182 research outputs found
A Qualitative Study of an Integrated Maternity, Drugs and Social Care Service for Drug-using Women
Background: The care of drug-using pregnant women is a growing health and social care concern in many countries. A specialist clinic was established offering multidisciplinary care and advice to pregnant drug users in and around Aberdeen (UK) in 1997. The majority of women stabilise and reduce their drug use. By determining the needs and views of the women more appropriate
services and prevention strategies may be developed. There has been little research conducted in this area and none in Scotland.
Methods: This is a qualitative study that aimed to gain an understanding of the experiences of women drug users, seeking and receiving prenatal care and drug services from a specialist clinic. Twelve women participated in semi-structured one-to-one interviews.
Results: The women preferred the multidisciplinary clinic (one-stop shop) to traditional prenatal care centred within General Practice. The relationships of the clients to the range of Clinic professionals and in hospital were explored as well as attitudes to Clinic care. The study
participants attributed success in reducing their drug use to the combination of different aspects of care of the multi-agency clinic, especially the high level prenatal support. It is this arrangement of all aspects of care together that seem to produce better outcomes for mother and child than single care elements delivered separately. Some women reported that their pregnancy encouraged them
to rapidly detoxify due to the guilt experienced. The most important aspects of the Clinic care were found to be non-judgemental attitude of staff, consistent staff, high level of support, reliable information and multi-agency integrated care.
Conclusion: There is an impetus for women drug users to change lifestyle during pregnancy. The study highlighted a need for women to have access to reliable information on the effects of drugs on the baby.
Further research is required to determine whether positive outcomes related to clinic attendance in the prenatal period are sustained in the postnatal period. Early referral to a specialist clinic is of benefit to the women, as they reported to receive more appropriate care, especially in relation to their drug use. A greater awareness of needs of the pregnant drug user could help the design of more effective prevention strategies
Regiospecific analysis of Mono and Diglycerides in Glycerolysis products by GC x GC TOF-MS.
Comprehensive bidimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOF-MS) was used for the characterization of regiospecific mono- and diglycerides (MG-DG) content in the glycerolysis products derived from five different lipids included lard (LA), sun flower seed oil (SF), corn oil (CO), butter (BU), and palm oil (PA). The combination of fast and high temperature non-orthogonal column set namely DB17ht (6 m × 0.10 mm × 0.10 μm) as the primary column and SLB-5 ms (60 cm × 0.10 mm × 0.10 μm) as the secondary column was applied in this work. System configuration involved high oven ramp temperature to obtain precise mass spectral identification and highest effluent’s resolution. 3-Monopalmitoyl-sn-glycerol (MG 3-C16) was the highest concentration in LA, BU and PA while monostearoyl-sn-glycerol (MG C18) in CO and 1,3-dilinoleol-rac-glycerol (DG C18:2c) in SF. Principal component analysis accounted 82% of variance using combination of PC1 and PC2. The presence of monostearoyl-sn-glycerol (MG C18), 3-Monopalmitoyl-sn-glycerol (MG 3-C16), 1,3-dilinoleol-rac-glycerol (DG C18:2c), 1,3-dipalmitoyl-glycerol (DG 1,3-C16), and 1,3-dielaidin (DG C18:1t) caused differentiation of the samples tested
Distinctions in gastric cancer gene expression signatures derived from laser capture microdissection versus histologic macrodissection
<p>Abstract</p> <p>Background</p> <p>Gastric cancer samples obtained by histologic macrodissection contain a relatively high stromal content that may significantly influence gene expression profiles. Differences between the gene expression signature derived from macrodissected gastric cancer samples and the signature obtained from isolated gastric cancer epithelial cells from the same biopsies using laser-capture microdissection (LCM) were evaluated for their potential experimental biases.</p> <p>Methods</p> <p>RNA was isolated from frozen tissue samples of gastric cancer biopsies from 20 patients using both histologic macrodissection and LCM techniques. RNA from LCM was subject to an additional round of T7 RNA amplification. Expression profiling was performed using Affymetrix HG-U133A arrays. Genes identified in the expression signatures from each tissue processing method were compared to the set of genes contained within chromosomal regions found to harbor copy number aberrations in the tumor samples by array CGH and to proteins previously identified as being overexpressed in gastric cancer.</p> <p>Results</p> <p>Genes shown to have increased copy number in gastric cancer were also found to be overexpressed in samples obtained by macrodissection (LS <it>P </it>value < 10<sup>-5</sup>), but not in array data generated using microdissection. A set of 58 previously identified genes overexpressed in gastric cancer was also enriched in the gene signature identified by macrodissection (LS <it>P </it>< 10<sup>-5</sup>), but not in the signature identified by microdissection (LS <it>P </it>= 0.013). In contrast, 66 genes previously reported to be underexpressed in gastric cancer were enriched in the gene signature identified by microdissection (LS <it>P </it>< 10<sup>-5</sup>), but not in the signature identified by macrodissection (LS <it>P </it>= 0.89).</p> <p>Conclusions</p> <p>The tumor sampling technique biases the microarray results. LCM may be a more sensitive collection and processing method for the identification of potential tumor suppressor gene candidates in gastric cancer using expression profiling.</p
Assessing quality of life on the day of chemotherapy administration underestimates patients’ true symptom burden
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.
Sphingolipid imbalance is the culprit in a variety of neurological diseases, some affecting the myelin sheath. We have used whole-exome sequencing in patients with undetermined leukoencephalopathies to uncover the endoplasmic reticulum lipid desaturase DEGS1 as the causative gene in 19 patients from 13 unrelated families. Shared features among the cases include severe motor arrest, early nystagmus, dystonia, spasticity, and profound failure to thrive. MRI showed hypomyelination, thinning of the corpus callosum, and progressive thalamic and cerebellar atrophy, suggesting a critical role of DEGS1 in myelin development and maintenance. This enzyme converts dihydroceramide (DhCer) into ceramide (Cer) in the final step of the de novo biosynthesis pathway. We detected a marked increase of the substrate DhCer and DhCer/Cer ratios in patients' fibroblasts and muscle. Further, we used a knockdown approach for disease modeling in Danio rerio, followed by a preclinical test with the first-line treatment for multiple sclerosis, fingolimod (FTY720, Gilenya). The enzymatic inhibition of Cer synthase by fingolimod, 1 step prior to DEGS1 in the pathway, reduced the critical DhCer/Cer imbalance and the severe locomotor disability, increasing the number of myelinating oligodendrocytes in a zebrafish model. These proof-of-concept results pave the way to clinical translation
Expression of a Constitutively Active Calcineurin Encoded by an Intron-Retaining mRNA in Follicular Keratinocytes
Hair growth is a highly regulated cyclical process. Immunosuppressive immunophilin ligands such as cyclosporin A (CsA) and FK506 are known as potent hair growth modulatory agents in rodents and humans that induce active hair growth and inhibit hair follicle regression. The immunosuppressive effectiveness of these drugs has been generally attributed to inhibition of T cell activation through well-characterized pathways. Specifically, CsA and FK506 bind to intracellular proteins, principally cyclophilin A and FKBP12, respectively, and thereby inhibit the phosphatase calcineurin (Cn). The calcineurin (Cn)/NFAT pathway has an important, but poorly understood, role in the regulation of hair follicle development. Here we show that a novel-splicing variant of calcineurin Aß CnAß-FK, which is encoded by an intron-retaining mRNA and is deficient in the autoinhibitory domain, is predominantly expressed in mature follicular keratinocytes but not in the proliferating keratinocytes of rodents. CnAß-FK was weakly sensitive to Ca2+ and dephosphorylated NFATc2 under low Ca2+ levels in keratinocytes. Inhibition of Cn/NFAT induced hair growth in nude mice. Cyclin G2 was identified as a novel target of the Cn/NFATc2 pathway and its expression in follicular keratinocytes was reduced by inhibition of Cn/NFAT. Overexpression of cyclin G2 arrested the cell cycle in follicular keratinocytes in vitro and the Cn inhibitor, cyclosporin A, inhibited nuclear localization of NFATc2, resulting in decreased cyclin G2 expression in follicular keratinocytes of rats in vivo. We therefore suggest that the calcineurin/NFAT pathway has a unique regulatory role in hair follicle development
Health – related quality of life of Kuwaiti women with breast cancer: a comparative study using the EORTC Quality of Life Questionnaire
<p>Abstract</p> <p>Background</p> <p>The Kuwaiti perspective on quality of life (QOL) in breast cancer is important because it adds the contribution from a country where the disease affects women at a relatively younger age and seems to be more aggressive. We used the EORTC QLQ – C30 and its breast-specific module (BR-23) to highlight the health-related QOL of Kuwaiti women with breast cancer, in comparison with the international data, and assessed the socio-demographic and clinical variables that predict the five functional scales and global QOL (GQOL) scale of the QLQ – C30.</p> <p>Methods</p> <p>Participants were consecutive clinic attendees for chemotherapy, in stable condition, at the Kuwait Cancer Control Center.</p> <p>Results</p> <p>The 348 participants were aged 20–81 years (mean 48.3, SD 10.3); 58.7% had stages III and IV disease. Although the mean scores for QLQ – C30 (GQOL, 45.3; and five functional scales, 52.6%–61.2%) indicated that the patients had poor to average functioning, only 5.8% to 11.2% had scores that met the </= 33% criterion for problematic functioning, while 12.0% to 40.0% met the >66% criterion for more severe symptoms. Most (47.8%–70.1%) met the >66% criterion for "good functioning" on the BR-23 functional scales. The mean scores of the QLQ – C30 indicated that, despite institutional supports, Kuwaiti women had clinically significantly poorer global QOL and functional scale scores, and more intense symptom experience, in comparison with the international data (i.e., </= 10% difference between groups). For the BR-23, Kuwaiti women seemed to have clinically significantly better functional scale scores, but more severe symptoms, especially systemic side effects and breast symptoms. Younger women had poorer HRQOL scores. In regression analysis, social functioning accounted for the highest proportion of variance for GQOL.</p> <p>Conclusion</p> <p>The relatively high number that met the criterion for good functioning on the functional scales is an evidence base to boost national health education about psychosocial prognosis in cancer. In view of the poor performance on the symptom scales, clinicians treating Kuwaiti women with breast cancer should prepare them for the acute toxicities of treatment and address fatigue. The findings call for the institution of a psycho-oncology service to address psycho-social issues.</p
Kinetic regulation of multi-ligand binding proteins
Background: Second messengers, such as calcium, regulate the activity of multisite binding proteins in a concentration-dependent manner. For example, calcium binding has been shown to induce conformational transitions in the calcium-dependent protein calmodulin, under steady state conditions. However, intracellular concentrations of these second messengers are often subject to rapid change. The mechanisms underlying dynamic ligand-dependent regulation of multisite proteins require further elucidation. Results: In this study, a computational analysis of multisite protein kinetics in response to rapid changes in ligand concentrations is presented. Two major physiological scenarios are investigated: i) Ligand concentration is abundant and the ligand-multisite protein binding does not affect free ligand concentration, ii) Ligand concentration is of the same order of magnitude as the interacting multisite protein concentration and does not change. Therefore, buffering effects significantly influence the amounts of free ligands. For each of these scenarios the influence of the number of binding sites, the temporal effects on intermediate apo- and fully saturated conformations and the multisite regulatory effects on target proteins are investigated. Conclusions: The developed models allow for a novel and accurate interpretation of concentration and pressure jump-dependent kinetic experiments. The presented model makes predictions for the temporal distribution of multisite protein conformations in complex with variable numbers of ligands. Furthermore, it derives the characteristic time and the dynamics for the kinetic responses elicited by a ligand concentration change as a function of ligand concentration and the number of ligand binding sites. Effector proteins regulated by multisite ligand binding are shown to depend on ligand concentration in a highly nonlinear fashion
Pathogenic <i>SPTBN1</i> variants cause an autosomal dominant neurodevelopmental syndrome
SPTBN1 encodes βII-spectrin, the ubiquitously expressed β-spectrin that forms micrometer-scale networks associated with plasma membranes. Mice deficient in neuronal βII-spectrin have defects in cortical organization, developmental delay and behavioral deficiencies. These phenotypes, while less severe, are observed in haploinsufficient animals, suggesting that individuals carrying heterozygous SPTBN1 variants may also show measurable compromise of neural development and function. Here we identify heterozygous SPTBN1 variants in 29 individuals with developmental, language and motor delays; mild to severe intellectual disability; autistic features; seizures; behavioral and movement abnormalities; hypotonia; and variable dysmorphic facial features. We show that these SPTBN1 variants lead to effects that affect βII-spectrin stability, disrupt binding to key molecular partners, and disturb cytoskeleton organization and dynamics. Our studies define SPTBN1 variants as the genetic basis of a neurodevelopmental syndrome, expand the set of spectrinopathies affecting the brain and underscore the critical role of βII-spectrin in the central nervous system
Factors associated with quality of life of outpatients with breast cancer and gynecologic cancers and their family caregivers: a controlled study
<p>Abstract</p> <p>Background</p> <p>Quality of life (QOL) issues are of interest in cancer because effective methods of treatment and detection have led to an increase in the number of long-term survivors. The objectives of the study were: to assess the subjective QOL of stable Sudanese women cancer outpatients and their family caregivers, using the WHO 26-item QOL Instrument; compare with matched general population groups, as well as diabetic and psychiatric patient groups; examine patient-caregiver concordance in ratings; and assess the variables associated with their QOL, with a view to identifying factors that can enhance quality of care.</p> <p>Methods</p> <p>Responses of oncology outpatients with breast cancer (117), cervical cancer (46) and ovarian cancer (18) (aged 44.6, SD 11.5) were compared with those of their family caregivers and matched general population groups. Data were analyzed by univariate and multivariate statistics.</p> <p>Results</p> <p>The cancer groups had similar QOL domain scores, which were significantly lower than those of their caregivers, but higher than the control group as well as those of psychiatric and diabetic patients studied previously. Patients who were married, with higher education, better employment, and with longer duration of illness had higher QOL. Patients on radiotherapy and their caregivers had higher QOL scores. Correlations between patient's ratings and caregiver impression of patient's QOL were high. Caregiver impression was a significant predictor of patient's and caregiver's QOL. Other predictors for the patient were: currently feeling sick and duration of illness; for the caregiver: feeling sick, relationship to patient, and age.</p> <p>Conclusion</p> <p>Cancer patients in stable condition and with psychosocial support can hope to enjoy good QOL with treatment. The findings constitute an evidence base for the country's cancer care program, to boost national health education about prognosis in cancer. Families living with women cancer patients are vulnerable and need support if the patient is recently diagnosed, less educated, single, not formally employed; and the caregiver is female, parent, younger, less educated, unemployed and feels sick. Clinicians need to invest in the education and support of family caregivers. The patient-caregiver dyad should be regarded as a unit for treatment in cancer care.</p
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