Tales of the Tail and Sperm Head Aches --Changing concepts on the prognostic significance of sperm pathologies affecting the head, neck and tail

This article presents an update on the variable prognostic significance of different sperm pathologies in patients with severe male factor infertility due to morphology and motility disorders. Severe asthenozoospermia is one of the leading causes of male infertility as spermatozoa cannot reach the oocyte and/or penetrate normally. Identifying structural causes of sperm immotility was of great concern before the advent of intracytoplasmic sperm injection （ICSI）, because immotility was the limiting factor in the treatment of these patients. In these cases, in vitro methods are used to identify live spermatozoa or stimulate sperm motility to avoid selection of non-viable cells. With these advances, fertilization and pregnancy results have improved dramatically. The identification of genetic phenotypes in asthenozoospermia is important to adequately inform patients of treatment outcomes and risks. The one sperm characteristic that seriously affects fertility prognosis is teratozoospermia, primarily sperm head and neck anomalies. Defects of chromatin condensation and acrosomal hypoplasia are the two most common abnormalities in severe teratozoospermia. The introduction of microscopic methods to select spermatozoa and the development of new ones to evaluate sperm quality before ICSI will assure that ultrastructural identification ofsperm pathologies will not only be of academic interest, but will also be an essential tool to inform treatment choice. Herein, we review the differential roles played by sperm components in normal fertilization and early embryo development and explore how assisted reproductive technologies have modified our concepts on the prognostic significance of sperm pathologies affecting the head, neck, mid-piece and tail.

Pregnancies established through intracytoplasmic sperm injection (ICSI) using spermatozoa with dysplasia of fibrous sheath

Aim:Dysplasia of the fibrous sheath(DFS)is an anomaly found in asthenozoospermic patients with extremely lowor absent motility.In order to determine the efficacy of ICSI in these patients,a retrospective analysis of ICSI results inDFS patients has been done.Methods:Ten ICSI attempts were performed in 6 patients with diagnosis of Dysplasiaof the Fibrous Sheath studied by transmission and scanning electron microscopy.Results:In the cases studied,sperm concentration was(29.62±18.05)×10^(6)/mL,total motility was 1.14±1.31%.Progressive motility was 0%except for one case with 0.1%.One hundred and three preovulatory oocytes were obtained and 94 metaphaseⅡoocyteswere injected.Sixty-nine of them showed two pronuclei(fertilization rate:73.4%).Forty-nine embryos were ob-tained and 34 were transferred(mean:3.4 embryos per transfer).Five pregnancies were diagnosed byβ-hCG plasmalevel determinations that resulted to be one preclinical abortion,one clinical abortion and three deliveries.Anotherpregnancy(ongoing)was achieved from a cryopreserved embryo transfer.Conclusion:These results showed thatICSI provides a suitable solution for patients suffering from irreversible sperm defects such as DFS.Nevertheless,it ismandatory to inform couples of possible transmission risks to offspring,which are unknown at present.Only when theetiology of this problem is disclosed,it will be possible to assess the real genetic risk.

Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease

AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular disease.METHODS:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up program.NAFLD was diagnosed by abdominal ultrasonography.The metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ criteria.Five years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered questionnaire.RESULTS:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular events.But simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular disease.CONCLUSION:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate model.NAFLD is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.

MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

Epithelial ovarian cancer(EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers(mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as micro RNAs(miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish mi RNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers.

A determination of the quality of life of children and adolescents with type 1 diabetes and their parents

Objective: Type 1 diabetes is a chronic illness which can have a negative effect on the health care and development of children and can put their lives in danger. This descriptive study aimed to determine the quality of life and the factors affecting it of children and adolescents with type 1 diabetes using the Pediatric Quality of Life Inventory (PedsQL).Methods: The study was conducted in the Child Endocrinology Unit of a University Hospital in Bursa, Turkey. Totally 64 children eight-12 years and 85 adolescents aged 13-18 with type 1 diabetes and their parents were recruited. HbA1c measurements were obtained from the records of the endocrinology clinicare, which were made once every three months, and the average of the last three measurements was taken in the study. The PedsQL was used to measure quality of life of the children and adolescents. The data was analyzed using SPSS version 20.0 and P<0.05 was considered significant. The demographic data of the children and parents were analyzed using means and percentiles. Pearson's correlation analysis was used to assess the relationship between two averages. Results: Of the sub-groups on the scale, affective and school function scores were somewhat low, and social function scores were high. The quality of life scores of the children and adolescents were found to correlate with those of their parents. A negative correlation was found between HbA1c levels and adolescent quality of life, a positive correlation was found between the child's age and the quality of life of the child and parents, and a negative correlation was found between the number of children in the family and the quality of life of the child and parents. Conclusions: An evaluation of the quality of life after a diagnosis of diabetes can be used to assess the problems which may be faced by children and adolescents and to combat these problems.

The high incidence of acute hemolysis due to favism in Ahvaz,Iranclinical features and laboratory findings

Objective:To collect comprehensive information about the features of favic patients in Ahvaz (Capital of Khouzestan,Iran) and analyze the extent of the differences with their corresponding in other regions.Methods:A total of 103 patients with acute hemolysis admitted to pediatric division of Abouzar Hospital located in the city of Ahvaz,Iran during 21st of June 2008 to 20th of June 2009 were analyzed retrospectively.Results:95.14% of the patients had favism while 4.86% of them underwent hemolysis due to other reasons.These patients were male(68.93%) and female children(31.06%) admitted mostly during the spring season.The three main symptoms were urine discoloration,jaundice and vomiting.At the admission time,the main hematologic findings were as follows:G6PD sufficient status(45.63%),G6PD deficient status(54.36%) and hemoglobin concentration:2.5-11.8(mean±SD:6.45±2.12) g/dL.Conclusions:In conclusion,Ahvaz was determined as a black zone for favism in which the disease can be considered a life threatening health problem.Moreover,slight differences were observed in the three main symptoms compared with favic patients in other regions.

Recreational team sports: The motivational medicine

Remember way back when?When we were kids?We played games like soccer,basketball,rugby,and volleyball because they were fun.If we stayed with it long enough(and became good enough)we might have played competitively,where the objective was to win.Herman Edwards,a former head coach in the National Football League(NFL)。

Identification of individuals with non-alcoholic fatty liver disease by the diagnostic criteria for the metabolic syndrome

AIM:To clarify the efficiency of the criterion of metabolic syndrome to detecting non-alcoholic fatty liver disease(NAFLD).METHODS:Authors performed a cross-sectional study involving participants of a medical health checkup program including abdominal ultrasonography.This study involved 11 714 apparently healthy Japanese men and women,18 to 83 years of age.NAFLD was defined by abdominal ultrasonography without an alcohol intake of more than 20 g/d,known liver disease,or current use of medication.The revised criteria of the National Cholesterol Education Program Adult Treatment PanelⅢ were used to characterize the metabolic syndrome.RESULTS:NAFLD was detected in 32.2%(95%CI:31.0%-33.5%)of men(n=1874 of 5811)and in 8.7%(95%CI:8.0%-9.5%)of women(n=514 of 5903).Among obese people,the prevalence of NAFLD was as high as 67.3%(95%CI:64.8%-69.7%)in men and 45.8%(95%CI:41.7%-50.0%)in women.Although NAFLD was thought of as being the liver phenotype of metabolic syndrome,the prevalence of the metabolic syndrome among subjects with NAFLD was low both in men and women.66.8%of men and 70.4%of women with NAFLD were not diagnosed with the metabolic syndrome.48.2%of men with NAFLD and 49.8%of women with NAFLD weren't overweight[body mass index(BMI)≥25 kg/m2].In the same way,68.6%of men with NAFLD and 37.9%of women with NAFLD weren't satisfied with abdominal classification(≥90 cm for men and≥80 cm for women).Next,authors defined it as positive at screening for NAFLD when participants satisfied at least one criterion of metabolic syndrome.The sensitivity of the definition"at least 1 criterion"was as good as 84.8%in men and 86.6%in women.Separating subjects by BMI,the sensitivity was higher in obese men and women than in non-obese men and women(92.3%vs 76.8%in men,96.1%vs 77.0%in women,respectively).CONCLUSION:Authors could determine NAFLD effectively in epidemiological study by modifying the usage of the criteria for metabolic syndrome.

Isolated micropenis reveals partial androgen insensitivity syndrome confirmed by molecular analysis

Partial androgen insensitivity syndrome （PAIS） is the milder variant of androgen receptor （AR） defects. The subtle effects of AR mutations present in a patient with micropenis, peno-scrotal hypospadias, infertility, clitoromegaly and posterior labial fusion. We studied the association of isolated micropenis with the genetic defects resulting in androgen resistance, that is, AR gene defects and 5-α reductase type 2 （SRD5A2） deficiency. We describe two cases of isolated micropenis： one in a 14-year-old boy and the other in a 3-year-old boy who was followed until he was 10 years old. There were no findings of hypospadias, cryptorchidism or gynecomastia in either of these patients. Serum gonadotrophin and androgen levels were obtained and karyotyping was done. Human chorionic gonadotropin （hCG） stimulation testing assessed the functional capacity of the testes. DNA was extracted from peripheral leukocytes, and all exons of the SRD5A2 and AR genes were amplified by polymerase chain reaction and sequenced. In both patients, baseline testosterone （T） level was low and the values were elevated after hCG testing. The sequence of the SRD5A2 gene was normal in patient 1, and a heterozygous polymorphism, V89L, was found in patient 2. Two known mutations, P390S and A870V, were identified in patients 1 and 2, respectively. Mutations in the AR gene can be associated with isolated micropenis without other features of PAIS, such as hypospadias or gynecomastia. This underlines the importance of including AR gene analysis in the evaluation of isolated micropenis with normal plasma T to ensure proper management of the patient and appropriate genetic counseling for the family.

Artificial Sweeteners as a Cause of Obesity: Weight Gain Mechanisms and Current Evidence

The obesity epidemic gathers growing media attention recently, as overweight and obesity’s prevalence keeps rising. This comes along with an increase in the intake of artificial sweeteners in food products. A causal relationship between the consumption of sweeteners and obesity is so far not clear in the medical literature. This paper describes the development of artificial sweeteners in a historical context. It collects epidemiological and experimental evidence that possibly relates the use of artificial sweeteners with weight gain. Finally, these effects are explained based on the neuroscience of food reward, the possible effects of glucose on the metabolism and the association between sweeteners and gut microbiota.

Polycystic Ovary Syndrome and the Role of Metformin in Ovulation Induction

The Polycystic Ovary Syndrome (PCOS) is frequently associated with comorbidities such as obesity, reduced glucose tolerance, hypertension, macrovascular disease and dyslipidemia. The Metabolic syndrome occurs in 30% of women with PCOS. Metformin has increasingly been used in this therapy due to its effects in reducing insulin resistance. Treatment of PCOS aims to reduce the symptoms of hyperandrogenism, regularize the menstrual cycle, reduce metabolic abnormalities, and lower the risk of type 2 diabetes mellitus and of cardiovascular disease. Additionally it is important to prevent hyperplasia and endometrial cancer, and to offer contraception to those who do not wish pregnancy, and to help to induce ovulation to those who do. The effectiveness of metformin in this treatment is assessed in the light of the current best evidence.

Intestinal Microbiota, Obesity and Insulin Resistance—What Are the Relationships?

Obesity is a public health problem and its prevalence increases every year, resulting from a complex interaction between genetic, metabolic and environmental factors, as well as cultural influences. The Intestinal Microbiota is composed of trillions of microorganisms by forming a symbiotic relationship with the host and helping the absorption of various nutrients, increasing the extraction of components of the diet, the lipogenesis and intestinal permeability. Studies show that there is difference between the composition of the intestinal microbiota of an obese person and a healthy one. The purpose of this article is to review the literature on the relationship between the Intestinal Microbiota, Obesity and Insulin Resistance and also illustrate some studies on the subject.

Growth Hormone Replacement Therapy in Patients without Adult Growth Hormone Deficiency: What Answers Do We Have So Far?

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been suggested as “anti-aging” therapies, or for improving quality of life with aging. In this study, we focus on the actions of GH in the main organs and organ systems of the human body, like skeletal muscle, bones and brain, particularly in regard to data and research on the use of GH replacement therapy in adults without growth hormone deficiency, especially elderly patients. Several different studies have been carried out to show what the effects and side effects of GH replacement in healthy people and what would be the impact in quality of life and life span. In this review, we demonstrate what answers we have so far about the effects of GH replacement in many organs and systems in healthy people.

The Role of Fructose in Public Health and Obesity

We are in the so-called nutritional transition, in which obesity and its comorbidities have emerged as an important research topic, and the information on food composition is fundamental to promote nutritional safety. Fructose is the sweetest carbohydrate, and this sweetness, along with its low cost, is the key factor for its use in commercial drinks and sweets. The global average consumption of fructose per capita has increased from 56 g/day in 1986 to 65 g/day in 2007. Experimental models associate high fructose intake with the development of obesity and induced insulin resistance. In recent studies, diabetic patients have been reported to use fructose more frequently than glucose. Fructose acts differently in the hypothalamus and generates less satiety than glucose;thus, fructose has a high lipogenic potential. Replacing fructose with another isocaloric carbohydrate is associated with better glycemic control.

2型糖尿病患者强化血糖控制的利与弊

糖尿病是全球主要的健康问题,治疗花费高,有较高的发病率、致残率和死亡率,显著影响患者生活质量。绝大多数糖尿病患者属于2型糖尿病。从既往研究看,减少2型糖尿病并发症的主要策略是加强血糖控制。然而大量证据表明,除了降低非致死性心肌梗死的发生率外,强化(相对于适度)血糖控制对重要的微血管和大血管并发症预后没有显著获益。但是,严格的血糖控制却会增加严重低血糖的风险,并会增加药物种类、副作用和成本等额外负担。此外,来自心血管结局研究的数据表明,使用特定类别的降糖药可大大改善心血管、肾脏和死亡的结果,而这些效应在很大程度上不是由降糖作用带来的。因此,为2型糖尿病患者提供基于循证医学的、以患者为中心的诊疗,需要转变范式并脱离以血糖为中心的糖尿病管理观点。与其优先考虑加强血糖控制,不如将重点放在确保患者获得足够的糖尿病照护,使血糖目标和患者的目标与情况保持一致,最大程度地减少短期和长期并发症,减轻治疗负担以及改善生活质量上。

Understanding the impact of stress on teleostean reproduction

Fishes exert stress response in a various ways depending on the type of the stressor.The stress responses are activated through a cascade mechanism stimulated by the stressor which involves the hypothalamus-hypophyseal-interrenal(HHI)axis,catecholamines(CA),and gonadotropins.Adaptive stress responses may positively impact the fish survival and reproduction,while continuous or prolonged stress causes adverse effects on the fish reproduction.Corticotropin-releasing factor and adrenocorticotropic hormone are the principal hormones responsible for producing corticosteroids through the HHI axis.Cortisol acts differentially on the stress response as it helps at the early developmental stage;conversely,it impairs the gonadal function.CA have a critical role in maintaining body homeostasis and intermediary metabolism,and they also have a predominant role in reproductive function.Besides hormones,few genetic and epigenetic factors have been identified to understand the molecular responses to stress however,genome-wide associated studies will be initiated to investigate a complete picture of the stress mechanism.Further,recent evidence suggests a growing concern in determining the correlation between the stress hormone level and its associated gene function.Hence,this review highlights the regulation of stress responses in different axes,genetic and epigenetic factors related to stress,and the integration of recent technologies and novel hypotheses to unravel the stress response mechanism in fish reproduction.

钠-葡萄糖共转运蛋白-2抑制剂或胰高血糖素样肽-1受体激动剂治疗成人2型糖尿病:临床实践指南

临床问题对于存在不同心血管风险及肾脏结局的2型糖尿病患者,在原有生活方式干预和/或其他降糖药物的基础上加用钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂的获益及风险是什么?现行做法几十年来,2型糖尿病的治疗决策都以控制血糖为主导。SGLT-2抑制剂和GLP-1受体激动剂在传统观念中常被用于二甲双胍治疗后血糖仍控制不佳的患者。目前这一现状已经发生了改变,这得益于多项临床研究结果。研究显示SGLT-2抑制剂和GLP-1受体激动剂拥有独立于药物降糖作用之外的对于动脉粥样硬化性心血管病(CVD)和慢性肾脏病(CKD)的获益。建议本指南阐述了针对不同风险分层的成人2型糖尿病患者使用SGLT-2抑制剂或GLP-1受体激动剂的建议。•伴有3种或更少的心血管风险因素且不存在CVD或CKD:不建议启动SGLT-2抑制剂或GLP-1受体激动剂治疗。(推荐等级:弱)•伴有3种以上心血管风险因素且不存在CVD或CKD:建议启动SGLT-2抑制剂治疗,不建议启动GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD或CKD:建议启动SGLT-2抑制剂治疗和GLP-1受体激动剂治疗。(推荐等级:弱)•已经存在CVD和CKD:建议启动SGLT-2抑制剂治疗(推荐等级:强)和GLP-1受体激动剂治疗。(推荐等级:弱)•对于那些想要进一步降低CVD和CKD结局风险的患者:推荐优先启用SGLT-2抑制剂治疗而非GLP-1受体激动剂治疗。(推荐等级:弱)这项指南是如何制订的一个由患者、临床医生和方法学家共同组成的国际小组提出了这些推荐意见。这些推荐意见基于可信度较高的指南的标准,并使用GRADE分级方法进行评估。该小组采用了息者个体化的观点。证据一项关于获益与风险的系统综述和网络meta分析(764项随机对照研究,包括421346例参与者)发现SGLT-2抑制剂和GLP-1受体激动剂可以降低总体死亡率、心肌梗死发生率、终末期肾病或肾衰竭的发生率(中等至高等质量的证据)。在不同的亚组中这些药物对卒中、因心力衰竭所致住院和其他主要不良事件有不同的影响。药物绝对获益的程度因患者个体风险的不同有很大的差异。(例如,对于接受了超过5年药物治疗的1000例患者,在最低风险人群中死亡人数减少了5人,在最高风险人群中死亡人数减少了48人)。一项关于预后的综述确认了14种风险预测模型,其中一种(RECODe)在证据总结中报告了大部分基线风险评估数据,小组利用该模型以支持风险分层的建议。考虑到患者的价值观及个体差异,指南推荐的支撑证据包括一项对已发表论文的系统综述、一项患者焦点小组研究、一项临床问题总结,以及一项指南调查。指南解读我们依据不同的CVD和CKD风险水平,综合考虑获益、风险和其他因素的平衡,以及每一个风险组别的实际问题,来对推荐意见进行分层。本指南强烈建议CVD和CKD患者使用SGLT-2抑制剂治疗,这说明专家组认为其具有显著的获益。而对于其他成人2型糖尿病患者,推荐等级较弱,这说明专家组想要在获益、风险及治疗花费上取得一个更好的平衡。临床医生通过该指南可以使用可靠的风险计算模型,如RECODe,来明确其患者的个体心血管和肾脏疾病风险。医患交互式总结临床证据和制订决策有助于患者知晓治疗选择,包括进行共同决策。2型糖尿病人群(全球患病率不断增长1-2)正面临着不断增加的心血管疾病、肾脏病和其他并发症的风险3。数十年来,2型糖尿病的管理始终以控制血糖及糖化血红蛋白(HbA1c)为治疗目标4-5,但是,最近的高质量随机对照研究已经对这种以血糖为中心的治疗模式发起了挑战。研究结果显示,强化血糖控制未必会降低大血管不良事件,它还可能带来不利影响监管机构现在要求新型糖尿病药物必须证明其具有心血管和肾脏获益才能获得批准。对两类新药--钠-葡萄糖共转运蛋白2(SGLT-2)抑制剂和胰高血糖素样肽1(GLP-1)受体激动剂(见框图1)的临床试验结果显示,在现有治疗方案(常规治疗)之上加用这些药物,对死亡、心肌梗死、卒中、心力衰竭和肾脏的结局(如进展为终末期肾病)都有获益8-12。