There is a pressing need for detailed knowledge of the range of pathogens, extent of co-infection and clinical impact of reproductive tract infections (RTIs) among pregnant women. We present prevalence and correlates of RTIs (Mycoplasma genitalium, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum subspecies pallidum, bacterial vaginosis and vulvovaginal candidiasis) in a longitudinal study of women in pregnancy and postpartum in Papua New Guinea (PNG). 699 pregnant women were recruited at their first antenatal clinic visit and followed up at childbirth, one, six and twelve months postpartum. Self-collected vaginal swabs were tested for M.genitalium using real-time PlexPCR® (SpeeDx) which provides results for five point mutations associated with macrolide resistance. Urine samples or vaginal swabs were tested for C.trachomatis, N.gonorrhoea and T.vaginalis using GeneXpert. A vaginal smear was examined for BV and VVC. Routine antenatal services tested for syphilis using Alere DetermineTM Syphilis. Most pregnant women (74.1%) had at least one RTI, with a curable current sexually-transmitted infection (STI) detected in 37.7%. We found M. genitalium, an emerging pathogen in PNG, in 12.5% of pregnant women, decreasing to 6.1% at six months postpartum, with no evidence of macrolide resistance. Prevalence of other curable STIs (C. trachomatis, N. gonorrhoeae and T. vaginalis) were all high in in pregnancy (19.1%, 5.5% and 20.1% respectively), with prevalence decreasing immediately postpartum but rising again by 12 months postpartum. Clinical symptoms missed at least 75% of infections and there was little use of contraception; 98.4% report never having used barrier contraception. This study highlights a high prevalence of a RTIs in pregnancy and postpartum. Most of these infections are curable when diagnosis is made available and syndromic management alone is insufficient. This high prevalence of disease negatively affects sexual and reproductive health and these findings have important public health implications in PNG and the region.

Aim To investigate the suitability of metabolic equivalents (METs) for determining exercise intensity in phase-IV post-myocardial infarction (MI) men during the modified Bruce treadmill walking test (MBWT). Methods Twenty phase-IV post-MI men (mean±SD, aged 64.4±5.8 years) and 20 healthy non-cardiac male controls (59.8±7.6 years) participated. Participants performed a MBWT. Throughout the participants’ heart rate (HR), heart rhythm, expired air parameters and ratings of perceived exertion (RPEs) were measured. MET values were compared between groups and those currently ascribed to each stage of the MBWT. Results General linear model analysis found no significant differences between groups during the MBWT for VO2, VCO2, HR, METs or RPEs (Borg 6–20 scale). Ascribed METs did not differ from mean METs of post-MIs or controls other than at stage 5 where post-MI METs were significantly lower. Irrespective, the post-MI group worked at a higher percentage of their anaerobic threshold (AT) (respiratory exchange ratio, RER=1.0) (F(2,5)=7.22, p<0.008), higher RER (F(2,5)=11.25, p<0.001) with increased breathing frequency (F(2,5)=7.22, p<0.001). Regression analysis revealed AT to be VO2 25.6 (mL/kg/min) for post-MI versus VO2 31.1 (mL/kg/min) for controls. Gross energy expenditure (kcal/min) was greater for the post-MI group compared with controls (F(2,5)=11.22, p<0.001). Throughout the MBWT, post-MI group worked at a higher %AT/MET than controls (F(2,196)=211.76, p<0.01). Body composition did not strongly influence %AT/MET, parameters of VO2, METs or RPE. Conclusion During the MBWT, post-MI men worked more anaerobically per MET (%AT/MET) than controls. Therefore, current METs based on non-cardiac individuals appear unsuitable in determining the full metabolic load of the exercise intensity for cardiac patients during the MBWT.

This study determined the effects of 24 weeks of walking on risk factors and insulin sensitivity associated with metabolic syndrome (MetS) in men. Forty-eight (28.4±3.2 BMI) sedentary/low-active men were randomly selected into controls (n=19,52.4±8.0) or walkers (n=29, 54.9±8.0 yrs). Over a 24-week period, 156.4±26.5 min·walking·wk-1 was performed in 7.2±2.9 sessions·wk-1 for a mean of 25.1±10.3 min·session-1 at an estimated relative VO2 max of 50.6±9.1%. GLM statistical analysis using the baseline values as a covariate was employed. Bonferroni correction set significance at P

A role for mechanical stimulation in the control of cell fate has been proposed and mechanical conditioning of mesenchymal stem cells (MSCs) is of interest in directing MSC behavior for tissue engineering applications. This study investigates strain-induced differentiation and proliferation of MSCs, and investigates the cellular mechanisms of mechanotransduction. MSCs were seeded onto a collagen-coated silicone substrate and exposed to cyclic tensile mechanical strain of 2.5% at 0.17 Hz for 1–14 days. To examine mechanotransduction, cells were strained in the presence of the stretch-activated cation channel (SACC) blocker, gadolinium chloride (GdCl3); the extracellular regulated kinase (ERK) inhibitor, U0126; the p38 inhibitor, SB203580; and the phosphatidylinosito1 3-kinase (PI3-kinase) inhibitor, LY294002. Following exposure to strain, the osteogenic markers Cbfα1, collagen type I, osteocalcin, and BMP2 were temporally expressed. Exposure to strain in the presence of GdCl3 (10 μM) reduced the induction of collagen I expression, thus identifying a role for SACC, at least in part, as mechanosensors in strain-induced MSC differentiation. The strain-induced synthesis of BMP2 was found to be reduced by inhibitors of the kinases, ERK, p38, and PI3 kinase. Additionally, mechanical strain reduced the rate of MSC proliferation. The identification of the mechanical control of MSC proliferation and the molecular link between mechanical stimulation and osteogenic differentiation has consequences for regenerative medicine through the development of a functional tissue engineering approach.

Mechanical conditioning of mesenchymal stem cells (MSCs) has been adopted widely as a biophysical signal to aid tissue engineering applications. The replication of in vivo mechanical signaling has been used in in vitro environments to regulate cell differentiation, and extracellular matrix synthesis, so that both the chemical and mechanical properties of the tissue-engineered construct are compatible with the implant site. While research in these areas contributes to tissue engineering, the effects of mechanical strain on MSC apoptosis remain poorly defined. To evaluate the effects of uniaxial cyclic tensile strain on MSC apoptosis and to investigate mechanotransduction associated with strain-mediated cell death, MSCs seeded on a 2D silicone membrane were stimulated by a range of strain magnitudes for 3days. Mechanotransduction was investigated using the stretch-activated cation channel blocker gadolinium chloride, the L-type voltage-activated calcium channel blocker nicardipine, the c-jun NH2-terminal kinase (JNK) blocker D-JNK inhibitor 1, and the calpain inhibitor MDL 28170. Apoptosis was assessed through DNA fragmentation using the terminal deoxynucleotidyl transferase mediated-UTP-end nick labeling method. Results demonstrated that tensile strains of 7.5% or greater induce apoptosis in MSCs. L-type voltage-activated calcium channels coupled mechanical stress to activation of calpain and JNK, which lead to apoptosis through DNA fragmentation. The definition of the in vitro boundary conditions for tensile strain and MSCs along with a proposed mechanism for apoptosis induced by mechanical events positively contributes to the development of MSC biology, bioreactor design for tissue engineering, and development of computational methods for mechanobiology.

The combination of a β-tricalcium phosphate (βTCP) block with a scaffold-free chondrocyte sheet formed by the centrifugation of chondrocytes in a well was investigated with the aim of constructing an osteochondral-like structure.Human and porcine articular cartilage chondrocytes were respectively centrifuged in a 96-well plate or cell culture insert (0.32 cm2) that was set in a 24-well plate, cultivated in the respective vessel for 3 weeks, and the cell sheets were harvested. In some cases, a cylindrical βTCP block (diameter 5 mm, height 3 mm) was placed on the sheet on days 1–7. The sheet size, cell number, and sulfated glycosaminoglycan accumulation were determined.The use of a 96-well plate for not suspension but adhesion culture and the initial centrifugation of a well containing cells were crucial to obtaining a uniformly thick cell sheet. The glycosaminoglycan density of the harvested cell sheet was comparable to that of the pellet culture. An inoculum cell number of more than 31 × 105 cells tended to result in a curved cell sheet. Culture involving 18.6 × 105 cells and the 96-well plate for adhesion culture showed no curving of the cell sheet (thickness of 0.85 mm), and these were found to be the best of the culture conditions tested. The timing of the addition of a βTCP block to the cell sheet (1–7 days) markedly affected the balance between the thickness of cell sheet parts on and in the βTCP block.Centrifugation and subsequent cultivation of chondrocytes (18.6 × 105 cells) in a 96-well plate for adhesion culture led to the production of a scaffold-free cartilage-like cell sheet with a thickness of 0.85 mm. A combined osteochondral-like structure was produced by putting a βTCP block on the cell sheet. The thickness of the cell sheet on the βTCP block and the binding strength between the cell sheet and the βTCP block could be optimized by adjusting the inoculum cell number and timing of βTCP block addition.