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Recent foodborne outbreaks and recalls involving Listeria monocytogenes and Salmonella -contaminated peaches have caused significant economic losses to the peach industry. This study evaluated the effectiveness of chlorine, a commonly used sanitizer in the fresh produce industry, against L. monocytogenes and Salmonella and its ability to control cross-contamination in fresh peaches. Peaches inoculated with L. monocytogenes or Salmonella (~6 log 10 CFU/peach) were treated with 50-150 mg/L of free chlorine (FC, pH6.8) 24 h post-inoculation. The results revealed that chlorine had similar efficacy against L. monocytogenes and Salmonella on peaches ( p > 0.05). A 30 s treatment at 50, 100, and 150 mg/L FC resulted in dose-dependent reductions ( p < 0.05), achieving reductions of 0.88-0.92, 1.54-1.61, and 1.73-1.79 log 10 CFU/peach, respectively. Extending the contact time to 2 min slightly but significantly enhanced the chlorine efficacy ( p < 0.05). Additionally, a 30 s to 2 min exposure to chlorine with 50-150 mg/L FC resulted in a 1.05-1.43 log 10 CFU/peach reduction in yeasts and molds. Tap water exposure led to substantial cross-contamination between inoculated and uninoculated fruits and processed water, with Salmonella exhibiting higher transfer rates than L. monocytogenes . The application of chlorine mitigated the cross-contamination of both pathogens but did not entirely prevent it. These findings offer valuable insights for the peach and other stone fruit industries to verify process controls.

Due to the exclusive maternal transmission, oocyte mitochondrial dysfunction reduces fertility rates, affects embryonic development, and programs offspring to metabolic diseases. However, mitochondrial DNA (mtDNA) are vulnerable to mutations during oocyte maturation, leading to mitochondrial nucleotide variations (mtSNVs) within a single oocyte, referring to mtDNA heteroplasmy. Obesity (OB) accounts for more than 40% of women at the reproductive age in the USA, but little is known about impacts of OB on mtSNVs in mature oocytes. It is found that OB reduces mtDNA content and increases mtSNVs in mature oocytes, which impairs mitochondrial energetic functions and oocyte quality. In mature oocytes, OB suppresses AMPK activity, aligned with an increased binding affinity of the ATF5-POLG protein complex to mutated mtDNA D-loop and protein-coding regions. Similarly, AMPK knockout increases the binding affinity of ATF5-POLG proteins to mutated mtDNA, leading to the replication of heteroplasmic mtDNA and impairing oocyte quality. Consistently, AMPK activation blocks the detrimental impacts of OB by preventing ATF5-POLG protein recruitment, improving oocyte maturation and mitochondrial energetics. Overall, the data uncover key features of AMPK activation in suppressing mtSNVs, and improving mitochondrial biogenesis and oocyte maturation in obese females., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

DNA methylation is influenced by various exogenous factors such as nutrition, temperature, toxicants, and stress. Bulls from the Pacific Northwest region of the United States and other northern areas are exposed to extreme cold temperatures during winter. However, the effects of cold exposure on the methylation patterns of bovine sperm remain unclear. To address, DNA methylation profiles of sperm collected during late spring and winter from the same bulls were analyzed using whole genome bisulfite sequencing (WGBS). Bismark (0.22.3) were used for mapping the WGBS reads and R Bioconductor package DSS was used for differential methylation analysis. Cold exposure induced 3,163 differentially methylated cytosines (DMCs) with methylation difference ≥10% and a q-value < 0.05. We identified 438 differentially methylated regions (DMRs) with q-value < 0.05, which overlapped with 186 unique genes. We also identified eight unique differentially methylated genes (DMGs) ( Pax6, Macf1, Mest, Ubqln1, Smg9, Ctnnb1, Lsm4, and Peg10 ) involved in embryonic development, and nine unique DMGs ( Prmt6, Nipal1, C21h15orf40, Slc37a3, Fam210a, Raly, Rgs3, Lmbr1, and Gan) involved in osteogenesis. Peg10 and Mest , two paternally expressed imprinted genes, exhibited >50% higher methylation. The differential methylation patterns of six distinct DMRs: Peg10, Smg9 and Mest related to embryonic development and Lmbr1, C21h15orf40 and Prtm6 related to osteogenesis, were assessed by methylation-specific PCR (MS-PCR), which confirmed the existence of variable methylation patterns in those locations across the two seasons. In summary, cold exposure induces differential DNA methylation patterns in genes that appear to affect embryonic development and osteogenesis in the offspring. Our findings suggest the importance of replicating the results of the current study with a larger sample size and exploring the potential of these changes in affecting offspring development., Competing Interests: Author MM was employed by ABS Global. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hossain, Gao, Hatfield, de Avila, McClure and Du.)

Wiskott-Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency resulting from a diversity of mutations distributed across all 12 exons of the WAS gene. WAS encodes a hematopoietic-specific and developmentally regulated cytoplasmic protein (WASp). The objective of this study was to develop a gene correction strategy potentially applicable to most WAS patients by employing nuclease-mediated, site-specific integration of a corrective WAS gene sequence into the endogenous WAS chromosomal locus. In this study, we demonstrate the ability to target the integration of WAS 2-12 -containing constructs into intron 1 of the endogenous WAS gene of primary CD34 + hematopoietic stem and progenitor cells (HSPCs), as well as WASp-deficient B cell lines and WASp-deficient primary T cells. This intron 1 targeted integration (TI) approach proved to be quite efficient and restored WASp expression in treated cells. Furthermore, TI restored WASp-dependent function to WAS patient T cells. Edited CD34 + HSPCs exhibited the capacity for multipotent differentiation to various hematopoietic lineages in vitro and in transplanted immunodeficient mice. This methodology offers a potential editing approach for treatment of WAS using patient's CD34 + cells., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: Following muscle injury, fibro-adipogenic progenitors (FAPs) are rapidly activated and undergo apoptosis at the resolution stage, which is required for proper muscle regeneration. When excessive FAPs remain, it contributes to fibrotic and fatty infiltration, impairing muscle recovery. Mechanisms controlling FAP apoptosis remain poorly defined. We hypothesized that AMP-activated protein kinase (AMPK) in FAPs mediates their apoptosis during the muscle regeneration., Methods: To test, AMPKα1 fl/fl PDGFRα Cre mice were used to knock out AMPKα1 in FAPs. Following AMPKα1 knockout, the mice were injected with phosphate-buffered saline or glycerol to induce muscle injury. Tibialis anterior muscle and FAPs were collected at 3, 7 and 14 days post-injury (dpi) for further analysis., Results: We found that AMPKα1 deletion in FAPs enhanced p65 translocation to the nuclei by 110% (n = 3; P < 0.01). AMPKα1 knockout group had a higher gene expression of MMP-9 (matrix metalloproteinase-9) by 470% (n = 3; P < 0.05) and protein level by 39% (n = 3; P < 0.05). Loss of AMPKα1 up-regulated the active TGF-β1 (transforming growth factor-β1) levels by 21% (n = 3; P < 0.05). TGF-β promoted apoptotic resistance, because AMPKα1-deficient group had 36% lower cleaved Caspase 3 (cCAS3) content (n = 3; P < 0.05). Fibrotic differentiation of FAPs was promoted, with increased collagen protein level by 54% (n = 3; P < 0.05). Moreover, obesity decreased phosphorylation of AMPK by 54% (n = 3; P < 0.05), which decreased cCAS3 in FAPs by 44% (n = 3; P < 0.05) and elevated collagen accumulation (52%; n = 3; P < 0.05) during muscle regeneration., Conclusions: These data suggest that AMPK is a key mediator of FAPs apoptosis, and its inhibition due to obesity results in fibrosis of regenerated muscle., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Obesity in pregnancy is currently the leading cause of gestational complications for the mother and fetus worldwide. Maternal obesity (MO), common in western societies, impedes development of intestinal epithelium in the fetuses, which causes disorders in the nutrient absorption and intestine-related immune responses in offspring. Here, using a mouse model of maternal exercise (ME), we found that exercise during pregnancy protects the impairment of fetal intestinal morphometrical formation and epithelial development due to MO. MO decreased villus length and epithelial proliferation markers in E18.5 fetal small intestine, which was increased due to ME. The expression of the epithelial differentiation markers, Lyz1 , Muc2 , and Tff3 , in fetal small intestine was decreased due to MO, but protected by ME. Consistently, the biomarkers related to mitochondrial biogenesis and oxidative metabolism were downregulated in MO fetal small intestine but recovered by ME. Apelin injection to dams partially mirrored the beneficial effects of ME. ME and apelin injection activated AMPK, the downstream target of apelin receptor signaling, which might mediate the improvement of fetal epithelial development and oxidative metabolism. These findings suggest that ME, a highly accessible intervention, is effective in improving fetal intestinal epithelium of obese dams. Apelin-AMPK-mitochondrial biogenesis axis provides amenable therapeutic targets to facilitate fetal intestinal development of obese mothers.

Collagen is the main component of connective tissue surrounding adipocytes. Collagen cross-linking affects adipose remodeling, which is crucial for maintaining function and metabolic homeostasis of adipose tissue. However, the effects of obesity on collagen cross-linking and adipose fibrosis remain to be examined. Therefore, the objective of this study was to investigate obesity-induced collagen cross-linking in adipose tissue and explore the underlying mechanisms. We found that obesity increased mature nonreducible collagen cross-linking in white adipose tissue (WAT) of mice, which was associated with inhibition of AMPK, up-regulation of transforming growth factor-β (TGF-β) signaling and the expression of lysyl oxidase (LOX), a key enzyme catalyzing the synthesis of mature cross-linking products. In SVCs and 3T3-L1 adipocytes, AMPK activation by metformin or AICAR inhibited TGF-β1-induced fibrogenesis and expression of LOX, which was further confirmed by ectopic expression of AMPK WT and K45R mutant. Consistently, in vivo, knocking out AMPK increased fibrosis and collagen cross-linking. Our study showed that AMPK downregulation due to obesity increases TGF-β signaling and LOX expression, which enhances adipose fibrosis and collagen cross-linking. Thus, AMPK is a therapeutic target for ameliorating the obesity-induced fibrosis, improving metabolic health of adipose tissue., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Sarcolipin and uncoupling protein 3 (UCP3) mediate muscle-based non-shivering thermogenesis (NST) to improve metabolic homeostasis. The impacts of maternal obesity (MO) and maternal exercise (ME) on NST in offspring muscle remain unexamined., Methods: Female mice were fed with a control diet or high fat diet to induce obesity. Then, obese mice were further separated into two groups: obesity only (OB) and OB plus daily exercise (OB/Ex). Fetal muscle was collected at embryonic day 18.5 and offspring mice at 3-month-old. Apelin administration during pregnancy and apelin receptor (APJ) knockout mouse were further used for investigating the mediatory role of APJ on muscle-based thermogenesis. To explore the direct effects of exercise on AMP-activated protein kinase (AMPK) downstream targets, AMPK knockout mouse was used., Findings: MO inhibited while ME activated AMPK and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) in fetal muscle. AMPK activation increased sarcolipin expression, which inhibited the uptake of calcium ions into sarcoplasmic reticulum, thereby activating CaMKK2. Consistently, the expression of UCP3 and sarcolipin was suppressed due to MO but activated in ME fetal muscle. Importantly, changes of UCP3 and sarcolipin maintained in offspring muscle, showing the transgenerational effects. Furthermore, apelin administration during pregnancy mimicked the effects of ME on AMPK and CaMKK2 activation, and UCP3 and sarcolipin expression, underscoring the mediatory roles of apelin-AMPK signaling in improving fetal muscle development., Interpretation: ME, via activation of apelin signaling-AMPK axis, enhances NST gene expression in fetal and offspring muscle impaired due to MO, which intergenerationally protects offspring from diet-induced obesity and metabolic disorders., Funding: This work was supported by National Institutes of Health Grant R01-HD067449., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Maternal obesity (MO) predisposes offspring to obesity and metabolic disorders but little is known about the contribution of offspring brown adipose tissue (BAT). We find that MO impairs fetal BAT development, which persistently suppresses BAT thermogenesis and primes female offspring to metabolic dysfunction. In fetal BAT, MO enhances expression of Dio3, which encodes deiodinase 3 (D3) to catabolize triiodothyronine (T3), while a maternally imprinted long noncoding RNA, Dio3 antisense RNA (Dio3os), is inhibited, leading to intracellular T3 deficiency and suppression of BAT development. Gain and loss of function shows Dio3os reduces D3 content and enhances BAT thermogenesis, rendering female offspring resistant to high fat diet-induced obesity. Attributing to Dio3os inactivation, its promoter has higher DNA methylation in obese dam oocytes which persists in fetal and adult BAT, uncovering an oocyte origin of intergenerational obesity. Overall, our data uncover key features of Dio3os activation in BAT to prevent intergenerational obesity and metabolic dysfunctions., (© 2021. The Author(s).)

Obesity during pregnancy leads to adverse health outcomes in offspring. However, the initial effects of maternal obesity (MO) on embryonic organogenesis have yet to be thoroughly examined. Using unbiased single-cell transcriptomic analyses (scRNA-seq), the effects of MO on the myogenic process is investigated in embryonic day 9.5 (E9.5) mouse embryos. The results suggest that MO induces systematic hypoxia, which is correlated with enhanced BMP signaling and impairs skeletal muscle differentiation within the dermomyotome (DM). The Notch-signaling effectors, HES1 and HEY1, which also act down-stream of BMP signaling, suppress myogenic differentiation through transcriptionally repressing the important myogenic regulator MEF2C. Moreover, the major hypoxia effector, HIF1A, enhances expression of HES1 and HEY1 and blocks myogenic differentiation in vitro. In summary, this data demonstrate that MO induces hypoxia and impairs myogenic differentiation by up-regulating BMP signaling within the DM, which may account for the disruptions of skeletal muscle development and function in progeny., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Maternal stress during pregnancy is prevailing worldwide, which exposes fetuses to intrauterine hyper glucocorticoids (GC), programming offspring to obesity and metabolic diseases. Despite the importance of brown adipose tissue (BAT) in maintaining long-term metabolic health, impacts of prenatal hyper GC on postnatal BAT thermogenesis and underlying regulations remain poorly defined. Pregnant mice were administrated with synthetic GC dexamethasone (DEX) at levels comparable to fetal GC exposure of stressed mothers. Prenatal GC exposure dose-dependently reduced BAT thermogenic activity, contributing to lower body temperature and higher mortality of neonates; such difference was abolished under thermoneutrality, underscoring BAT deficiency was the major contributor to adverse changes in postnatal thermogenesis due to excessive GC. Prenatal GC exposure highly activated Redd1 expression and reduced Ppargc1a transcription from the alternative promoter ( Ppargc1a -AP) in neonatal BAT. During brown adipocyte differentiation, ectopic Redd1 expression reduced Ppargc1a -AP expression and mitochondrial biogenesis; and the inhibitory effects of GC on mitochondrial biogenesis and Ppargc1a -AP expression were blocked by Redd1 ablation. Redd1 reduced protein kinase A phosphorylation and suppressed cyclic adenosine monophosphate (cAMP) -responsive element-binding protein (CREB) binding to the cAMP regulatory element (CRE) in Ppargc1a -AP promoter, leading to Ppargc1a- AP inactivation. In summary, excessive maternal GC exposure during pregnancy dysregulates Redd1 - Ppargc1a -AP axis, which impairs fetal BAT development, hampering postnatal thermogenic adaptation and metabolic health of offspring., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Epidemiological studies robustly show the beneficial effects of maternal exercise in reducing maternal birth complications and improving neonatal outcomes, though underlying mechanisms remain poorly understood. To facilitate mechanistic exploration, a protocol for maternal exercise of mice is established, with the regimen following the exercise guidelines for pregnant women. Compared to volunteer wheel running, treadmill running allows precise control of exercise intensity and duration, dramatically reducing variations among individual mouse within treatments and facilitating translation into maternal exercise in humans. Based on the maximal oxygen consumption rate (VO 2 max) before pregnancy, the treadmill exercise protocol is separated into three stages: early stage (E1.5 to E7.5 at 40% VO 2 max), mid stage (E8.5 to E14.5 at 65% VO 2 max), and late stage of pregnancy (E15.5 to birth at 50% VO 2 max), which demonstrated persistent beneficial effects on maternal health and fetal development. This protocol can be useful for standardizing maternal treadmill exercise using mice as an experimental model., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (Copyright © 2020 The Authors; exclusive licensee Bio-protocol LLC.)

Although maternal exercise (ME) becomes increasingly uncommon, the effects of ME on offspring muscle metabolic health remain largely undefined. Maternal mice are subject to daily exercise during pregnancy, which enhances mitochondrial biogenesis during fetal muscle development; this is correlated with higher mitochondrial content and oxidative muscle fibers in offspring muscle and improved endurance capacity. Apelin, an exerkine, is elevated due to ME, and maternal apelin administration mirrors the effect of ME on mitochondrial biogenesis in fetal muscle. Importantly, both ME and apelin induce DNA demethylation of the peroxisome proliferator-activated receptor γ coactivator-1α (Ppargc1a) promoter and enhance its expression and mitochondrial biogenesis in fetal muscle. Such changes in DNA methylation were maintained in offspring, with ME offspring muscle expressing higher levels of PGC-1α1/4 isoforms, explaining improved muscle function. In summary, ME enhances DNA demethylation of the Ppargc1a promoter in fetal muscle, which has positive programming effects on the exercise endurance capacity and protects offspring muscle against metabolic dysfunction., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: During muscle regeneration, excessive formation of adipogenic and fibrogenic tissues, from their respective fibro/adipogenic progenitors (FAPs), impairs functional recovery. Intrinsic mechanisms controlling the proliferation and differentiation of FAPs remain largely unexplored., Methods: Here, we investigated the role of retinoic acid (RA) signalling in regulating FAPs and the subsequent effects on muscle restoration from a cardiotoxin-induced injury. Blockage of retinoic acid receptor (RAR) signalling was achieved through dominant negative retinoic acid receptor α (RARα403) expression specific in PDGFRα+ FAPs in vivo and by BMS493 treatment in vitro. Effects of RAR-signalling on FAP cellularity and muscle regeneration were also investigated in a high-fat diet-induced obese mice model., Findings: Supplementation of RA increased the proliferation of FAPs during the early stages of regeneration while suppressing FAP differentiation and promoting apoptosis during the remodelling stage. Loss of RAR-signalling caused ectopic adipogenic differentiation of FAPs and impaired muscle regeneration. Furthermore, obesity disrupted the cellular transition of FAPs and attenuated muscle regeneration. Supplementation of RA to obese mice not only rescued impaired muscle fibre regeneration, but also inhibited infiltration of fat and fibrotic tissues during muscle repair. These beneficial effects were abolished after blocking RAR-signalling in FAPs of obese mice., Interpretation: These data suggest that RAR-signalling in FAPs is a critical therapeutic target for suppressing differentiation of FAPs and facilitating the regeneration of muscle and other tissues., Funding: This study was supported by grants from the National Institutes of Health (R01-HD067449 and R21-AG049976) to M.D., Competing Interests: Declarations of Competing Interests The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Maternal stress during pregnancy exposes fetuses to hyperglucocorticoids, which increases the risk of metabolic dysfunctions in offspring. Despite being a key tissue for maintaining metabolic health, the impacts of maternal excessive glucocorticoids (GC) on fetal brown adipose tissue (BAT) development and its long-term thermogenesis and energy expenditure remain unexamined. For testing, pregnant mice were administered dexamethasone (DEX), a synthetic GC, in the last trimester of gestation, when BAT development is the most active. DEX offspring had glucose, insulin resistance, and adiposity and also displayed cold sensitivity following cold exposure. In BAT of DEX offspring, Ppargc1a expression was suppressed, together with reduced mitochondrial density, and the brown progenitor cells sorted from offspring BAT demonstrated attenuated brown adipogenic capacity. Increased DNA methylation in Ppargc1a promoter had a fetal origin; elevated DNA methylation was also detected in neonatal BAT and brown progenitors. Mechanistically, fetal GC exposure increased GC receptor/DNMT3b complex in binding to the Ppargc1a promoter, potentially driving its de novo DNA methylation and transcriptional silencing, which impaired fetal BAT development. In summary, maternal GC exposure during pregnancy increases DNA methylation in the Ppargc1a promoter, which epigenetically impairs BAT thermogenesis and energy expenditure, predisposing offspring to metabolic dysfunctions., (© 2020 by the American Diabetes Association.)

The obesity rate is rapidly increasing, which has been attributed to lack of exercise and excessive energy intake. Here, we found a previously unidentified explanation, due to lack of maternal exercise. In this study, healthy maternal mice were assigned either to a sedentary lifestyle or to exercise daily, and fetal brown adipose tissue (BAT) development and offspring metabolic health were analyzed. Compared to the sedentary group, maternal exercise enhanced DNA demethylation of Prdm16 promoter and BAT development and prevented obesity of offspring when challenged with a high-energy diet. Apelin, an exerkine, was elevated in both maternal and fetal circulations due to exercise, and maternal administration of apelin mimicked the beneficial effects of exercise on fetal BAT development and offspring metabolic health. Together, maternal exercise enhances thermogenesis and the metabolic health of offspring mice, suggesting that the sedentary lifestyle during pregnancy contributes to the obesity epidemic in modern societies., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: Tamoxifen-inducible Cre/lox site-specific recombination technology has been widely used to generate conditional transgenic mice. As an estrogen receptor ligand, tamoxifen itself potentially affects energy metabolism, which may confound interpretation of data especially in metabolic studies. Considering sexual dimorphism, in this study, the effects of low-dose tamoxifen administration on energy metabolism, and browning of adipose tissues in female and male mice were investigated., Methods: Female and male C57/BL6 mice were injected with tamoxifen oil solution (i.p.) and then housed at both room temperature (23 ± 2 °C) and cold environment (6 ± 1 °C). Serum, brown and white adipose tissues were obtained, and the effects of tamoxifen administration on energy metabolism and the browning of adipose tissues were evaluated., Results: At 25 mg/kg body weight (BDW), tamoxifen administration for 3 alternative days decreased the percentage of inguinal and gonadal white adipose tissue weights in female mice accompanied by the up-regulation of thermogenesis in adipose tissues. In contrast, this dosage of tamoxifen did not induce noticeable changes in the energy metabolism and thermogenesis of adipose tissue in male mice under room temperature. Consistently, under cold stimulus, substantial browning of adipose tissues was observed in female mice injected with tamoxifen (50 mg/kg BDW, single injection) but not in male mice. Two-way ANOVA tests also demonstrated significant interactions between tamoxifen treatment and gender on the expression of thermogenic markers in adipose tissues., Conclusion: Tamoxifen, even at a low dose, remarkably increases thermogenesis in adipose tissues of female mice; meanwhile, such a low dose could be used in male mice for inducing gene recombination without confounding the interpretation of data related to metabolism and thermogenesis of adipose tissues.

Key Points: Maternal exercise improves the metabolic health of maternal mice challenged with a high-fat diet. Exercise intervention of obese mothers prevents fetal overgrowth. Exercise intervention reverses impaired placental vascularization in obese mice. Maternal exercise activates placental AMP-activated protein kinase, which was inhibited as a result of maternal obesity., Abstract: More than one-third of pregnant women in the USA are obese and maternal obesity (MO) negatively affects fetal development, which predisposes offspring to metabolic diseases. The placenta mediates nutrient delivery to fetuses and its function is impaired as a result of MO. Exercise ameliorates metabolic dysfunction resulting from obesity, although its effect on placental function of obese mothers has not been explored. In the present study, C57BL/6J female mice were randomly assigned into two groups fed either a control or a high-fat diet (HFD) and then the mice on each diet were further divided into two subgroups with/without exercise. In HFD-induced obese mice, daily treadmill exercise during pregnancy reduced body weight gain, lowered serum glucose and lipid concentration, and improved insulin sensitivity of maternal mice. Importantly, maternal exercise prevented fetal overgrowth (macrosomia) induced by MO. To further examine the preventive effects of exercise on fetal overgrowth, placental vascularization and nutrient transporters were analysed. Vascular density and the expression of vasculogenic factors were reduced as a result of MO but were recovered by maternal exercise. On the other hand, the contents of nutrient transporters were not substantially altered by MO or exercise, suggesting that the protective effects of exercise in MO-induced fetal overgrowth were primarily a result of the alteration of placental vascularization and improved maternal metabolism. Furthermore, exercise enhanced downstream insulin signalling and activated AMP-activated protein kinase in HFD placenta. In sum, maternal exercise prevented fetal overgrowth induced by MO, which was associated with improved maternal metabolism and placental vascularization in obese mothers with exercise., (© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.)

Background: Vitamin A and its metabolite, retinoic acid (RA), are important regulators of cell differentiation and organ morphogenesis. Its impact on beef cattle muscle growth remains undefined., Method: Angus steer calves were administrated with 0 (control) or 150,000 IU vitamin A (retinyl palmitate in glycerol, i.m.) per calf at birth and 1 month of age. At 2 months of age, a biopsy of the Biceps femoris muscle was obtained to analyze the immediate effects of vitamin A injection on myogenic capacity of muscle cells. The resulting steers were harvested at 14 months of age., Results: Vitamin A administration increased cattle growth at 2 months. At 2 months of age, Vitamin A increased PAX7 positive satellite cells and the expression of myogenic marker genes including PAX7 , MYF5 , MYOD and MYOG . Muscle derived mononuclear cells were further isolated and induced myogenesis in vitro. More myotubes and a higher degree of myogenesis was observed in vitamin A groups. Consistently, vitamin A increased Latissimus dorsi (LD) muscle fiber size at harvest. In addition, vitamin A increased the ratio of oxidative type I and type IIA fibers and reduced the glycolic type IIX fibers. Furthermore, we found that RA, a key bioactive metabolite of vitamin A, activated PPARGC1A promoter, which explains the upregulated expression of PPARGC1A in skeletal muscle., Conclusion: Vitamin A administration to neonatal calves enhanced postnatal muscle growth by promoting myogenesis and increasing satellite cell density, accompanied with a shift to oxidative muscle fibers., Competing Interests: Animal use protocol of this project was approved by Washington State University Institutional Animal Care and Use Committee (Animal Subjects Protocol #04354).Not applicable.The authors declare that they have no competing interests.

Development of brown and beige/brite adipocytes increases thermogenesis and helps to reduce obesity and metabolic syndrome. Our previous study suggests that dietary raspberry can ameliorate metabolic syndromes in diet-induced obese mice. Here, we further evaluated the effects of raspberry on energy expenditure and adaptive thermogenesis and determined whether these effects were mediated by AMP-activated protein kinase (AMPK). Mice deficient in the catalytic subunit of AMPKα1 and wild-type (WT) mice were fed a high-fat diet (HFD) or HFD supplemented with 5% raspberry (RAS) for 10 weeks. The thermogenic program and related regulatory factors in adipose tissue were assessed. RAS improved the insulin sensitivity and reduced fat mass in WT mice but not in AMPKα1 -/- mice. In the absence of AMPKα1, RAS failed to increase oxygen consumption and heat production. Consistent with this, the thermogenic gene expression in brown adipose tissue and brown-like adipocyte formation in subcutaneous adipose tissue were not induced by RAS in AMPKα1 -/- mice. In conclusion, AMPKα1 is indispensable for the effects of RAS on brown and beige/brite adipocyte development, and prevention of obesity and metabolic dysfunction., (Copyright © 2018. Published by Elsevier Inc.)

Clinically, low and moderate alcohol intake improves human health with protection against metabolic syndromes, including type 2 diabetes; however, mechanisms that are associated with these effects remain to be elucidated. The aims of this study were to investigate the effects of moderate alcohol intake on thermogenic brown/beige adipocyte formation and glucose and lipid homeostasis, as well as the involvement of retinoic acid (RA) signaling in the entire process. C57BL6 male mice were supplemented with 8% (w/v) alcohol in water for 1 or 4 mo. Alcohol intake prevented body weight gain, induced the formation of uncoupling protein 1-positive beige adipocytes in white adipose tissue, and increased thermogenesis in mice, which is associated with decreased serum glucose and triacylglycerol levels. Mechanistically, alcohol intake increased RA levels in serum and adipose tissue, which was associated with increased expression of aldehyde dehydrogenase family 1 subfamily A1 ( Aldh1a1 ). When RA receptor-α signaling was conditionally blocked in platelet-derived growth factor receptor-α-positive adipose progenitors, the effects of alcohol on beige adipogenesis were largely abolished. Finally, moderate alcohol prevented high-fat diet-induced obesity and metabolic dysfunction. In conclusion, moderate alcohol intake induces thermogenic brown/beige adipocyte formation and promotes glucose and lipid oxidation via elevation of RA signaling.-Wang, B., Wang, Z., de Avila, J. M., Zhu, M.-J., Zhang, F., Gomez, N. A., Zhao, L., Tian, Q., Zhao, J., Maricelli, J., Zhang, H., Rodgers, B. D., Du, M. Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling., (© FASEB.)

Maternal vitamin A intake varies but its impact on offspring metabolic health is unknown. Here we found that maternal vitamin A or retinoic acid (RA) administration expanded PDGFRα + adipose progenitor population in progeny, accompanied by increased blood vessel density and enhanced brown-like (beige) phenotype in adipose tissue, protecting offspring from obesity. Blockage of retinoic acid signaling by either BMS493 or negative RA receptor (RARαDN) over-expression abolished the increase in blood vessel density, adipose progenitor population, and beige adipogenesis stimulated by RA. Furthermore, RA-induced beige adipogenesis was blocked following vascular endothelial growth factor receptor (VEGFR) 2 knock out in PDGFRα + cells, suggesting its mediatory role. Our data reveal an intrinsic link between maternal retinoid level and offspring health via promoting beige adipogenesis. Thus, enhancing maternal retinoids is an amiable therapeutic strategy to prevent obesity in offspring, especially for those born to obese mothers which account for one third of all pregnancies., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze characteristics of type II odontoid fracture (TII-OF), including clinical and radiographic factors, that influence surgical planning in 8 Latin American centers., Methods: Retrospective chart review was performed of 88 patients with TII-OF between 2004 and 2015 from 8 Latin American centers. Parameters studied included 1) demographic data and causes of TII-OF, 2) clinical and neurologic presentation, 3) characteristics of fracture (degree of odontoid displacement, displacement of odontoid relative to C2 body, anatomy of fracture line, distance between fragments, presence of comminution, contact area between odontoid and C2 body), 4) type of treatment, and 5) clinical and radiographic outcome. Bone fusion was assessed using computed tomography., Results: Mean patient age was 45.33 years ± 23.54; 78.4% of patients were male. Surgery was the primary treatment in 65 patients (73.8%), with an anterior approach in 64.6%. Surgery was usually preferred in patients with posterior or horizontal oblique fracture lines, local pain, and a smaller bone contact surface between the odontoid and the body of C2. A posterior approach was chosen when distance between the fractured bone fragments was >2 mm or after failed conservative or anterior odontoid screw treatment in a symptomatic patient., Conclusion: The treatment of choice for TII-OF in 8 Latin American trauma centers was surgery through an anterior approach using screw fixation. Posterior segmental C1-C2 fixation was indicated when distance between bone fragments was >2 mm and in symptomatic patients with nonunion., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: An increase of sedentary behaviors far from the Mediterranean lifestyle is happening in spite of the impact on health. The aims of this study were to describe sedentary behaviors in children and adolescents., Methods: A representative sample of 424 Spanish children and adolescents (38% females) involved in the ANIBES study was analyzed regarding their sedentary behaviors, together with the availability of televisions, computers, and consoles by means of the HELENA sedentary behavior questionnaire., Results: For the total sample of children, 49.3% during weekdays and 84% during weekends did not meet the recommendation of less than 2 hours of screen viewing per day. The use of TV was higher during weekdays (p < 0.05) and there were significant differences between adolescents and children (16.9 vs. 25.1%, p < 0.05). The use of computer, console games and of internet for non-study reasons was higher during weekends (p < 0.001). Adolescents played more computer games and used more internet for non-study reasons than children during both weekdays and weekends (p < 0.05 and p < 0.001, respectively). The use of internet for academic reasons was lower in children (p < 0.001) than adolescents during weekends; however, no significant differences were found between sexes. In addition, more than 30% of the children and adolescents had at least one electronic device in their bedrooms., Conclusions: Spanish children and adolescents are not meeting the recommendations regarding the maximum of screen viewing (<2 h/day), especially during the weekend, for all of sedentary behaviors. Urgent strategies and intervention studies are needed to reduce sedentary behavior in young people.

Generating the correct balance of inhibitory and excitatory neurons in a neural network is essential for normal functioning of a nervous system. The neural network in the dorsal spinal cord functions in somatosensation where it modulates and relays sensory information from the periphery. PTF1A is a key transcriptional regulator present in a specific subset of neural progenitor cells in the dorsal spinal cord, cerebellum and retina that functions to specify an inhibitory neuronal fate while suppressing excitatory neuronal fates. Thus, the regulation of Ptf1a expression is critical for determining mechanisms controlling neuronal diversity in these regions of the nervous system. Here we identify a sequence conserved, tissue-specific enhancer located 10.8kb 3' of the Ptf1a coding region that is sufficient to direct expression to dorsal neural tube progenitors that give rise to neurons in the dorsal spinal cord in chick and mouse. DNA binding motifs for Paired homeodomain (Pd-HD) and zinc finger (ZF) transcription factors are required for enhancer activity. Mutations in these sequences implicate the Pd-HD motif for activator function and the ZF motif for repressor function. Although no repressor transcription factor was identified, both PAX6 and SOX3 can increase enhancer activity in reporter assays. Thus, Ptf1a is regulated by active and repressive inputs integrated through multiple sequence elements within a highly conserved sequence downstream of the Ptf1a gene., (Copyright © 2016 Elsevier Inc. All rights reserved.)

An international multi-disciplinary group of 24 researchers met to discuss ocean acidification (OA) during the Brazilian OA Network/Surface Ocean-Lower Atmosphere Study (BrOA/SOLAS) Workshop. Fifteen members of the BrOA Network (www.broa.furg.br) authored this review. The group concluded that identifying and evaluating the regional effects of OA is impossible without understanding the natural variability of seawater carbonate systems in marine ecosystems through a series of long-term observations. Here, we show that the western South Atlantic Ocean (WSAO) lacks appropriate observations for determining regional OA effects, including the effects of OA on key sensitive Brazilian ecosystems in this area. The impacts of OA likely affect marine life in coastal and oceanic ecosystems, with further social and economic consequences for Brazil and neighboring countries. Thus, we present (i) the diversity of coastal and open ocean ecosystems in the WSAO and emphasize their roles in the marine carbon cycle and biodiversity and their vulnerabilities to OA effects; (ii) ongoing observational, experimental, and modeling efforts that investigate OA in the WSAO; and (iii) highlights of the knowledge gaps, infrastructure deficiencies, and OA-related issues in the WSAO. Finally, this review outlines long-term actions that should be taken to manage marine ecosystems in this vast and unexplored ocean region.

Background: The emancipatory nature of education requires research as its fundamental base, because physicians can only improve their skills and knowledge through enquiry. The number and quality of scientific publications by Latin-American spine surgeons found in the Medline database was low between 2000 and 2011. Nevertheless, the research Bank Survey of AOSpine Latin America (AOSLA) members showed that 96% of responders were very interested and motivated to perform scientific research., Methods and Population: The research officer of AOSLA together with the Country Council and the AOSpine Research Commission established a competency-based curriculum to improve understanding of what is necessary to produce research and the best methods to achieve this goal. The research curriculum was divided into four main components: (1) research educational plan, (2) performing research, (3) technical and professional support and (4) assessment., Results: The competences, learning outcomes and a syllabus on knowledge in research were developed to enable the participants to understand and perform investigations effectively. The eLearning module was designed to improve the competences to access, evaluate and use scientific information available in the main databases efficiently. Research courses were given as an isolated activity four times in Brazil and Mexico and as precourse activities six times in Brazil, Mexico and Peru. The result was an increased number of articles published and works presented at congresses., Conclusions: The project of education in research can be effectively disseminated and applied across regions, across students and across specialties.

Despite ubiquitous phenanthrene contamination in aquatic coastal areas, little is known regarding its potential effects on estuarine fishes. The present work evaluated the response of a large suite of oxidative stress- and DNA damage-related biomarkers to phenanthrene exposure (10, 20 and 200 μg L(-1), 96 h) using DMSO as the solvent in estuarine guppy Poecilia vivipara (salinity 24 psu). Phenanthrene affected oxidative stress-related parameters, and decreased antioxidant defenses and reactive oxygen species in the gills and muscle overall. Lipid peroxidation occurred in muscle at 200 μg L(-1) phenanthrene. Genotoxicity was increased at 20 μg L(-1), while 200 μg L(-1) caused a relative decrease in erythrocyte release into the bloodstream. These findings indicated that phenanthrene is genotoxic and can induce oxidative stress, depending on tissue and phenanthrene concentration analyzed. Thus, some of the biomarkers analyzed in the present study are sufficiently sensitive to monitor the exposure of the guppy P. vivipara to phenanthrene in salt water. However, further studies are required for a better interpretation of the dose-response patterns observed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Despite the small contribution of LA in the Science Citation Index (SCI), a growing contribution by LA research to international literature has been observed in recent years., Study Design: Systematic review., Purpose: To evaluate the scientific contribution of Latin American (LA) Spine Surgeons in the last decade., Methods: A literature search of publications by LA spinal surgeons on topics concerning the spine or spinal cord was performed using an online database; Pubmed.gov. The results were limited to articles published from January 2000 to December 2011. The quality of the publication was evaluated with the journal impact factor (IF), Oxford classification and number of citations., Results: This study comprised 320 articles published in the Medline database by LA spine surgeons from 2000 to 2011. In recent years, there has been an increase in the number of publications by LA spine surgeons. It was observed that 38.4% of LA papers were published in LA journals. 46.6% of the articles were published in journals with an IF lower than 1, and there was no statistically significant difference in the number of articles published in journals with a higher IF during the period. Linear-by-linear association analysis demonstrated an improvement in the level of evidence provided by LA articles published in recent years., Conclusions: This study showed a growth in the number of publications in last 12 years by LA spinal surgeons. It is necessary to discuss a way to increase quantity and quality of scientific publications, mainly through a better education in research.

The objective of this research was to examine the population structure of full-blood (100%) Wagyu cattle registered in the United States with the American Wagyu Association, with the aim of estimating and comparing the levels of inbreeding from both pedigree and genotypic data. A total of 4132 full-blood Wagyu cattle pedigrees were assessed and used to compute the inbreeding coefficients (FIT and FST ) and the effective population size (Ne ) from pedigree data for the period 1994 to 2011. In addition to pedigree analysis, 47 full-blood Wagyu cattle representing eight prominent sire lines in the American Wagyu cattle population were genotyped using the Illumina BovineSNP50 BeadChip. Genotypic data were then used to estimate genomic inbreeding coefficients (FROH ) by calculating runs of homozygosity. The mean inbreeding coefficient based on the pedigree data was estimated at 4.80%. The effective population size averaged 17 between the years 1994 and 2011 with an increase of 42.9 in 2000 and a drop of 1.8 in 2011. Examination of the runs of homozygosity revealed that the 47 Wagyu cattle from the eight prominent sire lines had a mean genomic inbreeding coefficient (FROH ) estimated at 9.08% compared to a mean inbreeding coefficient based on pedigree data of 4.8%. These data suggest that the mean genotype inbreeding coefficient of full-blood Wagyu cattle exceeds the inbreeding coefficient identified by pedigree. Inbreeding has increased slowly at a rate of 0.03% per year over the past 17 years. Wagyu breeders should continue to utilize many sires from divergent lines and consider outcrossing to other breeds to enhance genetic diversity and minimize the adverse effects of inbreeding in Wagyu., (© 2014 Blackwell Verlag GmbH.)

Breast cancer is the most common cancer among women worldwide and breast self-examination (BSE) is considered as the most cost-effective approach for early breast cancer detection. The general objective of this paper is to design and develop a computer vision algorithm to evaluate the BSE performance in real-time. The first stage of the algorithm presents a method for detecting and tracking the nipples in frames while a woman performs BSE; the second stage presents a method for localizing the breast region and blocks of pixels related to palpation of the breast, and the third stage focuses on detecting the palpated blocks in the breast region. The palpated blocks are highlighted at the time of BSE performance. In a correct BSE performance, all blocks must be palpated, checked, and highlighted, respectively. If any abnormality, such as masses, is detected, then this must be reported to a doctor to confirm the presence of this abnormality and proceed to perform other confirmatory tests. The experimental results have shown that the BSE evaluation algorithm presented in this paper provides robust performance.

Background/aims: The Food Consumption Survey, conducted for over 20 years by the Spanish Ministry of Agriculture, Food and Environment (MAGRAMA), is the most reliable source of data to evaluate the food consumption and dietary patterns of Spain. The aim of the present article was to review the diet trends in Spain and its evolution. Food availability assessment per capita per day, which allows the calculation of energy and nutrient intake and comparison with the Recommended Nutrient Intakes for the Spanish population is described. In addition, different markers of the quality of the diet have been also evaluated., Methods: The sample consisted of consumption and distribution data, obtained from the nationwide representative Food Consumption Survey for the period 2000- 2012. A two-stage sampling method was applied, where in the first stage the units to be sampled were towns or local entities, and in the second stage households which were going to be part of the final sample from those entities were selected. Units consisted of towns or local entities in the national territory. The data allowed the calculation of energy and nutrient intakes, using the Food Composition Tables (Moreiras et al, 2013). The quality of the diet was also evaluated: the adequacy of the diet in meeting the recommended intakes for energy and nutrients; energy profile; dietary fat quality; dietary protein quality; nutrient density; Mediterranean diet adequacy indices. The present data were compared with previous data obtained by our research group in 1964, 1981 and 1991., Results: Using the most recent data, average intake comprised: milk and derivatives (356 g/person/day), fruits (323 g/person/day), vegetables and greens (339 g/ person/day), cereals and derivatives (197 g/person/day), meat and meat products (181 g/day), fish (88,6 g/person/ day), oils and fats (41,6 g/person/day), sugar and derivatives (25,6 g/person/day), eggs (27,1 g/person/day), legumes (13,9 g/person/day) . There was also a high consumption of non-alcoholic beverages (437 g/person/day) and decreasing for alcoholic beverages (192 g/person/day) compared to previous surveys. In consequence, meat and meat product consumption was higher than the recommendations, whereas for cereals and their derivatives, vegetables and greens, fruit, and legumes and pulses, consumption was below recommendations for the Spanish population (GRUNUMUR, 2004; SENC, 2007). Some staple and traditional Mediterranean foods (bread, potatoes and olive oil) showed a dramatic decline when compared to data from Household Budget Surveys in 1964 data. Energy intake showed a marked decline when compared to the 1960's mean consumption, and show marked differences for food groups contributors. Energy profile shows too much coming from lipids vs carbohydrates and slightly higher from proteins., Conclusion: Food consumption patterns in Spain and energy and nutrient intakes have changed markedly in the last forty years, differing somewhat at present from the traditional and healthy Mediterranean Diet., (Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.)

Introduction: The intermediate screw in a fractured vertebra works as a pressure point with an anterior vector thus creating a lordotic force that corrects kyphosis, provides appropriate three-point fixation and decreases the lever effect., Objective: To describe the course of non-pathologic traumatic fractures of the thoracolumbar spine after instrumentation of the fractured vertebra., Material and Methods: A total of 37 patients with a diagnosis of traumatic vertebral fracture in the thoracolumbar area (T9-L4) were operated from January 2008 to December 2012. Patients included 28 males (75.6%) and 9 females (24.4%); mean age was 41.8 years., Results: Correcting the total diameter of the spinal canal results in a 2.11 times higher chance of neurologic improvement; the relative risk of fusion was 0.97 with autologous graft as compared with a heterologous graft (CI 95% = 0.69-1.36) and 1.18 with instrumentation of the fractured vertebra (CI 95% = 0.42-3.31)., Conclusions: Pedicle screw fixation at the fracture level is a safe and effective method to treat thoracolumbar fractures; it provides additional fixation points that assist in fracture reduction and correction of kyphosis, improving at the same time back pain and maintaining the corrective effect. Procedure indications include integrity of the posterior ligament complex and at least one intact pedicle in the fractured vertebra.

Introduction: The quality of life of patients with periprosthetic fracture is complex; it interacts with the severity of the lesion, their independence level, and available resources, all of which could cause alterations secondary to their condition., Objective: To know the quality of life and clinical course of patients after periprosthetic hip fracture surgery., Material and Methods: Patients with periprosthetic hip fracture were assessed. Physical exam was performed and the SF-36 questionnaire was applied., Results: A total of 15 patients were included, 8 (53.3%) females and 7 (46.7%) males, with mean age 74 years (SD 12.51). Concerning underlying conditions, 5 patients had none (33.3%), one had hypertension (6.7%), one had a neoplasia (epidermoid), and 8 had more than one underlying condition. A predictive variable model was designed. In the overall score a 75.6% positive correlation was found, and a 57.2% determination coefficient. There was no statistical significance (p = 0.162). The same variables as in the previous model were included. Correlation was 0.678 and determination 45.9%, without statistical significance, p = 0.332., Conclusions: Patients reported feeling fair from the perspective of their overall health, physical function, physical role, emotional role, and social function; mental health wise, 50% reported feeling calm and full of life, and 50% reported anxiety and fear.

The objective of the present study was to investigate vascular endothelial growth factor A (VEGFA) isoform regulation of cell fate decisions of spermatogonial stem cells (SSC) in vivo. The expression pattern and cell-specific distribution of VEGF isoforms, receptors, and coreceptors during testis development postnatal d 1-180 suggest a nonvascular function for VEGF regulation of early germ cell homeostasis. Populations of undifferentiated spermatogonia present shortly after birth were positive for VEGF receptor activation as demonstrated by immunohistochemical analysis. Thus, we hypothesized that proangiogenic isoforms of VEGF (VEGFA(164)) stimulate SSC self-renewal, whereas antiangiogenic isoforms of VEGF (VEGFA(165)b) induce differentiation of SSC. To test this hypothesis, we used transplantation to assay the stem cell activity of SSC obtained from neonatal mice treated daily from postnatal d 3-5 with 1) vehicle, 2) VEGFA(164), 3) VEGFA(165)b, 4) IgG control, 5) anti-VEGFA(164), and 6) anti-VEGFA(165)b. SSC transplantation analysis demonstrated that VEGFA(164) supports self-renewal, whereas VEGFA(165)b stimulates differentiation of mouse SSC in vivo. Gene expression analysis of SSC-associated factors and morphometric analysis of germ cell populations confirmed the effects of treatment on modulating the biological activity of SSC. These findings indicate a nonvascular role for VEGF in testis development and suggest that a delicate balance between VEGFA(164) and VEGFA(165)b isoforms orchestrates the cell fate decisions of SSC. Future in vivo and in vitro experimentation will focus on elucidating the mechanisms by which VEGFA isoforms regulate SSC homeostasis.

Objective: To determine the direct cost of complete cervical spinal cord injury., Material and Methods: 34 patients over 16 years of age with a diagnosis of complete cervical spinal cord injury. The cost calculation was done considering nine groups: bed days, specialty consultation, laboratory, X-rays, computed axial tomography, magnetic resonance imaging, anterior surgery, posterior surgery, anterior and posterior surgery. The micro costing technique was used and the mean cost per patient was obtained., Results: 41% of patients had injury at C4-C5; mean age was 36 years; total cost was $8,622,793.00 mexican pesos, and the mean cost in patients who survived was $2,536,115.59 mexican pesos, which represented 29.4% of the total cost; the cost for the patients who died was $6,086,677.41 mexican pesos (70.6%). The percent distribution of the different components analyzed clearly shows that 51% of the total cost corresponded to hospitalization. The estimated annual cost of caring for these patients is $2,155,905.70 Mexican pesos, with an annual increase of $819,905.53 Mexican pesos., Conclusions: The major cost was hospitalization, so specific clinical management guidelines should be used to optimize economic resources and prevent complications that may increase the costs.

Background: Risk factors are the endogenous or exogenous factors that may be controlled and they are responsible for disease. The objective of this paper is to describe the risk factors affecting vertebral fusion in patients with lumbar spine instability seen at our hospital and to see how they relate to nutritional factors., Material and Methods: Patients undergoing vertebral fusion due to several diagnoses were analyzed. Different parameters were captured to determine the interaction among them and assess the factors affecting vertebral fusion healing. They were compared with patients with pseudoarthrosis to determine its risk factors. Patients were divided into two groups: the control group, who underwent fusion, and the cases, who had pseudoarthrosis., Results: A total of 59 patients were examined; 15 (25.4%) were cases (pseudoarthrosis) and 44 (74.6%) were controls (fusion). The demographic distribution was 27 (45.8%) females and 32 (54.2%) males; mean age was 51 +/- 12 years, with a minimum age of 20 and a maximum of 85. The diagnostic-based distribution was as follows: 29 (49.1%) spondylolistheses, 21 (35.6%) fractures, 5 (8.5%) herniated discs, 3 (5.1%) infections, and one (1.7%) tumor. Mean body weight was 75.9 kg, height was 160 cm, BMI 24.5, Hb 15.2, Hct 35.9, and Alb 3.5. Various risk factors were analyzed including the following: age over 60 years, which showed a 49% higher chance of pseudoarthrosis compared with the control group, with a 95% CI, 0.12-2.27; body weight over 90 kg, which showed an 82% higher chance of pseudoarthrosis compared with the fusion group, with a 95% CI, 0.03-0.43; BMI, which showed a 25% higher chance of pseudoarthrosis, with a 95% CI, 0.18-3.18; hypoalbuminemia < 3.4 mg/100 ml, which showed a 78% higher chance of pseudoarthrosis, with a 95% CI, 0.06-0.75., Conclusions: This study found that pseudoarthrosis is caused by risk factors linked to the nutritional profile, i.e., obesity, and hypoalbuminemia; its chance of occurring is 1.5 greater than in individuals with normal values. For this reason it is important to assess these values and correct them early on during the preoperative period with supportive measures allowing for an appropriate metabolic control and the consequent optimum result, i.e., fusion.

A spinal cord hemi-section with a homologous transplant of medullar tissue at the level of C5-C6 and preservation of the anterior spinal artery was used to evaluate the histological characteristics such as quantity and quality of axons, myelin index and blood vessels after quadriplegia recovery. Vascular changes after spinal injury results in severe endothelial damage, axonal edema, neuronal necrosis and demyelinization as well as cysts and infarction. Preservation of the anterior spinal artery has demonstrated clinical recuperation; therefore, in addition to the lesion we included a homologous transplant to visualize changes at a cellular level. Two groups of dogs (hemi-section and transplant) went through a traumatic spinal cord hemi-section of 50% at the level of C5-C6. The transplant group formed by animals which simultaneously had 4 mm of spinal cord removed and the equal amount substituted from a donor animal at the level of C5-C6 corresponding to the half right side; both preserving the anterior spinal artery. Histological evaluation of all groups took place at days 3 (acute) and 28 (chronic) post-operation. Changes of degeneration and axonal regeneration were found in the hemi-section and transplant groups at acute and chronic time, as well as same quadriplegia recovery at chronic time in the hemi-section and transplant groups which closely related to mechanisms which participate in regeneration and functional recuperation due to the preservation of the anterior spinal artery and presence of new blood vessels., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

The aneurysmal bone cyst (ABC) of the lumbar spine is an infrequent entity, of undefined nature and aggressive behavior; there are only a few reports in Mexico, so we present the case of a patient with radicular and lumbar pain that progressed to pelvic limb paresthesia. Lesions in the vertebral body of L1 were located with imaging studies and confirmed with biopsy; treatment with corticosteroids was started and later resection of the lesion was performed together with stabilization of the spine using first a posterior approach and at a second stage an anterior approach. Corticosteroid therapy led to remission of tumor progression, so only vacuolated areas and destruction of the posterior wall were found, leading to instability and radiculopathy. This type of lesions usually appears in long bones and less often in the spine, but it is even rarer in the lumbar spine. The prognosis of ABC is usually good, with the exception of the rare cases of extremely disseminated cysts located in the spine. It is therefore important to consider this before deciding what the best approach is for each patient, as well as the appropriate medico-surgical measures.

Background/objectives: The Food Consumption Survey (FCS), conducted for over 20 years by the Spanish Ministry of Agriculture, Fisheries and Food (MARM), is the most reliable source of data to evaluate the food consumption and dietary patterns of Spain. The aim of this study was to assess population food availability per capita per day, which allows the calculation of energy and nutrient intake and comparison with the Recommended Nutrient Intakes for the Spanish population. In addition, different markers of the quality of the diet have been evaluated., Subjects/methods: The sample consisted of consumption and distribution data, obtained from the nationwide representative FCS for the period 2000-2006. A two-stage sampling method was applied, where in the first stage the units to be sampled were towns or local entities, and in the second stage households that were going to be part of the final sample from those entities were selected. Units consisted of towns or local entities in the national territory. The sample size was 619 selected entities. Units in the second stage were households from the selected towns (8200 homes). The data allowed the calculation of energy and nutrient intakes, using food composition tables. The quality of the diet was also evaluated: the adequacy of the diet in meeting the recommended intakes for energy and nutrients; energy profile; dietary fat quality; dietary protein quality; nutrient density; and Mediterranean diet adequacy indices. The present data were compared with previous data obtained by our research group in 1964, 1981 and 1991., Results: Using the most recent data, average intake comprised milk and derivatives (379 g/person/day), fruit (310 g/person/day), vegetables and greens (302 g/person/day), cereals and derivatives (214 g/person/day), meat and meat products (179 g/day), fish (100 g/person/day), oil and fat (48 g/person/day), precooked food (34 g/person/day), eggs (32 g/person/day), and legumes and pulses (11.9 g/person/day). There was also a high consumption of non-alcoholic beverages (433 g/person/day) and alcoholic beverages (247 g/person/day). In consequence, meat and meat product consumption was higher than the recommendations, whereas for cereals and their derivatives, vegetables and greens, fruit, and legumes and pulses, consumption was below recommendations for the Spanish population. Some staple and traditional Mediterranean foods (bread, potatoes and olive oil) showed a dramatic decline when compared with data from Household Budget Surveys in 1964 data. Energy intake declined by about 300 kcal/person/day, when compared with the 1964 mean consumption. Insufficient nutrient intakes were found in the young adult population for zinc and folic acid in both sexes, and for iron in women, when compared with dietary reference values., Conclusions: Food consumption patterns in Spain and energy and nutrient intakes have changed markedly in the last 40 years, differing at present from the traditional and healthy Mediterranean diet.

The purpose of this study was to identify factors that contribute to bovine testis development and donor age-dependent differences in the abilities of bovine ectopic testis tissue grafts to produce elongated spermatids. We used real-time RT-PCR and microarrays to evaluate and to identify the expression of genes that are involved in Sertoli and germ cell development in bovine testis tissues. Testis tissues were obtained from 2-, 4-, and 8-wk-old bull calves and were grafted immediately. Grafted bovine testis tissue was removed from mice, RNA was isolated from the grafts, and real-time RT-PCR was used to evaluate gene expression during the grafting period. In addition, the gene expression in the donor tissue was analyzed using Affymetrix Bovine GeneChips, to identify differentially expressed genes. Examination of the testis tissue grafts indicated that Sertoli cell-specific gene expression was lower in 8-wk donor tissue grafts compared to the donors of other ages. Furthermore, the expression of KIT, which is a germ cell-specific gene, was low in testis tissue grafts. Microarray analysis of the donor tissue showed that several genes that are involved in angiogenesis or tissue growth were differentially expressed in 2-, 4-, and 8-wk-old bovine testes. The levels of expression of the genes for angiogenin, transgelin, thrombomodulin, early growth response 1, insulin-like growth factor 2, and insulin-like growth factor-binding protein 3 were lower in testis tissues from older animals. Using these data, it will be possible in the future to manipulate the testis xenograft microenvironment so as to improve the efficiency of sperm production within the graft.

Aim: Alpha 1-antitrypsin (AAT) deficiency is the most common genetic cause of liver disease in children. The Pi*S carrier rate among Filipinos is <1%. Its significance in Filipino infants with neonatal cholestasis has not been investigated. The aim of the study was to determine the incidence of AAT deficiency among Filipino infants presenting with neonatal cholestasis., Methods: Genotype determination that detects Pi*S and Pi*Z alleles was performed using Elucigene AAT reagents (Cellmark Diagnostics, UK). AAT inclusions were identified by light microscopy using periodic acid-Schiff (PAS) stain., Results: Ninety-six infants (mean age: 89 days, 48 males) with a history of jaundice since 2 weeks old and a direct bilirubin level>20% of the total were recruited. Only one patient (1 month old, male) was positive for Pi*S allele and 95 were negative for Pi*S and Pi*Z alleles, with an annual incidence of 0.7%. Of the 96, 49 infants underwent diagnostic percutaneous liver biopsy. All liver biopsy specimen were subjected to PAS stain and two infants, 2 and 4 months old, both with idiopathic neonatal hepatitis, had suspicious findings of AAT globules that was confirmed on immunostain. Both infants were negative for Pi*S alleles. The only patient positive for Pi*S allele was negative for PAS globule on liver biopsy., Conclusion: Our results showed a low incidence of AAT deficiency caused by the Pi*S and Pi*Z alleles among Filipino infants presenting with neonatal cholestasis, similar to the low carrier rate in the population.

Some nutritional unbalances have been observed in menus served at dining rooms of schools from the Community of Madrid (CM): small portions, inter-day variations up to 50% of energy intake, unbalances in caloric and lipidic profiles, little variety, lack of parental information, etc. The Education Council of the CM considered necessary to plan and regulate the basic conditions that menus of these dinning rooms should meet. The Spanish Nutrition Foundation (FEN) and the Nutrition Department of the Complutense University of Madrid (UCM) were put in charge of elaborating the bases to develop the Regulation (BOCM 24-05-01, 10-09-02). Collective catering companies were called for a tender to provide menus adapted to such Regulation. This work describes the adaptation of programmed dietary schemes of officially approved companies and mainly the impact on energy and nutritional content of menus and their adaptation to the recommended caloric and lipidic profiles. So far, a random sample of 171 schools with dining rooms (more than 37,000 schoolboys) has been visited by nutritionists, with no previous announcement, to control served menus. For this, at each centre a duplicate of the portion served that day was gathered. The energy and nutrient content was determined and the fatty acid composition was analysed. The adaptation to the Regulation by catering companies has substantially improved the menus as compared to previous times: more presence of vegetables, better quality of fat and less amount of fat and proteins at the expense of carbohydrates.

Bovine ectopic testis tissue grafting is a technique that can be used to study bovine spermatogenesis and for the production of germ cells for a variety of applications. Approximately 10% of seminiferous tubule cross sections in testis grafts contain spermatids, providing a unique tool to investigate what regulates germ cell differentiation. We hypothesized that manipulation of testis tissue grafts would increase the percentage of seminiferous tubule cross sections undergoing complete germ cell differentiation. To test this hypothesis, bovine testis tissue was treated with vascular endothelial growth factor (VEGF) at the time of grafting or explant cultured for 1 wk prior to grafting. For the VEGF experiment, 8-wk donor tissue and graft sites were treated with 1 microg of VEGF in order to increase angiogenesis at the graft site. For the testis tissue culture experiment, 4-wk-old donor testis was cultured for 1 wk prior to grafting to stimulate spermatogonial stem cell proliferation. Testis tissue grafts were removed from the mice 24 wk after grafting. VEGF treatment increased graft weight and the percentage of seminiferous tubule cross sections with elongating spermatids at the time of graft removal. Cultured testis tissue grafts were smaller and had fewer seminiferous tubules per graft. However, there was no difference in the percentage of seminiferous tubule cross sections that contained any germ cell type between groups. These data indicate for the first time that bovine testis tissue can be manipulated to better support germ cell differentiation in grafted tissue.

Bovine testis tissue xenografts contain elongating spermatids 6 mo after grafting. The percentage of seminiferous tubule cross sections with elongating spermatids at the time of graft removal varies depending on donor age and rarely exceeds 10%. These data indicate significant changes are occurring to bovine testicular cells during the first weeks of life. The objective of this research was to xenograft testis tissue from multiple ages of bull calves for 24 or 36 wk in order to gain a better understanding of early bovine testis development. Testis tissue from 1-, 2-, 4-, and 8-wk-old calves was grafted onto the backs of castrated immunodeficient mice. Testis tissue from all donor ages grew, differentiated, and produced testosterone and elongating spermatids. Testis tissue grafts from 1- and 8-wk-old calves had elongating spermatids in greater than 5.5% of seminiferous tubule cross sections at the time of graft removal regardless of grafting period. Four-week-old donor tissue never had more than 5.2% of seminiferous tubule cross sections with elongating spermatids. Extending the grafting period from 24 to 36 wk resulted in an increase in the percentage of seminiferous tubule cross sections with elongating spermatids from 2% to 10% in 2-wk donor tissue. These data demonstrate that both donor age and grafting period may be important factors regulating the maturation of bovine testis xenografts, indicating that intrinsic differences exist within testis tissue at these donor ages. These data provide the framework for further study of bovine spermatogenesis using ectopic testis xenografting.