Model Atmospheric Aerosols Convert to Vesicles upon Entry into Aqueous Solution.

Aerosols are abundant on the Earth and likely played a role in prebiotic chemistry. Aerosol particles coagulate, divide, and sample a wide variety of conditions conducive to synthesis. While much work has centered on the generation of aerosols and their chemistry, little effort has been expended on their fate after settling. Here, using a laboratory model, we show that aqueous aerosols transform into cell-sized protocellular structures upon entry into aqueous solution containing lipid. Such processes provide for a heretofore unexplored pathway for the assembly of the building blocks of life from disparate geochemical regions within cell-like vesicles with a lipid bilayer in a manner that does not lead to dilution. The efficiency of aerosol to vesicle transformation is high with prebiotically plausible lipids, such as decanoic acid and decanol, that were previously shown to be capable of forming growing and dividing vesicles. The high transformation efficiency with 10-carbon lipids in landing solutions is consistent with the surface properties and dynamics of short-chain lipids. Similar processes may be operative today as fatty acids are common constituents of both contemporary aerosols and the sea. Our work highlights a new pathway that may have facilitated the emergence of the Earth's first cells.

In an Ovine Model of Polycystic Ovary Syndrome (PCOS) Prenatal Androgens Suppress Female Fetal Renal Gluconeogenesis.

Increased maternal androgen exposure during pregnancy programmes a polycystic ovary syndrome (PCOS)-like condition, with metabolic dysfunction, in adult female offspring. Other in utero exposures associated with the development of insulin resistance, such as intrauterine growth restriction and exposure to prenatal glucocorticoids, are associated with altered fetal gluconeogenesis. We therefore aimed to assess the effect of maternal androgenisation on the expression of PEPCK and G6PC in the ovine fetus. Pregnant Scottish Greyface sheep were treated with twice weekly testosterone propionate (TP; 100mg) or vehicle control from day 62 to day 102 of gestation. At day 90 and day 112 fetal plasma and liver and kidney tissue was collected for analysis. PEPCK and G6PC expression were analysed by quantitative RT-PCR, immunohistochemistry and western blotting. PEPCK and G6PC were localised to fetal hepatocytes but maternal androgens had no effect on female or male fetuses. PEPCK and G6PC were also localised to the renal tubules and renal PEPCK (P<0.01) and G6PC (P = 0.057) were lower in females after prenatal androgenisation with no change in male fetuses. These tissue and sex specific observations could not be explained by alterations in fetal insulin or cortisol. The sexual dimorphism may be related to the increase in circulating estrogen (P<0.01) and testosterone (P<0.001) in females but not males. The tissue specific effects may be related to the increased expression of ESR1 (P<0.01) and AR (P<0.05) in the kidney when compared to the fetal liver. After discontinuation of maternal androgenisation female fetal kidney PEPCK expression normalised. These data further highlight the fetal and sexual dimorphic effects of maternal androgenisation, an antecedent to adult disease and the plasticity of fetal development.

The local effects of ovarian diathermy in an ovine model of polycystic ovary syndrome.

In order to develop a medical alternative to surgical ovarian diathermy (OD) in polycystic ovary syndrome (PCOS) more mechanistic information is required about OD. We therefore studied the cellular, molecular and vascular effects of diathermy on the ovary using an established ovine model of PCOS. Pregnant sheep were treated twice weekly with testosterone propionate (100 mg) from day 30-100 gestation. Their female offspring (n = 12) were studied during their second breeding season when the PCOS-like phenotype, with anovulation, is fully manifest. In one group (n = 4) one ovary underwent diathermy and it was collected and compared to the contralateral ovary after 24 hours. In another group a treatment PCOS cohort underwent diathermy (n = 4) and the ovaries were collected and compared to the control PCOS cohort (n = 4) after 5 weeks. Ovarian vascular indices were measured using contrast-enhanced ultrasound and colour Doppler before, immediately after, 24 hours and five weeks after diathermy. Antral follicles were assessed by immunohistochemistry and ovarian stromal gene expression by quantitative RT-PCR 24 hours and 5 weeks after diathermy. Diathermy increased follicular atresia (P<0.05) and reduced antral follicle numbers after 5 weeks (P<0.05). There was an increase in stromal CCL2 expression 24 hours after diathermy (P<0.01) but no alteration in inflammatory indices at 5 weeks. Immediately after diathermy there was increased microbubble transit time in the ovarian microvasculature (P = 0.05) but this was not seen at 24 hours. However 24 hours after diathermy there was a reduction in the stromal Doppler blood flow signal (P<0.05) and an increased ovarian resistance index (P<0.05) both of which persisted at 5 weeks (P<0.01; P<0.05). In the ovine model of PCOS, OD causes a sustained reduction in ovarian stromal blood flow with an increased ovarian artery resistance index associated with atresia of antral follicles.

An integrative review of self-efficacy and patient recovery post acute injury.

AIM: To present an integrative literature review examining the relationship between self-efficacy and patient recovery post acute injury. BACKGROUND: Self-efficacy is a belief in one's ability to perform a set of actions; the greater a person's confidence, the more likely they will initiate and continue activity that will produce a positive outcome in terms of recovery. Increasingly, research indicates that application of self-efficacy theory into clinical practice is likely to promote recovery in the rehabilitation setting. This review examines self-efficacy in the post acute injury group. DESIGN: Integrative literature review. DATA SOURCES: A database search was conducted in PSYCHINFO, MEDLINE and CINAHL between 1990-2012. REVIEW METHODS: Whittemore and Knafl's theoretical framework was used to guide the review in conjunction with a critical appraisal template. Findings from studies were extracted, critically examined and grouped into key themes under factors (interventions) and outcomes relating to self-efficacy. RESULTS: Eighteen articles met the inclusion criteria. Level of education may be a significant factor related to self-efficacy. Educational, physical and psychological interventions to improve self-efficacy emerged, but few interventions led to significantly enhanced self-efficacy. Self-efficacy was found to influence outcomes, including pain and disability, adherence to discharge instructions, locomotion recovery and quality of life. CONCLUSION: Interventions addressing the connection between physical and psychological health with respect to mood, emotion, stress, fear and anxiety to improve the psychological response to acute injury may enhance self-efficacy and patient recovery.

Factors associated with self-efficacy for managing recovery in the trauma intensive care population: a prospective cohort study.

OBJECTIVE: The aim of this paper was to identify factors associated with self-efficacy for managing recovery in the trauma intensive care population. INTRODUCTION: Injury accounts for 6.5% of disease burden in Australia, with similar levels being reported in other developed countries. While some studies regarding self-efficacy have identified a relationship to patient recovery post acute injury, others have been inconclusive. This study will identify factors associated with self-efficacy for managing recovery in the trauma intensive care population. METHODS: A prospective cohort study of patients aged ≥ 18 years, admitted to a metropolitan tertiary hospital in South East Queensland between June 2008 and August 2010 for the acute treatment of injury. Demographic, injury, acute care and psychosocial factors were considered. The primary outcome was self-efficacy measured by the 6-item self-efficacy scale (SES) 1 and 6 months post hospital discharge. All factors significant (p<0.10) on univariate analysis were included in multivariable modelling where p<0.05 was considered significant. RESULTS: A total of 88 patients were included. The mean self-efficacy score at 1 and 6 months was similar (6.8 vs 6.9 respectively). Self-efficacy at 1 month, psychological distress (K-10) Score and illness perception (K10) Score accounted for 68.4% (adjusted R(2)) of the variance in 6 month self-efficacy (F3,75)=57.17, p<0.001. Illness perception was the strongest contributor to 6 month self-efficacy (beta=-0.516), followed by psychological distress (beta=-0.243) and self-efficacy at 1 month (beta=0.205). CONCLUSION: Significant factors associated with self-efficacy for managing recovery at 6 months included 1 month self-efficacy, illness perception and psychological distress. To promote patient recovery, screening patients at 1 month in order to commence relevant interventions could be beneficial.

Excess androgens in utero alters fetal testis development.

Prenatal androgenization induces a polycystic ovary syndrome-like phenotype in adult female offspring, which is associated with alterations that can be detected in the fetal ovary, suggesting gestational origins of this condition. We therefore investigated whether increased prenatal androgen exposure also altered testicular development using ovine animal models. Biweekly maternal testosterone propionate (TP; 100 mg) from day 62 to day 70/day 90 of gestation altered male developmental trajectory. In male fetuses serum LH was decreased (P < .01), and testicular STAR, CYP11, and CYP17 abundance were reduced. Coincident with this, basal testicular T synthesis was decreased in vitro (P < .001). Leydig cell distribution was severely perturbed in all testes prenatally exposed to TP (P < .001). To examine the contribution of estrogens, fetuses were injected with TP (20 mg), the potent estrogen agonist, diethylstilbestrol (DES; 20 mg), or vehicle control at day 62 and day 82 and assessed at day 90. The effects of fetal (direct) TP treatment, but not DES, paralleled maternal (indirect) TP exposure, supporting a direct androgen effect. Cessation of maternal androgenization at day 102 returned Leydig cell distribution to normal but increased basal T output, at day 112, demonstrating Leydig cell developmental plasticity. Earlier maternal androgen exposure from day 30 similarly influenced Leydig cell development at day 90 but additionally affected the expression of Sertoli and germ cell markers. We show in this study that increased prenatal androgen exposure alters development and function of Leydig cells at a time when androgen production is paramount for male development. This supports the concept that gestational antecedents associated with polycystic ovary syndrome may have effects on the male fetus.

The pancreas is altered by in utero androgen exposure: implications for clinical conditions such as polycystic ovary syndrome (PCOS).

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection - MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key ß-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of ß-cells (P<0.05). The fetal pancreas expressed androgen receptors in islets and genes involved in ß-cell development and function (PDX1, IGF1R, INSR and INS) were up-regulated in female fetuses after d62MI-TP treatment (P<0.05-0.01). In addition the d62MI-TP pancreas showed increased insulin secretion under euglycaemic conditions (P<0.05) in vitro. The same effects were not seen in the male fetal pancreas or when MI-TP was started at d30, before the male programming window. As d62MI-TP increased both fetal plasma testosterone (P<0.05) and estradiol concentrations (P<0.05) we assessed the relative contribution of androgens and estrogens. FI-TP (commencing d62) (not FI-DES treatment) caused elevated basal insulin secretion in vitro and the genes altered by d62MI-TP treatment were similarly altered by FI-TP but not FI-DES. In conclusion, androgen over-exposure alters fetal pancreatic development and ß-cell numbers in offspring. These data suggest that that there may be a primary pancreatic phenotype in models of PCOS, and that there may be a distinct male and female pancreas.

Avicin D: a protein reactive plant isoprenoid dephosphorylates Stat 3 by regulating both kinase and phosphatase activities.

Avicins, a class of electrophilic triterpenoids with pro-apoptotic, anti-inflammatory and antioxidant properties, have been shown to induce redox-dependant post-translational modification of cysteine residues to regulate protein function. Based on (a) the cross-talk that occurs between redox and phosphorylation processes, and (b) the role of Stat3 in the process of apoptosis and carcinogenesis, we chose to study the effects of avicins on the processes of phosphorylation/dephosphorylation in Stat3. Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3. The expression of Stat3-regulated proteins such as c-myc, cyclin D1, Bcl2, survivin and VEGF were reduced in response to avicin treatment. Underlying avicin-induced dephosphorylation of Stat3 was dephosphorylation of JAKs, as well as activation of protein phosphatase-1. Downregulation of both Stat3 activity and expression of Stat 3-controlled pro-survival proteins, contributes to the induction of apoptosis in avicin treated tumor cells. Based on the role of Stat3 in inflammation and wounding, and the in vivo inhibition of VEGF by avicins in a mouse skin carcinogenesis model, it is likely that avicin-induced inhibition of Stat3 activity results in the suppression of the pro-inflammatory and pro-oxidant stromal environment of tumors. Activation of PP-1, which also acts as a cellular economizer, combined with the redox regulation by avicins, can aid in redirecting metabolism from growth promoting anabolic to energy sparing pathways.

Avicin D, a plant triterpenoid, induces cell apoptosis by recruitment of Fas and downstream signaling molecules into lipid rafts.

Avicins, a family of triterpene electrophiles originally identified as potent inhibitors of tumor cell growth, have been shown to be pleiotropic compounds that also possess antioxidant, anti-mutagenic, and anti-inflammatory activities. We previously showed that Jurkat cells, which express a high level of Fas, are very sensitive to treatment with avicins. Thus, we hypothesized that avicins may induce cell apoptosis by activation of the Fas pathway. By using a series of cell lines deficient in cell death receptors, we demonstrated that upon avicin D treatment, Fas translocates to the cholesterol- and sphingolipid-enriched membrane microdomains known as lipid rafts. In the lipid rafts, Fas interacts with Fas-associated death domain (FADD) and Caspase-8 to form death-inducing signaling complex (DISC) and thus mediates cell apoptosis. Interfering with lipid raft organization by using a cholesterol-depleting compound, methyl-beta-cyclodextrin, not only prevents the clustering of Fas and its DISC complex but also reduces the sensitivity of the cells to avicin D. Avicin D activates Fas pathways independent of the association between extracellular Fas ligands and Fas receptors. A deficiency in Fas and its downstream signaling molecules leads to the resistance of the cells to avicin D treatment. Taken together, our results demonstrate that avicin D triggers the redistribution of Fas in the membrane lipid rafts, where Fas activates receptor-mediated cell death.

The effect of first metatarsophalangeal arthrodesis on transverse plane deviation of the second toe: a retrospective radiographic study.

The purpose of this retrospective, radiographic study was to examine the effect of first metatarsophalangeal arthrodesis on the transverse plane deviation of the second metatarsophalangeal joint. Sixty-nine patients (76 feet) were separated into 3 groups based on preoperative diagnosis: group 1, hallux valgus; group 2, hallux rigidus; and group 3, rheumatoid forefoot deformity with concomitant lesser metatarsal head resection. Intermetatarsal, hallux abduction, and second metatarsophalangeal angles were measured on preoperative and follow-up anteroposterior radiographs. Multivariate analysis found a significant postoperative change (P < .001) in both the intermetatarsal and hallux abduction angles for all groups, but no significant change in the second metatarsophalangeal angle for any group. There was also no significant difference in the number of patients with medial versus lateral second toe deviation in each group. The addition of a second ray procedure, such as a digital arthrodesis or second metatarsal decompression osteotomy, in groups 1 and 2 did not correlate to the amount of change in second metatarsophalangeal deviation. However, there was a significant correlation (r = .330; P = .004) between the amount of change in the hallux abduction angle and the amount of change in the second metatarsophalangeal angle. A lack of change in the second metatarsophalangeal angle in patients with hallux valgus and hallux rigidus suggests that the creation of a stable medial buttress may protect the lesser digits. However, in patients with rheumatoid, this lack of change denotes a postoperative recurrence of lateral deviation of the second toe despite lesser metatarsal head resection and stabilization of the hallux.

The use of external fixation for treatment of the acute Jones fracture: a retrospective review of 10 cases.

The purpose of this retrospective clinical study was to evaluate the clinical outcome of patients who underwent external fixation of acute Jones fractures. There were 10 patients with a mean age of 25.2 years; 9 of the patients were actively involved in athletics. Chart and radiograph review showed the mean clinical and radiographic healing times to be 5.7 and 6.5 weeks, respectively. Patients returned to preinjury activity levels at a mean 9 weeks postoperatively. Complications included 1 case each of localized cellulitis, asymptomatic nonunion, and refracture. Telephone inquiry performed at a mean 46 months postoperatively determined all patients to be pain-free and continuing to participate at their preinjury activity levels. External fixation is quick and easy to perform and provides a viable alternative to intramedullary screw fixation of Jones fractures in the young, active patient.

First metatarsocuneiform arthrodesis and Reverdin-Laird osteotomy for treatment of hallux valgus: an intermediate-term retrospective outcomes study.

The authors present a retrospective study of 14 patients (20 feet) treated with first metatarsocuneiform arthrodesis and Reverdin-Laird osteotomy and distal soft tissue alignment for hallux valgus associated with hypermobility of the first ray and an increased proximal articular set angle. The purpose of this study was 3-fold: (1) to determine clinical outcome of this procedure combination, (2) to evaluate the effect of this procedure on the radiographic parameters of hallux valgus, and (3) to determine the degree of first ray shortening. At a mean 50.1 months postoperatively, patients were evaluated according to the American Orthopedic Foot and Ankle Society's Hallux-First Metatarsophalangeal-Interphalangeal Clinical Rating Scale. Preoperative and follow-up radiographs were compared for changes in the following measurements: 1-2 intermetatarsal angle (IMA), hallux abduction angle (HAA), proximal articular-set angle (PASA), and metatarsal protrusion distance (MPD). Statistical analysis using the Student t test showed a significant increase in total scores from a mean 43.6 to 92.6 of 100. A significant decrease was found in the IMA from a mean 16.9 degrees to 7.1 degrees, in the HAA from a mean 37.1 degrees to 5.2 degrees, in the PASA from a mean 20.3 degrees to 3.4 degrees (P <.001), and a significant change in the was found in the MPD of 7.7 mm (P <.001). Given the high rating scale scores, first ray shortening did not appear to hamper our patients' clinical outcome.

The effect of first metatarsophalangeal joint arthrodesis on the first ray and the medial longitudinal arch: a radiographic study.

The purpose of this study was to examine the effect of first metatarsophalangeal arthrodesis on the sagittal plane orientation of the first ray and the medial longitudinal arch. Lateral weightbearing radiographs of 48 patients (54 feet) having undergone the procedure were retrospectively reviewed. Patients were separated into three groups based on their preoperative diagnosis: hallux rigidus, hallux valgus, or rheumatoid forefoot deformity. First metatarsal declination, talometatarsal, talar declination, calcaneal inclination, and talocalcaneal angles were measured on pre- and postoperative radiographs. Multivariate analysis of variance determined that there was a significant postoperative change (p < .001) in angular measurements, particularly in the first metatarsal declination, talometatarsal, and talocalcaneal angles. There was also a significant difference (p < .01) in the angular measurements between the hallux rigidus group and the other two groups. However, the amount of change from pre- to postoperatively did not vary significantly between the groups. A calculation of Pearson correlation coefficients found no significant correlation between the hallux dorsiflexion angle and changes in angular measurements. The radiographic changes found in this study support Hicks' windlass model: fixed dorsiflexion of the hallux causes plantarflexion of the first ray and an increase in the medial longitudinal arch.