An evaluation of the effect of altering nutrition and nutritional strategies in early lactation on reproductive performance and estrous behavior of high-yielding Holstein-Friesian dairy cows

Reproductive performance in the high-yielding dairy cow has severely decreased in the last 40 yr. The aim of this study was to compare the effectiveness of 4 nutritional strategies in improving the reproductive performance of high-yielding dairy cows. It was hypothesized that offering cows a high-starch ration in early lactation would enhance the onset of luteal activity, and that decreasing the severity of negative energy balance in the early postcalving period would improve reproductive parameters. Nutritional regimens aimed at improving fertility were applied to 96 Holstein-Friesian dairy animals. Upon calving, animals were allocated in a balanced manner to one of 4 dietary treatments. Primiparous animals were balanced according to live weight, body condition score and calving date. Multiparous animals were balanced according to parity, previous lactation milk yield, liveweight, body condition score and calving date. Treatment 1 was based on an industry best practice diet (control) to contain 170 g of crude protein/kg of dry matter. Treatment 2 was an individual cow feeding strategy, whereby the energy balance (EB) of individual animals was managed so as to achieve a predetermined target daily EB profile (+/- 10 MJ/d). Treatment 3 was a high-starch/high-fat combination treatment, whereby an insulinogenic (high-starch) diet was offered in early lactation to encourage cyclicity and followed by a lipogenic (low-starch, high-fat) diet to promote embryo development. Treatment 4 was a low-protein diet, containing 140 g of crude protein/kg of dry matter, supplemented with protected methionine at an inclusion level of 40 g per animal per day. The nutritional strategies implemented in this study had no statistically significant effects on cow fertility measures, which included the onset of luteal activity, conception rate, in-calf rate, and the incidence of atypical cycles. The individual cow feeding strategy improved EB in early lactation but had no benefit on conception rate to first insemination. However, conception rate to second insemination, 100-d pregnancy rate (from the commencement of breeding), and overall pregnancy rate tended to be higher in this group. The high-starch/high-fat treatment tended to decrease the proportion of delayed ovulations and increase the proportion of animals cycling by d 50 postcalving. Animals that failed to conceive to first insemination had a significantly longer luteal phase in the first cycle postpartum and a longer inter-ovulatory interval in the second cycle postpartum. With regards to estrous behavior, results indicate that as the size of the sexually active group increased, the intensity of estrus and the expression of mounting or attempting to mount another cow also increased. Furthermore, cows that became pregnant displayed more intense estrous behavior than cows that failed to become pregnant.

Pharmaceutical care of patients with congestive heart failure: Interventions and outcomes

We evaluated a structured pharmaceutical care program for elderly patients (> 65 yrs) with congestive heart failure (CHF) based on objective measures of disease control, quality of life, and use of health care facilities in a randomized, controlled, longitudinal, prospective clinical trial. The 42 patients in group A received education from a pharmacist on the disease and its treatment, and lifestyle changes that could help control symptoms. Patients also were encouraged to monitor their symptoms and comply with prescribed drug therapy. If necessary, dosage regimens were simplified in liaison with hospital physicians. The 41 control patients (group B) received standard care. The following outcome measures were assessed in all patients at baseline (before the start of the trial) and at 3, 6, 9, and 12 months: 2-minute walk test, blood pressure, body weight, pulse, forced vital capacity, quality of life [disease-specific (Minnesota Living with Heart Failure questionnaire) and generic (SF-36)], knowledge of symptoms and drugs, compliance with therapy, and use of health care facilities (hospital admissions, visits to emergency room, emergency calls). Patients in group A showed improved compliance with drug therapy, which in turn improved their exercise capacity compared with those in group B; education on management of symptoms, lifestyle changes, and dietary recommendations were also of benefit. Group A patients significantly improved knowledge of their drug therapy over the 12-month study and had fewer hospital admissions compared with group B patients. They also had improved outcomes compared with group B, despite the small samples. An extension of this trial to other sites with pooling of results would provide additional evidence of the value of this structured program in elderly patients with CHF.

Modification of biomaterial surface characteristics by body fluids in vitro

In practice, polyvinyl chloride endotracheal tubes and polyurethane urinary catheters are located in areas where they are exposed to the conditioning fluids saliva and urine, respectively. Samples of both biomaterials were incubated in these conditioning fluids and, following treatment, dynamic contact angle measurement and surface roughness assessment by atomic force microscopy were used to analyse surface characteristics. Over a 24 h period of contact with the conditioning fluids, the surface of both materials became significantly more hydrophilic (p

ARE ARTIFICIAL NEURAL NETS AS SMART AS A RAT

The origins of artificial neural networks are related to animal conditioning theory: both are forms of connectionist theory, which in turn derives from the empiricist philosophers' principle of association. The parallel between animal learning and neural nets suggests that interaction between them should benefit both sides.

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial.

Purpose
To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD).

Design
Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560).

Participants
People >50 years of age with untreated nAMD in the study eye who read =25 letters on the Early Treatment Diabetic Retinopathy Study chart.

Methods
We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review.

Main Outcome Measures
The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs.

Results
Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001).

Conclusions
The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety.

Financial Disclosure(s)
Proprietary or commercial disclosures may be found after the references.

Randomised controlled trial of ranitidine versus omeprazole in combination with antibiotics for eradication of Helicobacter pylori

This study compared high dose ranitidine versus low dose omeprazole with antibiotics for the eradication of H pylori. 80 patients (mean age 48 years, range 18-75) who had H pylori infection were randomised in an investigator-blind manner to either a two-week regime of omeprazole 20 mg daily, amoxycillin 500 mg tid and metronidazole 400 mg tid (OAM), or ranitidine 600 mg bd, amoxycillin 500 mg tid and metronidazole 400 mg tid (RAM), or omeprazole 20 mg daily and clarithromycin 500 mg tid (OC), or omeprazole 20 mg daily and placebo (OP). H pylori was eradicated in 6 of 19 patients in the OAM group (32%); 8 of 18 in the RAM group (44%), 4 of 15 in the OC group (27%); none of 18 in the OP group (0%). [<P0.005 for OAM, RAM, OC vs OP; P = N.S. between OAM, RAM, OC]. Overall metronidazole resistance was unexpectedly high at 58%. Eradication rates in metronidazole sensitive patients were 71% (5/7) and 100% (3/3) for OAM and RAM respectively. In conclusion, H pylori eradication rates using high dose ranitidine plus amoxycillin and metronidazole may be similar to that of low dose omeprazole in combination with the same antibiotics for omeprazole with clarithromycin. Overall eradication rates were low due to a high incidence of metronidazole resistance but were higher in metronidazole-sensitive patients. Even high dose ranitidine with two antibiotics achieves a relatively low eradication rate. These metronidazole-based regimens cannot be recommended in areas with a high incidence of metronidazole resistance.

Treatment options for cutaneous warts in family practice

Natural regression should not be advocated as a treatment option for cutaneous warts, given the infectious nature of this condition. Although there are numerous treatments for this condition reported in the literature, many trials are uncontrolled and many regimens are unsuitable for general practice. Specific treatment is influenced by age of patients, number and sites of warts and availability of treatment. This paper reviews the international literature on treatment methods, with particular emphasis on effectiveness, patient acceptability and application in family practice.

Oxaliplatin/capecitabine versus oxaliplatin/infusional 5-FU in advanced colorectal cancer: The MRC COIN Trial.

Background:

COIN compared first-line continuous chemotherapy with the same chemotherapy given intermittently or with cetuximab in advanced colorectal cancer (aCRC).


Methods:

Choice between oxaliplatin/capecitabine (OxCap) and oxaliplatin/leucovorin (LV)/infusional 5-FU (OxFU) was by physician and patient choice and switching regimen was allowed. We compared OxCap with OxFU and OxCap+cetuximab with OxFU+cetuximab retrospectively in patients and examined efficacy, toxicity profiles and the effect of mild renal impairment.


Results:

In total, 64% of 2397 patients received OxCap(±cetuximab). Overall survival, progression free survival and overall response rate were similar between OxCap and OxFU but rate of radical surgeries was higher for OxFU. Progression free survival was longer for OxFU+cetuximab compared with OxCap+cetuximab but other efficacy measures were similar. Oxaliplatin/LV/infusional 5-FU (±cetuximab) was associated with more mucositis and infection whereas OxCap(±cetuximab) caused more gastrointestinal toxicities and palmar-plantar erythema. In total, 118 patients switched regimen, mainly due to toxicity; only 16% came off their second regimen due to intolerance. Patients with creatinine clearance (CrCl) 50–80?ml?min-1 on OxCap(±cetuximab) or OxFU+cetuximab had more dose modifications than those with better renal function.


Conclusions:

Overall, OxFU and OxCap are equally effective in treating aCRC. However, the toxicity profiles differ and switching from one regimen to the other for poor tolerance is a reasonable option. Patients with CrCl 50–80?ml?min-1 on both regimens require close toxicity monitoring.

A multinational, randomised, 12-week, comparative study of donepezil and rivastigmine in patients with mild to moderate Alzheimer's disease

This 12-week, multinational study compared the tolerability and cognitive effects of donepezil (up to 10 mg once daily) and rivastigmine (up to 6 mg twice daily) in 111 patients with mild to moderate Alzheimer's disease. Both medications were administered open label according to recommended dosing regimens from the respective product labelling available during the conduct of the study. More patients in the donepezil group (89.3%) completed the study compared with the rivastigmine group (69.1%; p=0.009), and 10.7% of the donepezil group and 21.8% of the rivastigmine group discontinued due to adverse events (AEs); 87.5% of donepezil-treated patients and 47.3% of rivastigmine-treated patients remained on the maximum approved dose of each drug at the last study visit. Both groups showed comparable improvements on the ADAS-cog administered by raters blind to study medication at weeks 4 and 12. Thus, using the recommended dosing schedules, donepezil was better tolerated with fewer discontinuations due to AEs, and both agents improved cognition to a similar extent.

Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens--aspirin plus extended-release dipyridamole (ASA-ERDP) versus clopidogrel.

The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection):a randomised placebo-controlled trial

Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients.

Postconditioning for salvage of ischemic skeletal muscle from reperfusion injury:efficacy and mechanism

We tested our hypothesis that postischemic conditioning (PostC) is effective in salvage of ischemic skeletal muscle from reperfusion injury and the mechanism involves inhibition of opening of the mitochondrial permeability transition pore (mPTP). In bilateral 8x13 cm pig latissimus dorsi muscle flaps subjected to 4 h ischemia, muscle infarction increased from 22+/-4 to 41+/-1% between 2 and 24 h reperfusion and remained unchanged at 48 (38+/-6%) and 72 (40+/-1%) h reperfusion (P

Efficacy and mechanism of hypoxic postconditioning in salvage of ex vivo human rectus abdominis muscle from hypoxia/reoxygenation injury

In reconstructive surgery, skeletal muscle may endure protracted ischemia before reperfusion, which can lead to significant ischemia/reperfusion injury. Ischemic postconditioning induced by brief cycles of reperfusion/reocclusion at the end of ischemia has been shown to salvage skeletal muscle from ischemia/reperfusion injury in several animal models. However, ischemic postconditioning has not been confirmed in human skeletal muscle. Using an established in vitro human skeletal muscle hypoxic conditioning model, we tested our hypothesis that hypoxic postconditioning salvages ex vivo human skeletal muscle from hypoxia/reoxygenation injury and the mechanism involves inhibition of opening of the mitochondrial permeability transition pore (mPTP) and preservation of ATP synthesis. Muscle strips (~0.5×0.5×15mm) from human rectus abdominis muscle biopsies were cultured in Krebs-Henseleit-HEPES buffer, bubbled with 95%N(2)/5%CO(2) (hypoxia) or 95%O(2)/5%CO(2) (reoxygenation). Samples were subjected to 3h hypoxia/2h reoxygenation. Hypoxic postconditioning was induced by one or two cycles of 5min reoxygenation/5min hypoxia after 3h hypoxia. Muscle injury, viability and ATP synthesis after 2h of reoxygenation were assessed by measuring lactate dehydrogenase (LDH) release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction and ATP content, respectively. Hypoxic postconditioning or treatment with the mPTP-opening inhibitors Cyclosporine A (CsA, 5×10(-6)M) or N-Methyl-4-isoleucine Cyclosporine (NIM811, 5×10(-6)M) 10min before reoxygenation decreased LDH release, increased MTT reduction and increased muscle ATP content (n=7 patients; P

The meaning of medications:another look at compliance

Most research on compliance with medical regimens takes a doctor-centered perspective and proceeds from certain assumptions. This paper presents an alternative, patient-centered approach to managing medications, using data from 80 in-depth interviews of people with epilepsy. This approach focuses on the meanings of medication in people's everyday lives and looks at why people take their medications as well as why they do not. I argue that from a patient's perspective the issue is more one of self-regulation than compliance. When we examine 'noncompliance' beyond difficulties with 'side effects' an drug efficacy, the meanings of self-regulation include testing, controlling dependence destigmatization and creating a practical practice. What appears to be noncompliance from a medical perspective may actually be a form of asserting control over one's disorder.

Conditioned ethanol preference in rats

The question of whether ethanol has intrinsically rewarding properties, or whether, as a discriminative stimulus, it can become a conditioned reinforcer as a function of context association was examined. Paired rats consumed more of an ethanol solution than isolated rats over a 15 day 'conditioning' phase and their ingestion rate was increased significantly over the 15 day period. Furthermore, animals exposed to the solution with a conspecific companion during this conditioning phase subsequently showed a marked preference for ethanol over water throughout a 10 day test phase (when all animals were alone) compared to those with prior experience of the solution in isolation. Both groups consumed significantly more ethanol than the controls (with no prior ethanol experience at all) during this test phase. The results suggest that the total context of initial exposure to ethanol mediate its subsequent reinforcing properties, with the prior pleasurable context of being with a conspecific companion generalizing to the ethanol stimulus for the paired group.