DNA polymerase theta-mediated DNA repair is a functional dependency and therapeutic vulnerability in DNMT3A deficient leukemia cells.

Myeloid malignancies carrying somatic DNMT3A mutations (DNMT3Amut) are usually resistant to standard therapy. DNMT3Amut leukemia cells accumulate toxic DNA double strand breaks (DSBs) and collapsed replication forks, rendering them dependent on DNA damage response (DDR). DNA polymerase theta (Polθ), a key element in Polθ-mediated DNA end-joining (TMEJ), is essential for survival and proliferation of DNMT3Amut leukemia cells.

Is pelvic ultrasound useful in the clinical assessment and management of women with right iliac fossa pain? A single-centre retrospective study.

Introduction: Acute right iliac fossa (RIF) pain is a common presenting symptom in surgical patients, with a wide range of differentials, particularly in premenopausal females. This study explores ultrasound usage in the management of women aged 16-55 years presenting with RIF pain.

Methods: A total of 1,082 patients who presented to a tertiary hospital over 12 months were included.

Embryo cryopreservation leads to sex-specific DNA methylation perturbations in both human and mouse placentas.

In vitro fertilization (IVF) is associated with DNA methylation abnormalities and a higher incidence of adverse pregnancy outcomes. However, which exposure(s), among the many IVF interventions, contributes to these outcomes remains unknown. Frozen embryo transfer (ET) is increasingly utilized as an alternative to fresh ET, but reports suggest a higher incidence of pre-eclampsia and large for gestational age infants.

Use of a capillary specimen in the laboratory to verify a point-of-care international normalized ratio: Avoidance of a venipuncture in a pediatric setting.

Introduction: Point-of-care (POC) international normalized ratio (INR) values above an institutional cutoff are confirmed in the laboratory using a gold standard venous specimen. This can be problematic in a pediatric setting.

Method: In this study, 449 consecutive POC INR results were compared to an INR performed in the laboratory on a capillary citrate specimen collected from the same finger-stick.

Parents' perception of quality of life in their sons with haemophilia.

Aim: Quality of life (QOL) in haemophilia involves both physical and psychological issues. This study was performed to determine parents' perceptions of the QOL of their sons with haemophilia and compare this to their children's own assessment.

Methods: In this study, we used the Haemo-QoL questionnaire for haemophilia, to compare the responses of 22 parents to the responses of their children within the age groups 4-7, 8-12 and 13-16 and also for the severity groups mild versus moderate-severe.

Mechanism-Based QSAR Modeling of Skin Sensitization.

Many chemicals can induce skin sensitization, and there is a pressing need for non-animal methods to give a quantitative indication of potency. Using two large published data sets of skin sensitizers, we have allocated each sensitizing chemical to one of 10 mechanistic categories and then developed good QSAR models for the seven categories that have a sufficient number of chemicals to allow modeling. Both internal and external validation checks showed that each model had good predictivity.

Pediatric thrombotic events: a single-center study.

Recent literature has reported an apparent increase in the incidence of pediatric venous thromboembolism over the last 10 years. In our study, data were collected from all children (ages 0 to 18 y) with a thrombotic event between January 2000 and May 2012, to determine whether an increased incidence of thromboembolism (TE) was evident and to investigate mitigating factors in the development of the TE. A total of 134 patients were entered into the study, 42% under the age of 1 year.

Acute Budd-Chiari syndrome due to a simple liver cyst.

Simple liver cysts are common, rarely causing significant morbidity or mortality. Budd-Chiari syndrome (BCS) is caused by obstruction of hepatic venous outflow and is the leading cause of postsinusoidal liver failure. We present a rare case of BCS caused by a simple hepatic cyst.

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

Background: Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P.

Chronic thromboembolic pulmonary hypertension: treat the patient not the haemodynamics.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disabling condition that is being increasingly recognised. It is unique as a cause of pulmonary hypertension in that it is surgically curable. We wish to highlight the importance of recognition and early referral of any patient who may have CTEPH even in the absence of resting pulmonary hypertension as excellent results can be achieved by restoring pulmonary vascular anatomy, reducing exercise-induced pulmonary hypertension, and reducing dead-space ventilation.

Is primary endocrine therapy effective in treating the elderly, unfit patient with breast cancer?

Introduction: Elderly patients with oestrogen receptor (ER)-positive breast cancer wishing to avoid surgery or those who are considered unsuitable for a general anaesthetic may be treated with primary endocrine therapy. We have reviewed all patients with ER-positive breast cancer who were initially treated with primary hormone therapy (PHT) at a district general hospital in south Wales and investigated their outcome in order to evaluate the appropriateness of this method of managing breast cancer.

Materials And Methods: All patients with breast cancer who were initially treated with PHT between January 2002 and December 2008 were identified from a single consultant's prospectively maintained database.

A review of needle core biopsy diagnosed radial scars in the Welsh Breast Screening Programme.

Introduction: Radial scars are benign breast lesions; their appearance on mammography may, however, mimic carcinoma. Needle core biopsy is performed for pre-operative diagnosis and, currently in Wales, all lesions with benign biopsy results are surgically excised. We have reviewed all cases of needle core biopsy-diagnosed radial scars from the Welsh breast screening programme, Breast Test Wales (BTW), and investigated the outcome of radial scars based on histology from surgical excision in order to evaluate the appropriateness of the current management of these lesions in Wales.

Discrepancy in factor VIII 1-stage/2-stage activity in a child with Arg(531)--> His mutation.

Routine screening of infants born to known hemophilia carriers includes a factor VIII (FVIII) level. In routine practice, mild FVIII deficiency variants may be missed by laboratories that exclusively use a one-stage activated partial thromboplastin time-based activity assay. This case illustrates such a possibility with a discrepancy between the one-stage and two-stage assays performed on a child who carries the Arg(531) --> His mutation.

Breast disease diagnostic ability of nurse practitioners and surgeons.

Aim: This paper is a report of a study to compare history-taking and breast and axillary examination skills of nurse practitioners and surgeons.

Background: In the United Kingdom, patients referred by their general practitioners with suspected breast cancer should be seen within 2 weeks by a specialist. As a result of the European Working Time Directive there has been a reduction in junior doctors' working hours within the European Union.

Use of a chaperone during breast examination: the attitude and practice of consultant breast surgeons in the United Kingdom.

Background: Professional guidelines and clinical practice regarding use of chaperones vary substantially in different health care settings. Although there are several studies in primary care practice, no such studies are available in a breast care setting. We have undertaken a questionnaire survey of practicing consultant breast surgeons in the U.

Increased thrombophilic tendency in pediatric cystic fibrosis patients.

Thrombophilia has recently been reported to be increased in patients with cystic fibrosis (CF). We wanted to determine whether this was applicable to our population with CF and how our patients compared to the previously reported groups. Seventy one pediatric CF patients were assessed for a thrombophilic tendency, using a lupus anticoagulant screen, protein C, protein S, antithrombin assay, and activated protein C resistance (APCR) screen.

Patients' attitude towards the use of a chaperone in breast examination.

Introduction: The aim of this study was to assess the attitude and the preferences of patients towards the use of a chaperone during breast examination.

Patients And Methods: A two-part questionnaire was circulated among 204 consecutive new patients, attending both symptomatic breast and screened assessment clinics.

Results: A total of 200 questionnaires were fully completed and returned.