, colon, and lung tissues were 85% accurate using trace element levels in paired malignant-normal tissues and 91% accurate using trace element levels in tumor tissues only.

Reconstructive hand surgery for quadriplegic persons.

Reconstructive hand surgery is one approach to restoring lost hand function in quadriplegic patients. This paper describes Craig Hospital's experience with the two-stage procedure for achieving active grasp and pinch for C7 spinal cord-injured patients. It describes the hand clinic, patient selection and education, the surgery itself, and postsurgical occupational therapy. It also includes follow-up results on all patients treated since the program's inception.

Soft drug use after pregnancy compared to use before and during pregnancy.

With the use of information gathered through the course of pregnancy and data collected after delivery, the changing patterns of alcohol, nicotine, and marijuana use of 288 women participating in the Ottawa Prenatal Prospective Study were investigated. The time periods considered were the year before pregnancy, each trimester of pregnancy, and 1, 6, and 12 months post partum. Alcohol use showed the most marked reduction of the three drugs during pregnancy, but a year after delivery prepregnancy drinking patterns (including binging) had been reestablished. An exception to this was a continued reduction of alcohol consumption by those categorized as heavy social drinkers prior to pregnancy. Although not as marked as the alcohol reduction, nicotine use was reduced during pregnancy and continued to remain at the reduced level 1 year post partum. Heavy marijuana use was the least reduced of the drugs during pregnancy and consumption returned to prepregnancy levels a year after the birth of the baby.

Tissue and urinary glycosaminoglycan patterns associated with a fast, an intermediate, and a slow-growing Morris hepatoma.

The purpose of this investigation was to evaluate the glycosaminoglycans (GAG's) in different behavioral-histological types of i.m.-transplanted hepatomas and in the liver and urine of animals bearing these tumors. Groups of 10 Buffalo rats carrying fast-growing (7777), intermediate (5123tc), and slow-growing (9618A) Morris hepatomas were studied as the tumors reached 3 cm. Urinary and tissue GAG's were isolated by proteolysis, separated as cetylpyridinium complexes, and measured as uronic acid. The GAG's were further purified using anion-exchange chromatography and characterized with mucopolysaccharidases. Tissue GAG,s were also evaluated histochemically using Alcian blue staining and mucopolysaccharidases. Tissue from fast-growing, intermediate, and slow-growing tumors exhibited greater GAG levels than did normal liver in the hyaluronic acid (0.4 M NaCl-soluble) fraction and in the chondroitin sulfate-heparan sulfate (1.2 M NaCl-soluble) fraction. The livers of tumor-bearing animals exhibited GAG levels similar to those of normal liver. Increased urinary GAG excretion was appreciated in animals bearing Tumors 5123tc and 9618A but not in those bearing Tumor 7777.