Long-term clinical and socio-economic outcomes following wrist fracture: a systematic review and meta-analysis.

A comprehensive review of studies shows that patients with wrist fracture, aged over 50 years, experience pain and functional limitation long after fracture. This is associated with increased healthcare costs, and reduced quality of life. Understanding factors that predict poor outcomes is important for future healthcare policy and planning. PURPOSE: To summarise and appraise evidence on the prognosis and long-term clinical and socio-economic outcomes following wrist fracture among adults aged 50 years and over. METHODS: Five databases (MEDLINE, EMBASE, AMED, CINAHL-P and PsycINFO) were comprehensively searched (supplemented by a grey-literature search) from inception till June 2021 for prospective/retrospective cohort studies of patients (≥ 50 years) with a history of wrist fracture and reporting long-term (≥ 6 months) outcomes. Peer study selection, data extraction and risk of bias assessment were conducted. A random effects meta-analysis was used to summarise estimates of pain and function outcomes. RESULTS: 78 studies (n = 688,041 patients) were included. Patients report persistent moderate to severe pain (range: 7.5%-62%) and functional limitations (range: 5.5-78%) up to 12-months or later after wrist fracture. Mean Patient-Rated Wrist Evaluation (PRWE) score for pain and function (9 studies, n = 1759 patients) was 15.23 (95%CI 12.77, 17.69) at 6-months to 13-years follow-up. Mean disabilities of the arm, shoulder and hand (DASH) score (9 studies, n = 1346 patients) was 13.82 (95%CI 12.71, 14.93)( at 6- to 17-months follow-up. A 10-20% increase in healthcare encounters in the first 12-months after fracture was observed. Twelve prognostic factors were associated with poor long-term outcomes. CONCLUSION: Evidence shows that a high proportion of people aged over 50 years with wrist fracture experience pain and functional limitation > 6 months after fracture. This is associated with increased healthcare costs, and reduced quality of life. Exploratory evidence was found for several candidate prognostic factors. Their predictive performance needs to be investigated further. PROSPERO: CRD42018116478.

Understanding successful and unsuccessful landings of aerial maneuver variations in professional surfing.

Although performing aerial maneuvers can increase wave score and winning potential in competitive surfing, the critical features underlying successful aerial performance have not been systematically investigated. This study aimed to analyze highly skilled aerial maneuver performance and to identify the critical features associated with successful or unsuccessful landing. Using video recordings of the World Surf League's Championship Tour, every aerial performed during the quarterfinal, semifinal, and final heats from the 11 events in the 2015 season was viewed. From this, 121 aerials were identified with the Frontside Air (n = 15) and Frontside Air Reverse (n = 67) being selected to be qualitatively assessed. Using chi-squared analyses, a series of key critical features, including landing over the center of the surfboard (FS Air χ2  = 14.00, FS Air Reverse χ2  = 26.61; P < .001) and landing with the lead ankle in dorsiflexion (FS Air χ2  = 3.90, FS Air Reverse χ2  = 13.64; P < .05), were found to be associated with successful landings. These critical features help surfers land in a stable position, while maintaining contact with the surfboard. The results of this study provide coaches with evidence to adjust the technique of their athletes to improve their winning potential.

VENUM (Vascular Education iN Undergraduate Medicine): a multicentre evaluation of undergraduate vascular education in the UK.

INTRODUCTION: Vascular surgery is a recognised surgical subspecialty covering an array of circulatory conditions predominately affecting geriatric and diabetic patients. As such, a wide breadth of clinicians will see patients with vascular pathologies, but it is unclear how detailed their knowledge base is. Key to this is the education of medical students, which has been poorly documented during undergraduate training in the UK. VENUM aimed to establish students' perceptions of vascular surgery and their confidence in performing vascular objective structured clinical examination (OCSE) skills. METHODS: During the academic year of 2022/2023, final-year medical students were invited to complete a JISC survey (collaborative authorship). Seventy-seven research leads were recruited to disseminate the survey. Quantitative and thematic analysis was used to assess the data. RESULTS: In total, 240 final-year medical students completed the survey (54% female; 26 medical schools represented). Forty-five per cent of students reported never having had a vascular placement, 24% had never completed a vascular-focused clinical examination and 26% reported low confidence in performing ankle brachial pressure index measurement. An assessment of peripheral arterial disease morbidity was answered correctly in 17% of respondents compared with 92% for angina (chi-square test p<0.001). Students perceived the specialty to be non-inclusive and that early exposure to vascular surgery was required for better engagement with the specialty. CONCLUSION: Students have experienced little exposure to vascular surgery. This may affect future recruitment to vascular surgery and overall knowledge of vascular conditions in UK-trained doctors, which may affect long-term patient management.

A meta-analysis of brief high-impact exercises for enhancing bone health in premenopausal women.

UNLABELLED: A snapshot of current evidence from 6 randomised controlled trials for the effects of short bouts of high-impact exercises in 256 women via meta-analysis reveals that ample osteogenic response could be realised at the femoral neck and trochanter of premenopausal women with rest-inserted bouts of few mechanical bone loading cycles. INTRODUCTION: Exercise is an important means of improving bone health and preventing osteoporosis. Brief bouts of simple exercises may be useful for aiding lifestyle compliance to physical activity. This study aimed to review the evidence on the effect of brief, high-impact exercise on bone health among premenopausal women. METHODS: A structured and comprehensive search of databases was undertaken along with hand searching of key journals and reference lists to locate relevant studies published and unpublished up to January 2011. Six randomised controlled trials met predetermined inclusion criteria. Brief high-impact exercises (<30 min) were examined for their effect on bone mineral density (BMD) among premenopausal women. Trial quality was assessed using the Effective Public Health Practice Project quality assessment tool. Study outcomes for analysis, absolute change (grams per square centimetre) or relative change (in percent) in BMD at femoral neck, trochanter and lumbar spine were compared by calculating standardised mean difference (SMD) using fixed- and random effects models. RESULTS: Quality of included trials varied from medium to high on a scale of 1 to 3. Brief bouts of exercise led to significant increases in femoral neck BMD (SMD = 0.64, 95% confidence interval (CI) = 0.38, 0.90, overall effect Z value = 4.84, p = 0.001); a modest increase in trochanteric BMD (SMD = 0.36, 95% CI = 0.10, 0.61, Z value = 2.08, p = 0.04) and no increase in spinal BMD (SMD = 0.04, 95% CI= -0.23, 0.31, Z value = 0.26, p = 0.79). CONCLUSION: Based on the meta-analysis, brief high-impact exercise improves BMD at the hip but not at the lumbar spine. Effectiveness of this form of exercise as a lifestyle physical activity for prevention of osteoporosis should be explored in larger populations.

Prevalence of elevated blood lead levels and risk factors among children living in Patna, Bihar, India 2020.

Childhood lead exposure remains a key health concern for officials worldwide, contributing some 600,000 new cases of intellectually disabled children annually. Most children affected by high exposure to lead live in low- and middle-income countries. The leaded gasoline phase out in India was completed in 2000. Yet, in 2020, an estimated 275 million children aged 0 to 9 years had blood lead levels (BLLs) ≥ 5 µg/dL known to adversely affect intelligence and behavior. Lead sources reported in India include spices, cookware, paint, traditional medicines and cosmetics, and lead-acid battery recycling and repair. However, their relative contribution has not been characterized. More than 200 lead pollution sites related to battery recycling and repair activities were identified in Bihar and Jharkhand, India. Ninety percent of the recycling sites had soil lead concentrations exceeding the US Environmental Protection Agency's standards. We compared blood and environmental lead levels in two groups of children in Patna, Bihar. Households in proximity to battery recycling operations (Proximal n = 67) versus households distal to these operations (Distal n = 68). The average age of children was 40 months; 46% were female. Overall, the geometric mean (GM) BLL was 11.6 µg/dL. GM BLLs of children in Proximal and Distal households were not significantly different (10.2 µg/dL vs. 13.1 µg/dL respectively; p≤0.07). About 87% children, 56 Proximal and 62 Distal had BLLs ≥5 µg/dl. Lead concentrations in environmental samples were significantly higher in Proximal households (soil mean 9.8 vs. 1.6 µg/ft2; dust mean 52.9 vs. 29.9 µg/ft2 p<0.001; Proximal vs. Distal respectively) whereas concentrations in all spices were higher in Distal households (mean 46.8 vs 134.5 ppm p<0.001; Proximal vs. Distal respectively), and turmeric (mean 59.4 vs. 216.9 ppm Proximal vs. Distal respectively). In multivariate analyses for all children lead in spices and turmeric and number of rooms in the house were significant while for the Proximal group only lead in spices remained in the model. The predictive value of these models was poor. For the Distal group, a model with lead concentration in spices, turmeric and soil and number of rooms in the house was a much better fit. Of the 34 water samples collected, 7 were above the Indian standard of 10 ppb for lead in drinking water (2 in the Proximal area, 5 in the Distal area). Children in Patna, Bihar, India are exposed to multiple sources of lead, with lead levels in house dust and loose, locally sourced spices the most likely to increase blood lead levels. A holistic approach to blood lead testing and source identification and remediation are necessary to prevent lead exposure.

Comparison of in vitro and in vivo approaches to studying brain colonization by breast cancer cells.

Brain metastases occur in 20 to 40% of patients with metastatic breast cancer. The process is complex and depends on successful cancer cell evasion from the primary tumor, distribution and survival within the blood stream and cerebral microvasculature, penetration of the blood brain barrier and proliferation within the brain microenvironment. The initial steps of brain colonization are difficult to study in vivo. Therefore, in vitro assays have been developed to mimic this process. Most commonly, in vitro studies of brain colonization focus on tumor cell adhesion to brain endothelial cells and transendothelial migration. We previously investigated breast cancer brain colonization from the blood stream in vivo and defined the time and process of brain entry for five different cancer cell lines in a mouse model. We now investigated if in vitro approaches can reliably emulate the initial steps that determine successful brain colonization in vivo. To this end, we optimized an in vitro model of the vascular blood brain barrier and compared the brain invasion properties of the in vivo characterized cell models with their ability to interact with and penetrate the blood brain barrier model in vitro. Our results show that the in vitro findings correlate only poorly with the vivo results. The limitations of the in vitro approaches are discussed in light of the in vivo processes. We conclude that investigation of mechanisms supporting the earliest steps of breast cancer brain metastasis from the blood stream will depend on in vivo analyses.

Polymorphisms of the angiotensin converting enzyme gene in relation to intrauterine growth restriction.

The aim of this case-control study was to explore the relation between maternal and infant angiotensin converting enzyme (ACE) activity and its genotypes in uncomplicated term pregnancies (> or =37 weeks) and pregnancies with growth-restricted infants (birthweight at or below the 5th centile). Venous cord bloods and maternal venous samples were obtained for serum ACE activity and ACE genotype. Growth-restricted infants (< or =5th centile) were more likely to be of the DD genotype compared to appropriately grown infants (42 vs. 13%, p = 0.003). There was no significant difference in the frequency of the maternal DD genotype between the two groups (33 vs. 22%, p = 0.43) and similarly no significant differences in the maternal or fetal ACE activities. Within the intrauterine growth restriction (IUGR) group, infants of the DD genotype had higher ACE activity compared to appropriately grown infants (p = 0.03). In conclusion, the DD genotype of the ACE gene appears to be associated with fetal growth and may be a factor in the increased risk of adult onset chronic diseases among growth-restricted infants.

Nanosecond X-ray diffraction from biological samples with a laser-produced plasma source.

By using 4.45-angstrom radiation generated by Cl+15 ions in a laser plasma and nanosecond exposures, low-angle x-ray diffraction patterns were obtained from dried rat spinal nerves and a powder of cholesterol. Three to four 400-picosecond, 45-joule pulses were required for the exposure. This new technique should have wide application in structural kinetic studies.

Modulation of the affinity of integrin alpha IIb beta 3 (GPIIb-IIIa) by the cytoplasmic domain of alpha IIb.

Intracellular signaling alters integrin adhesive functions in inflammation, immune responses, hemostasis, thrombosis, and retinal development. By truncating the cytoplasmic domain of alpha IIb, the affinity of integrin alpha IIb beta 3 for ligand was increased. Reconstitution with the cytoplasmic domain from integrin alpha 5 did not reverse the increased affinity. Thus, the cytoplasmic domain of the alpha subunit of GPIIb-IIIa controls ligand binding affinity, which suggests mechanisms for inside-out transmembrane signaling through integrins. These findings imply the existence of hitherto unappreciated hereditary and acquired thrombotic disorders in humans.

Do LCPUFAs influence cardiovascular function in early childhood?

In recent years there have been reports linking breast milk intake in infancy to lower blood pressure during childhood. The mechanisms underlying the relationship remain uncertain however there has been recent interest in the role of long chain polyunsaturated fatty acids (LCPUFAs). Several studies involving human adults have reported a lowering of blood pressure with n-3 fatty acid supplementation. Data relating to children are limited: however, two published randomised controlled studies report that LCPUFA supplementation in infancy may be associated with lower blood pressure in early childhood.

Correlation of angiotensin converting enzyme activity and the genotypes of the I/D polymorphism in the ACE gene with preterm birth and birth weight.

OBJECTIVE: Preterm birth remains one of the most challenging areas in obstetrics. The pathogenesis of preterm labor is multifactorial and research on preterm birth has focused principally on infection and inflammatory markers. Recently the focus has turned to potential genetic factors influencing preterm birth. Uteroplacental insufficiency and thrombotic vasculopathy are considered part of the pathogenesis of preterm labor. Investigating the gene expression in the maternal/fetal interface seems of importance to expand our knowledge of the pathophysiology of preterm birth. The renin-angiotensin system (RAS) appears to play an important role in fetal/placental development and uteroplacental circulation. Hence, the aim of this study was to investigate angiotensin converting enzyme (ACE) activity and I/D polymorphisms in the ACE gene in mothers and infants with appropriately grown infants in relation to preterm birth and infant birth weight. STUDY DESIGN: We conducted a cross-sectional study of 113 term pregnancies (> or =37 weeks) and 18 preterm pregnancies (<37 weeks). Umbilical cord bloods (venous and arterial) were obtained from the placenta immediately after delivery for serum ACE activity, ACE genotype analysis of the I/D polymorphism and the acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. RESULTS: The distribution of the maternal ACE genotypes was similar for preterm and term births as was maternal ACE activity. Preterm infants were more likely to be of the DD genotype than term infants (7/18 (39%) vs. 11/83 (13%), p=0.02) (adjusted p=0.04). There was no correlation between ACE activity and birth weight (r(2) 0.00, p=0.82). CONCLUSIONS: These findings suggest that the ACE genotype of the infant may influence the risk of preterm birth among appropriately grown fetuses.

Compliance with NICE guidelines when commissioning varicose vein procedures.

BACKGROUND: Varicose veins impair quality of life and can lead to chronic leg ulcers. National Institute for Health and Care Excellence (NICE) guidelines (CG168) set out evidence-based standards for patient management. In England, Clinical Commissioning Groups (CCGs) fund NHS care within their locality. The objective of this study was to evaluate CCGs' commissioning policies and compare them with CG168. METHODS: Searches were made for the published policies of all 206 English CCGs. They were reviewed for compliance with NICE guidelines and the associated quality standard. Areas of disagreement were analysed for themes. RESULTS: Some 203 CCGs (98·5 per cent) had a published policy and 190 (93·6 per cent) of these were published after publication of CG168. Only 73 of the policies (36·0 per cent) were compliant with CG168. Treatment was restricted on the basis of clinical disease severity in 119 CCGs (58·6 per cent); 29 (14·3 per cent) stipulated delay of treatment using a 'trial' of conservative treatment; 22 (10·8 per cent) used lifestyle-related factors such as BMI and smoking status to ration treatment. Treatment was commissioned for uncomplicated symptomatic varicose veins in 87 CCGs (42·9 per cent), but some applied additional rationing mechanisms; 109 CCGs (53·7 per cent) would treat oedema, 183 (90·1 per cent) would treat skin and soft tissue damage, 202 (99·5 per cent) healed ulceration, and all would allow active ulcers to be treated. DISCUSSION: The majority of CCGs in England have commissioning policies that contradict NICE guidelines. Rationing strategies include disease severity, delay and patient lifestyle-related factors, creating unwarranted geographical variation for varicose vein treatment, disregarding the NHS Constitution for England, and perhaps leading to an increase in costly treatment of chronic complications in the long term.

Reduced surface expression and binding of fibronectin by thrombin-stimulated thrombasthenic platelets.

Thrombin stimulation results in increased surface expression of endogeneous fibronectin and binding of plasma fibronectin to human platelets. Platelets of patients with Glanzmann's thrombasthenia, a bleeding disorder, exhibit reduced thrombin-induced platelet aggregation, little or no clot retraction, and abnormal platelet spreading on glass surfaces. Thrombin stimulation of patient platelets from four thrombasthenic kindreds resulted in little fibronectin binding. Nevertheless, thrombin did induce serotonin secretion from these cells, indicating that stimulation was occurring. Thrombasthenic platelets did not inhibit thrombin-stimulated fibronectin binding to coincubated normal cells, suggesting that their defect was not due to the presence of a soluble inhibitor of fibronectin binding. Thrombin-stimulated afibrinogenemic platelets bound similar quantities of fibronectin to normal cells, indicating that the thrombasthenic deficit is not secondary to reduced fibrinogen content or binding. The thrombasthenic cells had an endogenous fibronectin content of 2.9 +/- 0.7 micrograms/10(9) platelets, whereas cells simultaneously prepared from five normal individuals contained 1.8 +/- 0.7 micrograms/10(9) platelets, a statistically insignificant difference. Nevertheless, thrombin stimulation did not increase expression of endogeneous fibronectin antigen on the surface of the thrombasthenic platelets as judged by immunofluorescence. These defects in platelet fibronectin binding and surface expression may account for some of the manifestations of Glanzmann's thrombasthenia.

The influence of mode of delivery and ACE genotype on serum angiotensin converting enzyme (ACE) activity in the mother and infant at term.

OBJECTIVE: Angiotensin converting enzyme (ACE) and its genotype have been shown to play a role in the pathophysiology of pregnancy complications such as pre-eclampsia and intrauterine growth restriction and possibly in adult onset chronic diseases. The physiological changes of ACE and the influence of its genotype during the intrapartum period are not well known. Hence the aim of this study was to assess serum ACE activity and its genotype in mothers and infants at term in relation to labour and mode of delivery. STUDY DESIGN: A cross sectional study of 99 women who laboured and 27 women who delivered by elective caesarean section after 36 completed weeks gestation with uncomplicated pregnancies. Venous cord bloods were obtained immediately after delivery of the placenta for serum ACE activity, ACE genotype and acid-base status. Maternal venous samples were obtained just after delivery for analysis of ACE activity and ACE genotype. Univariate analyses were performed using parametric tests for normally distributed data and nonparametric tests for the data that were not normally distributed. A multiple regression model was developed to adjust for potential confounding factors. RESULTS: The umbilical venous ACE activity was similar for infants delivered following labour compared to those delivered by elective caesarean section, 47.2 U/L (35-64) versus 40.1 U/L (31-60) (adjusted p=0.21). Maternal ACE activities were 28.9 U/L (22-35) and 32.1 U/L (22-40) respectively (adjusted p=0.17). The ACE activity in infants was higher than that of mothers 46 U/L versus 22 U/L, respectively (p= or <0.001). Neither the mode of delivery nor the presence of suspected fetal compromise influenced maternal or infant ACE activity. There was no influence of the infants' genotype on ACE activity in relation to mode of delivery. The DD genotype was associated with higher ACE activity in mothers (p=0.001) but not in infants (p=0.56). CONCLUSIONS: This study shows that intrapartum events do not affect ACE activity. These results will enhance our ability to investigate the role of ACE and its genotype in abnormal fetal growth and in subsequent adult onset chronic disease.

Trans-dominant inhibition of integrin function.

Occupancy of integrin adhesion receptors can alter the functions of other integrins and cause partition of the ligand-occupied integrin into focal adhesions. Ligand binding also changes the conformation of integrin extracellular domains. To explore the relationship between ligand-induced conformational change and integrin signaling, we examined the effect of ligands specific for integrin alpha IIb beta 3 on the functions of target integrins alpha 5 beta 1 and alpha 2 beta 1. We report that binding of integrin-specific ligands to a suppressive integrin can inhibit the function of other target integrins (trans-dominant inhibition). Trans-dominant inhibition is due to a blockade of integrin signaling. Furthermore, this inhibition involves both a conformational change in the extracellular domain and the presence of the beta cytoplasmic tail in the suppressive integrin. Similarly, ligand-induced recruitment of alpha IIb beta 3 to focal adhesions also involves a conformational rearrangement of its extracellular domain. These findings imply that the ligand-induced conformational changes can propagate from an integrin's extracellular to its intracellular face. Trans-dominant inhibition by integrin ligands may coordinate integrin signaling and can lead to unexpected biological effects of integrin-specific inhibitors.

Some chronobiological considerations related to physical exercise.

Variables associated with physical activity show circadian rhythms in resting subjects; these rhythms have both exogenous (due to the individual's lifestyle and environment) and endogenous (due to the "body clock") components. During exercise, many of the rhythms persist, even though some show decreasing amplitude with increasing severity of exercise. Whilst the value of physical fitness is not disputed (for elite athletes, for individuals who just want to be physically fit, or for patients undertaking physical rehabilitation regimens), there are certain times of the day when special care is needed. These times are soon after waking--when there is the possibility of an increased risk of cardiovascular morbidity and damage to the spine--and late in the day--when there is an increased risk of respiratory difficulties. Since physical exercise is inextricably linked with thermoregulation, there are special considerations to bear in mind when exercise takes place in cold or hot environments. Further, due to the effects of the body clock, exercise and activity during night work and after time-zone transitions presents problems peculiar to these circumstances. In addition, the menstrual cycle affects physical performance, and these circatrigintan rhythms interact with the circadian ones. Bearing in mind these factors, advice that is based upon knowledge of circadian and circatrigintan rhythms can be given to all those contemplating physical activity. Chronobiologically, there is advantage in undertaking physical activity programmes towards the middle of the waking day and not at times when a sleep or nap has just been taken.

Association study of dopamine receptor gene polymorphisms with drug-induced hallucinations in patients with idiopathic Parkinson's disease.

Some patients with idiopathic Parkinson's disease experience hallucinations as a result of treatment with levodopa and dopamine agonists. There is evidence for some heterogeneity in these hallucinating patients based on duration of Parkinson's disease at onset of hallucinations. We compared the frequency of polymorphisms in the dopamine D2 and D3 receptor genes between patients with drug-induced hallucinations and non-hallucinating patients. Two polymorphisms close to DRD2 and one in DRD3 were studied. No association was found with the whole group of hallucinating patients and their controls. However, an association was found with late-onset hallucinations and the C allele of the TaqIA polymorphism, 10.5 kb 3' to DRD2. This polymorphism may be in linkage disequilibrium with a mutation in DRD2 or a nearby gene that predisposes to drug-induced hallucinations which occur later in the course of idiopathic Parkinson's disease.

The health of somatic cell cloned cattle and their offspring.

The cloning syndrome is a continuum with the consequences of abnormal reprogramming manifest throughout gestation, the neo-natal period, and into adulthood in the cloned generation, but it does not appear to be transmitted to subsequent offspring following sexual reproduction. Most in vivo studies on bovine somatic cell cloning have focused on development during pregnancy and the neo-natal period. In this paper, we report on the viability and health of cloned cattle in adulthood. From our studies at AgResearch, we find that between weaning and 4 years of age, the annual mortality rate in cattle cloned from somatic cells is at least 8%. Although the reasons for death are variable and some potentially preventable, the main mortality factor in this period is euthanasia due to musculoskeletal abnormalities. This includes animals with severely contracted flexor tendons and those displaying chronic lameness, particularly in milking cows. In contrast, no deaths beyond weaning have so far been encountered with the offspring of clones where the oldest animals are 3 years of age. In surviving cloned cattle, blood profiles and other indicators of general physiological function such as growth rate, reproduction, rearing of offspring, and milk production are all within the normal phenotypic ranges.

Cloned cattle derived from a novel zona-free embryo reconstruction system.

As the demand for cloned embryos and offspring increases, the need arises for the development of nuclear transfer procedures that are improved in both efficiency and ease of operation. Here, we describe a novel zona-free cloning method that doubles the throughput in cloned bovine embryo production over current procedures and generates viable offspring with the same efficiency. Elements of the procedure include zona-free enucleation without a holding pipette, automated fusion of 5-10 oocyte-donor cell pairs and microdrop in vitro culture. Using this system, zona-free embryos were reconstructed from five independent primary cell lines and cultured either singularly (single-IVC) or as aggregates of three (triple-IVC). Blastocysts of transferable quality were obtained at similar rates from zona-free single-IVC, triple-IVC, and control zona-intact embryos (33%, 25%, and 29%, respectively). In a direct comparison, there was no significant difference in development to live calves at term between single-IVC, triple-IVC, and zona-intact embryos derived from the same adult fibroblast line (10%, 13%, and 15%, respectively). This zona-free cloning method could be straightforward for users of conventional cloning procedures to adopt and may prove a simple, fast, and efficient alternative for nuclear cloning of other species as well.