A retrospective cohort study evaluating pregnancy outcomes in women with MIDD.

AIMS: The most common pathogenic mitochondrial mutation associated with mitochondrial disease is m.3243A>G. Increased obstetric complications, such as spontaneous abortion, gestational diabetes (GDM), preterm delivery, and preeclampsia, have been reported in women carrying this mutation. We aimed to determine the fetal and maternal outcomes in pregnant women with mitochondrial disease. METHODS: We retrospectively studied the obstetric and perinatal outcomes in 88 pregnancies of 26 women with genetically confirmed mitochondrial disease (m.3243A>G in the MTTL1 gene (n = 25); m.12258C>A in the MT-TS2 gene (n = 1)). Outcomes included pregnancy related complications, mode of delivery, gestational age at delivery and birthweight. RESULTS: Mean heteroplasmy rate was 18%. The miscarriage rate was higher than background at 25%. 21 pregnancies (24%) were complicated by GDM; 9 pregnancies (13.6%) had a preterm delivery and 2 of them (3%) an extreme premature delivery < 32 weeks. One woman had preeclampsia and one had a postpartum hemorrhage. The caesarean section (CS) rate was 20%. For every unit increase in maternal heteroplasmy levels there was a 26% increased risk of undergoing an assisted operative vaginal delivery (OR 1.26, 95% CI 1.04-1.53, P = 0.002, Bonferroni corrected P = 0.005) and an 18% increased risk of undergoing a CS (OR 1.18, 95% CI 1.01-1.39, P = 0.01, Bonferroni corrected P = 0.03) compared to a spontaneous vaginal delivery. There was a statistical significant correlation between maternal and offspring heteroplasmy levels. Spearman correlation rho = 0.96, 95% CI 0.78-0.99, P = 0.0002. CONCLUSION: Women with mitochondrial disease appear to have more frequent obstetric complications including miscarriage and GDM. Pre-pregnancy diagnosis of m.3243A>G will enable the counseling of women and increase awareness of possible obstetric complications.

tRNA-derived fragments are altered in diabetes.

AIMS: Maternally inherited diabetes and deafness (MIDD) is a rare form of adult-onset diabetes that can be difficult to diagnose due to its variable clinical phenotype. Transfer RNA-derived small fragments are a novel, emerging class of small non-coding RNAs (sncRNAs) that have significant potential as serum biomarkers due to their stress-induced generation, abundance, stability and ease of detection. METHODS: We investigated the levels of tiRNA 5'ValCAC (alone and in combination with miR-23b-3p) identified from small RNA sequencing studies in serum samples from healthy controls, type 1 diabetes, type 2 diabetes and MIDD subjects. RESULTS: Serum levels of 5'ValCAC were reduced in MIDD and type 2 diabetes subjects compared to controls. Type 2 diabetes subjects had higher serum levels of miR-23b-3p compared to all other subjects. Receiver Operating Characteristic analysis showed the potential of 5'ValCAC and miR-23b-3p as MIDD biomarkers, with the combination showing excellent separation from type 2 diabetes subjects. CONCLUSIONS: This is the first report showing altered serum levels of tiRNAs in diabetes subjects. The combined use of 5'ValCAC and miR-23b-3p as serum biomarkers could potentially differentiate between MIDD subjects and type 2 diabetes subjects.

Introduction of the Simple One-Step stool Xpert Ultra method to detect TB in children and adults.

SETTING: In 2020, the National TB Programme (NTP) of Vietnam conducted an implementation pilot of the Simple One-Step (SOS) stool processing method using Xpert® MTB/RIF Ultra (Ultra) among children and people living with HIV (PLHIV) with signs and symptoms of TB.DESIGN and OBJECTIVES: Using data from this pilot and collecting information on healthcare workers´ (HCWs) perceptions, we assessed the feasibility, acceptability and potential impact of routine stool testing for TB.RESULTS: HCWs perceived collection of stools from children as least stressful of all sample types, stool processing as acceptable and the SOS stool method as easy to perform. After a 3-month induction period, the proportion of initial non-determinate Ultra stool tests was less than 5%. Combined Ultra testing of a respiratory sample and stool resulted in an increase in the proportion of bacteriologically confirmed TB among PLHIV and children by respectively 4.1% (95% CI 1.6-6.6) and 3.9% (95% CI 1.6-6.2). Among children, Mycobacterium tuberculosis was more often detected in stool (26.1%) than in respiratory samples (23.4%) (P = 0.06), including one child with rifampicin resistance.CONCLUSION: Stool testing can be feasibly implemented both in adult PLHIV and in children in routine settings, providing a non-invasive alternative sample type for the diagnosis of TB for patients who cannot produce sputum.

An intersectional analysis of sociodemographic disparities in Covid-19 vaccination: A nationwide register-based study in Sweden.

BACKGROUND: Studies on sociodemographic disparities in Covid-19 vaccination uptake in the general population are still limited and mostly focused on older adults. This study examined sociodemographic differences in Covid-19 vaccination uptake in the total Swedish population aged 18-64 years. METHODS: National Swedish register data within the SCIFI-PEARL project were used to cross-sectionally investigate sociodemographic differences in Covid-19 vaccination among Swedish adults aged 18-64 years (n = 5,987,189) by 12 October 2021. Using logistic regression models, analyses were adjusted for sociodemographic factors, region of residence, history of Covid-19, and comorbidities. An intersectional analysis approach including several cross-classified subgroups was used to further address the complexity of sociodemographic disparities in vaccination uptake. FINDINGS: By 12 October 2021, 76·0% of the Swedish population 18-64 years old had received at least two doses of Covid-19 vaccine, an additional 5·5% had received only one dose, and 18·5% were non-vaccinated. Non-vaccinated individuals were, compared to vaccinated, more often younger, male, had a lower income, were not gainfully employed, and/or were born outside Sweden. The social patterning for vaccine dose two was similar, but weaker, than for dose one. After multivariable adjustments, findings remained but were attenuated indicating the need to consider different sociodemographic factors simultaneously. The intersectional analysis showed a large variation in vaccine uptake ranging from 32% to 96% in cross-classified subgroups, reflecting considerable sociodemographic heterogeneity in vaccination coverage. INTERPRETATION: Our study, addressing the entire Swedish population aged 18-64 years, showed broad sociodemographic disparities in Covid-19 vaccine uptake but also wide heterogeneities in coverage. The intersectional analysis approach indicates that focusing on specific sociodemographic factors in isolation and group average risks without considering the heterogeneity within such groups will risk missing the full variability of vaccine coverage. FUNDING: SciLifeLab / Knut & Alice Wallenberg Foundation, Swedish Research Council, Swedish government ALF agreement, FORMAS.

DSC Perfusion MRI-Derived Fractional Tumor Burden and Relative CBV Differentiate Tumor Progression and Radiation Necrosis in Brain Metastases Treated with Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: Differentiation between tumor and radiation necrosis in patients with brain metastases treated with stereotactic radiosurgery is challenging. We hypothesized that MR perfusion and metabolic metrics can differentiate radiation necrosis from progressive tumor in this setting. MATERIALS AND METHODS: We retrospectively evaluated MRIs comprising DSC, dynamic contrast-enhanced, and arterial spin-labeling perfusion imaging in subjects with brain metastases previously treated with stereotactic radiosurgery. For each lesion, we obtained the mean normalized and standardized relative CBV and fractional tumor burden, volume transfer constant, and normalized maximum CBF, as well as the maximum standardized uptake value in a subset of subjects who underwent FDG-PET. Relative CBV thresholds of 1 and 1.75 were used to define low and high fractional tumor burden. RESULTS: Thirty subjects with 37 lesions (20 radiation necrosis, 17 tumor) were included. Compared with radiation necrosis, tumor had increased mean normalized and standardized relative CBV (P = .002) and high fractional tumor burden (normalized, P = .005; standardized, P = .003) and decreased low fractional tumor burden (normalized, P = .03; standardized, P = .01). The area under the curve showed that relative CBV (normalized = 0.80; standardized = 0.79) and high fractional tumor burden (normalized = 0.77; standardized = 0.78) performed the best to discriminate tumor and radiation necrosis. For tumor prediction, the normalized relative CBV cutoff of ≥1.75 yielded a sensitivity of 76.5% and specificity of 70.0%, while the standardized cutoff of ≥1.75 yielded a sensitivity of 41.2% and specificity of 95.0%. No significance was found with the volume transfer constant, normalized CBF, and standardized uptake value. CONCLUSIONS: Increased relative CBV and high fractional tumor burden (defined by a threshold relative CBV of ≥1.75) best differentiated tumor from radiation necrosis in subjects with brain metastases treated with stereotactic radiosurgery. Performance of normalized and standardized approaches was similar.

The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Hand-arm vibration and outcomes of surgery for Dupuytren's contracture.

BACKGROUND: Dupuytren's contracture was recently designated a prescribed occupational disease when it occurs in patients with previous hand-arm vibration (HAV) exposure. AIMS: The aims of this study were to describe the impact of self-reported HAV exposure on upper limb function and satisfaction following surgery for Dupuytren's contracture. METHODS: Paired pre- and postoperative Quick version of Disabilities of the Arm, Shoulder and Hand (QuickDASH) and patient satisfaction questionnaires were prospectively collected from all patients undergoing surgery for Dupuytren's contracture over a 6-year period. Patients self-reported HAV exposure duration. RESULTS: Results were available for 425 hands (65%) at mean 13 months postoperatively. There were 111 patients (26%) that reported HAV exposure. The prevalence of HAV exposure was significantly greater in male compared with female patients (32% versus 4%; P < 0.001). A statistically significant difference in preoperative (difference 7.47; 95% confidence interval 4.78-10.17; P < 0.001) and postoperative QuickDASH score (difference 6.78; 95% confidence interval 2.69-10.88; P < 0.001) was observed between the two groups, but difference in QuickDASH improvement was not significantly different (difference 1.76; 95% confidence interval -1.58 to 5.10; P > 0.05). No significant difference in satisfaction rate or return to work was observed between the two groups. CONCLUSIONS: Previous HAV exposure influenced the pre and postoperative function in patients undergoing surgery for Dupuytren's contracture, but had no effect on satisfaction or return to work. Further prospective research will be required to determine whether the introduction of a compensatory framework will have a more profound effect on the functional outcomes of surgery.

Changes in the provision of instrumental support by older adults in nine European countries during 2004-2015: a panel data analysis.

BACKGROUND: Providing support to others has been shown to be beneficial to older adults. As people age, their health and social relationships change. These changes may also relate to changes in social support provision. We examined the trajectory of instrumental support provision by older people in three European regions throughout 11 years of follow-up. We then examined the extent to which age at baseline, sex, and region (representing welfare state regime) influenced the variations in the trajectory. METHODS: Data collected from 8354 respondents who had completed at least waves 1 and 6 of the Survey of Health, Ageing and Retirement in Europe (SHARE) was analysed. Instrumental support provision was determined from asking a single question regarding whether the respondent provided help personally for people outside their household. Region, sex, and age at baseline were the main predictors tested. We used growth modelling to address the aims of this study. RESULTS: The northern European region (Sweden and Denmark) had the highest odds ratio of instrumental support provision. The likelihood of being involved in providing instrumental support decreased by 8% annually (OR: 0.916, 95%CI: 0.893,0.940) over the 11 years of follow-up. Older respondents were less likely to provide instrumental support and their trajectories declined faster than those of the younger respondents. Sex difference in instrumental support provision was more apparent among younger-older people in the southern European region. CONCLUSIONS: Older European adults are an important source of instrumental support, especially for their families. The probability of instrumental support provision by European older adults declines over time. Age, sex, and welfare state regime predict this trajectory.

One-year Oxford knee scores should be used in preference to 6-month scores when assessing the outcome of total knee arthroplasty.

PURPOSE: The primary aim of this study was to assess whether there was a clinically significant difference in the mean Oxford knee score (OKS) between 6 and 12 months after total knee arthroplasty (TKA). The secondary aim was to identify variables associated with a clinically significant change in the OKS between 6 and 12 months. METHODS: A retrospective cohort study was undertaken using an established arthroplasty database of 1574 primary TKA procedures. Patient demographics, body mass index (BMI), comorbidities, OKS and EuroQoL 5-domain (EQ-5D) score were collected preoperatively and at 6 and 12 months postoperatively. A clinically significant change in the OKS was defined as 5 points or more. RESULTS: There was a 1.1-point increase in the OKS between 6 and 12 months postoperatively, which was statistically significant (95% confidence (CI) 0.8-1.3, p < 0.0001). There were 381 (24.2%) patients who had a clinically significant improvement in their OKS from 6 to 12 months. After adjusting for confounding, patients with a lower BMI (p = 0.028), without diabetes mellitus (p < 0.001), a better preoperative OKS (p < 0.001) or a worse 6-month OKS (p < 0.001) were more likely to have a clinically significant improvement. A 6-month OKS < 36 points was a reliable predictor of a clinically significant improvement in the 6-month to 12-month OKS (area under the curve 0.73, 95% CI 0.70-0.75, p < 0.001). CONCLUSION: Overall, there was no clinically significant change in the OKS from 6 to 12 months; however, a clinically significant improvement was observed in approximately a quarter of patients and was more likely in those scoring less than 36 points at 6 months. LEVEL OF EVIDENCE: retrospective diagnostic study, level III.

Sagittal alignment of the cemented femoral component in revision total knee arthroplasty influences the anterior and posterior condylar offset: Stem length does not affect these variables.

BACKGROUND: The position of the femoral component can influence knee kinematics by altering the posterior (PCO) and anterior condylar offset (ACO). The primary aim of this study was to assess whether the length of the cemented stem influences the sagittal position of the femoral component after revision total knee arthroplasty (rTKA). The secondary aim was to determine the influence of the sagittal position on PCO and ACO. METHODS: There were 172 consecutive patients over a seven-year period that underwent rTKA with a cemented semi-constrained prosthesis. The 172 patients were separated into two groups: 115 with short stems (50 mm) and 57 with longer stems (100 or 150 mm). Using rotationally acceptable lateral radiographs, the degree of flexion(+)/extension(-) of the femoral components, PCO, and ACO were measured. RESULTS: There was no significant difference (p > 0.25) between the two groups for sagittal position, PCO, or ACO. The average flexion of the femoral component with short stems was 2.2 ±â€¯4.1° and 2.2 ±â€¯3.4° for long stems (difference = 0.0, 95% confidence intervals (CI) -1.3 to 1.2). The average PCO ratio was 1.02 ±â€¯0.15 for short stems and 0.99 ±â€¯0.17 for long stems (difference = 0.03, 95% CI -0.02 to 0.08). The average ACO ratio was at 0.07 ±â€¯0.08 for short stems and 0.08 ±â€¯0.08 for long stems (difference = 0.01, 95% CI -0.01 to 0.04). There was a significant correlation between sagittal alignment of the femoral component and PCO (flexion increased PCO, r = 0.39, p < 0.0001) and ACO (flexion decreased ACO, r = -0.34, p < 0.0001). CONCLUSIONS: Cemented stem length does not influence the position of femoral component in the sagittal axis, PCO, or ACO. Surgical technique and sizing of the femoral component may be more predictive.

Phenotype, genotype and glycaemic variability in people with activating mutations in the ABCC8 gene: response to appropriate therapy.

AIMS: To examine the phenotypic features of people identified with ABCC8-maturity-onset diabetes of the young (MODY) who were included in the adult 'Mater MODY' cohort and to establish their response to sulfonylurea therapy. METHODS: Ten participants with activating ABCC8 mutations were phenotyped in detail. A 2-hour oral glucose tolerance test was performed to establish glycaemic tolerance, with glucose, insulin and C-peptide measurements taken at baseline and 30-min intervals. Insulin was discontinued and sulfonylurea therapy initiated after genetic diagnosis of ABCC8-MODY. A blinded continuous glucose monitoring sensor was used to establish glycaemic control on insulin vs a sulfonylurea. RESULTS: The mean age at diagnosis of diabetes was 33.8 ± 11.1 years, with fasting glucose of 18.9 ± 11.5 mmol/l and a mean (range) HbA1c of 86 (51,126) mmol/mol [10.0 (6.8,13.7)%]. Following a genetic diagnosis of ABCC8-MODY three out of four participants discontinued insulin (mean duration 10.6 ± 1.69 years) and started sulfonylurea treatment. The mean (range) HbA1c prior to genetic diagnosis was 52 (43,74) mmol/mol (6.9%) and the post-treatment change was 44 (30,57) mmol/mol (6.2%; P=0.16). Retinopathy was the most common microvascular complication in this cohort, occurring in five out of 10 participants. CONCLUSIONS: Low-dose sulfonylurea therapy resulted in stable glycaemic control and the elimination of hypoglycaemic episodes attributable to insulin therapy. The use of appropriate therapy at the early stages of diabetes may decrease the incidence of complications and reduce the risks of hypoglycaemia associated with insulin therapy.

Cellular and Acellular Assays for Measuring Oxidative Stress Induced by Ambient and Laboratory-Generated Aerosols.

INTRODUCTION: Many studies have established associations between exposure to air pollution, or atmospheric particulate matter (PM), and adverse health effects. An increasing array of studies have suggested oxidative stress as a possible mechanism by which PM-induced health effects arise, and as a result, many chemical and cellular assays have been developed to study PM-induced oxidant production. Although significant progress has been made in recent years, there are still many gaps in this area of research that have not been addressed. Many prior studies have focused on the aerosol of primary origin (e.g., the aerosol emitted from combustion engines) although the aerosol formed from the oxidation of volatile species, secondary organic aerosol (SOA), has been shown to be the predominant type of aerosol even in urban areas. Current SOA health studies are limited in number, and as such, the health effects of SOA are poorly characterized. Also, there is a lack of perspective in terms of the relative toxicities of different SOA systems. Additionally, although chemical assays have identified some SOA constituents associated with adverse health endpoints, the applicability of these results to cellular responses has not been well established. SPECIFIC AIMS: The overall objective of this study was to better understand the oxidative properties of different types and components of PM mixtures (especially SOA) through systematic laboratory chamber experiments and ambient field studies. The study had four specific aims.1 To develop a cellular assay optimized for measuring reactive oxygen and nitrogen species (ROS/RNS) production resulting from PM exposure and to identify a robust parameter that could represent ROS/RNS levels for comparison with different endpoints.2 To identify ambient PM components associated with ROS/RNS production and evaluate whether results from chemical assays represented cellular responses in terms of ROS/RNS production.3 To investigate and provide perspective on the relative toxicities of SOA formed from common biogenic and anthropogenic precursors under different conditions (e.g., humidity, nitrogen oxides [NOx], and redox-active metals) and identify bulk aerosol properties associated with cellular responses.4 To investigate the effects of photochemical aging on aerosol toxicity. METHODS: Ambient PM samples were collected from urban and rural sites in the greater Atlanta area as part of the Southeastern Center for Air Pollution and Epidemiology (SCAPE) study between June 2012 and October 2013. The concentrations of water-soluble species (e.g., water-soluble organic carbon [WSOC], brown carbon [Br C], and metals) were characterized using a variety of instruments. Samples for this study were chosen to span the observed range of dithiothreitol (DTT) activities.Laboratory studies were conducted in the Georgia Tech Environmental Chamber (GTEC) facility in order to generate SOA under well-controlled photooxidation conditions. Precursors of biogenic origin (isoprene, α-pinene, and ß-caryophyllene) and anthropogenic origin (pentadecane, m-xylene, and naphthalene) were oxidized under various formation conditions (dry vs. humid, NOx, and ammonium sulfate vs. iron sulfate seed particles) to produce SOA of differing chemical composition and mass loading. For the naphthalene system, a series of experiments were conducted with different initial hydrocarbon concentrations to produce aerosols with various degree of oxidation. A suite of instruments was utilized to monitor gas- and particle-phase species. Bulk aerosol properties (e.g., O:C, H:C, and N:C ratios) were measured using a high-resolution time-of-flight aerosol mass spectrometer. Filter samples were collected for chemical oxidative potential and cellular measurements. For the naphthalene system, multiple filter samples were collected over the course of a single experiment to collect aerosols of different photochemical aging.For all filter samples, chemical oxidative potentials were determined for water-soluble extracts using a semiautomated DTT assay system. Murine alveolar macrophages and neonatal rat ventricular myocytes were also exposed to PM samples extracted in cell culture medium to investigate cellular responses. ROS/RNS production was detected using the intracellular ROS/RNS probe, carboxy-2',7'-dichlorodihydrofluorescein diacetate (carboxy-H2DCFA), whereas cellular metabolic activity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Finally, cytokine production, that is, secreted levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were measured post-exposure using an enzyme-linked immunosorbent assay (ELISA). To identify PM constituents associated with oxidative properties, linear regressions between oxidative properties (cellular responses or DTT activity) and aerosol composition (metals, elemental ratios, etc.) were evaluated using Pearson's correlation coefficient, where the significance was determined using multiple imputation and evaluated using a 95% confidence interval. RESULTS: We optimized several parameters for the ROS/RNS assay, including cell density (2 × 104 cells/well for macrophages and 3.33 × 104 cells/well for cardiomyocytes), probe concentration (10 µM), and sample incubation time (24 hours). Results from both ambient and laboratory-generated aerosols demonstrate that ROS/RNS production was highly dose-dependent and nonlinear with respect to PM dose. Of the dose-response metrics investigated in this study (maximum response, dose at which the response is 10% above the baseline [threshold], dose at which 50% of the response is attained [EC50], rate at which the maximum response is attained [Hill slope], and area under the dose-response curve [AUC]), we found that the AUC was the most robust parameter whose informativeness did not depend on dose range.A positive, significant correlation was observed between ROS/RNS production as represented by AUC and chemical oxidative potential as measured by DTT for ambient samples collected in summer. Conversely, a relatively constant AUC was observed for ambient samples collected in winter regardless of the corresponding DTT activity. We also identified several PM constituents (WSOC, BrC, iron, and titanium) that were significantly correlated with AUC for summer samples. The strong correlation between organic species and ROS/RNS production highlights a need to understand the contribution of organic aerosols to PM-induced health effects. No significant correlations were observed for other ROS/RNS metrics or PM constituents, and no spatial trends were observed.For laboratory-generated aerosol, precursor identity influenced oxidative potentials significantly, with isoprene and naphthalene SOA having the lowest and highest DTT activities, respectively. Both precursor identity and formation condition significantly influenced inflammatory responses induced by SOA exposure, and several response patterns were identified for SOA precursors whose photooxidation products share similar carbon-chain length and functionalities. The presence of iron sulfate seed particles did not have an apparent effect on oxidative potentials; however, a higher level of ROS/RNS production was observed for all SOA formed in the presence of iron sulfate compared with ammonium sulfate. We also identified a significant positive correlation between ROS/RNS production and average carbon oxidation state, a bulk aerosol property. It may therefore be possible to roughly estimate ROS/RNS production using this property, which is readily obtainable. This correlation may have significant implications as aerosols have an atmospheric lifetime of a week, during which average carbon oxidation state increases because of atmospheric photochemical aging. Our results suggest that aerosols might become more toxic as they age in the atmosphere. Finally, in the context of ambient samples, laboratory-generated SOA induced comparable or higher levels of ROS/RNS. Oxidative potentials for all laboratory SOA systems, with the exception of naphthalene (which was higher), were all comparable with oxidative potentials observed in ambient samples.

Prebiotic Phosphorylation of Uridine using Diamidophosphate in Aerosols.

One of the most challenging fundamental problems in establishing prebiotically plausible routes for phosphorylation reactions using phosphate is that they are thermodynamically unfavorable in aqueous conditions. Diamidophosphate (DAP), a potentially prebiotically relevant compound, was shown to phosphorylate nucleosides in aqueous medium, albeit at a very slow rate (days/weeks). Here, we demonstrate that performing these reactions within an aerosol environment, a suitable model for the early Earth ocean-air interface, yields higher reaction rates when compared to bulk solution, thus overcoming these rate limitations. As a proof-of-concept, we demonstrate the effective conversion (~6.5-10%) of uridine to uridine-2',3'-cyclophosphate in less than 1 h. These results suggest that aerosol environments are a possible scenario in which prebiotic phosphorylation could have occurred despite unfavorable rates in bulk solution.

What determines gender inequalities in social capital in Ukraine?

BACKGROUND: Social capital is a social determinant of health that has an impact on equity and well-being. It may be unequally distributed among any population. The aims of this study are to investigate the distribution of different forms of social capital between men and women in Ukraine and analyse how potential gender inequalities in social capital might be explained and understood in the Ukrainian context. METHOD: The national representative cross-sectional data from the European Social Survey (wave 6) was used with a sample of 1377 women and 797 men. Seven outcomes that represent cognitive and structural social capital were constructed i.e. institutional trust, generalised trust, reciprocity, safety, as well as bonding, bridging and linking forms. Multivariate logistic regression and post-regression Fairlies decompositions were used for the analyses. RESULTS: There are several findings that resulted from the analyses i), access to institutional trust, linking and bridging social capital is very limited; ii), the odds for almost all forms of social capital (besides safety) are lower for men; iii), feeling about income and age explain most of the gender differences and act positively, as well as offsetting the differences. CONCLUSION: Social capital is unequally distributed between different population groups. Some forms of social capital have a stronger buffering effect on women than on men in Ukraine. Reducing gender and income inequalities would probably influence the distribution of social capital within the society.

Quantum work statistics and resource theories: Bridging the gap through Rényi divergences.

The work performed on or extracted from a nonautonomous quantum system described by means of a two-point projective-measurement approach is a stochastic variable. We show that the cumulant generating function of work can be recast in the form of quantum Rényi-α divergences, and by exploiting the convexity of this cumulant generating function, derive a single-parameter family of bounds for the first moment of work. Higher order moments of work can also be obtained from this result. In this way, we establish a link between quantum work statistics in stochastic approaches and resource theories for quantum thermodynamics, a theory in which Rényi-α divergences take a central role. To explore this connection further, we consider an extended framework involving a control switch and an auxiliary battery, which is instrumental to reconstructing the work statistics of the system. We compare and discuss our bounds on the work distribution to findings on deterministic work studied in resource-theoretic settings.

Nutrient availability in the Setiu Wetland Lagoon, Malaysia: trends, possible causes and environmental impacts.

The objective of this study was to identify the spatial and temporal variabilities of selected nutrients in the Setiu Wetlands Lagoon (SWL), Malaysia. Water samples were collected quarterly at ten monitoring sites. This study presents results from a 10-year field investigation (2003 to 2010 and 2014 to 2015) of water quality in the SWL. For the spatial pattern, four clusters were identified with hierarchical cluster analysis. Analysis of the temporal trend shows that the high total suspended solid loading in 2010 was due to large-scale land clearing upstream of the SWL. The enrichment of ammonium after 2010 could plausibly be due to land-based aquaculture diffuse discharges. In 2005-2007, expansion of oil palm plantations within the Setiu catchment had doubled the phosphorus concentration in the SWL. The natural and anthropogenic alterations of the lagoon inlets profoundly influenced the spatial distribution patterns of nutrients in the SWL. These results suggest that intense anthropogenic disturbances close to the SWL accounted for the water quality deterioration.

Synchronous polypectomy during endoscopic diagnosis of colorectal cancer - is the risk of tumour implantation at the polypectomy site significant?

BACKGROUND: Synchronous polypectomy in colonic malignancies is contentious due to the perceived risks of tumour implantation at polypectomy sites (PS). We assess the risks of tumour implantation after synchronous polypectomy. METHODS: An analysis of all endoscopies for cancer that were accompanied by synchronous polypectomies from 2005 to 2009 was performed. The incidence of metachronous colorectal cancers located at the same segment of a previous PS was the surrogate for tumour implantation. Data on patient demographics, tumour and polyp location(s) and follow-up outcomes were extracted. The rate of metachronous lesions at the same segment of a previous PS between patients who had all synchronous PS resected (Group A) and patients with PS left in-situ (Group B) were compared. RESULTS: Two hundred and eighty-four patients had synchronous polypectomy performed during their initial endoscopy for cancer. Three patients were lost to follow-up and, in the remaining 281 patients, 87 (31.0%) were in Group A while 194 (69%) were in Group B. Median age, gender, tumour location, tumour stage, and pathological characteristics were similar between both groups. 2 (0.7%) patients developed local recurrences. Six (2.1%) patients developed metachronous lesions, four of which were located at the same segment where synchronous polypectomy was previously performed. The rates of metachronous lesions at the PS in groups A and B were similar at 1.1% (1/87) and 1.5% (3/194), respectively (p = 0.795). CONCLUSION: Malignant implantation after synchronous polypectomy in the setting of a newly diagnosed cancer remains unproven. Even if tumor implantation did occur, the incidence is likely low.

Polycystic ovary syndrome: a common reproductive syndrome with long-term metabolic consequences.

Polycystic ovary syndrome is the most common endocrine disorder among women of reproductive age. Although traditionally viewed as a reproductive disorder, there is increasing appreciation that it is associated with significantly increased risk of cardiometabolic disorders. Women with polycystic ovary syndrome may present to clinicians via a variety of different routes and symptoms. Although the impact on reproduction predominates during the reproductive years, the increased cardiometabolic problems are likely to become more important at later stages of the life course. Women with polycystic ovary syndrome have an approximately 2- to 5-fold increased risk of dysglycaemia or type 2 diabetes, and hence regular screening with oral glucose tolerance test is warranted. Although the diagnostic criteria for polycystic ovary syndrome are still evolving and are undergoing revision, the diagnosis is increasingly focused on the presence of hyperandrogenism, with the significance of polycystic ovarian morphology in the absence of associated hyperandrogenism or anovulation remaining uncertain. The management of women with polycystic ovary syndrome should focus on the specific needs of the individual, and may change according to different stages of the life course. In view of the clinical manifestations of the condition, there is recent debate about whether the current name is misleading, and whether the condition should be renamed as metabolic reproductive syndrome.