Childhood Sex-Typed Behavior and Gender Change in Individuals with 46,XY and 46,XX Disorders of Sex Development: An Iranian Multicenter Study

Disorders of sex development (DSD) are congenital conditions in which the typical genetic and hormonal profiles are affected and thereby the usual process of sexual differentiation. Most of these studies, however, have been conducted in Western countries. In the present study, preschool sex-typed activities of Iranian individuals with DSD and their age-matched non-affected male and female relatives were assessed using the Pre-School Activities Inventory (PSAI) modified for retrospective self-report. A total of 192 individuals participated in our study, including 33 46,XX individuals with congenital adrenal hyperplasia (CAH; M age?=?10.36, SD?=?5.52), 15 46,XY individuals with complete androgen insensitivity syndrome (CAIS; M age?=?19.8, SD?=?7.14), and 16 46,XY individuals with 5-alpha reductase deficiency type-2 (5α-RD-2; M age?=?17.31, SD?=?7.28), as well as one age-matched non-affected male and female relative for each patient. With regard to PSAI scores, male-identifying participants with 5α-RD-2 and male controls reported similar levels of male-typical childhood play. Female-identifying participants with 5α-RD-2 and CAH showed comparable scores: significantly less masculine and more feminine than male controls, but significantly more masculine and less feminine than females with CAIS and female controls. These findings support the role of androgens in the development of sex-typical childhood play behavior, with those being exposed to higher levels of fetal functional androgens expressing more masculine behavior at preschool ages.     

Consistent and precise localization of brain activity in human primary visual cortex by MEG and fMRI

The tomographic localization of activity within human primary visual cortex (striate cortex or V1) was examined using whole-head magnetoencephalography (MEG) and 4-T functional magnetic resonance imaging (fMRI) in four subjects. Circular checkerboard pattern stimuli with radii from 1.8 to 5.2 degrees were presented at eccentricity of 8 degrees and angular position of 45 degrees in the lower quadrant of the visual field to excite the dorsal part of V1 which is distant from the V1/V2 border and from the fundus of the calcarine sulcus. Both fMRI and MEG identified spatially well-overlapped activity within the targeted area in each subject. For MEG, in three subjects a very precise activation in V1 was identified at 42 ms for at least one of the two larger stimulus sizes (radii 4.5 and 5.2 degrees ). When this V1 activity was present, it marked the beginning of a weak wave of excitations in striate and extrastriate areas which ended at 50 ms (M50). The beginning of the next wave of activations (M70) was also marked by a brief V1 activation, mainly between 50 and 60 ms. The mean separation between V1 activation centers identified by fMRI and the earliest MEG activation was 3-5 mm.     

Effectiveness of an interprofessional education model based on the transtheoretical model of behaviour change to improve interprofessional collaboration

This study aimed to assess the effectiveness of an interprofessional education model (IPE) based on the transtheoretical model to improve the participants’ interprofessional collaborative practice. The study was conducted in Iran using a controlled before-and-after study design. The participants (n = 91) were the residents of emergency medicine and nurses of the emergency units from two teaching hospitals affiliated to Iran University of Medical Sciences. The participants in the intervention group (n = 40) were 22 residents and 18 nurses. The control group (n = 51) consisted of 20 residents and 31 nurses. The participants were classified based on their stage of readiness to change. The interventions were two-day workshops for each stage (i.e., attitude and intention). We used the Interprofessional Collaborator Assessment Rubric (ICAR) to assess the effectiveness of the developed model. The interprofessional collaboration of the participants in the intervention and control groups was assessed at four time points before and after the intervention in the real emergency unit environment. Student’s t-test and repeated measures analysis of variance (RM-ANOVA) were used to analyse the data. We used partial eta-squared (η²) for effect size calculations. The mean values of ICAR scores in the intervention and control groups were 95.63 ± 19.14 and 89.19 ± 16.11 before the intervention. The mean values of ICAR scores at 3 months after the intervention were 99.82 ± 22.32 and 88.29 ± 16.87 in the intervention and control groups, respectively. After 6 months, the mean values of ICAR scores of the intervention and control groups were 98.6 ± 23.40 and 87.98 ± 16.01, respectively. The results showed that the intervention had a medium educational effect size (partial η² = 0.06) on performance of the participants. Our results showed that an IPE model that is tailored to the learners’ stage of readiness to change improves interprofessional collaboration in the participants. The developed model could be applied for improving interprofessional collaborative performance in other IPE programmes.     

Variants in FIX propeptide associated with vitamin K antagonist hypersensitivity: functional analysis and additional data confirming the common founder mutations

One of the most common and unwanted side effects during oral anticoagulant therapy (OAT) is bleeding complications. In rare cases, vitamin K antagonist (VKA)-related bleeding events are associated with mutations affecting the F9 propeptide at amino acid position 37 due to a substitution of alanine to either valine or threonine. Based on our actual cohort of 18 patients, we update the knowledge on this rare phenotype and its origin. A founder mutation for both variants was reconfirmed by haplotype analysis of intronic and extragenic short tandem repeat (STR) polymorphisms with a higher prevalence in Switzerland than in other regions of Europe. Screening of healthy individuals for the presence of these F9 gene mutations did not identify any of these variants, thus proving the rare occurrence of this genotype. Furthermore, both variants were expressed in vitro and warfarin dose responses were studied. Our warfarin dose response analysis confirmed higher sensitivity of both variants to warfarin with the effect being more apparent for Ala37Thr. Thus, although F9 propeptide mutation-associated hypersensitivity to VKA is a rare phenomenon, awareness towards this bleeding phenotype is important to identify patients at risk.     

Unicompartmental and bicompartmental knee osteoarthritis show different patterns of mononuclear cell infiltration and cytokine release in the affected joints

It is still controversial which cell types are responsible for synovial inflammation in osteoarthritic (OA) joints. The aim of this study was to quantify the mononuclear cell populations and their cytokines in patients with different knee OA subtypes. Synovial membrane (SM), synovial fluid (SF) and peripheral blood (PB) were harvested from patients with unicompartmental (UC) and bicompartmental (BC) knee OA. Frequencies of mononuclear cells were assessed by flow cytometry in PB and SM. Naive SF samples were analysed for a broad variety of cytokines by multiplex analysis. SM of both groups displayed a distinct mononuclear cell infiltration, with CD14⁺ macrophages being the major cell population, followed by CD4⁺ T cells and only small numbers of CD8⁺ T, CD19⁺ B and CD16⁺CD56⁺ natural killer (NK) cells. Between the two groups, SM of BC OA showed significantly higher amounts of mononuclear cells (135·7 ± 180 versus 805 ± 675 cells/mg, P = 0·0009) and higher CD4⁺ T cell presence (3·4 ± 4·6 versus 9·1 ± 7·5%, P = 0·0267). SF of BC OA displayed significantly higher concentrations for a number of proinflammatory cytokines [CXCL1, eotaxin, interferon (IFN)‐γ, interleukin (IL)‐7, IL‐8, IL‐9, IL‐12]. UC and BC OA show significant differences in their synovial inflammatory pattern. Whereas in UC OA CD14⁺ macrophages are the predominant cell population, BC OA has a higher inflammatory profile and seems to be driven by CD14⁺ macrophages and CD4⁺ T cells. Inclusion of clinical information into the analysis of cellular and molecular results is pivotal in understanding the pathophysiology of OA.     

Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer

Purpose

According to previous studies, vitamin D exhibits protective effects against breast cancer via the vitamin D receptor (VDR). There is growing evidence that breast cancer incidence is associated with various polymorphisms of the VDR gene. This study investigates the association of VDR poly(A) microsatellite variants with 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk.

Methods

Polymorphism analysis was performed on a total of 261 blood samples, which were collected from 134 women with breast cancer and 127 controls. Single strand conformation polymorphism was assessed by polymerase chain reaction in combination with sequencing to detect poly(A) lengths for each sample. The vitamin D levels of samples were determined by electrochemiluminescence.

Results

The poly(A) variant L allele frequency was significantly higher in cancer patients than in controls (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.16-2.57; p=0.006). Thus, carriers of the L allele (LS and LL genotypes) have a higher risk for breast cancer (OR, 1.86; 95% CI, 1.13-3.05; p=0.013). A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels.

Conclusion

The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.     

Novel in Vitro Efficiency of Chitosan Biomolecule against Trichomonas gallinae

Background

Development of new natural agents for parasitic diseases treatment has unexpectedly increased to overcome effectively against emergence and re-emergence of parasitic diseases, the appearance of drug resistant organisms and toxic side effects of current agents. The aim of the study was to evaluate antiprotozoal activities of chitosan biomolecule on trophozoites of Trichomonas gallinae.

Methods

The antitrichomonal activity of various low molecular weight chitosan concentrations including 125, 250, 500 and 1250 µg ml⁻¹ against T. gallinae trophozoites cultured in trypticase-yeast extract-maltose medium supplemented with heat-inactivated cold horse serum was evaluated in vitro. Samples containing medium without chitosan were also assayed as controls.

Results

The mortality rates at 0, 3 and 6 h post treatment with all concentrations were significantly different from control group (P<0.05). Treated trophozoites showed more susceptibility to the highest concentration reaching mortality rate of 100% at 3h post inoculation. However, at this time, results for 125, 250 and 500 µg ml⁻¹ were 93%, 95% and 96.7%, respectively.

Conclusion

The results demonstrate that the application of chitosan biomolecule is a promising option for treatment of trichomoniasis in pigeons.     

Significance of albumin and C-reactive protein variations in 300 end stage renal disease patients in Tehran University of Medical Sciences Hospitals during year 2010

Protein- energy malnutrition, wasting and inflammation are frequent complication among patients with end-stage renal disease (ESRD). Malnutrition is associated with cardiac co-morbidity, inflammation and poor survival in ESRD patients. Serum albumin is a well-known marker of nutrition in ESRD patients. Serum albumin is still the most commonly used nutritional marker in ESRD patients. C-reactive protein (CRP), the major acute phase response (APR) protein is elevated in these patients. High CRP levels are linked to the degree of atherosclerosis in coronary, peripheral, and extracranial brain arteries. The aim of the present study was to investigate nutritional factor (albumin) and CRP levels in ESRD patients. In this cross- sectional study a total of 300 patients who had ESRD and had been on hemodialysis treatment for at least 6 months were selected. The laboratory tests consisted of measurement of CRP and albumin using high sensitive ELISA kits. The study patients included 157 males (52.3%) and 143 females (47.7%) with average age of 41.5 ± 14.3 years. Mean CRP level was 7.96 mg/ dl (±1.52), mean serum albumin was 4.07 g/dl (±0.19).Of 300 patients, 21 died (7%). These were patients with serum albumin <4 g/dl and CRP>9.5 mg/dl. This study showed that low albumin and high CRP levels are the main predictors for death. There was a significant difference between CRP and albumin levels in ESRD patients (P<0.0001). Measuring CRP as a marker of inflammation can be helpful in managing these patients.     

Detection of West Nile virus genome and specific antibodies in Iranian encephalitis patients

West Nile virus (WNV) is a mosquito-borne flavivirus which circulates in birds, horses and humans. An estimated 80% of WNV infections are asymptomatic. Fewer than 1% of infected persons develop neuroinvasive disease, which typically presents as encephalitis, meningitis, or acute flaccid paralysis. This study was conducted from January 2008 to June 2009 in Isfahan, Iran. Patients attending the emergency department with fever and loss of consciousness were consecutively included. Cerebrospinal fluids (CSF) were initially analysed through bacteriology and biochemistry examinations, resulting in those with evidence of meningitis being excluded. Patients' CSF and serum were diagnosed by serological and molecular assays. A total of 632 patients with fever and loss of consciousness were tested by CSF analyses. Samples of the remaining patients (39·4%) were referred for WNV investigation. Three (1·2%) of the patients were positive for both serum and CSF by RT-PCR, and six (2·4%) were positive only for IgG antibodies. History of insect bite, and blood transfusion and transplantation were risk factors for being positive by RT-PCR (P=0·048) and being IgG positive (P=0·024), respectively. The results of this study showed that the prevalence of West Nile fever is low in patients with encephalitis.