Ureaplasma urealyticum biovar determination in women attending a family planning clinic in Guiné-Bissau, using polymerase chain reaction of the multiple-banded antigen gene

Although Ureaplasma urealyticum is commonly found in the genital tract of asymptomatic women, it has been suggested that only certain subgroups of this microorganism are disease associated. Vaginal specimens were collected to determine the distribution of U. urealyticum biovars and to estimate their possible association with age, absence of lactobacilli, and tetracycline resistance. Of the 94 women studied, 40 (43%) carried U. urealyticum and were biotyped by polymerase chain reaction (PCR). Twenty-nine (73%) strains presented with parvo biovar, 10 (25%) with T960 biovar, and one (2.5%) with both biovars. Parvo biovar was predominant in all age groups and appears to be more frequent in women 20-25 years of age (41%), whereas T960 was common in women 30-35 years of age (22%). In this study, U. urealyticum was not associated with changes in vaginal flora, although the inverse apparently was true for Mycoplasma hominis. However, T960 biovar was more associated with the loss of lactobacilli than was parvo biovar. The number of T960 biovar strains that presented tetracycline (40%) or multiple (100%) resistance was higher than that of parvo biovar strains (27% and 69%, respectively).     

The value of variable number of tandem-repeat polymorphisms in cases of disputed paternity not resolved by conventional markers: two case reports

Disputed paternity cases are routinely tested in the authors' laboratory for red cell antigen, plasma protein, red cell enzyme, and HLA polymorphisms. This report concerns two cases in which the above test results made exclusion of paternity doubtful. In one case, exclusion of paternity was based on one discrepancy in the Duffy blood group system only, a unique situation in the investigators' experience of more than 2500 cases; the investigators were, therefore, reluctant to use this as the only evidence of exclusion. In the other case, it was necessary to postulate the presence of a rare haplotype, MSu, in the MNS blood group system to explain paternity. It was therefore decided to investigate allelic variable number of tandem-repeat (VNTR) DNA polymorphisms in these disputed paternity trios. VNTR DNA typing convincingly excluded these accused men from paternity.     

Exploring digenic inheritance in arrhythmogenic cardiomyopathy

Background

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder, characterized by the substitution of heart muscle with fibro-fatty tissue and severe ventricular arrhythmias, often leading to heart failure and sudden cardiac death. ACM is considered a monogenic disorder, but the low penetrance of mutations identified in patients suggests the involvement of additional genetic or environmental factors.

Methods

We used whole exome sequencing to investigate digenic inheritance in two ACM families where previous diagnostic tests have revealed a PKP2 mutation in all affected and some healthy individuals. In family members with PKP2 mutations we determined all genes that harbor variants in affected but not in healthy carriers or vice versa. We computationally prioritized the most likely candidates, focusing on known ACM genes and genes related to PKP2 through protein interactions, functional relationships, or shared biological processes.

Results

We identified four candidate genes in family 1, namely DAG1, DAB2IP, CTBP2 and TCF25, and eleven candidate genes in family 2. The most promising gene in the second family is TTN, a gene previously associated with ACM, in which the affected individual harbors two rare deleterious-predicted missense variants, one of which is located in the protein’s only serine kinase domain.

Conclusions

In this study we report genes that might act as digenic players in ACM pathogenesis, on the basis of co-segregation with PKP2 mutations. Validation in larger cohorts is still required to prove the utility of this model.

     

Preclinical assessment of purging with VP-16-213: key role for long- term marrow cultures

An evaluation of the effects of VP-16 on normal human marrow cells and representative lymphoma-leukemia cell lines was performed to assess this agent's applicability to ex vivo marrow purging. Tumoricidal dose curves were defined using malignant lymphoid (SK-DHL2 and Reh) and myeloid (HL-60) cells admixed with a 20-fold excess of irradiated marrow cells to simulate a borderline remission marrow. One-hour treatments yielded ID50 of less than 5 mumol/L of VP-16 for clonogenic units from each cell line; rare-to-zero clonogenic units survived exposure to 50 to 100 mumol/L. CFU-Mix, BFU-E, and CFU-GM were equal in their sensitivity to VP-16 (ID50s25 to 30 mumol/L). Marrows treated with 75 mumol/L were completely depleted of these colony-forming cells but produced CFU-GM in one-stage long-term marrow cultures (LTMCs). This dose had little adverse effect on the proliferative capacity of marrow stromal progenitors, as measured by CFU-F (ID50 271 mumol/L) and by the unperturbed development of adherent layers in LTMCs. Furthermore, these stromal layers were able to support hematopoiesis as well as controls in co-culture experiments with autologous marrow cells (two-stage LTMCs). In conclusion, doses of VP-16 that cleanse marrow of lymphoma-leukemia cells spare hematopoietic and stromal progenitors as demonstrated by LTMCs. These data favor the use of VP-16 in the clinical autotransplant setting.     

Predictors of “Liking” Three Types of Health and Fitness-Related Content on Social Media: A Cross-Sectional Study

Background

Adolescence and young adulthood are key periods for developing norms related to health behaviors and body image, and social media can influence these norms. Social media is saturated with content related to dieting, fitness, and health. Health and fitness–related social media content has received significant media attention for often containing objectifying and inaccurate health messages. Limited research has identified problematic features of such content, including stigmatizing language around weight, portraying guilt-related messages regarding food, and praising thinness. However, no research has identified who is “liking” or “following” (ie, consuming) such content.

Objective

This exploratory study aimed to identify demographics, mental health, and substance use–related behaviors that predicted consuming 3 types of health and fitness–related social media content—weight loss/fitness motivation pages (ie, “fitspiration”), detox/cleanse pages, and diet/fitness plan pages—among young social media users.

Methods

Participants (N=1001; age: median 21.06, IQR 17.64-24.64; female: 723/1001, 72.23%) completed a cross-sectional 112-question online survey aimed at social media users aged between 15-29 years residing in Victoria, Australia. Logistic regression was used to determine which characteristics predicted consuming the 3 types of health and fitness–related social media content.

Results

A total of 378 (37.76%) participants reported consuming at least 1 of the 3 types of health and fitness–related social media content: 308 (30.77%) fitspiration pages, 145 (14.49%) detox pages, and 235 (23.48%) diet/fitness plan pages. Of the health and fitness–related social media content consumers, 85.7% (324/378) identified as female and 44.8% (324/723) of all female participants consumed at least 1 type of health and fitness–related social media content. Predictors of consuming at least one type of health and fitness–related social media content in univariable analysis included female gender (OR 3.5, 95% CI 2.5-4.9, P<.001), being aged 15-17 years (OR 3.0, 95% CI 2.2-4.0, P<.001), residing outside a major city (OR 2.0, 95% CI 1.4-2.9, P<.001), having no post–high school education (OR 2.2, 95% CI 1.7-2.9, P<.001), being born in Australia (OR 2.0, 95% CI 1.2-3.2, P=.006), having a self-reported eating disorder (OR 2.4, 95% CI 1.5-3.9, P<.001), being a victim of bullying (OR 1.7, CI 1.3-2.3, P<.001), misusing detox/laxative teas or diet pills (OR 4.6, 95% CI 2.8-7.6, P<.001), never using illegal drugs (OR 1.6, 95% CI 1.2-2.0, P=.001), and not engaging in risky single occasion drinking on a weekly basis (OR 2.0, 95% CI 1.3-3.0, P=.003).

Conclusions

Consumers of health and fitness–related social media content were predominantly teenaged girls. There is a need to ensure that this social media content portrays responsible health messages and to research further the role of fitspiration pages, detox pages, and diet/fitness plan pages in influencing body image and health behaviors.     

Fibrin and fibrinogen degradation products with an intact D-domain C- terminal gamma chain inhibit an early step in accessory cell-dependent lymphocyte mitogenesis

Although the low molecular weight degradation products of fibrinogen (FgDP) and fibrin (FbDP) are known to inhibit lymphocyte blastogenesis, the effect of purified macro-molecular FgDP and FbDP (molecular weight, 90 to 200 Kd) is unclear. We have examined the effect of these latter FgDP and FbDP and find that products that contain the D domain inhibit lymphocyte proliferation in response to T-cell mitogens, allogeneic mononuclear leukocytes, and anti-CD3 in vitro. Plasmic digestion of D1 in the absence of calcium with removal of the C-terminal end of the gamma chain or disruption of the gamma-gamma C-terminal cross-link site of D-dimer (DD) by puffadder venom (PAV-D) abrogates their inhibitory potential. Prior incubation of monocytes with DD or D1 inhibits subsequent lymphocyte transformation. Binding studies with radiolabeled DD and PAV-D confirm that monocytes interact only with DD. This specific binding may be competitively inhibited by monoclonal antibodies to CD11b/CD18 or by peptide analogues of the C-terminal gamma chain of fibrinogen that mimic the adhesion recognition site of integrins. We postulate that DD and D1 bind to CD11b/CD18 on adherent monocytes and modulate lymphocyte activation. These products are typically present in the plasma of patients with disseminated intravascular coagulation with sepsis and could therefore influence inflammatory processes in vivo.     

Loss of cytokeratin 10 indicates malignant transformation in actinic cheilitis

Objectives

The aim of this study was to investigate the relationship the expression of cytokeratins (CK10 and CK13) and the cell proliferation index determined by Ki-67 of lip squamous cell carcinoma and actinic cheilitis with different degrees of dysplasia.

Materials and methods

Forty-five paraffin-embedded actinic cheilitis with and without dysplasia and 20 lip squamous cell carcinoma were analyzed by immunohistochemistry using anti-human anti-CK10, anti-CK13, and anti-Ki-67 antibodies.

Results

The majority of actinic cheilitis showed immunopositivity for CK10 and CK13 with decrease or loss of expression in dysplastic areas. In lip squamous cell carcinoma of the lip, heterogeneous expression of CK13 and immunonegativity for CK10 were observed. There was a statistically significant difference between CK10 expression in lip squamous cell carcinoma and in actinic cheilitis with or without dysplasia (p?<?0.001). The cell proliferation index was higher in actinic cheilitis with dysplasia and lip squamous cell carcinoma than in actinic cheilitis without epithelial dysplasia. A significant correlation was found between the intensity of the epithelial dysplasia and the cell proliferation index (p?<?0.001).

Conclusion

These results provide evidence that there is a downregulation of CK10 expression in dysplastic areas of patients with actinic cheilitis and in those with lip squamous cell carcinoma (LSCC) and that the index of cell proliferation, determined by Ki-67, is directly correlated with the intensity of the epithelial dysplasia.

Clinical relevance

Altogether, these results suggest that CK10 expression and the epithelial cell proliferation index can help to identify malignant transformation in the lip region.