Omics sciences and precision medicine in colon cancer.

Abstract: Colon cancer presents a complex pathophysiological landscape, which poses a significant challenge to the precise prediction of patient prognosis and treatment response. However, the emergence of omics sciences such as genomics, transcriptomics, proteomics, and metabolomics has provided powerful tools to identify molecular alterations and pathways involved in colon cancer development and progression. To address the lack of literature exploring the intersection of omics sciences, precision medicine, and colon cancer, we conducted a comprehensive search in ScienceDirect and PubMed databases. We included systematic reviews, reviews, case studies, clinical studies, and randomized controlled trials that were published between 2015-2023. To refine our search, we excluded abstracts and non-English studies. This review provides a comprehensive summary of the current understanding of the latest developments in precision medicine and omics sciences in the context of colon cancer. Studies have identified molecular subtypes of colon cancer based on genomic and transcrip-tomic profiles, which have implications for prognosis and treatment selection. Furthermore, precision medicine (which involves tailoring treatments, based on the unique molecular characteristics of each patient's tumor) has shown promise in improving outcomes for colon cancer patients. Omics sciences and precision medicine hold great promise for identifying new therapeutic targets and developing more effective treatments for colon cancer. Although not strictly designed as a systematic review, this review provides a readily accessible and up-to-date summary of the latest developments in the field, highlighting the challenges and opportunities for future research.

Omics sciences and precision medicine in pancreas cancer.

Abstract: Pancreatic cancer is a leading cause of death worldwide, associated with poor prognosis outcomes and late treatment interventions. The pathological nature and extreme tissue heterogeneity of this disease has hampered all efforts to correctly diagnose and treat it. Omics sciences and precision medicine have revolutionized our understanding of pan-creatic cancer, providing a new hope for patients suffering from this devastating disease. By analyzing large-scale biological data sets and developing personalized treatment strategies, researchers and clinicians are working together to improve patient outcomes and ultimately find a cure for pancreatic cancer.

Nutrigenomics: SNPs correlated to vitamins' deficiencies.

Abstract: Nutrients can influence the physiological processes in the body by interacting with molecular systems. Including nutrigenetics and nutrigenomics, nutritional genomics focuses on how bio-active food components interact with the genome. The purpose of this study is to clarify how nutrigenomics and vitamin dietary deficits relate to one another. Food tolerances among human sub-populations are known to vary due to genetic variation, which may also affect dietary needs. This raises the prospect of tailoring a person's nutritional intake for optimum health and illness prevention, based on their unique genome. To better understand the interplay between genes and nutrients and to plan tailored weight loss, nutrigenetic testing may soon become a key approach.

Unraveling the Role of Prickly Pear Extract as a Potent Nutraceutical Agent Against Metabolic Syndromes.

Background: Prickly pear (Opuntia) extracts have garnered con-siderable attention in recent years due to their promising medicinal and nutritional properties. This comprehensive review explores the multifaceted potential of prickly pear extracts in mitigating various chronic diseases, including cardiovascular diseases (CVDs), diabetes, obesity, cancer, neuronal diseases, and renal diseases. Methods: This review provides a comprehensive overview of the diverse therapeutic applications of Opuntia extracts in managing chronic diseases. The collective evidence underscores the potential of prickly pear as a valuable natural resource for addressing global health challenges. Further research and clinical investigations are warranted to unlock the full potential of Opuntia in the prevention and treatment of chronic diseases. Results: Studies have suggested that the bioactive compounds within prickly pear may influence glucose metabolism by improving insulin sensitivity, reducing insulin resistance, and modulating gut microbiota composition. These pathways exhibit potential in the reduction of hyperglycemia, which is a fundamental aspect of metabolic syndromes. Opuntia extracts demonstrate also antioxidant, anti-inflammatory capabilities that can contribute to improving health in various conditions. Conclusion: Further research and clinical investigations are warranted to unlock the full potential of Opuntia in the prevention and treatment of chronic diseases.

Olive tree polyphenols as effective and sustainable grain preservatives

Abstract: Whole grains play a crucial role in the human diet. Despite being cultivated in distinct regions, they are shipped everywhere, therefore making biosafety and security essential throughout the grain industry, from harvest to distribution. Phytopathogens, which have an impact on crop yield, induce grain spoiling and reduce grain quality in a number of ways, providing a constant danger to crop storage and distribution. Chemical control approaches, such as the use of pesticides and fungicides, are detrimental to the environment and hazardous to human health. The development of alternative, environmentally friendly, and generally acceptable solutions to ensure increased grain yield, biosafety, and quality during storage is crucial in order to guarantee sufficient food and feed supplies. As a means of self-defense against microbial infection and spoilage, plant matrices feature antimicrobial natural chemicals, which have led to their widespread usage as food preservatives in recent decades. Olive tree extracts, known for their high polyphenol content, have been widely used in the food preservation industry with great success, and are highly welcomed by people all over the world. In addition to their well-known health advantages, polyphenols are a valuable plant secondary metabolite because of their great antibacterial capabilities as natural preservatives. This article discusses the promising usage of polyphenols from olive trees as a natural alternative preservative, while also highlighting the future of olive eaves in the food industry.

Effects of Carob Extract on the Intestinal Microbiome and Glucose Metabolism: A Systematic Review and Meta-Analysis.

Abstract: The legume tree known as carob (Ceratonia siliqua L.) is indigenous to the Mediterranean area and over the centuries its pods had been traditionally used mostly as animal feed. However, it has gained great attention in human nutrition due to the molecular compounds it contains, which could offer many potential health benefits: for example, carob is renowned for its high content of fiber, vitamins, and minerals. Moreover, in traditional medicine it is credited with the ability to control glucose metabolism and gut microbiome. Modern science has also extensively acknowledged the numerous health advantages deriving from its consumption, including its anti-diabetic, anti-inflammatory, and antioxidant properties. Due to its abundant contents of pectin, gums, and polyphenols (such as pinitol), carob has garnered significant attention as a well-researched plant with remarkable therapeutic properties. Notably, carob is extensively used in the production of semi-finished pastry products, particularly in ice cream and other creams (especially as a substitute for cocoa/chocolate): these applications indeed facilitate the exploration of its positive effects on glucose metabolism. Our study aimed at examining the effects of carob extract on intestinal microbiota and glucose metabolism. In this review, we conducted a thorough examination, comprising in vitro, in vivo, and clinical trials to appraise the consequences on human health of polyphenols and pectin from different carob species, including recently discovered ones with high polyphenol contents. Our goal was to learn more about the mechanisms through which carob extract can support a balanced gut flora and improve one's glucose metabolism. These results could influence the creation of novel functional foods and dietary supplements, to help with the management and prevention of chronic illnesses like diabetes and obesity.

Nutrigenomics: SNPs correlated to minerals' deficiencies.

Abstract: Nutrigenetics and nutrigenomics are two interrelated fields that explore the influence of genetic diversity on nutrient responses and function. While nutrigenetics investigates the effects of hereditary ge-netic variations on micronutrient metabolism, nutrigenomics examines the intricate relationship between diet and the genome, studying how genetic variants impact nutrient intake and gene expression. These disciplines offer valuable insights into predicting and managing chronic diseases through personalized nutritional approaches. Nutrigenomics employs cutting-edge genomics technologies to study nutrient-genome interactions. Key principles involve genetic variability among ethnic groups, affecting nutrient bioavailability and metabolism, and the influence of dietary choices based on cultural, geographic, and socioeconomic factors. Polymorphisms, particularly single-nucleotide polymorphisms (SNPs), significantly influence gene activity and are associated with specific phenotypes that are related to micronutrient deficiencies. Minerals are inorganic elements, vital for various physiological functions. Understanding the SNPs associated with mineral deficien-cies is crucial for assessing disease risk and developing personalized treatment plans. This knowledge can inform public health interventions, targeted screening programs, educational campaigns, and fortified food products to address deficiencies effectively. Nutrigenomics research has the potential to revolutionize clinical and nutritional practices, providing personalized recommendations, enhancing illness risk assessment, and advancing public health initiatives. Despite the need for further research, harnessing nutrigenomics' potential can lead to more focused and efficient methods for preventing and treating mineral deficiencies.

Nutrigenomics: SNPs Correlated to Lipid and Carbohydrate Metabolism.

Background: Nutrigenomics - the study of the interactions between genetics and nutrition - has emerged as a pivotal field in personalized nutrition. Among various genetic variations, single-nucleotide polymorphisms (SNPs) have been extensively studied for their probable relationship with metabolic traits. Methods: Throughout this review, we have employed a targeted research approach, carefully handpicking the most representative and relevant articles on the subject. Our methodology involved a systematic review of the scientific literature to ensure a comprehensive and accurate overview of the available sources. Results: SNPs have demonstrated a significant influence on lipid metabolism, by impacting genes that encode for enzymes involved in lipid synthesis, transport, and storage. Furthermore, they have the ability to affect enzymes in glycolysis and insulin signaling pathways: in a way, they can influence the risk of type 2 diabetes. Thanks to recent advances in genotyping technologies, we now know numerous SNPs linked to lipid and carbohydrate metabolism. The large-scale studies on this topic have unveiled the potential of personalized dietary recommendations based on an individual's genetic makeup. Personalized nutritional interventions hold promise to mitigate the risk of various chronic diseases; however, translating these scientific insights into actionable dietary guidelines is still challenging. Conclusions: As the field of nutrigenomics continues to evolve, collaborations between geneticists, nutritionists, and healthcare providers are essential to harness the power of genetic information for improving metabolic health. By unraveling the genetic basis of metabolic responses to diet, this field holds the potential to revolutionize how we approach dietary recommendations and preventive healthcare practices.

Nutrigenomics: SNPs correlated to physical activity, response to chiropractic treatment, mood and sleep.

Abstract: Nutrigenomics, a rapidly evolving field that bridges genetics and nutrition, explores the intricate interactions between an individual's genetic makeup and how they respond to nutrients. At its core, this discipline focuses on investigating Single Nucleotide Polymorphisms (SNPs), the most common genetic variations, which significantly influence a person's physiological status, mood regulation, and sleep patterns, thus playing a pivotal role in a wide range of health out-comes. Through decoding their functional implications, researchers are able to uncover genetic factors that impact physical fitness, pain perception, and susceptibility to mood disorders and sleep disruptions. The integration of nutrigenomics into healthcare holds the promise of transformative interventions that cater to individual well-being. Notable studies shed light on the connection between SNPs and personalized responses to exercise, as well as vulnerability to mood disorders and sleep disturbances. Understanding the intricate interplay between genetics and nutrition informs targeted dietary approaches, molding individual health trajectories. As research advances, the convergence of genetics and nourishment is on the brink of reshaping healthcare, ushering in an era of personalized health management that enhances overall life quality. Nutrigenomics charts a path toward tailored nutritional strategies, fundamentally reshaping our approach to health preservation and preventive measures.

Nutrigenomics: SNPs correlated to detoxification, antioxidant capacity and longevity.

Abstract: Nutritional genomics, also known as nutrigenomics, is the study of how a person's diet and genes interact with each other. The field of nutrigenomics aims to explain how common nutrients, food additives and preservatives can change the body's genetic balance towards either health or sickness. This study reviews the effects of SNPs on detoxification, antioxidant capacity, and longevity. SNPs are mutations that only change one nucleotide at a specific site in the DNA. Specific SNPs have been associated to a variety of biological processes, including detoxification, antioxidant capacity, and longevity. This article mainly focuses on the following genes: SOD2, AS3MT, CYP1A2, and ADO-RA2A (detoxification); LEPR, TCF7L2, KCNJ11, AMY1, and UCP3 (antioxidant capacity); FOXO3 and BPIFB4 (longevity). This review underlines that many genes-among which FOXO3, TCF7L2, LEPR, CYP1A2, ADORA2A, and SOD2-have a unique effect on a person's health, susceptibility to disease, and general well-being. Due to their important roles in numerous biological processes and their implications for health, these genes have undergone intensive research. Examining the SNPs in these genes can provide insight into how genetic variants affect individuals' responses to their environment, their likelihood of developing certain diseases, and their general state of health.

Nutrigenomics: SNPs correlated to Food Preferences and Susceptibilities.

Background: Nutrigenomics explores the intricate interplay between single nucleotide polymorphisms (SNPs), food preferences, and susceptibilities. Methods: This study delves into the influence of SNPs on food sensitivities, allergies, tyramine intolerance, and taste preferences. Genetic factors intricately shape physiological reactions to dietary elements, with polymorphisms contributing to diverse sensitivities and immune responses. Results: Tyramine intolerance, arising from metabolic inefficiencies, unveils genetic markers exerting influence on enzyme function. SNPs transcend genetic diversity by exerting substantial impact on food sensitivities/allergies, with specific variants correlating to heightened susceptibilities. Genes accountable for digesting food components play pivotal roles. Given the rising prevalence of food sensitivities/allergies, understanding genetic foundations becomes paramount. In the realm of taste and food preferences, SNPs sculpt perception and choice, yielding variances in taste perception and preferences for sweetness, bitterness, and umami. This genetic medley extends its reach to encompass wider health implications. Conclusions: In this review article, we have focused on how polymorphisms wield significant sway over physiological responses, sensitivities, and dietary inclinations. Unraveling these intricate relationships illuminates the path to personalized nutrition, potentially revolutionizing tailored recommendations and interventions.

Revisiting the impact of ejaculatory abstinence on semen quality and intracytoplasmic sperm injection outcomes.

BACKGROUND: Regulatory bodies recommend inconsistent ejaculatory abstinence lengths before semen analysis. The literature exploring the effect of ejaculatory abstinence length on the outcomes of intracytoplasmic sperm injection is scarce. OBJECTIVE: To study the influence of ejaculatory abstinence length on semen quality and intracytoplasmic sperm injection outcomes. MATERIALS AND METHODS: This prospective cohort study included 818 patients undergoing conventional semen analysis from October 2015 to October 2016, in a private university-affiliated IVF centre. Generalized linear models adjusted for potential confounders were used to investigate the associations between ejaculatory abstinence length and seminal parameters and intracytoplasmic sperm injection outcomes. RESULTS: Increasing ejaculatory abstinence length was positively correlated with semen volume, sperm concentration, total sperm count, total motile sperm count and sperm DNA fragmentation index. Significant inverse correlations were observed between ejaculatory abstinence length and fertilization rate, blastocyst formation rate, implantation rate and pregnancy rate. A discriminant analysis showed a mean ejaculatory abstinence length in the positive pregnancy group of 3.14 ± 1.64 days and 4.83 ± 3.66 days in the negative pregnancy group. A cut-off point was established halfway between ejaculatory abstinence length averages, at 4 days. The ejaculatory abstinence ≤4 days group showed significant lower semen volume, sperm concentration, total sperm count and total motile sperm count compared to ejaculatory abstinence > 4 days group. The ejaculatory abstinence ≤ 4 days group showed significant lower sperm DNA fragmentation index, and higher rates of fertilization, high-quality embryos on day 3, blastocyst development, implantation and pregnancy compared to ejaculatory abstinence > 4 days group. The implantation rate was significantly higher and the pregnancy rate tended to be higher with one day of ejaculatory abstinence, compared to 2-4 days of ejaculatory abstinence. CONCLUSIONS: Ejaculatory abstinence periods of >4 days have a detrimental effect on sperm DNA and intracytoplasmic sperm injection outcomes. One day of ejaculatory abstinence significantly improves implantation rate and tends to increase pregnancy rate, compared to 2, 3 and 4 days of ejaculatory abstinence.

Influence of Biliopancreatic Diversion on Pregnancy Outcomes in Comparison to Other Bariatric Surgery Procedures.

BACKGROUND: Pregnancy after bariatric surgery (BS) has an increased risk for small-for-gestational-age infants (SGA), shorter length of gestation, and probably perinatal mortality. The aim of this study was to investigate if biliopancreatic diversion could impair pregnancy outcomes in comparison to other bariatric surgery procedures. METHODS: We conducted a cohort retrospective single-center study in 65 women before and after BS. Thirty-one pregnancies occurred before BS, while 109 after BS, amongst which n = 51 after biliopancreatic diversion (BPD) and n = 58 after non-malabsorptive procedures. RESULTS: The pregnancy outcomes after BS in comparison with those before BS resulted less affected by diabetes, hypertensive disorders, macrosomia, and large-for-gestational-age (LGA), but more complicated by preterm births (14.5 versus 4.0%) and low birth weight (LBW) infants (28.9 versus 0%). Moreover, mean birth weight resulted lower after BS than before BS (p < 0.001). In pregnancies after BPD in comparison to those before BS, the LBW rate (42.5%) resulted a drastic increase (p < 0.001), and mean birth weight (p < 0.001) and mean birth weight centile (p < 0.001) were lower after BPD. When pregnancy outcomes after BPD were compared with those after non-malabsorptive procedures, the rate of congenital anomalies, preterm births, LBW, and SGA resulted an increase (p = 0.002, 0.008, 0.032, and < 0.001, respectively). CONCLUSIONS: BPD drastically reduced diabetes, hypertensive disorders, macrosomia, and LGA; however, it was associated with the poorest pregnancy outcomes in comparison to those observed after other BS procedures. On the basis of the present study, we recommend a cautious multidisciplinary selection of severely obese patients for BPD during the fertile age.

Sperm morphological normality under high magnification is correlated to male infertility and predicts embryo development.

Human sperm morphology has been described as an essential parameter for the diagnosis of male infertility and a prognostic indicator of natural or assisted pregnancies. Nevertheless, standard morphological assessment remains a subjective analysis and its impact on intracytoplasmic sperm injection (ICSI) is also of limited value. The objective of this prospective cohort study was to investigate whether motile sperm organelle morphology examination (MSOME) can improve semen analysis by better defining male infertility and providing a better prognosis for ICSI up to a year later. Data were obtained from 483 patients undergoing conventional semen analysis from June 2015 to June 2017 in a private university-affiliated in vitro fertilization (IVF) center. The correlation of MSOME with seminal parameters was evaluated. One hundred and thirty patients underwent ICSI up to a year later, and the correlation between MSOME and ICSI outcomes was established. Except for volume, all seminal parameters were positively correlated with MSOME I+II. MSOME was also distinct between World Health Organization (WHO) classification groups, with normozoospermic and oligoasthenoteratozoospermic presenting the higher and the lower proportion of MSOME I+II, respectively. MSOME I+II was prognostic for fertilization rate, high-quality cleavage-stage embryos rate, and blastocyst rate. The normality cutoff value based on blastocyst rate was MSOME I+II≥ 5.5%. MSOME could be a useful tool for the diagnosis of infertility severity as it is correlated with sperm morphology, motility, and concentration. Men who had higher MSOME I+II had better ICSI outcomes. The future use of MSOME as a routine method for semen analysis may be a reliable form of assessing male infertility.

Intensive lifestyle modifications with or without liraglutide 3mg vs. sleeve gastrectomy: A three-arm non-randomised, controlled, pilot study.

BACKGROUND/OBJECTIVES: As only 1% of clinically eligible subjects choose to undergo surgical treatment for obesity, other options should be investigated. This study aimed to assess the effects of intensive lifestyle modification (ILM) with or without 3-mg liraglutide daily vs. sleeve gastrectomy (SG) on BMI after 1 year. SUBJECTS/METHODS: In this study performed at an Italian university hospital, non-diabetic patients eligible for bariatric surgery were recruited from a weight-loss clinic and had the option to choose from three possible weight-loss programmes up to an allocation of 25 subjects in each arm matched by BMI and age. ILM consisted in 813kcal of a very low-calorie diet (VLCD) for 1 month, followed by a diet of 12kcal/kg body weight of high protein and high fat for 11 months plus 30min of brisk walking daily and at least 3h of aerobic exercise weekly. SG patients followed a VLCD for 1 month and a free diet thereafter. Patients were evaluated at baseline and at 1, 3, 6, 9 and 12 months. RESULTS: A total of 75 patients were enrolled; retention was 100% in the SG and 85% in the two medical arms. SG reduced BMI by 32% (P<0.001 vs. medical arm), while ILM+liraglutide and ILM led to BMI reductions of 24% and 14%, respectively (P<0.001). More women allocated themselves to the ILM+liraglutide group. Weight loss was 43kg with SG, 26kg with ILM+liraglutide and 15kg with ILM alone. Lean body mass reductions were -11.6kg with SG, -6.3kg with ILM and -8.3kg with ILM+liraglutide. Prevalence of prediabetes was significantly lower with ILM+liraglutide, and insulin resistance was reduced by about 70% by both ILM+liraglutide and SG vs. 39% by ILM alone. Cardiometabolic risk factors were greatly reduced in all three groups. DISCUSSION: At least in the short-term, liraglutide 3.0mg once daily associated with drastic calorie-intake restriction and intensive physical activity promoted a 24% weight loss, which was almost two times greater than ILM alone and only about 25% less than with SG, while preserving lean body mass. Although this study was non-randomised, it was designed to explore the efficacy of medical treatments for obesity in everyday clinical practice.

Total motile sperm count has a superior predictive value over the WHO 2010 cut-off values for the outcomes of intracytoplasmic sperm injection cycles.

The objective of this study was to compare (i) the intracytoplasmic sperm injection outcomes among groups with different total motile sperm count ranges, (ii) the intracytoplasmic sperm injection outcomes between groups with normal and abnormal total motile sperm count, and (iii) the predictive values of WHO 2010 cut-off values and pre-wash total motile sperm count for the intracytoplasmic sperm injection outcomes, in couples with male infertility. This study included data from 518 patients undergoing their first intracytoplasmic sperm injection cycle as a result of male infertility. Couples were divided into five groups according to their total motile sperm count: Group I, total motile sperm count <1 × 10(6) ; group II, total motile sperm count 1-5 × 10(6) ; group III, total motile sperm count 5-10 × 10(6) ; group IV, total motile sperm count 10-20 × 10(6) ; and group V, total motile sperm count >20 × 10(6) (which was considered a normal total motile sperm count value). Then, couples were grouped into an abnormal and normal total motile sperm count group. The groups were compared regarding intracytoplasmic sperm injection outcomes. The predictive values of WHO 2010 cut-off values and total motile sperm count for the intracytoplasmic sperm injection outcomes were also investigated. The fertilization rate was lower in total motile sperm count group I compared to total motile sperm count group V (72.5 ± 17.6 vs. 84.9 ± 14.4, p = 0.011). The normal total motile sperm count group had a higher fertilization rate (84.9 ± 14.4 vs. 81.1 ± 15.8, p = 0.016) and lower miscarriage rate (17.9% vs. 29.5%, p = 0.041) compared to the abnormal total motile sperm count group. The total motile sperm count was the only parameter that demonstrated a predictive value for the formation of high-quality embryos on D2 (OR: 1.18, p = 0.013), formation of high-quality embryos on D3 (OR: 1.12, p = 0.037), formation of blastocysts on D5 (OR: 1.16, p = 0.011), blastocyst expansion grade on D5 (OR: 1.27, p = 0.042), and the odds of miscarriage (OR: 0.52, p < 0.045). The total motile sperm count has a greater predictive value than the WHO 2010 cut-off values for laboratory results and pregnancy outcomes in couples undergoing intracytoplasmic sperm injection as a result of male infertility.

The negative influence of sperm cryopreservation on the quality and development of the embryo depends on the morphology of the oocyte.

The present case-control study aimed to identify the effect of sperm cryopreservation on the quality of the embryo and on the probability of blastocyst formation when oocytes free of dimorphisms are injected and when at least one dymorphism is present. The study included 22 186 zygotes, obtained from 2802 patients undergoing intracytoplasmic sperm injection cycles, in a private assisted reproduction center, using either fresh or cryopreserved sperm. The effect of sperm cryopreservation on the embryo quality on cleavage stage and blastocyst formation chance were evaluated when oocytes free of dimorphisms are injected and when at least one dymorphism is present. The quality of the embryo on cleavage stage as well as the chance for blastocyst formation was not influenced by the origin of the spermatozoa when the quality of the oocyte was not considered. When at least one oocyte defect was present, a negative influence of sperm cryopreservation on cleavage stage embryo quality and the chance for blastocyst formation was noted. In oocytes with extra-cytoplasmic dimorphisms, the injection of cryopreserved sperm did not affect the quality of the embryo during the cleavage stage, but did affect the chance for blastocyst formation. Conversely, in oocytes with intracytoplasmic defects, the quality of the embryos on cleavage stage and the chance of blastocyst formation were negatively influenced by the injection of cryopreserved sperm. The results suggest an oocyte quality-dependent negative effect of sperm cryopreservation on embryo quality and on the probability of blastocyst formation.

Effects of biliopancreatic diversion on diurnal leptin, insulin and free fatty acid levels.

BACKGROUND: Free fatty acid (FFA) levels are raised in obesity as a consequence of increased production and reduced clearance. They may link obesity with insulin resistance. Bariatric surgery can result in considerable weight loss and reduced insulin resistance, but the mechanism of action is not well understood. Although drugs such as metformin that lower insulin resistance can contribute to weight loss, a better understanding of the links between obesity, weight loss and changes in insulin resistance might lead to new approaches to patient management. METHODS: Variations in circulating levels of leptin, insulin and FFAs over 24 h were studied in severely obese (body mass index over 40 kg/m(2) ) women before and 6 months after biliopancreatic diversion (BPD). Body composition was measured by dual-energy X-ray absorptiometry. A euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Levels of insulin, leptin and FFAs were measured every 20 min for 24 h. Pulsatile hormone and FFA analyses were performed. RESULTS: Among eight patients studied, insulin sensitivity more than doubled after BPD, from mean(s.d.) 39·78(7·74) to 96·66(27·01) mmol per kg fat-free mass per min, under plasma insulin concentrations of 102·29(9·60) and 93·61(9·95) µunits/ml respectively. The secretory patterns of leptin were significantly different from random but not statistically different before and after BPD, with the exception of the pulse height which was reduced after surgery. Both plasma insulin and FFA levels were significantly higher throughout the study day before BPD. Based on Granger statistical modelling, lowering of daily FFA levels was linked to decreased circulating leptin concentrations, which in turn were related to the lowering of daily insulin excursions. Multiple regression analysis indicated that FFA level was the only predictor of leptin level. CONCLUSION: Lowering of circulating levels of FFAs after BPD may be responsible for the reduction in leptin secretion, which in turn can decrease circulating insulin levels. Surgical relevance Insulin resistance is a common feature of obesity and type II diabetes. These patients are also relatively insensitive to the biological effects of leptin, a satiety hormone produced mainly in subcutaneous fat. Biliopancreatic diversion, a malabsorptive bariatric operation that drastically reduces circulating lipid levels, improves insulin resistance independently of weight loss. The mechanism of action, however, has still to be elucidated. This study demonstrated that normalization of insulin sensitivity after bariatric surgery was associated with a reduction in 24-h free fatty acid concentrations and changes in the pattern of leptin peaks in plasma. Bariatric surgery improves the metabolic dysfunction of obesity, and this may be through a reduction in circulating free fatty acids and modification of leptin metabolism.

Intracytoplasmic morphologically selected sperm injection is beneficial in cases of advanced maternal age: a prospective randomized study.

OBJECTIVE: To evaluate advanced maternal age as a rationale for performing intracytoplasmic morphologically selected sperm injection (IMSI). STUDY DESIGN: This study included couples undergoing intracytoplasmic sperm injection (ICSI) as a result of advanced maternal age (≥37 years old). Sample size calculations were based on the assumption that a 15% difference in implantation rate would mean a clinically significant difference. To achieve this difference, 33 cycles would be needed in each treatment arm (with a significance level of 5% and power of 85%). Couples were randomly allocated to one of two sperm selection procedures (ICSI, n=33; or IMSI, n=33). Sperm selection in the ICSI group was analyzed under a magnification of 400×. Sperm selection in the IMSI group was analyzed under high magnification of 6600×. The groups were compared with regard to the outcome of the cycles. RESULTS: IMSI cycles showed significantly higher implantation (4/33, 12.1% vs. 18/47, 38.3%, p=0.026) and pregnancy (4/29, 13.8 vs. 18/30, 60.0%, p<0.001) rates. The IMSI procedure positively influenced the blastocyst formation rate (RC: 15.00, R2: 49.9%, p=0.001) and implantation rate (RC: 24.04, R2: 9.6, p=0.027), and was determinant to the increased odds of pregnancy (OR: 9.0, CI: 2.17-37.38, p=0.001). CONCLUSION: It seems that the injection of a morphologically normal spermatozoon overcomes the low oocyte quality in older women, resulting in improved embryo quality and in a 9-fold increase in the clinical pregnancy rate in couples with advanced maternal age.