Interleukins-6 and −8 Levels in Sera and Cervical Mucus of Fertile,Idiopathic Infertile,and Immunoinfertile Women: Implication in Infertility

PROBLEM: The purpose of this study was to investigate the levels of interleukin-6 and ?8 (IL-6 and IL-8) in sera and cervical mucus of infertile (idiopathic and immunoinfertile) women and to compare the levels with those in age-matched normally cycling fertile women. METHODS: Levels of IL-6 and IL-8 were measured in the sera and cervical mucus of fertile and infertile women by the enzyme-linked immunosorbent assay (ELISA). A non-parametric Mann-Whitney test was used to evaluate significance between the means. Linear regression analysis of IL-6 and IL-8 concentrations in serum versus cervical mucus and with antisperm antibody titers was performed by condition as well as all groups together. P < 0.05 was considered significant. RESULTS: Both IL-6 and IL-8 were detected in sera and cervical mucus of fertile as well as infertile groups. Although serum levels of IL-6 and IL-8 were significantly different between fertile and infertile groups, the differences were more pronounced in the cervical mucus samples. Cervical mucus of idiopathic and immunoinfertile women demonstrated significantly (P = 0.002 to < 0.0001) greater concentrations of IL-6 and IL-8 compared to fertile controls. In general, there was no significant correlation between the serum and cervical mucus IL-6 and IL-8 levels, whether analyzed by condition or all groups together. CONCLUSIONS: Elevated levels of IL-6 and IL-8 in cervical mucus of infertile groups may play a role in etiology of idiopathic and immunologic infertility. These findings suggest that the measurements of cytokines (especially IL-6 and IL-8) in cervical mucus may provide a tool for specific diagnosis and possibly treatment of infertility, especially idiopathic infertility.     

Presence of antibodies to sperm YLP(12) synthetic peptide in sera and seminal plasma of immunoinfertile men

Using an enzyme-linked immunosorbent assay (ELISA), sera (n = 15) and seminal plasma (n = 30) from antisperm antibody-positive immunoinfertile men (n = 45) and from fertile men (n = 45), were tested for the immunoreactivity with the synthetic YLP(12) sperm peptide. Of the 15 immunoinfertile sera tested, 46% were positive for immunoglobulin (Ig)M, 73% for IgG, and 40% for IgA. Of the 30 samples of immunoinfertile seminal plasma tested, 10% were positive for IgM, 20% for IgG, and 43% for IgA. None of the sera or seminal plasma from fertile men showed a positive reaction. There was no significant correlation between the sperm immobilization technique (SIT) or tray agglutination technique (TAT) titres or percentage binding in immunobead binding technique (IBT) and the antibody reactivity for any class in the ELISA. The YLP(12) peptide conjugated to bovine serum albumin-Sepharose 4B beads pulled out IgG antibodies from the serum of the immunoinfertile, but not the fertile, men. The beads pulled out IgA antibodies from the immunoinfertile, but not the fertile, seminal plasma. The immuno-affinity purified antipeptide antibodies reacted with a specific band of 72 +/- 5 kDa in the human testis and with a specific band of approximately 50 +/- 5 kDa in the human sperm extracts. The YLP(12) peptide may have applications in the specific diagnosis and treatment of male infertility and in contraceptive vaccine development.     

The influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis

OBJECTIVE: To investigate the influence of age at symptom onset and length of followup on mortality in patients with recent-onset inflammatory polyarthritis (IP), and to examine predictors of mortality in relation to disease duration. METHODS: From 1990 to 1994, patients with recent-onset IP were registered with the Norfolk Arthritis Register (NOAR) and followed up prospectively. Standardized mortality ratios (SMRs) were calculated for all-cause and cardiovascular disease (CVD) mortality and for those who were younger than age 55 years at disease onset and for the first 5 and 10 years of followup. Cox proportional hazards models were developed to assess predictors of early and later mortality. RESULTS: Of 1,098 patients, 224 (20%) had died by the end of 2004. All-cause and CVD mortality were increased in rheumatoid factor (RF)-positive patients and in this subgroup, CVD mortality was increased at both early and later followup (SMR 5-year followup 1.93 [95% confidence interval 1.08-3.19]; SMR 10-year followup 2.00 [95% confidence interval 1.37-2.80]). CVD mortality was highest in seropositive patients<55 years of age at disease onset (SMR 5.58 [95% confidence interval 2.24-11.50]). In multivariate models, age at onset, male sex, RF positivity, Health Assessment Questionnaire score>or=1.5, and nodules were predictors of early and later mortality. CONCLUSION: Patients with IP had higher rates of CVD mortality throughout the followup period studied, and this was highest in seropositive patients who were <55 years of age at symptom onset. This subgroup deserves particular attention in terms of disease and risk factor modification. Nodules were independent predictors of CVD mortality, suggesting that extraarticular/vascular inflammation identifies patients at particularly high CVD risk.     

Comparative effects of estradiol, methyl-piperidino-pyrazole, raloxifene, and ICI 182 780 on gene expression in the murine uterus

Selective estrogen receptor modulators (SERMs) are potentially useful in treating various endometrial disorders, including endometrial cancer, as they block some of the detrimental effects of estrogen. It remains unclear whether each SERM regulates a unique subset of genes and, if so, whether the combination of a SERM and 17beta-estradiol has an additive or synergistic effect on gene expression. We performed microarray analysis with Affymetrix Mouse Genome 430 2.0 short oligomer arrays to determine gene expression changes in uteri of ovariectomized mice treated with estradiol (low and high dose), methyl-piperidino-pyrazole (MPP), ICI 182 780, raloxifene, and combinations of high dose of estradiol with one of the SERM and dimethyl sulfoxide (DMSO) vehicle control. The nine treatments clustered into two groups, with MPP, raloxifene, and high dose of estradiol in one, and low dose of estradiol, ICI + estradiol, ICI, MPP + estradiol, and raloxifene + estradiol in the second group. Surprisingly, combining a high dose of estradiol with a SERM markedly increased (P<0.02) the number of regulated genes compared with each individual treatment. Analysis of expression for selected genes in uteri of estradiol and SERM-treated mice by quantitative (Q)RT-PCR generally supported the microarray results. For some cancer-associated genes, including Klk1, Ihh, Cdc45l, and Cdca8, administration of MPP or raloxifene with estradiol resulted in greater expression than estradiol alone (P<0.05). By contrast, ICI 182 780 suppressed more genes governing DNA replication compared with MPP and raloxifene treatments. Therefore, ICI 182 780 might be superior to MPP and raloxifene to treat estrogen-induced endometrial cancer in women.     

Infections in travellers returning to Turkey from the Arabian peninsula: a retrospective cross-sectional multicenter study

Mass gatherings pooling people from different parts of the world—the largest of which is to Mecca, Saudi Arabia, for Hajj—may impose risks for acquisition and dissemination of infectious diseases. A substantial number of pilgrims to Hajj and Umrah are Turkish citizens (456,000 in 2014) but data are lacking on scale of the problem. We did a retrospective cross-sectional multicenter study in Turkey to explore the range of infections among inpatients who had recently returned from the Arabian Peninsula. Our inclusion criteria were patients who had acquired an infection during their trip to an Arabian Peninsula country, or who became symptomatic within 1 week of their return. The data were collected retrospectively for January 1, 2013 and March 1, 2015. 185 Turkish patients were recruited to the study across 15 referral centers with travel associated infectious diseases after returning from Arabian Peninsula countries (predominantly Saudi Arabia 163 [88.1 %] for religious purposes 162 [87.5 %]). Seventy four (40.0 %) of them were?≥?65 years old with numerous comorbidities including diabetes (24.3 %) and COPD (14.1 %). The most common clinical diagnosis was respiratory tract infections (169 [91.5 %]), followed by diarrheal diseases (13 [7 %]), and there was one case of MERS-CoV. Patients spent a median of 5 (3–7) days as hospital inpatients and overall mortality was 1.1 %. Returning travellers from the Arabian Peninsula present as inpatients with a broad range of infectious diseases similar to common community acquired infections frequently seen in daily medical practices in Turkey.     

Etiology of acute viral respiratory infections common in Pakistan: A review

Respiratory infections, especially those of the lower respiratory tract, remain a foremost cause of mortality and morbidity of children greater than 5 years in developing countries including Pakistan. Ignoring these acute‐level infections may lead to complications. Particularly in Pakistan, respiratory infections account for 20% to 30% of all deaths of children. Even though these infections are common, insufficiency of accessible data hinders development of a comprehensive summary of the problem. The purpose of this study was to determine the prevalence rate in various regions of Pakistan and also to recognize the existing viral strains responsible for viral respiratory infections through published data. Respiratory viruses are detected more frequently among rural dwellers in Pakistan. Lower tract infections are found to be more lethal. The associated pathogens comprise respiratory syncytial virus (RSV), human metapneumovirus (HMPV), coronavirus, enterovirus/rhinovirus, influenza virus, parainfluenza virus, adenovirus, and human bocavirus. RSV is more dominant and can be subtyped as RSV‐A and RSV‐B (BA‐9, BA‐10, and BA‐13). Influenza A (H1N1, H5N1, H3N2, and H1N1pdm09) and Influenza B are common among the Pakistani population. Generally, these strains are detected in a seasonal pattern with a high incidence during spring and winter time. The data presented include pneumonia, bronchiolitis, and influenza. This paper aims to emphasise the need for standard methods to record the incidence and etiology of associated pathogens in order to provide effective treatment against viral infections of the respiratory tract and to reduce death rates.     

Influence of single‐nucleotide polymorphisms in the IFNG towards susceptibility to tuberculosis in a Pakistani population

Tuberculosis (TB) is a global issue as one‐third of the population worldwide is considered to be infected. TB has become a critical public health problem as a result of increasing drug resistance, which poses a challenge to current control strategies. Similar to environmental factors, genetic makeup of the host equally contributes to disease onset. We performed genotypic analysis to examine the relationship between IFNG and TB onset and drug resistance in a Pakistani population comprising 689 subjects. Notable differences were observed in the IFNG polymorphism (+874T/A) between the case and control groups. The frequency of the wild‐type genotype (TT) in the controls (43.2%) was significantly higher than in the cases (25.3%) (odds ratio [OR] = 0.77, p < 0.0001), while the mutant genotype frequency (AA) (38.57%) in the cases was significantly higher than in the controls (22.6%) (OR = 1.46, p < 0.0001). The heterozygous genotype frequency (TA) did not significantly differ between the control and case groups. Compared with the controls, the variant allele (A) was approximately twice as frequent in the cases. Females and older people have a higher chance of disease development. Finally, the IFNG (+874T/A) polymorphism was not associated with drug sensitivity or resistance. However, a genotypic polymorphism of IFNG (+874T/A) was significantly associated with susceptibility to TB, and the T allele conferred protection against TB. Additional studies involving larger cohorts are needed to further explore this relationship between genetics and disease vulnerability.     

Intrafamilial variability of XYLT2-related spondyloocular syndrome

Spondyloocular syndrome is characterized by generalized osteoporosis, multiple fractures and severe ocular findings. The causative XYLT2 mutations have recently been identified with the use of whole exome sequencing. We report on two siblings with spondyloocular syndrome who presented with varying clinical severity. A novel XYLT2 missense mutation was detected in a region evolutionary conserved across the species. This report along with the previous reports demonstrates that variable expressivity may be possible even within the same family. These two siblings with a novel mutation further expand the clinical and mutational spectrum of spondyloocular syndrome.