Fluoxetine increased adult neurogenesis is mediated by 5-HT3 receptor.

Adult neurogenesis is an aspect of structural plasticity that remains active during adulthood in some brain regions. One of them is the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. Adult neurogenesis is reduced by different factors and in disorders of the CNS, including major depression. Antidepressant treatments, such as chronic fluoxetine administration, recover the normal level of adult neurogenesis. Fluoxetine treatment increases the free concentration of the neurotransmitter serotonin and this monoamine is implicated in the regulation of the neurogenic process; however, the target of the action of this neurotransmitter has not been fully elucidated. In this study, we have tried to determine the relevance of the serotonin receptor 3 (5-HT3) in the hippocampal neurogenesis of adult rats. We have used fluorescent immunohistochemistry to study the expression of the 5-HT3 receptor in different neurogenesis stages in the SGZ, identifying its expression in stem cells, amplifying neural progenitors and immature neurons. Moreover, we have studied the impact of a 5-HT3 antagonist (ondansetron) in the fluoxetine-induced adult neurogenesis. We observed that fluoxetine alone increases the number of both proliferating cells (ki67 positive) and immature neurons (DCX positive) in the SGZ. By contrast, co-treatment with ondansetron blocked the increase in proliferation and neurogenesis. This study demonstrates that the activation of 5-HT3 receptors is necessary for the increase of adult neurogenesis induced by fluoxetine.

Development of Bioglass/PEEK Composite Coating by Cold Gas Spray for Orthopedic Implants.

Cold gas spray (CGS) technology has allowed the development of biofunctional coatings composed of 45S5 and polyetheretherketone (PEEK). The combination of a bioactive glass material embedded in a polymeric matrix makes this composite an interesting material for orthopedic applications since this composite meets the biomechanical and biological requirements of an implant. In the present study, blends of bioactive glass 45S5 and PEEK powder with different granulometry and 45S5/PEEK ratio have been prepared. These mixtures of powders have been deposited onto PEEK substrates by CGS with the goal of incorporating a bioactive additive to the biocompatible polymer, which can improve the bone-implant interaction of PEEK. The deposition efficiency (DE) of the coatings has been evaluated, and from the results obtained, it was possible to conclude that DE is significantly affected by the granulometry and by the 45S5/PEEK ratio of the blends. By scanning electron microscopy (SEM) inspection, it was observed that the use of blends with high 45S5/PEEK ratio lead to the deposition of coatings with high content of 45S5. Finally, the friction behavior of the coatings was analyzed performing ball-on-disk tests and these experiments showed that the presence of glass particles has a beneficial role in the wear resistance.

Circulating miR-30b-5p levels in plasma as a novel potential biomarker for early detection of breast cancer.

BACKGROUND: Recently, microRNAs have been demonstrated to be potential non-invasive biomarkers for diagnosis, prognosis assessment or prediction of response to treatment in cancer. In this study, we evaluate the potential of miR-30b-5p as a biomarker for early diagnosis of breast cancer (BC) in tissue and plasma. METHODS: Expression of miR-30b-5p was determined in a series of 112 BC and 40 normal breast tissues. Circulating miR-30b-5p levels in plasma samples were determined in a discovery cohort of 38 BC patients and 40 healthy donors and in a validation cohort of 83 BC patients and 83 healthy volunteers. miR-30b-5p expression was measured by quantitative real-time PCR and receiver operating characteristics curve analysis was carried out. RESULTS: The miR-30b-5p expression was significantly lower in BC tissue than in healthy breast samples. In contrast, circulating miR-30b-5p levels were significantly higher in BC patients compared with healthy donors. Furthermore, circulating miR-30b-5p levels were significantly higher in patients with positive axillary lymph node and de novo metastatic patients. Receiver operating characteristics curve analysis demonstrated a good diagnostic potential of miR-30b-5p to detect BC even at an early stage of the disease. CONCLUSION: Thus, we highlight the potential of miR-30b-5p as a non-invasive, fast, reproducible and cost-effective diagnostic biomarker of BC.

Role of the orthopaedic surgeon in 3D printing: current applications and legal issues for a personalized medicine. / Papel del cirujano ortopédico y traumatólogo en la impresión 3D: aplicaciones actuales y aspectos legales para una medicina personalizada.

3D printing (I3D) is an additive manufacturing technology with a growing interest in medicine and especially in the specialty of orthopaedic surgery and traumatology. There are numerous applications that add value to the personalised treatment of patients: advanced preoperative planning, surgeries with specific tools for each patient, customised orthotic treatments, personalised implants or prostheses and innovative development in the field of bone and cartilage tissue engineering. This paper provides an update on the role that the orthopaedic surgeon and traumatologist plays as a user and prescriber of this technology and a review of the stages required for the correct integration of I3D into the hospital care flow, from the necessary resources to the current legal recommendations.

In-vitro comparison of hydroxyapatite coatings obtained by cold spray and conventional thermal spray technologies.

Hydroxyapatite (HA) coatings onto Ti6Al4V alloy substrates were obtained by several thermal spray technologies: atmospheric plasma spray (APS) and high velocity oxy fuel (HVOF), together with the cold spray (CS) technique. A characterization study has been performed by means of surface and microstructure analyses, as well as biological performance. In-vitro tests were performed with primary human osteoblasts at 1, 7 and 14 days of cell culture on substrates. Cell viability was tested by MTS and LIVE/DEAD assays, cell differentiation by alkaline phosphatase (ALP) quantification, and cell morphology was analyzed by scanning electron microscopy. The HA coatings showed an increase of HA crystallinity from 62,4% to 89%, but also an increase of hydrophilicity from ∼32° to 0°, with the decrease of the operating temperature of the thermal spray techniques (APS > HVOF > CS). Additionally, APS HA coatings showed more surface micro-features than HVOF and CS HA coatings; cells onto APS HA coatings showed faster attachment by acquiring osteoblastic morphology in comparison with the rounded cell morphology observed onto CS HA coatings at 1 day of cell culture. HVOF HA coatings also showed proper cell adherence but did not show extended filopodia as cells onto APS HA coatings. However, at 14 days of cell culture, higher cell proliferation and differentiation was detected on HA coatings with higher crystallinity (HVOF and CS techniques). Cell attachment is suggested to be favoured by surface micro-features but also moderate surface wettability whereas cell proliferation and differentiation is suggested to be highly influenced by HA crystallinity and crystal size.

X-ray microtomographic characterization of highly rough titanium cold gas sprayed coating for identification of effective surfaces for osseointegration.

A highly rough titanium coating obtained by Cold Gas Spray (CGS) has been characterized by means of high-resolution 3D microtomography (micro-CT) with the aim to evaluate its open and close porosity for possible use in orthopaedic implants to promote osseointegration. Micro-CT allowed a qualitative and quantitative description of the main features, morphology of the pores and surface roughness of the coating. Several numerical values were obtained to describe size, form and distribution of the closed/inner and open/outer pores. Additionally, surface roughness and open porosity were image-analyzed to find the effective surface for osseointegration.

The impact of hip fracture on health-related quality of life and activities of daily living: the SPARE-HIP prospective cohort study.

PURPOSE: The medical morbidity and mortality associated with neck of femur fractures is well-documented, whereas there is limited data for patient-reported outcomes. The aim of this study was to characterize the impact of neck of femur fractures on activities of daily living and patient-reported health-related quality of life. METHODS: Design and participants: Multicentric prospective cohort study. Consecutive sample patients with fragility hip fracture over 50 years old admitted in 48 hospitals in Spain. OUTCOMES: daily living activity function (Barthel Index) and health-related quality of life (EQ-5D) pre-fracture, admission to hospital and at 1- and 4-month follow-up post-fracture. STATISTICS: Barthel and EQ-5D over time are described as mean (SD) and median (interquartile range). RESULTS: A total of 997 patients were recruited at baseline with 4-month outcomes available for, and 856 patients (89.5%). Barthel Index fell from 78.77 (23.75) at baseline to 43.62 (19.86) on admission to hospital with the fracture. Scores partially recovered to 54.89 (25.40) and 64.09 (21.35) at 1- and 4-month post-fracture, respectively. EQ-5D fell from a median of 0.75 (0.47-0.91) to - 0.01 (- 0.03 to 0.51) on admission. Partial recovery was observed again to (0.51 (- 0.06 to 0.67)) and (0.60 (0.10 to 0.80)) at 1- and 4-month post-fracture, respectively. CONCLUSIONS: Hip fracture results in a large decline in the ability to perform activities of daily living and patient-reported health-related quality of life with only partial recovery amongst survivors 4-month post-fracture.

In-vitro study of hierarchical structures: Anodic oxidation and alkaline treatments onto highly rough titanium cold gas spray coatings for biomedical applications.

Hierarchical structures were obtained applying two different nanotexturing surface treatments onto highly rough commercial pure titanium coatings by cold spray: (i) anodic oxidation and (ii) alkaline treatments. An extended surface characterization in terms of topography, composition, and wettability has been performed to understand how those parameters affect to cell response. Primary human osteoblasts extracted from knee were seeded onto the as-sprayed titanium surface before and after the nanotexturing treatments. Cell viability was tested by using MTS and LIVE/DEAD assays, as well as osteoblasts differentiation by alkaline phosphatase (ALP) quantification at 3 and 10 days of cell culture. The combination of micro-/nano-roughness results in a significantly increase of cell proliferation, as well as cell differentiation after 10 days of cell culture in comparison with the non-treated coatings.

Abdominal Drainage After Laparoscopic Appendectomy in Children: An Endless Controversy?

BACKGROUND: Routine prophylactic abdominal drains after laparoscopic appendectomy for perforated appendicitis in children are still controversial. Throughout the history of surgery, potential benefits of the abdominal drains have been described. However, in recent studies, no benefits were observed and serious complications have been reported. METHODS: From January 2000 to December 2013, all charts of the pediatric patients who underwent laparoscopic appendectomy in our tertiary center were revised. The data from 1736 appendectomies were analyzed. We only included those patients with perforated appendicitis treated with early appendectomy (n = 192). Prophylactic drains were established according to the surgeon's preference. The sample was divided into two groups, those with drain (n = 117) and those without drain (n = 75). Demographics, operative findings, and postoperative outcomes were analyzed in both groups. RESULTS: Of all patients, 121 were male and 71 were female with a mean age of 7.77 ± 3.4 years. There were not statistically significant differences between the groups in gender (p = 0.82) and mean age (p = 0.31). There were no statistically significant differences between the two groups in the rate of intra-abdominal abscess, wound infection, and bowel obstruction. However, the drainage group has been statistically associated with an increased requirement of antibiotic and analgesic medication, fasting time, operative time, and length of hospital stay. CONCLUSION: The prophylactic use of abdominal drainage after laparoscopic appendectomy for perforated appendicitis in children does not prevent postoperative complications and may be associated with negative outcomes. Prospective randomized studies will be necessary to verify this question.

Functionalized coatings by cold spray: An in vitro study of micro- and nanocrystalline hydroxyapatite compared to porous titanium.

Three different surface treatments on a Ti6Al4V alloy have been in vitro tested for possible application in cementless joint prosthesis. All of them involve the novelty of using the Cold Spray technology for their deposition: (i) an as-sprayed highly rough titanium and, followed by the deposition of a thin hydroxyapatite layer with (ii) microcrystalline or (iii) nanocrystalline structure. Primary human osteoblasts were extracted from knee and seeded onto the three different surfaces. Cell viability was tested by MTS and LIVE/DEAD assays, cell differentiation by alkaline phosphatase (ALP) quantification and cell morphology by Phalloidin staining. All tests were carried out at 1, 7 and 14 days of cell culture. Different cell morphologies between titanium and hydroxyapatite surfaces were exhibited. At 1 day of cell culture, cells on the titanium coating were spread and flattened, expanding the filopodia actin filaments in all directions, while cells on the hydroxyapatite coatings showed round like-shape morphology due to slower attachment. Higher cell viability was detected at all times of cell culture on titanium coating due to a better attachment at 1 day. However, from 7 days of cell culture, cells on hydroxyapatite showed good attachment onto surfaces and highly increased their proliferation, mostly on nanocrystalline, achieving similar cell viability levels than titanium coatings. ALP levels were significantly higher in titanium, in part, because of greatest cell number. Overall, the best cell functional results were obtained on titanium coatings whereas microcrystalline hydroxyapatite presented the worst cellular parameters. However, results indicate that nanocrystalline hydroxyapatite coatings may achieve promising results for the faster cell proliferation once cells are attached on the surface.

Osteoblastic cell response on high-rough titanium coatings by cold spray.

Highly rough and porous commercially pure titanium coatings have been directly produced for first time by the cold spray technology, which is a promising technology in front of the vacuum plasma spray for oxygen sensitive materials. The wettability properties as well as the biocompatibility evaluation have been compared to a simply sand blasted Ti6Al4V alloy substrate. Surface topographies were analysed using confocal microscopy. Next, osteoblast morphology (Phalloidin staining), proliferation (MTS assay), and differentiation (alkaline phosphatase activity) were examined along 1, 7 and 14 days of cell culture on the different surfaces. Finally, mineralization by alizarin red staining was quantified at 28 days of cell culture. The contact angle values showed an increased hydrophilic behaviour on the as-sprayed surface with a good correlation to the biological response. A higher cell viability, proliferation and differentiation were obtained for highly rough commercial pure titanium coatings in comparison with sand blasted substrates. Cell morphology was similar in all coatings tested; at 14 days both samples showed extended filopodia. A higher amount of calcium-rich deposits was detected on highly rough surfaces. In summary, in-vitro results showed an increase of biological properties when surface roughness increases.

Zwitterionic amidinates as effective ligands for platinum nanoparticle hydrogenation catalysts.

Ligand control of metal nanoparticles (MNPs) is rapidly gaining importance as ligands can stabilize the MNPs and regulate their catalytic properties. Herein we report the first example of Pt NPs ligated by imidazolium-amidinate ligands that bind strongly through the amidinate anion to the platinum surface atoms. The binding was established by 15N NMR spectroscopy, a precedent for nitrogen ligands on MNPs, and XPS. Both monodentate and bidentate coordination modes were found. DFT showed a high bonding energy of up to -48 kcal mol-1 for bidentate bonding to two adjacent metal atoms, which decreased to -28 ± 4 kcal mol-1 for monodentate bonding in the absence of impediments by other ligands. While the surface is densely covered with ligands, both IR and 13C MAS NMR spectra proved the adsorption of CO on the surface and thus the availability of sites for catalysis. A particle size dependent Knight shift was observed in the 13C MAS NMR spectra for the atoms that coordinate to the surface, but for small particles, ∼1.2 nm, it almost vanished, as theory for MNPs predicts; this had not been experimentally verified before. The Pt NPs were found to be catalysts for the hydrogenation of ketones and a notable ligand effect was observed in the hydrogenation of electron-poor carbonyl groups. The catalytic activity is influenced by remote electron donor/acceptor groups introduced in the aryl-N-substituents of the amidinates; p-anisyl groups on the ligand gave catalysts several times faster the ligand containing p-chlorophenyl groups.

Real-Time Protein and Cell Binding Measurements on Hydroxyapatite Coatings.

Although a lot of in vitro and in vivo assays have been performed during the last few decades years for hydroxyapatite bioactive coatings, there is a lack of exploitation of real-time in vitro interaction measurements. In the present work, real-time interactions for a plasma sprayed hydroxyapatite coating were measured by a Multi-Parametric Surface Plasmon Resonance (MP-SPR), and the results were compared with standard traditional cell viability in vitro assays. MP-SPR is proven to be suitable not only for measurement of molecule-molecule interactions but also molecule-material interaction measurements and cell interaction. Although SPR is extensively utilized in interaction studies, recent research of protein or cell adsorption on hydroxyapatite coatings for prostheses applications was not found. The as-sprayed hydroxyapatite coating resulted in 62.4% of crystalline phase and an average thickness of 24 ± 6 µm. The MP-SPR was used to measure lysozyme protein and human mesenchymal stem cells interaction to the hydroxyapatite coating. A comparison between the standard gold sensor and Hydroxyapatite (HA)-plasma coated sensor denoted a clearly favourable cell attachment on HA coated sensor as a significantly higher signal of cell binding was detected. Moreover, traditional cell viability and proliferation tests showed increased activity with culture time indicating that cells were proliferating on HA coating. Cells show homogeneous distribution and proliferation along the HA surface between one and seven days with no significant mortality. Cells were flattened and spread on rough surfaces from the first day, with increasing cytoplasmatic extensions during the culture time.

Long-term results after treatment of pertrochanteric femoral fractures with percutaneous compression plate (PCCP).

OBJECTIVE: This study sought to evaluate the long-term osteosynthesis results for AO/OTA 31.A1-A2 pertrochanteric fractures treated with the percutaneous compression plate (PCCP). MATERIALS AND METHODS: This investigation was a retrospective observational descriptive study of 335 patients, with a minimum follow-up of 2 years and a maximum follow-up of 8 years (2004-2011). RESULTS: The average post-operative hospital stay was 6.2 days, and the average decrease in haemoglobin levels after the intervention was 2.7 mg/dL, with transfusion required for one-third of the patients. Complications related to the implant were observed in 4.2 % of patients; the most notable complication was cut-out (2.4 % of patients), and 3 cases involved pseudarthrosis with breakage of the implant (0.9 % of patients). CONCLUSIONS: From the results obtained in this study and an analysis of previously published work, we believe that the PCCP may be the implant of choice for AO/OTA 31.A1-A2 fractures.

Incidence and risk factors of post-engraftment invasive fungal disease in adult allogeneic hematopoietic stem cell transplant recipients receiving oral azoles prophylaxis.

Studies that analyze the epidemiology and risk factors for invasive fungal disease (IFD) after engraftment in alloSCT are few in number. This single-center retrospective study included 404 alloSCT adult recipients surviving >40 days who engrafted and were discharged without prior IFD. All patients who received ⩾20 mg/day of prednisone were assigned to primary oral prophylaxis (itraconazole or low-dose voriconazole). The primary end point was the cumulative incidence (CI) of probable/proven IFD using the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) criteria. The independent prognostic factors after multivariate analyses were used to construct a post-engraftment IFD risk score. The 1-year CI of IFD was 11%. The non-relapse mortality was 40% in those developing IFD and 16% in those who did not. The intent-to-treat analysis showed that 17% of patients abandoned the assigned prophylaxis. Age >40 years, ⩾1 previous SCT, pre-engraftment neutropenia >15 days, extensive chronic GVHD and CMV reactivation were independent risk factors. The post-engraftment IFD score stratified patients into low risk (0-1 factor, CI 0.7%), intermediate risk (2 factors, CI 9.9%) and high risk (3-5 factors, CI 24.7%) (P<0.0001). The antifungal prophylaxis strategy failed to prevent post-engraftment IFD in 11% of alloSCT. Our risk score could be useful to implement risk-adapted strategies using antifungal prophylaxis after engraftment.

Effects of lung ventilation-perfusion and muscle metabolism-perfusion heterogeneities on maximal O2 transport and utilization.

KEY POINTS: We expanded a prior model of whole-body O2 transport and utilization based on diffusive O2 exchange in the lungs and tissues to additionally allow for both lung ventilation-perfusion and tissue metabolism-perfusion heterogeneities, in order to estimate V̇O2 and mitochondrial PO2 (PmO2) during maximal exercise. Simulations were performed using data from (a) healthy fit subjects exercising at sea level and at altitudes up to the equivalent of Mount Everest and (b) patients with mild and severe chronic obstructive pulmonary disease (COPD) exercising at sea level. Heterogeneity in skeletal muscle may affect maximal O2 availability more than heterogeneity in lung, especially if mitochondrial metabolic capacity (V̇ MAX ) is only slightly higher than the potential to deliver O2 , but when V̇ MAX is substantially higher than O2 delivery, the effect of muscle heterogeneity is comparable to that of lung heterogeneity. Skeletal muscle heterogeneity may result in a wide range of potential mitochondrial PO 2 values, a range that becomes narrower as V̇ MAX increases; in regions with a low ratio of metabolic capacity to blood flow, PmO2 can exceed that of mixed muscle venous blood. The combined effects of lung and peripheral heterogeneities on the resistance to O2 flow in health decreases with altitude. ABSTRACT: Previous models of O2 transport and utilization in health considered diffusive exchange of O2 in lung and muscle, but, reasonably, neglected functional heterogeneities in these tissues. However, in disease, disregarding such heterogeneities would not be justified. Here, pulmonary ventilation-perfusion and skeletal muscle metabolism-perfusion mismatching were added to a prior model of only diffusive exchange. Previously ignored O2 exchange in non-exercising tissues was also included. We simulated maximal exercise in (a) healthy subjects at sea level and altitude, and (b) COPD patients at sea level, to assess the separate and combined effects of pulmonary and peripheral functional heterogeneities on overall muscle O2 uptake (V̇O2) and on mitochondrial PO2 (PmO2). In healthy subjects at maximal exercise, the combined effects of pulmonary and peripheral heterogeneities reduced arterial PO2 (PaO2) at sea level by 32 mmHg, but muscle V̇O2 by only 122 ml min(-1) (-3.5%). At the altitude of Mt Everest, lung and tissue heterogeneity together reduced PaO2 by less than 1 mmHg and V̇O2 by 32 ml min(-1) (-2.4%). Skeletal muscle heterogeneity led to a wide range of potential PmO2 among muscle regions, a range that becomes narrower asV̇ MAX increases, and in regions with a low ratio of metabolic capacity to blood flow, PmO2 can exceed that of mixed muscle venous blood. For patients with severe COPD, peak V̇O2 was insensitive to substantial changes in the mitochondrial characteristics for O2 consumption or the extent of muscle heterogeneity. This integrative computational model of O2 transport and utilization offers the potential for estimating profiles of PmO2 both in health and in diseases such as COPD if the extent for both lung ventilation-perfusion and tissue metabolism-perfusion heterogeneity is known.

An experimental means of transmitting pancreas disease in Atlantic salmon Salmo salar L. fry in freshwater.

A challenge model for pancreas disease in Atlantic salmon, Salmo salar L. fry, was developed comparing two salmonid alphavirus (SAV) subtypes: SAV1 and SAV5. Viral doses of 3 × 10(5) TCID50  mL(-1) for SAV1 and 3 × 10(4) for SAV5 were tested in triplicate tanks, each containing 450 salmon fry. Cumulative mortalities of 1.2% were recorded. Titres of virus recovered from the mortalities ranged from 10(2) to 10(7) TCID50  mL(-1) . Fry were sampled at 3, 5 and 7.5 weeks post-challenge. Sampling after 3 weeks revealed a high prevalence of infection in the absence of clinical signs, and infectious virus was recovered from 80% and 43% of sampled fry infected with SAV1 and SAV5, respectively. After 5 weeks pancreas, heart and red skeletal muscle lesions were generally observed, whilst degeneration in white skeletal muscle was observed only in fish infected with SAV1. In situ hybridisation confirmed the presence of viral genome in infected pancreas, heart and muscle. After 7.5 weeks, infectious virus (both isolates) was recovered from 13.3% of the fish sampled, with a viral titre of 10(2) TCID50  mL(-1) . Clearly, salmon fry are susceptible to SAV infection and pancreas disease.

Improved bonding strength of bioactive cermet Cold Gas Spray coatings.

The fabrication of cermet biocompatible coatings by means Cold Gas Spray (CGS) provides prosthesis with outstanding mechanical properties and the required composition for enhancing the bioactivity of prosthetic materials. In this study, hydroxyapatite/Titanium coatings were deposited by means of CGS technology onto titanium alloy substrates with the aim of building-up well-bonded homogeneous coatings. Powders were blended in different percentages and sprayed; as long as the amount of hydroxyapatite in the feedstock increased, the quality of the coating was reduced. Besides, the relation between the particle size distribution of ceramic and metallic particles is of significant consideration. Plastic deformation of titanium particles at the impact eased the anchoring of hard hydroxyapatite particles present at the top surface of the coating, which assures the looked-for interaction with the cells. Coatings were immersed in Hank's solution for 1, 4 and 7 days; bonding strength value was above 60 MPa even after 7 days, which enhances common results of HAp coatings obtained by conventional thermal spray technologies.

Maternal aging affects life performance of progeny in a Holstein dairy cow model.

The development and life performance of 404 high-producing Holstein dairy cows was studied from birth onwards and during two lactations. The management, environment and parental genetics of the cows were known in detail. Cluster analysis identified four performance 'types': high-yielding (HY) cows and persistently high-yielding (PHY) cows, which accounted for 33% of the animals; medium-yielding (MY) cows, 41%; and low-yielding (LY) cows, 26%. Prenatal determinants of the life performance of the progeny were analyzed. Developmental and environmental factors were excluded as determinants of performance (including birth weight, level of passive immunity transfer, growth rate, age at first parturition and reproductive efficiency). Life performance did show minor seasonal effects, with more HY cows but less PHY being born during the cold season (90.1% in HY; 58.3% in PHY v. 81.5%). Instead, the single most important factor influencing life performance of daughters was maternal age. HY cows were born from the youngest mothers (1.89±1.14 parturitions, 3.12±1.42-year old), whereas LY cows were born from the oldest (2.72±1.80 parturitions, 3.97±2.01-year old; P<0.001). Life performance of the dams did not differ among clusters. In addition, metabolic parameters (fat and protein yield) were found to correlate significantly with yields between the first and second lactations (milk yield: r=0.357; fat yield: r=0.211; protein yield: r=0.277; P<0.0001), suggesting the influence of the individual. These results suggest that under optimal health, nutritional and environmental conditions, maternal aging is an important determinant of the life performance of progeny and argue for the need to identify conditions that contribute to health and disease in progeny according to the Developmental Origin of Health and Disease or DOHaD concept. Our findings may help the development of novel management guidelines for dairy farms.