Issues in the design, analysis, and application of rodent developmental neurotoxicology studies.

Developmental neurotoxicity (DNT) studies could benefit from revisions to study design, data analysis, and some behavioral test methods to enhance reproducibility. The Environmental Protection Agency (EPA) reviewed 69 studies submitted to the Office of Pesticide Programs. Two of the behavioral tests identified the lowest observable adverse effect level (LOAEL) 20 and 13 times, respectively, while the other two tests identified the LOAEL only 3 and 4 times, respectively. The EPA review showed that the functional observational battery (FOB) was least effective at detecting the LOAEL, whereas tests of learning and memory (L&M) had methodological shortcomings. Human neurodevelopmental toxicity studies over the past 30 years show that most of the adverse effects are on higher cognitive functions such as L&M. The results of human studies together with structure-function relationships from neuroscience, suggest that tests of working memory, spatial navigation/memory, and egocentric navigation/memory should be added to guideline studies. Collectively, the above suggest that EPA and EU DNT studies would better reflect human findings and be more relevant to children by aligning L&M tests to the same domains that are affected in children, removing less useful methods (FOB), and using newer statistical models to better account for random factors of litter and litter × sex. Common issues in study design and data analyses are discussed: sample size, random group assignment, blinding, elimination of subjective rating methods, avoiding confirmation bias, more complete reporting of species, housing, test protocols, age, test order, and litter effects. Litter in DNT studies should at least be included as a random factor in ANOVA models and may benefit from inclusion of litter × sex as random factors.

Conjugation as a Highly Sensitive Assay to Study Group II Intron Splicing In Vivo.

Group II introns are noncoding sequences that interrupt genes, and that must be removed or spliced-out at the RNA level during gene expression. Following the transcription of interrupted genes, group II introns self-splice while concurrently ligating their flanking exons to generate mature mRNAs ready for translation. Ll.LtrB, the model group II intron from the gram-positive bacterium Lactococcus lactis, interrupts the gene coding for a relaxase enzyme that initiates the transfer of mobile elements by conjugation. This functional link between group II intron splicing and conjugative transfer enabled us to engineer highly sensitive splicing assays using the native biological context of Ll.LtrB. The splicing efficiency/conjugation assay was developed to determine the splicing competence of various Ll.LtrB mutants, whereas the splicing selection/conjugation assay was established to isolate splicing-proficient variants from a randomly generated bank of mutated introns.

Sex-related and racial variations in orbital floor anatomy.

BACKGROUND: Repair of the orbital floor following trauma or tumor removal remains a challenge because of its complex three-dimensional shape. The purpose of the present study is to understand normal orbital floor anatomy by investigating its differences across four groups (Caucasian American and East Asian, males and females) via facial bone computed tomography (CT). METHODS: A total of 48 orbits in 24 patients between 20 and 60 years of age were evaluated. Although most patients underwent CT scanning following trauma, the orbital walls were intact in all patients. Linear and angular measurements of the orbital floor were obtained from CT images. RESULTS: Orbital floor width, length, angle between the orbital floor and medial wall, and distance from the inferior orbital rim to the lowest point of the orbital floor did not show a statistically significant difference between groups. Angles made by the infraorbital rim, the lowest point of the floor, and the anterior border of the infraorbital fissure were statistically significantly wider in East Asian females than in male groups. The floor depth in East Asian females was significantly smaller compared to all the other groups. CONCLUSION: East Asian female population had smaller curvature and depth of an orbital floor than the other groups, which means racial and sex-related differences should be considered in the orbital floor reconstruction.

Investigating the Molecular Genetic Basis of Cytoplasmic Sex Determination Caused by Wolbachia Endosymbionts in Terrestrial Isopods.

In animals, sexual differences between males and females are usually determined by sex chromosomes. Alternatively, sex may also be determined by vertically transmitted intracellular microbial endosymbionts. The best known cytoplasmic sex manipulative endosymbiont is Wolbachia which can, for instance, feminize genetic males into phenotypic females in the terrestrial isopod Armadillidium vulgare. However, the molecular genetic basis of cytoplasmic sex determination is unknown. To identify candidate genes of feminization induced by Wolbachia strain wVulC from A. vulgare, we sequenced the genome of Wolbachia strain wCon from Cylisticus convexus, the most closely related known Wolbachia strain to wVulC that does not induce feminization, and compared it to the wVulC genome. Then, we performed gene expression profiling of the 216 resulting wVulC candidate genes throughout host developmental stages in A. vulgare and the heterologous host C. convexus. We identified a set of 35 feminization candidate genes showing differential expression during host sexual development. Interestingly, 27 of the 35 genes are present in the f element, which is a piece of a feminizing Wolbachia genome horizontally transferred into the nuclear genome of A. vulgare and involved in female sex determination. Assuming that the molecular genetic basis of feminization by Wolbachia and the f element is the same, the 27 genes are candidates for acting as master sex determination genes in A. vulgare females carrying the f element.

Comparison of Thigh Muscle Strain Occurrence and Injury Patterns Between Male and Female High School Soccer Athletes.

CONTEXT: Thigh muscle strains are among the most common injuries in high school soccer for both males and females. Similar results have been reported among college soccer players, specifically for hamstring strains. In college soccer, males have a higher injury rate than women, although they share common injury characteristics. Currently, no studies exist comparing the injury rate or injury characteristics of thigh muscle strains between sexes playing high school soccer. OBJECTIVE: To compare thigh muscle strain injury rates and injury event characteristics among sexes participating in high school soccer. DESIGN: Descriptive epidemiology study. SETTING: A total of 100 nationally representative high schools that participated in the High School Sports-Related Injury Surveillance System, Reporting Information Online. PARTICIPANTS: High school soccer athletes who had a thigh muscle strain. MAIN OUTCOME MEASURES: Injury rates of thigh muscle strains were calculated between sexes. The occurrence of the following variables during a thigh muscle injury was compared between sexes: grade level, age, level of play, event type, time of practice, time of competition, basic injury mechanism, soccer activity, player position, field location, practice type, and time of season. RESULTS: Males had a lower injury rate of thigh muscle strains during competition than females (rate ratio = 0.66; 95% confidence interval, 0.47-0.93). No differences between sexes existed in the distribution of first-time or recurrent event characteristics. When combining sexes, recurrent strains (93%) occurred more frequently on the offensive side of the field than first-time strains (59%), P < .001. The majority of strains occurred among the varsity players (71%), during running activities (60%) and practices (58%). CONCLUSIONS: Males were less likely to sustain a thigh muscle strain during competitions, but no other differences existed between sexes. The events surrounding all thigh muscle strains may be described with some common properties. Consideration of these characteristics may assist in the development of preventive and rehabilitative programs as well as direct future research on thigh muscle strains among high school soccer players.

Risk factors and etiology in young adults with ischemic stroke / 国际脑血管病杂志

Objective To investigate the risk factors and etiology in young adults with ischemic stroke.Methods From June 2014 to June 2017,consecutive patients with first-ever ischemic stroke aged from 18 to 45 years and admitted to the Department of Neurology,the Third People's Hospital of Chengdu were collected retrospectively.The demographic data,vascular risk factors,National Institutes of Health Stroke Scale score,location of infarction,and etiological subtypes were documented.They were divided into either a male group or a female group according to the gender,and they were divided into 2 age groups of 18-35 years and 36-45 years.Results A total of 103 young adults with ischemic stroke were enrolled during the study.Among them,the proportion of men was higher than that of women (73.8％ vs.26.2％).The most common 5 risk factors were smoking,abnormal lipid metabolism,drinking alcohol,hypertension,and large atherosclerosis,respectively.The proportions of abnormal glucose metabolism (37.2％ vs.11.8％),hypertension (46.5％ vs.11.8％),and large artery atherosclerosis (37.2％ vs.11.8％) in the age group of 36-45 years were significantly higher than those in the age group of 18-35 years (all P＜0.05).The proportions of smoking (67.1％ vs.14.8％) and drinking alcohol (51.3％ vs.18.5％) in the male group were significantly higher than those in the female group (all P＜ 0.05).In the etiological aspect,the proportion of cryptogenic stroke in the age group of 18-35 years was significantly higher than that in the age group of 36-45 years (47.1％ vs.15.1％;P=0.006),while the proportion of the large artery atherosclerotic stroke was significantly lower than that in the age group of 36-45 years (11.8％vs.41.9％;P =0.019).There were no significant differences in the etiological subtypes between different sex groups.Conclusion The distribution of risk factors and etiological subtypes in young patients with ischemic stroke have some differences in different gender and age groups.Some common modifiable risk factors (such as smoking,drinking,abnormal lipid metabolism,etc.) still account for a higher proportion in young adults with ischemic stroke.

Single- and Multiple-Dose Trials to Determine the Pharmacokinetics, Safety, Tolerability, and Sex Effect of Oral Ginsenoside Compound K in Healthy Chinese Volunteers.

Background and objectives: Ginsenoside compound K (CK) is a candidate drug for rheumatoid arthritis therapy. The objective of this study was to investigate the pharmacokinetic properties, safety and tolerability of CK. Methods: In randomized, double-blind trials, 76 healthy Chinese subjects received 1 of 7 single oral doses (25, 50, 100, 200, 400, 600, 800 mg) of CK or placebo under fasting condition, and another 36 subjects received repeated oral doses (100, 200, or 400 mg) of CK or placebo for up to 9 days a week after a corresponding single dose, after breakfast. Both sexes were equally represented in the two trials. Pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD) were calculated and statistically analyzed according to the plasma concentration data. Tolerability was evaluated by adverse events (AEs) and laboratory examinations. Results: The range of time to maximum concentration (Tmax) was 1.5-6.0 h, with a linear increase in the exposure of CK over the dose range of 100-400 mg. Steady state was reached after the 7th administration, and the accumulation index range was 2.60-2.78. Sex differences were characterized by a higher exposure in females than males with the single administration after breakfast. In addition, no severe AEs were observed. Conclusion: CK was safe and well-tolerated over the treatment period. The sex- and food-related impacts on CK pharmacokinetics need further investigations to be validated. (Registration number: ChiCTR-TRC-14004824 and ChiCTR-IPR-15006107, http://www.chictr.org.cn/index.aspx).

A Report on Diabetic Foot and Amputation from the Korean Health Insurance Review & Assessment Service Data / 대한족부족관절학회지

PURPOSE: This study reports on limb amputations in diabetic patients according to gender, age, and region based on the data from the Korean Health Insurance Review & Assessment Service. MATERIALS AND METHODS: The number of amputations was compared by region, age, gender, and year, as well as by femoral region, lower leg, foot, and toe in diabetic patients who received limb amputation. This analysis was performed based on the data from the Korean Health Insurance Review & Assessment Service, between January 2009 and December 2014. RESULTS: The total number of amputations between the study period was 9,155. The number of patients who were treated at hospitals for diabetes in 2009 was 1.9 million, among which, 1,214 patients underwent amputation. In 2014, the incidence of diabetes was 1,747 in 2.58 million individuals. With this rising incidence of diabetes, the amputation of limbs due to diabetes is increasing every year. In particular, the following regions were amputated more often: femoral region, 2.3%; lower legs, 19.6%; feet, 18.1%; and toes 60.0%. Regarding gender differences, males showed a higher amputation rate than females for all body parts. With respect to region, Seoul was the highest with 30.2%, followed by Gyeonggi with 19.9%, and Busan with 8.8%. According to age, older age showed greater diabetic amputation rate. CONCLUSION: In accordance with the rising incidence of diabetes, the diabetic amputation is also increasing. Here, we showed that toes were amputated with the highest percentage and males had greater amputation rate than females for all body parts. Moreover, amputation rate was highest in older diabetic patients, especially for those in their seventies. Additionally, Seoul was the region with highest amputation rate.

Effects of gender on screening value of aldosterone-renin ratio for primary aldosteronism / 解放军医学杂志

Objective To explore the potential influence of gender on screening value of aldosterone-renin ratio (ARR) for primary aldosteronism (PA).Methods The biochemical parameters were collected of 451 PA patients and 300 essential hypertension (EH) patients who were diagnosed in the General Hospital of PLA from 1992 to 2014. Each group was then divided into two groups by gender. The clinical characteristics were compared and then the receiver operating characteristic curve (ROC) was conducted to evaluate the best cut-off value.Results The plasma aldosterone concentration (PAC), serum sodium and ARR were much higher, but the plasma rennin activity (PRA), serum potassium and BMI were much lower in PA patients than in EH patients (P0.05). The best cut-off value of ARR in male PA patients was 19.11, the relevant area under the curve (AUC) was 0.968, the sensitivity and specicantcity was 92.44% and 93.08%, and the Youden index (YI) was 0.86. The best cut-off value of ARR in female PA patients was 27.26, with AUC 0.956, sensitivity 92.07%, specicantcity 90.00% and YI 0.82, respectively. If the cut-off value was set at 27.26 in males, the specicantcity would rise a little, but the sensitivity and YI would sharply decrease. Similarly, the sensitivity would increase a little but the specicantcity and YI would fall substantially if the cut-off value in females was set at 19.11. The best cut-off value of ARR in men was smaller than the ocantcial value recommended by guidelines.Conclusion Gender is an important factor should be considered while ARR is used in PA screening, and the cut-off value of ARR in screening female PA patients should be setting higher.

The Clinical Significance of Ulnar Artery Morphology in Artificial Arterial-Venous Fistula for Hemodialysis.

BACKGROUND: The ulnar artery is a terminal branch of the brachial artery. The aim of this study is to provide comprehensive data concerning the morphology of the ulnar artery, with clinical implications for surgeons. METHODS: The current study includes the dissection of 68 upper limb specimens. It investigates the characteristics of the ulnar artery such as the internal diameter, external diameter, wall thickness, and distance of the ulnar artery origin. RESULTS: In this study, the ulnar artery arose distal to the superior margin of the head of the radius in 82.65% of cases. The angle degree of the ulnar artery with respect to the brachial artery ranges from to 8° to 30°. The internal and external diameters of the ulnar artery were found to decrease gradually from proximal to distal in both genders. The external and internal diameters of the ulnar artery are greater in males than in females. In all cases, the external and internal diameters and the thickness of the ulnar artery at three levels were found to be greater in the right ulnar artery than the left. CONCLUSION: The right ulnar artery may be the appropriate choice for artificial arterial-venous fistula for haemodialysis. Due to its wide diameter, the proximal part of the radial artery is a suitable site for the artificial arterial-venous fistula immediately below the origin prior to its profound course. Therefore, it is an easy access for artificial arterial-venous fistula for surgeons. The radiologists must alert the surgeons for surgical modification in the case of high brachial bifurcation.

Old lesbians: Gendered histories and persistent challenges.

AIM: This article provides an overview of how gender and historical contexts influence the well-being of old lesbians. It aims to inform the practice of aged care providers in addressing the needs of these women. METHODS: The lived experience of old lesbians is examined using feminist methodology with a focus on hegemonic femininity, social structures and cultural life. RESULTS: Old lesbians being selectively 'open', their use of health services and desire for lesbian-specific aged care are all influenced by lesbophobia, a complex of discriminations. The age women began living as lesbian and fluidity of orientation, are central to understanding their particular needs. Many old lesbians have created social groups and intentional communities where there is support and freedom. CONCLUSION: The current 'inclusivity' approach is insufficient for culturally appropriate aged care for old lesbians. Developing practices that meet their needs requires better understanding of lesbians' different life courses and why they created lesbian cultures.

The Clinical Significance of Ulnar Artery Morphology in Artificial Arterial-Venous Fistula for Hemodialysis

Background: The ulnar artery is a terminal branch of the brachial artery. The aim of this study is to provide comprehensive data concerning the morphology of the ulnar artery, with clinical implications for surgeons. Methods: The current study includes the dissection of 68 upper limb specimens. It investigates the characteristics of the ulnar artery such as the internal diameter, external diameter, wall thickness, and distance of the ulnar artery origin. Results: In this study, the ulnar artery arose distal to the superior margin of the head of the radius in 82.65% of cases. The angle degree of the ulnar artery with respect to the brachial artery ranges from to 8° to 30°. The internal and external diameters of the ulnar artery were found to decrease gradually from proximal to distal in both genders. The external and internal diameters of the ulnar artery are greater in males than in females. In all cases, the external and internal diameters and the thickness of the ulnar artery at three levels were found to be greater in the right ulnar artery than the left. Conclusion: The right ulnar artery may be the appropriate choice for artificial arterial-venous fistula for haemodialysis. Due to its wide diameter, the proximal part of the radial artery is a suitable site for the artificial arterial-venous fistula immediately below the origin prior to its profound course. Therefore, it is an easy access for artificial arterial-venous fistula for surgeons. The radiologists must alert the surgeons for surgical modification in the case of high brachial bifurcation

Impact of the apolipoprotein E polymorphism, age and sex on neurogenesis in mice: pathophysiological relevance for Alzheimer's disease?

Apolipoprotein E (ApoE) is found in three different forms in humans (ApoE2, ApoE3 and ApoE4), and ApoE polymorphism is recognized as a major risk factor for Alzheimer's disease (AD). ApoE is involved in lipid and cholesterol transport, cell repair, and amyloid-ß deposition and certain studies suggest potential implications in neurogenesis. In this regard, we investigated the possible impact of the three different human ApoE isoforms on neurogenesis. We used ApoE knock-in mice of different ages and sex, and quantified newborn cells in the hippocampus by flow cytometry. Young adult ApoE4 mice (10-12 week-old) from both sexes displayed reduced neurogenesis compared with wild-types and the other genotypes. In addition, young adult ApoE2 female mice showed improved hippocampal progenitor cell proliferation. In older mice (1 year), hippocampal neurogenesis was globally decreased, particularly in females, and the difference between ApoE4 and the other genotypes observed in young animals disappeared for the two sexes, except for aged ApoE3 females. Indeed, a surprising protective effect of the ApoE3 genotype was observed in aged females. Our study highlights the role of ApoE in neurogenesis, and shows for the first time an early inequality between the ApoE genotypes. The reduced neurogenesis observed for the ApoE4 genotype and the improved results obtained in young ApoE2 females support the idea of a difference in the balance between neuronal birth and death modulated by the ApoE polymorphism in young animals. The maintenance of this balance and its modulation can influence pathophysiological mechanisms predisposing to neurodegenerative diseases like AD.

Effects of gender on pharmacokinetics of propofol / 中华麻醉学杂志

Objective To evaluate the effects of gender on the pharmacokinetics of propofol in patients.Methods Twenty ASA physical status Ⅰ or Ⅱ patients of both sexes (10 male,10 female),aged 42-59 yr,weighing 46-76 kg,scheduled for elective surgery for gastrointestinal cancer,were randomly divided into 2 gender groups (n =10 each):male group and female group.Combined intravenous-inhalational anesthesia was performed during surgery.Anesthesia was induced with iv injection of 2％ propofol 2 mg/kg,remifentanil 1.5 μg/kg,and suxamethonium chloride 1.5 mg/kg.The patients were tracheally intubated and mechanically ventilated.Anesthesia was maintained with inhalation of the mixture of 1％-2 ％ isoflurane and nitrous oxide (N2 O ∶ O2 =1 ∶ 1.),iv infusion of remifentanil 0.2-0.3 μg/kg and intermittent iv boluses of atracurium.Blood samples were taken from the central vein before propofol administration,and at 1,2,3,4,6,10,15,30,45,60,90,120,180,240,360 and 720 min after propofol administration for determination of the plasma concentration of propofol by high-performance liquid chromatography.The blood concentration-time curve of propofol was drawn and the pharmacokinetic parameters were calculated.Results The blood concentrations of propofol were significantly lower at each time points within 10 rmin after administration of the single bolus of propofol in female group than in male group (P ＜0.05).The blood concentration-time curves of propofol were fitted to a three-compartment open model in the 2 groups.The central volume of distribution and clearance rate were significantly larger in female patients than in male patients (P ＜ 0.05).Conclusion After iv injection of propofol,the blood concentration of propofol is lower,and the central volume of distribution and clearance rate are larger in female than in male,suggesting that gender has significant effect on pharmacokinetics of propofol.