Inhibition and reversal of a TGF-ß1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors.

BACKGROUND: Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. METHODS: The transforming growth factor-ß1 (TGF-ß1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. RESULTS: Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-ß1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. CONCLUSIONS: Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism.

Assisted human reproduction legislation: Listening to the voice of patients.

OBJECTIVE: Legislation and policies regarding assisted human reproduction (AHR) vary widely across nations and societies. As one of only 5 European countries which currently lacks legislation, Ireland now has a unique opportunity to learn from other jurisdictions and introduce AHR law that is reflective of the ongoing myriad developments in this complex field. Draft legislation, initially published in 2017, was revised in 2022 with strong political commitment to enacting in the same year. This study sought to ascertain the views of fertility patients (service users) to the proposed AHR legislation in its current format, prior to its implementation. STUDY DESIGN: A survey questionnaire, previously designed to investigate the attitudes and perceptions of healthcare professionals (HCPs) towards a broad range of issues contained within the draft AHR Bill, was adapted for a patient/service user population. The survey link was distributed via secure email to all patients that had a doctor consult at our fertility clinic in 2020-2021. RESULTS: The survey link was sent to 4420 patients/service users, of whom 1044 (23.6%) responded. A majority had experienced AHR treatment. Service users indicated strong support for AHR regulation and for access to all AHR techniques for all patients, irrespective of relationship or gender status. A majority of respondents disagreed with aspects of the draft bill regarding mandatory counselling, the timing of assignment of parentage in surrogacy, the exclusion of international surrogacy and the exclusion of men from posthumous AHR. Interestingly, the fertility patient cohort were more liberal in their views and opinions regarding AHR than the Irish HCPs previously surveyed. CONCLUSION: This study demonstrates the views of a large group of AHR patients/service users towards proposed AHR legislation. Many of their views concur with but others differ from those of the drafters of the legislation and from those of healthcare professionals. Consideration of the views of all these groups and a collaborative approach would help ensure that Ireland has AHR legislation that is inclusive and fit for purpose in the 21st century.

Assisted human reproduction legislation: Acknowledging the voice of health care professionals.

OBJECTIVE: Ireland is one of 5 European countries which currently lacks specific legislation on Assisted Human Reproduction (AHR). Draft legislation was introduced in 2017 and revised in 2022 with a view to enacting legislation this year (2022). This study sought to ascertain the views of healthcare professionals to proposed AHR legislation, prior to the implementation of that legislation. STUDY DESIGN: A survey questionnaire based on all clinically relevant aspects of the Irish draft AHR Bill 2017 was distributed to relevant healthcare professionals using an online platform. RESULTS: Over 200 healthcare personnel indicated strong support for the availability of AHR techniques, access to treatment for all patient populations regardless of relationship or gender status, and appropriate legislation and regulation in the field. Views of respondents are at variance with several proposals surrounding surrogacy, with 84 % favouring a pre-birth order to assign parentage from birth, rather than the proposed birth order 6 weeks after birth. The majority also support legislation around international surrogacy. Contrary to the draft Bill, respondents believe that men, as well as women, should be able to use posthumously any stored gametes or embryos belonging to the deceased partner or the couple. While the majority favour altruistic gamete donation, respondents support more generous compensation for donors, such as compensation for time lost at work. CONCLUSION: This study has uniquely ascertained the views of healthcare professionals to imminent AHR legislation. It is hoped that the results will help inform the national legislation as it nears completion. Similar studies could help other countries, and policy bodies such as ESHRE to frame good legislation in this extremely specialised and complex field.

Biogeography of ammonia oxidizers in New England and Gulf of Mexico salt marshes and the potential importance of comammox.

Few studies have focused on broad scale biogeographic patterns of ammonia oxidizers in coastal systems, yet understanding the processes that govern them is paramount to understanding the mechanisms that drive biodiversity, and ultimately impact ecosystem processes. Here we present a meta-analysis of 16 years of data of ammonia oxidizer abundance, diversity, and activity in New England (NE) salt marshes and 5 years of data from marshes in the Gulf of Mexico (GoM). Potential nitrification rates were more than 80x higher in GoM compared to NE marshes. However, nitrifier abundances varied between regions, with ammonia-oxidizing archaea (AOA) and comammox bacteria significantly greater in GoM, while ammonia-oxidizing bacteria (AOB) were more than 20x higher in NE than GoM. Total bacterial 16S rRNA genes were also significantly greater in GoM marshes. Correlation analyses of rates and abundance suggest that AOA and comammox are more important in GoM marshes, whereas AOB are more important in NE marshes. Furthermore, ratios of nitrifiers to total bacteria in NE were as much as 80x higher than in the GoM, suggesting differences in the relative importance of nitrifiers between these systems. Communities of AOA and AOB were also significantly different between the two regions, based on amoA sequences and DNA fingerprints (terminal restriction fragment length polymorphism). Differences in rates and abundances may be due to differences in salinity, temperature, and N loading between the regions, and suggest significantly different N cycling dynamics in GoM and NE marshes that are likely driven by strong environmental differences between the regions.

Pyogenic granuloma - the quest for optimum treatment: audit of treatment of 408 cases.

Pyogenic granuloma is a common, acquired, benign vascular lesion of skin and mucous membranes which may occasionally present intravascularly or subcutaneously. Pyogenic granuloma occur in all age groups and although they may eventually regress, removal of unsightly, bleeding or uncomfortably positioned lesions is usually sought before this takes place. This is a retrospective study of 408 cases of pyogenic granuloma that were analysed by the Stoke Mandeville Histopathology laboratory between 1994 and 2004. This study was carried out to review the sex, age and anatomic distribution of the lesions and to assess the most successful form of treatment on the basis of recurrence risk and other measures such as aesthetic result, acceptability and appropriateness of the procedure with respect to the patient. There was a slight male preponderance especially among children. The exception to this was lesions on mucous membranes, which were more common in women. Head and neck was the most common anatomical location, in particular the cheek and intraoral locations. Fewest recurrences were noted following excision and direct closure although all techniques investigated showed an acceptably low recurrence rate. Whatever technique is used it must yield material for histopathological analysis to ensure the exclusion of differential diagnoses.

Incidence, mortality and survival in cutaneous melanoma.

Cutaneous melanoma remains a challenge despite increased levels of awareness, education and targeted health policies. Worldwide incidence rates for cutaneous melanoma have risen faster than those for any other malignancy in Caucasian populations over the last 30 years. Despite improving survival rates (defined as the ratio of those who survive the disease against incidence) over this period, mortality rates, generally, have continued to climb. Mortality from melanoma is greater than that caused by all other types of skin cancer, especially in men. In Britain the percentage of increase in the male age standardised mortality rate surpassed that of all other malignancies assessed (1993-2002) by Cancer Research UK. A literature-based study was conducted with review of publications identified through Medline and EMBase, 1980-December 2005, databases. We present a review of the current literature on incidence, mortality and survival rates of melanoma including a discussion on the aetiological factors, behaviour modification associated with public education campaigns and recent health policies and the effect these are having on melanoma figures. It is likely that any fall in mortality rates from melanoma in the near future will be secondary to early detection. Changes resulting from primary prevention are unlikely to be noticeable for several decades.

Comparison of neuropsychiatric side effects in an observational cohort of efavirenz- and protease inhibitor-treated patients.

PURPOSE: To compare the extent of neuropsychiatric disturbances in two similar groups of HIV-infected patients treated for >4 weeks with either efavirenz (EFV) or protease inhibitors (PIs) as part of their antiretroviral therapy (ART). METHOD: A cross-sectional, questionnaire-based cohort of HIV patients who received two nucleoside reverse transcriptase inhibitors combined with either EFV (n = 75) or one or more PIs (n = 77) for at least 4 weeks and were tolerating therapy. The extent of neuropsychiatric disturbances was evaluated based on self-reported symptoms using the psychological evaluation test SCL-90-R. Treatment duration was broken down into quartiles of 30-198 days, >198-365 days, >365-637 days, and >637 days. RESULTS: In the first 6 months of therapy, significantly higher (worse) scores were seen in 39/75 (52%) of the patients receiving EFV. The EFV-treated group had significantly higher scores for somatization, anxiety, obsessive-compulsive behavior, the Global Severity Index, and the Positive Symptom Distress Index, with trends for higher scores in paranoid ideation and depression symptom subcategories. Over the following 6 to 12 months of therapy, the EFV group scored higher than the PI group in somatization, anxiety, obsessive-compulsive behavior, hostility, depression, the Global Severity Index, and the Positive Symptom Total, but the differences were not significant. After 12 months of therapy, the EFV group had significantly lower scores than the PI group for somatization, interpersonal sensitivity, Global Severity Index, and Positive Symptom Total. CONCLUSION: EFV-induced neuropsychiatric symptoms can last up to 200 days after treatment initiation. However, symptom severity appears to decline over time in EFV-treated patients versus patients treated with a PI-based ART.

Changes in the metal content of surficial sediments of Boston Harbor since the cessation of sludge discharge.

Temporal trends of metals in surficial sediments (1991-1998) at two sites in Boston Harbor were analyzed to evaluate the effect of stopping sludge dumping in December 1991. Metal contents of sediments from the old sludge disposal site were higher than those of a station in the central Harbor. Since 1991, carbon, copper, and lead contents have significantly decreased in sediments from the disposal site. Chromium and Zn have shown smaller decreases while Fe, and Mn, have remained relatively constant. Metal content in the central Harbor station, located in an area of sediment reworking, has been quite variable, but, with the exception of Zn which has shown a large decrease relative to iron, the changes seemed to be well correlated with changes in the organic carbon content at this site due to resuspension. Ratios of metals in the sediments are fairly similar at both sites and similar to those of sewage-derived particles, with the exception of Cr, which appears to be enriched in the sediments.

Maintenance of elevated lead levels in drinking water from occasional use and potential impact on blood leads in children.

The variation in lead concentration was measured by thermal ionisation mass spectrometry isotope dilution in household tap water throughout the day when the plumbing system was not fully flushed. After collection of an initial 125-ml water sample containing 119 micrograms/l and a 2-l sample, 125-ml samples were collected at hourly intervals for 8 h. The concentrations in the hourly samples remained in the range 35-52 micrograms/l compared with 1.7 micrograms/l for fully flushed water. High precision lead isotopic measurements showed that approximately 50% of the lead in these water samples derives from the tap 'housing' compared with the overall household system. A health risk assessment was performed employing the US Environmental Protection Agency Integrated Exposure Uptake Biokinetic Model. Predicted blood lead levels in infants only exceeded the 'levels of concern' of 10 micrograms/dl when 100% of the water consumed contained 100 micrograms Pb/1. It would appear that unless the infant consumed 100% of first flush water at lead concentrations of approximately 100 micrograms/l, the blood lead would not exceed the recommended 'level of concern'. However, if more than 0.51 was consumed in drinks and formulae using first flush water, then the blood lead could easily exceed the recommended level. Likewise, a pregnant mother could be at risk of consuming considerably more than the 0.51/day first flush water of the concentrations measured, or throughout the day, if the system were not fully flushed.

The efficiency of removal of lead and other elements from domestic drinking waters using a bench-top water filter system.

The efficiency of removal of lead (Pb) and other elements from natural drinking waters using a bench-top water filter system was evaluated in three recently-built houses in Sydney, Australia, and two from rural centres. In addition, one filter system was tested for copper (Cu), Pb and cadmium (Cd) under rigorously-controlled laboratory conditions using Sydney water. For two Sydney houses, the efficiency was evaluated using special filter cartridges concomitant with the ordinary filters. Waters after passing through the filter, was sampled when the filter had been exposed to '0', 50, 100, 150, 200, and 250 l respectively and were analysed for lead isotopes and lead concentrations by high precision isotope dilution mass spectrometry. Samples that passed through the filter after '0', 50, 150 and 250 l collections were analysed for four anions and 39 cations by various methods. Sydney water was fairly uniform in its anion and cation composition, whereas water from the two rural areas contained higher concentrations of Ca, Mg and HCO3. Effects of the filter on the water compositions can be summarised into three groups: (1) elements removed during filtration--Ca, Mg, Sr, Ba, Cu, Pb, Zn and Ni. With 'age' of the filter, the efficiency of removal for Pb was maintained in the two houses with Pb concentrations greater than 10 micrograms/l in the first flush water and was maintained for Cu through all concentrations. Ca, Mg, Sr and Ba were largely removed in the first 50 1 of usage. (2) Elements added during filtration--K, Rb, Ag and P. Except for Ag, which was present throughout the testing period, these elements were added only in the first filtration. (3) Elements unaffected by filtration--Al, Si, Na, Fe, Cl and F. Efficiency of Pb removal from tap water by this system depends generally on the initial Pb content in the water. However, it also seems to depend, to some extent, on Pb speciation and water composition, as found in earlier studies of natural waters. The control in filtering efficiency as a function of Pb speciation and chemical composition becomes more important at low initial Pb concentrations in the water. However, the Pb concentrations at which speciation and water composition appear to play a role in filter efficiency are so low that these factors, though scientifically interesting, have no relevance from a practical point of view, especially the impact on human health. Acidification of six sets of duplicate water samples, one sample immediately after collection and the other acidified after more than 2 weeks, showed negligible changes in Pb or Cu concentrations between duplicates.

15N natural abundances and N use by tundra plants.

Plant species collected from tundra ecosystems located along a north-south transect from central Alaska to the north coast of Alaska showed large and consistent differences in 15N natural abundances. Foliar δ15N values varied by about 10% among species within each of two moist tussock tundra sites. Differences in 15N contents among species or plant groups were consistent across moist tussock tundra at several other sites and across five other tundra types at a single site. Ericaceous species had the lowest δ15N values, ranging between about -8 to -6‰. Foliar 15N contents increased progressively in birch, willows and sedges to maximum δ15N values of about +2‰ in sedges. Soil 15N contents in tundra ecosystems at our two most intensively studied sites increased with depth and δ15N values were usually higher for soils than for plants. Isotopic fractionations during soil N transformations and possibly during plant N uptake could lead to observed differences in 15N contents among plant species and between plants and soils. Patterns of variation in 15N content among species indicate that tundra plants acquire nitrogen in extremely nutrient-poor environments by competitive partitioning of the overall N pool. Differences in plant N sources, rooting depth, mycorrhizal associations, forms of N taken up, and other factors controlling plant N uptake are possible causes of variations in δ15N values of tundra plant species.

Effects of drainage and temperature on carbon balance of tussock tundra micrososms.

We examined the importance of temperature (7°C or 15°C) and soil moisture regime (saturated or field capacity) on the carbon (C) balance of arctic tussock tundra microcosms (intact blocks of soil and vegetation) in growth chambers over an 81-day simulated growing season. We measured gaseous CO2 exchanges, methane (CH4) emissions, and dissolved C losses on intact blocks of tussock (Eriophorum vaginatum) and intertussock (moss-dominated). We hypothesized that under increased temperature and/or enhanced drainage, C losses from ecosystem respiration (CO2 respired by plants and heterotrophs) would exceed gains from gross photosynthesis causing tussock tundra to become a net source of C to the atmosphere. The field capacity moisture regime caused a decrease in net CO2 storage (NEP) in tussock tundra micrososms. This resulted from a stimulation of ecosystem respiration (probably mostly microbial) with enhanced drainage, rather than a decrease in gross photosynthesis. Elevated temperature alone had no effect on NEP because CO2 losses from increased ecosystem respiration at elevated temperature were compensated by increased CO2 uptake (gross photosynthesis). Although CO2 losses from ecosystem respiration were primarily limited by drainage, CH4 emissions, in contrast, were dependent on temperature. Furthermore, substantial dissolved C losses, especially organic C, and important microhabitat differences must be considered in estimating C balance for the tussock tundra system. As much as ∼ 20% of total C fixed in photosynthesis was lost as dissolved organic C. Tussocks stored ∼ 2x more C and emitted 5x more methane than intertussocks. In spite of the limitations of this microcosm experiment, this study has further elucidated the critical role of soil moisture regime and dissolved C losses in regulating net C balance of arctic tussock tundra.