Caregiver mental health and HIV-infected child wellness: perspectives from Ugandan caregivers.

Prior studies indicate a substantial link between maternal depression and early child health but give limited consideration to the direction of this relationship or the context in which it occurs. We sought to create a contextually informed conceptual framework of this relationship through semi-structured interviews with women that had lived experience of caring for an HIV-infected child while coping with depression and anxiety symptoms. Caregivers explained their role in raising healthy children as complex and complicated by poverty, stigma, and isolation. Caregivers discussed the effects of their own mental health on child well-being as primarily emotional and behavioral, and explained how looking after a child could bring distress, particularly when unable to provide desired care for sick children. Our findings suggest the need for investigation of the reciprocal effects of child sickness on caregiver wellness and for integrated programs that holistically address the needs of HIV-affected families.

Case report: A rare case of eosinophilic cholecystitis presenting after talc pleurodesis for recurrent pneumothorax.

Eosinophilic cholecystitis (EC) is a rare inflammatory condition of the gallbladder, confirmed by a cellular infiltrate comprised of more than 90% eosinophils in the gallbladder wall on histological examination. Although the etiology of EC is largely unknown, local autoimmune reactions within the gallbladder wall to inflammatory mediators from distal sites of inflammation have been hypothesized. Talc pleurodesis (TP) is a common clinical procedure used within respiratory medicine. However, it is associated with activation of systemic acute inflammatory responses including an increase in serum interleukin-8 (IL-8), which is a potent mediator of eosinophil chemotaxis. We report a case of EC following a TP procedure for persistent, secondary pneumothorax.

Temperature and precipitation projections over Bangladesh and the upstream Ganges, Brahmaputra and Meghna systems.

South Asia is a region of complex atmospheric dynamics and therefore changes resulting from increasing greenhouse gas concentrations, combined with existing vulnerability to extreme weather events such as flooding, could put the region at particular risk from climate change. However, current climate projections for the region show a range of uncertainty, particularly in terms of changes in the variability and extremes of precipitation. Focusing on Bangladesh and the region encompassing parts of the Ganges, Brahmaputra and Meghna river basins, we aim to explore and quantify climate model uncertainty in climate change projections for the 21(st) century. We use results from a 17-member perturbed physics ensemble of projections from a global climate model which have been used to drive a higher resolution (25 km) regional climate model over the south Asia region from 1971 to 2099. The range of temperature and precipitation responses across the ensemble are assessed including representation of the annual cycle, trends, and changes in precipitation extremes. The 17 ensemble members consistently simulate increasing annual mean temperatures by 2100 compared with present day, ranging between 2.6 °C and 4.8 °C. Additionally, all ensemble members indicate increasing annual precipitation by 2100 of between around 8% and 28%, though with interdecadal variability which results in one ensemble member showing a slight decrease in precipitation in the mid-century period. The frequency of light precipitation events is projected to decrease in the future, but with an increase in the frequency of heavy events. Three members of the climate model ensemble, representing a range of projected climate outcomes, have been selected for use in further impacts modelling for the region.

Impacts of climate change and socio-economic scenarios on flow and water quality of the Ganges, Brahmaputra and Meghna (GBM) river systems: low flow and flood statistics.

The potential impacts of climate change and socio-economic change on flow and water quality in rivers worldwide is a key area of interest. The Ganges-Brahmaputra-Meghna (GBM) is one of the largest river basins in the world serving a population of over 650 million, and is of vital concern to India and Bangladesh as it provides fresh water for people, agriculture, industry, conservation and for the delta system downstream. This paper seeks to assess future changes in flow and water quality utilising a modelling approach as a means of assessment in a very complex system. The INCA-N model has been applied to the Ganges, Brahmaputra and Meghna river systems to simulate flow and water quality along the rivers under a range of future climate conditions. Three model realisations of the Met Office Hadley Centre global and regional climate models were selected from 17 perturbed model runs to evaluate a range of potential futures in climate. In addition, the models have also been evaluated using socio-economic scenarios, comprising (1) a business as usual future, (2) a more sustainable future, and (3) a less sustainable future. Model results for the 2050s and the 2090s indicate a significant increase in monsoon flows under the future climates, with enhanced flood potential. Low flows are predicted to fall with extended drought periods, which could have impacts on water and sediment supply, irrigated agriculture and saline intrusion. In contrast, the socio-economic changes had relatively little impact on flows, except under the low flow regimes where increased irrigation could further reduce water availability. However, should large scale water transfers upstream of Bangladesh be constructed, these have the potential to reduce flows and divert water away from the delta region depending on the volume and timing of the transfers. This could have significant implications for the delta in terms of saline intrusion, water supply, agriculture and maintaining crucial ecosystems such as the mangrove forests, with serious implications for people's livelihoods in the area. The socio-economic scenarios have a significant impact on water quality, altering nutrient fluxes being transported into the delta region.

Dynamic modeling of the Ganga river system: impacts of future climate and socio-economic change on flows and nitrogen fluxes in India and Bangladesh.

This study investigates the potential impacts of future climate and socio-economic change on the flow and nitrogen fluxes of the Ganga river system. This is the first basin scale water quality study for the Ganga considering climate change at 25 km resolution together with socio-economic scenarios. The revised dynamic, process-based INCA model was used to simulate hydrology and water quality within the complex multi-branched river basins. All climate realizations utilized in the study predict increases in temperature and rainfall by the 2050s with significant increase by the 2090s. These changes generate associated increases in monsoon flows and increased availability of water for groundwater recharge and irrigation, but also more frequent flooding. Decreased concentrations of nitrate and ammonia are expected due to increased dilution. Different future socio-economic scenarios were found to have a significant impact on water quality at the downstream end of the Ganga. A less sustainable future resulted in a deterioration of water quality due to the pressures from higher population growth, land use change, increased sewage treatment discharges, enhanced atmospheric nitrogen deposition, and water abstraction. However, water quality was found to improve under a more sustainable strategy as envisaged in the Ganga clean-up plan.

Modelling the increased frequency of extreme sea levels in the Ganges-Brahmaputra-Meghna delta due to sea level rise and other effects of climate change.

Coastal flooding due to storm surge and high tides is a serious risk for inhabitants of the Ganges-Brahmaputra-Meghna (GBM) delta, as much of the land is close to sea level. Climate change could lead to large areas of land being subject to increased flooding, salinization and ultimate abandonment in West Bengal, India, and Bangladesh. IPCC 5th assessment modelling of sea level rise and estimates of subsidence rates from the EU IMPACT2C project suggest that sea level in the GBM delta region may rise by 0.63 to 0.88 m by 2090, with some studies suggesting this could be up to 0.5 m higher if potential substantial melting of the West Antarctic ice sheet is included. These sea level rise scenarios lead to increased frequency of high water coastal events. Any effect of climate change on the frequency and severity of storms can also have an effect on extreme sea levels. A shelf-sea model of the Bay of Bengal has been used to investigate how the combined effect of sea level rise and changes in other environmental conditions under climate change may alter the frequency of extreme sea level events for the period 1971 to 2099. The model was forced using atmospheric and oceanic boundary conditions derived from climate model projections and the future scenario increase in sea level was applied at its ocean boundary. The model results show an increased likelihood of extreme sea level events through the 21st century, with the frequency of events increasing greatly in the second half of the century: water levels that occurred at decadal time intervals under present-day model conditions occurred in most years by the middle of the 21st century and 3-15 times per year by 2100. The heights of the most extreme events tend to increase more in the first half of the century than the second. The modelled scenarios provide a case study of how sea level rise and other effects of climate change may combine to produce a greatly increased threat to life and property in the GBM delta by the end of this century.

Assessing the impacts of climate change and socio-economic changes on flow and phosphorus flux in the Ganga river system.

Anthropogenic climate change has impacted and will continue to impact the natural environment and people around the world. Increasing temperatures and altered rainfall patterns combined with socio-economic factors such as population changes, land use changes and water transfers will affect flows and nutrient fluxes in river systems. The Ganga river, one of the largest river systems in the world, supports approximately 10% global population and more than 700 cities. Changes in the Ganga river system are likely to have a significant impact on water availability, water quality, aquatic habitats and people. In order to investigate these potential changes on the flow and water quality of the Ganga river, a multi-branch version of INCA Phosphorus (INCA-P) model has been applied to the entire river system. The model is used to quantify the impacts from a changing climate, population growth, additional agricultural land, pollution control and water transfers for 2041-2060 and 2080-2099. The results provide valuable information about potential effects of different management strategies on catchment water quality.

Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women.

The distributions of fatty acids in subcutaneous-adipose-tissue aspirates and their relation to intake as assessed by a semiquantitative food-frequency questionnaire were investigated in 115 postmenopausal US women free from cancer. Percentages of fatty acids in adipose tissue were significantly correlated with the percentage of total fat intake for polyunsaturated fatty acids (Spearman correlation = 0.37), n-3 fatty acids of marine origin (Spearman correlation = 0.48), and trans fatty acids (Spearman correlation = 0.51) but not for saturated and monounsaturated fatty acids. Correlations were somewhat stronger in 78 women with stable weight over the 6 mo before fat aspiration. These data suggest that intakes of polyunsaturated fatty acids, including n-3 fatty acids, and trans fatty acids are reflected in the adipose tissue but that intakes of saturated and monounsaturated fatty acids are not. The data also provide further support for the validity of the food-frequency questionnaire in the assessment of fat intake.

Antiproliferative effects exerted by recombinant human tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) on human pancreatic tumor cell lines.

Modulation of the growth of human pancreatic cancer cell lines in vitro by recombinant human tumor necrosis factor-alpha (TNF-alpha) and recombinant human interferon-gamma (IFN-gamma) was investigated. TNF-alpha exerted antiproliferative effects on three of nine pancreatic cancer cell lines and WiDR colorectal cancer cells. When administered together with IFN-gamma TNF-alpha showed enhanced antiproliferative effects on a subset of the pancreatic cancer cell lines tested, including those found to be insensitive to treatment with TNF-alpha alone. Thus the antiproliferative effect achieved by a combined treatment with TNF-alpha and IFN-gamma exceeded that observed with either drug alone in seven of nine pancreatic cancer cell lines.

Monitoring the optimal infusion of intravenous lipids. Detection of essential fatty acid deficiency.

Since increased amounts of the trienoic acid C20:3w9 are produced in patients with essential fatty acid (EFA) deficiency (EFAD) of the linoleic (w6) family, the trienoic (C20:3w9)-to-tetraenoic (C20:4w6) fatty acid ratio (T/T ratio) is used as a biochemical indicator of w6 EFAD. A T/T ratio above 0.02 is suggestive of w6 EFAD. Fatty acid profiles, listing the percent of individual and families of fatty acids, are useful in evaluating the effects of intravenous lipid infusions during treatment. We evaluated the condition of a patient with fat malabsorption treated with a soybean oil-based intravenous lipid solution and found that levels of linoleic acid and its derivatives did not reach reference levels, while linolenic acid and its derivatives quickly exceeded reference levels. A persistently elevated T/T ratio suggested that altered fatty acid metabolism characteristic of linoleic acid deficiency was not corrected by the treatment. Plasma levels of the EFA, ie, linoleic and linolenic acids, cannot be predicted from the lipid treatment or from the patient's clinical course; therefore, periodic measurements of EFA are required to monitor the effects of therapy. To provide the most effective therapy, the amounts and proportions of linoleic and linolenic acids provided in the intravenous infusions should be varied, as indicated by periodic monitoring of the fatty acid profile.

Constitutive activation of STAT3 in Sézary syndrome is independent of SHP-1.

Constitutive and persistent activation of STAT3 has been implicated in the pathogenesis of many malignancies. Studies of CTCL cell lines have previously suggested that aberrant activation of STAT3 is mediated via silencing of the negative regulator SHP-1 by promoter methylation. In this study of ex vivo tumour cell populations from 18 Sézary syndrome (SS) patients, constitutive phosphorylation of STAT3, JAK1 and JAK2 was present in all patients, but was absent in comparative CD4+ T-cells from healthy controls. Furthermore, no loss or significant difference in SHP-1 expression was observed between patients and healthy control samples. Methylation-specific PCR analysis of the SHP-1 CpG island in 47 SS patients and 11 healthy controls did not detect any evidence of methylation. Moreover, small interfering RNA knockdown of SHP-1 had no effect on phosphorylation of STAT3. In contrast, treatment of SS tumour cells with the pan-JAK inhibitor pyridone 6 led to downregulation of phosphorylated STAT3 (pSTAT3), its target genes and induction of apoptosis. No evidence for common JAK1/JAK2-activating mutations was found. These data demonstrate that constitutive activation of STAT3 in SS is not due to the loss of SHP-1, but is mediated by constitutive aberrant activation of JAK family members.

Prenatal detection of X-linked ichthyosis by maternal serum screening for Down syndrome.

Maternal serum unconjugated oestriol (uE3) was measured in 15,375 pregnancies during 2 years of second-trimester risk assessment for Down syndrome using biochemical markers. Very low levels of uE3 (< 0.1 MOM) were detected in 22 serum samples (0.14 per cent). Very low uE3 was associated with an adverse outcome in 13 pregnancies including fetal death and miscarriage (N = 11) anencephaly (N = 1), and Meckel-Gruber syndrome (N = 1). Dry scales on the skin appeared in the first year of life in four boys. From dermatological diagnosis, prenatal uE3 levels, and pedigree analysis, it is concluded that at least 5 in approximately 7500 male births in the study population are affected by steroid sulphatase deficiency, which is the biochemical defect in X-linked ichthyosis. Very low uE3 levels in the second trimester are indicative of this disease in pregnancies with normal ultrasound findings.

Femtomole oligosaccharide detection using a reducing-end derivative and chemical ionization mass spectrometry.

A bimodal reagent (pentafluorobenzyl aminobenzoate) has been synthesized to improve oligosaccharide isolation, detection, and structural characterization. The reagent is glycosidically attached to the reducing end of glycan residues, imparts fluorescent and uv properties for chromatographic detection, and functions as an efficient electron trap under negative ion chemical ionization mass spectrometry for femtomole detectability. Facile ester cleavage and pentafluorobenzyl elimination provides a single molecular-weight-related fragment in high abundance. Procedures are described for reagent synthesis, purification, and oligosaccharide conjugation. Carbohydrate samples derivatized with this reagent are evaluated by high-performance liquid chromatography and supercritical fluid chromatography (SFC) and for sensitivity by SFC negative ion chemical ionization mass spectrometry.

Adjustment formulae for maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated oestriol to maternal weight and smoking.

Serum levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated oestriol (uE3) were measured in serum samples of 4131 non-smoking and 1018 smoking women during the second trimester of pregnancy. The levels of all three analytes decreased with increasing body weight. The AFP median was significantly increased in smokers in a dose-response association; hCG decreased by 21 per cent and uE3 decreased by 3 per cent in smokers in a non-dose-related fashion. Regression functions for adjustment of serum levels for weight and smoking should be considered in risk estimation for Down syndrome in order to give a woman's individual risk more precisely.

Presymptomatic exclusion of myotonic dystrophy in a one-generation pedigree of half-siblings.

An unusual one-generation family with myotonic dystrophy is presented, in which genetic counseling was successfully carried out. The probability of an informative result, before marker typing, is analytically derived and amounts to at least 40%.

Risk of fetal Down's syndrome based on maternal age and varying combinations of maternal serum markers.

Serum samples from 320 women with chromosomally normal fetuses and from 50 women with fetuses affected by Down's syndrome were assayed retrospectively for human chorionic gonadotropin (hCG), pregnancy-specific beta 1 glycoprotein (SP1), alpha fetoprotein (AFP), and unconjugated estriol (uE3) between 14 and 21 weeks of gestation. Nonparametric discriminant analysis was applied to calculate Down syndrome risks on the basis of various combinations of serum parameters. At a risk threshold that falsely identifies 5% of controls as being affected, 46 to 48% of Down syndrome pregnancies were detected by combinations of hCG/AFP, hCG/AFP/uE3, and hCG/AFP/uE3/SP1 respectively. HCG, AFP, and uE3 were assayed in 652 serum samples from women who underwent amniocentesis because of maternal age (> or equal to 35 years in this prospective study). 49% of women with euploid fetal karyotype, 8 of 10 pregnancies with Down's syndrome, and 3 pregnancies with sex chromosomal anomalies were identified as being at an increased risk (> 1:380).

Ectopic NORs on human chromosomes 4qter and 8q11: rare chromosomal variants detected in two families.

Two different NOR bearing non-acrocentric chromosomes were detected during prenatal diagnosis performed on two probands because of advanced maternal age. In the first case, a chromosome 4 carried a NOR in the telomeric region of the long arm (4qs), while in the second case a NOR was inserted into chromosome 8q11. Family analysis showed the variant chromosomes to be transmitted through at least three generations in each family. There were no reports of reproductive problems or phenotypic effects in the carriers of these chromosomes, indicating the benign character of the aberrant chromosomes. In order to characterise the chromosomal variants more precisely, various differential banding techniques were applied.