MENOS4 trial: a multicentre randomised controlled trial (RCT) of a breast care nurse delivered cognitive behavioural therapy (CBT) intervention to reduce the impact of hot flushes in women with breast cancer: Study Protocol

BACKGROUND: Women who have been treated for breast cancer may identify vasomotor symptoms, such as hot flushes and night sweats (HFNS), as a serious problem. HFNS are unpleasant to experience and can have a significant impact on daily life, potentially leading to reduced adherence to life saving adjuvant hormonal therapy. It is known that Cognitive Behavioural Therapy (CBT) is effective for the alleviation of hot flushes in both well women and women who have had breast cancer. Most women with breast cancer will see a breast care nurse and there is evidence that nurses can be trained to deliver psychological treatments to a satisfactory level, whilst also maintaining treatment fidelity. The research team will assess whether breast care nurses can effectively deliver a CBT intervention to alleviate hot flushes in women with breast cancer.METHODS: This study is a multi-centre phase III individually randomised controlled trial of group CBT versus usual care to reduce the impact of hot flushes in women with breast cancer. 120-160 women with primary breast cancer experiencing seven or more problematic HFNS a week will be randomised to receive either treatment as usual (TAU) or participation in the group CBT intervention plus TAU (CBT Group). A process evaluation using May's Normalisation Process Theory will be conducted, as well as practical and organisational issues relating to the implementation of the intervention. Fidelity of implementation of the intervention will be conducted by expert assessment. The cost effectiveness of the intervention will also be assessed.DISCUSSION: There is a need for studies that enable effective interventions to be implemented in practice. There is good evidence that CBT is helpful for women with breast cancer who experience HFNS, yet it is not widely available. It is not yet known whether the intervention can be effectively delivered by breast care nurses or implemented in practice. This study will provide information on both whether the intervention can effectively help women with hot flushes and whether and how it can be translated into routine clinical practice.TRIAL REGISTRATION: ISRCTN 12824632 . Registered 25-01-2017.</p

The role of the human papillomavirus (HPV) in cervical cancer : a review about HPV-induced carcinogenesis and its epidemiology, diagnosis, management and prevention

The human papillomavirus (HPV) was the first virus known to induce carcinogenesis and is associated with cancers of the uterine cervix, anogenital tumors and malignancies of the head and neck. This paper reviews the structure and basic genomic characteristics of the virus and outlines the clinical involvement of the main HPV serotypes, focusing on the carcinogenic role of HPV-16 and 18. The mecha¬nisms that occur in the development of cervical neoplasia due to the oncogenic proteins E6 and E7 which interfere with the regulation of the cell cycle through their interaction with p53 and retinoblastoma protein are described. Epidemiological factors, diagnostic tools and the management of the disease are also reviewed, along with the available vaccines to prevent the viral infection. Insights on current research on involvement of oxidative stress and micro-RNAs in cervical carcinogenesis are also explored as they may unlock new means of diagnosis and treatment in the future.peer-reviewe

Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI):study protocol for a randomised controlled trial

Abstract Background Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. Methods/design Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below: Group 1 – Uva-ursi + advice to take ibuprofen Group 2 – Placebo + advice to take ibuprofen Group 3 – Uva-ursi + no advice to take ibuprofen Group 4 – Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2–4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. Discussion The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. Trial registration ISRCTN registry, ID: ISRCTN43397016 . Registered on 11 February 2015

Phospholipases Dα and δ are involved in local and systemic wound responses of cotton (G. hirsutum)

Phospholipases D (PLDs) catabolize structural phospholipids to produce phosphatidic acid (PtdOH), a lipid playing central role in signalling pathways in animal, yeast and plant cells. In animal cells two PLD genes have been studied while in model plant Arabidopsis twelve genes exist, classified in six classes (α-ζ). This underlines the role of these enzymes in plant responses to environmental stresses. However, information concerning the PLD involvement in the widely cultivated and economically important cotton plant responses is very limited. The aim of this report was to study the activity of conventional cotton PLD and its participation in plant responses to mechanical wounding, which resembles both biotic and abiotic stresses. PLDα activity was identified and further characterized by transphosphatidylation reaction. Upon wounding, cotton leaf responses consist of an acute in vitro increase of PLDα activity in both wounded and systemic tissue. However, determination of the in vivo PtdOH levels under the same wounding conditions revealed a rapid PtdOH formation only in wounded leaves and a late response of a PtdOH increase in both tissues. Εxpression analysis of PLDα and PLDδ isoforms showed mRNA accumulation of both isoforms in the wounded tissue, but only PLDδ exerts a high and sustainable expression in systemic leaves, indicating that this isoform is mainly responsible for the systemic wound-induced PtdOH production. Therefore, our data suggest that PLDα and PLDδ isoforms are involved in different steps in cotton wound signalling

Uva-ursi exract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial

BackgroundWomen with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use.Methods/designAdult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below:• Group 1 – Uva-ursi + advice to take ibuprofen• Group 2 – Placebo + advice to take ibuprofen• Group 3 – Uva-ursi + no advice to take ibuprofen• Group 4 – Placebo + no advice to take ibuprofenPatients and physicians will be blinded to the randomised group for the herb.The main outcome is symptom severity at days 2–4 recorded in a validated, self-report diary used in previous studies.Secondary outcomes include antibiotic use and symptom duration.In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint.In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package.DiscussionThe outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics.Trial registrationISRCTN registry, ID: ISRCTN43397016. Registered on 11 February 2015

Immune reconstitution in children following chemotherapy for Acute Lymphoblastic Leukaemia

Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimens on immunity, and thus infectious susceptibility and response to immunisation. Although survival rates for paediatric Acute Lymphoblastic Leukaemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long-term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at 6 time points, during and for 18-months following treatment, with 30-39 patients analysed at each time point.Total lymphocytes were reduced during maintenance chemotherapy and remained low 18-months following treatment completion. CD4 T cells remained significantly reduced 18-months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B-cells, particularly non class-switched memory B-cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B-cell numbers recover rapidly, disruption of memory/naïve balance persists and T cell compartment persist at 18-months. This highlights the impact of modern chemotherapy regimen<br/

Immune reconstitution in children following chemotherapy for acute leukemia

Abstract Although survival rates for pediatric acute lymphoblastic leukemia are now excellent, this is at the expense of prolonged chemotherapy regimens. We report the long‐term immune effects in children treated according to the UK Medical Research Council UKALL 2003 protocol. Peripheral blood lymphocyte subsets and immunoglobulin levels were studied in 116 participants, at six time points, during and for 18‐month following treatment, with 30‐39 patients analyzed at each time point. Total lymphocytes were reduced during maintenance chemotherapy and remained low 18 months following treatment completion. CD4 T cells remained significantly reduced 18 months after treatment, but CD8 cells and natural killer cells recovered to normal values. The fall in naïve B‐cell numbers during maintenance was most marked, but numbers recovered rapidly after cessation of treatment. Memory B cells, particularly nonclass‐switched memory B cells, remained below normal levels 18 months following treatment. All immunoglobulin subclasses were reduced during treatment compared to normal values, with IgM levels most affected. This study demonstrates that immune reconstitution differs between lymphocyte compartments. Although total B‐cell numbers recover rapidly, disruption of memory/naïve balance persists and T‐cell compartment persist at 18 months. This highlights the impact of modern chemotherapy regimens on immunity, and thus, infectious susceptibility and response to immunization

Soft sets and soft modules

Bu tezde, öncelikle soft kümelerin yapısı ve özellikleri incelenmiş ve bunlarla ilgili sonuçlar özetlenerek verilmiştir. Bu kapsamda ilk olarak soft kümeler üzerinde tanımlanmış olan soft gruplar, soft halkalar ve soft modüllerden oluşan cebirsel yapılar ayrıntılı olarak ele alınmış daha sonrada soft alt modül ailesinin toplamı ve direkt toplamı detaylı olarak araştırılmıştır.In this thesis, the structure and properties of soft sets are investigated and the results related to these sets are summarized. In this context, we first discuss in detail algebraic structures consisting of soft groups, soft rings and soft modules which are defined on soft sets. Then the sum and direct sum of the collection of soft submodules are investigated in detail

Additional file 2: of Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial

Participant Information Sheet Main Trial. (PDF 218 kb