A molecular staging model for accurately dating the endometrial biopsy.

Natural variability in menstrual cycle length, coupled with rapid changes in endometrial gene expression, makes it difficult to accurately define and compare different stages of the endometrial cycle. Here we develop and validate a method for precisely determining endometrial cycle stage based on global gene expression. Our 'molecular staging model' reveals significant and remarkably synchronised daily changes in expression for over 3400 endometrial genes throughout the cycle, with the most dramatic changes occurring during the secretory phase. Our study significantly extends existing data on the endometrial transcriptome, and for the first time enables identification of differentially expressed endometrial genes with increasing age and different ethnicities. It also allows reinterpretation of all endometrial RNA-seq and array data that has been published to date. Our molecular staging model will significantly advance understanding of endometrial-related disorders that affect nearly all women at some stage of their lives, such as heavy menstrual bleeding, endometriosis, adenomyosis, and recurrent implantation failure.

Spontaneous Distal Extrusion of Kuntscher Intramedullary Nail.

Migration of femoral Kuntscher intramedullary nail (K-nail) proximally or distally within the femoral medullary cavity is a well-known documented complication, but spontaneous extrusion of a distally migrated K-nail is a rare complication. This is a case report of a 33-year-old lady who complained of sudden onset left knee pain and presented with spontaneous extrusion of a Kuntscher nail 12 years postinsertion. She underwent a successful K-nail removal surgery and showed a good clinical outcome after 6 months of outpatient follow-up.

Clinical summary guide: reproduction in women with previous abdominopelvic radiotherapy or total body irradiation.

STUDY QUESTION: What is the evidence to guide the management of women who wish to conceive following abdominopelvic radiotherapy (AP RT) or total body irradiation (TBI)? SUMMARY ANSWER: Pregnancy is possible, even following higher doses of post-pubertal uterine radiation exposure; however, it is associated with adverse reproductive sequelae and pregnancies must be managed in a high-risk obstetric unit. WHAT IS KNOWN ALREADY: In addition to primary ovarian insufficiency, female survivors who are treated with AP RT and TBI are at risk of damage to the uterus. This may impact on its function and manifest as adverse reproductive sequelae. STUDY DESIGN SIZE DURATION: A review of the literature was carried out and a multidisciplinary working group provided expert opinion regarding assessment of the uterus and obstetric management. PARTICIPANTS/MATERIALS SETTING METHODS: Reproductive outcomes for postpubertal women with uterine radiation exposure in the form of AP RT or TBI were reviewed. This included Pubmed listed peer-reviewed publications from 1990 to 2019, and limited to English language.. MAIN RESULTS AND THE ROLE OF CHANCE: The prepubertal uterus is much more vulnerable to the effects of radiation than after puberty. Almost all available information about the impact of radiation on the uterus comes from studies of radiation exposure during childhood or adolescence.An uncomplicated pregnancy is possible, even with doses as high as 54 Gy. Therefore, tumour treatment doses alone cannot at present be used to accurately predict uterine damage. LIMITATIONS REASONS FOR CAUTION: Much of the data cannot be readily extrapolated to adult women who have had uterine radiation and the publications concerning adult women treated with AP RT are largely limited to case reports. WIDER IMPLICATIONS OF THE FINDINGS: This analysis offers clinical guidance and assists with patient counselling. It is important to include patients who have undergone AP RT or TBI in prospective studies to provide further evidence regarding uterine function, pregnancy outcomes and correlation of imaging with clinical outcomes. STUDY FUNDING/COMPETING INTERESTS: This study received no funding and there are no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Endometrial uNK cell counts do not predict successful implantation in an IVF population.

STUDY QUESTION: Are uterine natural killer (uNK) cell numbers and their distribution relative to endometrial arterioles altered in women with recurrent implantation failure (RIF) compared to women with embryo implantation success (IS)? SUMMARY ANSWER: uNK cell numbers and their distribution relative to endometrial arterioles are not significantly different in women with RIF compared to women in whom embryo implantation occurs successfully following IVF. WHAT IS ALREADY KNOWN: uNK cells are regulators of decidual angiogenesis and spiral arteriole remodelling during early pregnancy. Although some studies have shown that uNK cell numbers may be altered in women with RIF, the methods used to measure uNK cell numbers have proven inconsistent, making reproduction of these results difficult. It is unclear, therefore, whether the results reported so far are reproducible. Moreover, it is not known how uNK cell numbers may impact IVF outcomes. Despite the lack of conclusive evidence, uNK cell numbers are often evaluated as a prognostic criterion in women undergoing assisted reproductive procedures. STUDY DESIGN, SIZE, DURATION: Endometrial pipelle biopsies were collected 6-8 days post-LH surge in natural cycles from women with RIF (n = 14), women with IS (n = 11) and women with potential RIF at the time of the study (PRIF; n = 9) from 2013 to 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: uNK cells (i.e. CD56+ and/or CD16+ phenotypes) and their distribution relative to endometrial arterioles were investigated by standard immunohistochemistry protocols and quantified using Aperio ScanScopeXT images digitized by ImageJ and deconvoluted into binary images for single cell quantification using a Gaussian Blur and Yen algorithm. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in the cell density of CD56+ or CD16+ uNK cells in women with RIF compared to women with IS or PRIF. There was a higher proportion of uNK cells in the distal regions compared to the regions closest to the arterioles in all patient groups. Further, we identified a significant reduction in uNK cell density in women who had a previous pregnancy compared to those who had not, regardless of their current implantation status. LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Spiral arterioles could not always be accurately identified by digital image analysis; therefore, all endometrial arterioles were selected and analysed. Patient numbers for the study were low. However, as the clinical phenotypes of each patient were well defined, and endometrial dating was accurately determined by three independent pathologists, differences between patient groups with respect to the uNK numbers and distribution should have been measurable if uNK cell counts were to be useful as a prognostic marker of RIF. WIDER IMPLICATIONS OF THE FINDINGS: Our findings demonstrate that CD56+ and CD16+ uNK cell numbers are not significantly different in women with RIF in a typical cohort of women undergoing IVF. Further, prior pregnancy was associated with a significantly reduced number of uNK cells in both the RIF and IS patient groups, suggestive of a long-term pregnancy induced suppression of uNK cells. Combined, these findings do not support the clinical value of using uNK cell numbers as a prognostic indicator of implantation success with IVF treatment. STUDY FUNDING/COMPETING INTEREST(S): Funding for this work was provided by Royal Women's Hospital Foundation. P.P. was supported by an NHMRC Early Career Fellowship [TF 11/14] and W.T.T. was supported by an NHMRC Postgraduate Scholarship [1055814]. The authors do not have any competing interests with this study.

Impact of stroke-associated pneumonia on mortality, length of hospitalization, and functional outcome.

OBJECTIVES: Stroke-associated pneumonia (SAP) is common and associated with adverse outcomes. Data on its impact beyond 1 year are scarce. MATERIALS AND METHODS: This observational study was conducted in a cohort of stroke patients admitted consecutively to a tertiary referral center in the east of England, UK (January 2003-April 2015). Logistic regression models examined inpatient mortality and length of stay (LOS). Cox regression models examined longer-term mortality at predefined time periods (0-90 days, 90 days-1 year, 1-3 years, and 3-10 years) for SAP. Effect of SAP on functional outcome at discharge was assessed using logistic regression. RESULTS: A total of 9238 patients (mean age [±SD] 77.61 ± 11.88 years) were included. SAP was diagnosed in 1083 (11.7%) patients. The majority of these cases (n = 658; 60.8%) were aspiration pneumonia. After controlling for age, sex, stroke type, Oxfordshire Community Stroke Project (OCSP) classification, prestroke modified Rankin scale, comorbidities, and acute illness markers, mortality estimates remained significant at 3 time periods: inpatient (OR 5.87, 95%CI [4.97-6.93]), 0-90 days (2.17 [1.97-2.40]), and 91-365 days (HR 1.31 [1.03-1.67]). SAP was also associated with higher odds of long LOS (OR 1.93 [1.67-2.22]) and worse functional outcome (OR 7.17 [5.44-9.45]). In this cohort, SAP did not increase mortality risk beyond 1 year post-stroke, but it was associated with reduced mortality beyond 3 years. CONCLUSIONS: Stroke-associated pneumonia is not associated with increased long-term mortality, but it is linked with increased mortality up to 1 year, prolonged LOS, and poor functional outcome on discharge. Targeted intervention strategies are required to improve outcomes of SAP patients who survive to hospital discharge.

Recurrent transient visual loss in a middle aged woman.

Visual loss is a common presenting complaint in primary care. We present a case of recurrent transient visual loss in a middle aged woman. Her funduscopy showed bilateral optic disc swelling. We have highlighted the differentiation of bilateral optic disc swelling at the primary care level as the management differs according to the diagnosis.

Mechanical signatures of microbial biofilms in micropillar-embedded growth chambers.

Biofilms are surface-attached communities of microorganisms embedded in an extracellular matrix and are essential for the cycling of organic matter in natural and engineered environments. They are also the leading cause of many infections, for example, those associated with chronic wounds and implanted medical devices. The extracellular matrix is a key biofilm component that determines its architecture and defines its physical properties. Herein, we used growth chambers embedded with micropillars to study the net mechanical forces (differential pressure) exerted during biofilm formation in situ. Pressure from the biofilm is transferred to the micropillars via the extracellular matrix, and reduction of major matrix components decreases the magnitude of micropillar deflections. The spatial arrangement of micropillar deflections caused by pressure differences in the different biofilm strains may potentially be used as mechanical signatures for biofilm characterization. Hence, we submit that micropillar-embedded growth chambers provide insights into the mechanical properties and dynamics of the biofilm and its matrix.

Substituted ferrocenes and iodine as synergistic thermoelectrochemical heat harvesting redox couples in ionic liquids.

Combining ferrocene and iodine results in enhanced thermoelectrochemical (or thermogalvanic) waste heat harvesting abilities, for both the Seebeck coefficient and the overall power output. All systems displayed a mixture of ferrocene, ferrocenium, iodine and triiodide. The observed enhancement correlates with lower electron-density on the ferrocene; the synergistic improvement observed for mixtures of substituted ferrocenes and iodine is attributed to the formation of charge-transfer complexes. Combining dibutanoylferrocene and iodine resulted in the highest Seebeck coefficient of 1.67 mV K(-1).

Head and cervical spine posture in behaving rats: implications for modeling human conditions involving the head and cervical spine.

The aim of this study was to define the temporal and spatial (postural) characteristics of the head and cervical vertebral column (spine) of behaving rats in order to better understand their suitability as a model to study human conditions involving the head and neck. Time spent in each of four behavioral postures was determined from video tape recordings of rats (n = 10) in the absence and presence of an intruder rat. Plain film radiographic examination of a subset of these rats (n = 5) in each of these postures allowed measurement of head and cervical vertebral column positions adopted by the rats. When single they were quadruped or crouched most (∼80%) of the time and bipedal either supported or free standing for only ∼10% of the time. The introduction of an intruder significantly (P < 0.0001) reduced the proportion of time rats spent quadruped (median, from 71% to 47%) and bipedal free standing (median, from 2.9% to 0.4%). The cervical spine was orientated (median, 25-75 percentile) near vertical (18.8°, 4.2°-30.9°) when quadruped, crouched (15.4°, 7.6°-69.3°) and bipedal supported (10.5°, 4.8°-22.6°) but tended to be less vertical oriented when bipedal free standing (25.9°, 7.7°-39.3°). The range of head positions relative to the cervical spine was largest when crouched (73.4°) and smallest when erect free standing (17.7°). This study indicates that, like humans, rats have near vertical orientated cervical vertebral columns but, in contrast to humans, they displace their head in space by movements at both the cervico-thoracic junction and the cranio-cervical regions.

Magnetic reconnection in the near Venusian magnetotail.

Observations with the Venus Express magnetometer and low-energy particle detector revealed magnetic field and plasma behavior in the near-Venus wake that is symptomatic of magnetic reconnection, a process that occurs in Earth's magnetotail but is not expected in the magnetotail of a nonmagnetized planet such as Venus. On 15 May 2006, the plasma flow in this region was toward the planet, and the magnetic field component transverse to the flow was reversed. Magnetic reconnection is a plasma process that changes the topology of the magnetic field and results in energy exchange between the magnetic field and the plasma. Thus, the energetics of the Venus magnetotail resembles that of the terrestrial tail, where energy is stored and later released from the magnetic field to the plasma.

Bacterial contamination of hands and the environment in a microbiology laboratory.

This study investigated both the impact of glove usage on bacterial hand contamination of laboratory technicians and extent of environmental contamination of a microbiology laboratory with potential bacterial pathogens. Two groups of laboratory technologists participated in the study - one group who always used gloves when handling bacterial cultures and another group who did not. Semiquantitative bacterial sampling from technicians' hands was performed before and after a defined work period. Frequently touched areas of the laboratory were sampled over a four-week period and selective or chromogenic media utilised for the identification of meticillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Salmonella spp. and Enterobacteriaceae. Laboratory technicians who did not use gloves were at significantly greater risk of acquiring MRSA following their work periods but no protective effect was demonstrated for glove usage against acquisition of Enterobacteriaceae. Hand washing was equally effective at removing acquired bacterial pathogens in both groups of workers. Environmental sampling documented the presence of MRSA in one-fifth of sampled sites, with the most frequent recovery from computer keyboards. Enterobacteriaceae and P. aeruginosa were less commonly recovered from the environment. This study demonstrates that glove usage is protective against the acquisition of MRSA and that MRSA is the most frequently recovered bacterial pathogen from our microbiology laboratory environment.

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given. 15 cancers have been detected to date, from a total of 1236 screening measurements. This event rate and the tumour grades reported are compared with recent reports from other studies in women at high risk of breast cancer.

Ultrasound guided core biopsy of suspicious mammographic calcifications using high frequency and power Doppler ultrasound.

AIM: The pre-operative diagnosis of suspicious mammographic microcalcifications usually requires stereotactic needle biopsy. The aim of this study was to evaluate if high frequency 13 MHz ultrasound (HFUS) and power Doppler (PD) can aid visualization and biopsy of microcalcifications. MATERIALS AND METHODS: Forty-four consecutive patients presenting with microcalcifications without associated mammographic or palpable masses were examined with HFUS and PD. Ultrasound-guided core biopsy (USCB) was performed where possible. Stereotactic biopsy was carried out when US-guided biopsy was unsuccessful. Surgery was performed if a diagnosis of malignancy was made on core biopsy or if the repeat core biopsy was non-diagnostic. RESULTS: Forty-one patients (93%) had ultrasound abnormalities corresponding to mammographic calcification. USCB was performed on 37 patients. In 29/37, USCB obtained a definitive result (78.4%). USCB was non-diagnostic in 4/9 benign (44.4%) and 4/28 (14.3%) malignant lesions biopsied. The complete and absolute sensitivities for malignancy using USCB were 85.7% (24/28) and 81% (23/28), respectively. USCB correctly identified invasive disease in 12/23 (52.2%) cases. There was no significant difference in the presence of abnormal flow on PD between benign and malignant lesions. However, abnormal PD vascularity was present in 43.5% of invasive cancer and was useful in directing successful biopsy in eight cases. CONCLUSION: The combination of high frequency US with PD is useful in the detection and guidance of successful needle biopsy of microcalcifications particularly where there is an invasive focus within larger areas of DCIS.

The role of ultrasound in breast cancer screening. A consensus statement by the European Group for Breast Cancer Screening.

The members of the European Group for Breast Cancer Screening have considered the use of ultrasound in breast diagnosis and breast cancer screening. After wide consultation and a detailed literature review, the consensus of the Group on the role of ultrasound is as follows: current evidence indicates that ultrasound of the breast is an important adjunct to mammography and clinical examination in the further assessment of both palpable and impalpable breast abnormalities. However, the use of ultrasound in population screening of asymptomatic women is associated with unacceptably high rates of both false positive and false negative outcomes. At present there is little evidence to support the use of ultrasound in population breast cancer screening at any age.

Aspergillus sinusitis in patients with AIDS: report of three cases and review.

Invasive aspergillosis is an uncommon but increasingly reported complication of AIDS. Sinusitis, usually bacterial in etiology, is frequently seen among human immunodeficiency virus (HIV)-infected patients. We discuss the cases of three patients with AIDS and invasive aspergillus sinusitis seen at our institutions and those of 15 patients who are described in the literature. Seven of the 18 had brain involvement, 3 had orbital involvement, and 7 had mastoid or other bony disease. Three had evidence of concomitant invasive pulmonary aspergillosis. Of 15 patients with evaluable histories, 11 had recognized risks for invasive aspergillosis; 6 had previous sinusitis, otitis, or polyposis; and 11 had prior conditions indicative of advanced HIV-related disease. Despite aggressive surgical intervention and systemic antifungal therapy, nearly all patients died as a result of aspergillosis.

The significance of ipsilateral leg ischaemia after renal transplantation.

We present three renal transplant patients who have been investigated for leg ischaemia on the side of the transplant. All were men aged between 50 and 57 years. Two had an iliac stenosis proximal to the transplant kidney and were treated successfully by percutaneous transluminal angioplasty. The other, with an internal iliac anastomosis, had occlusion of the external iliac artery and underwent femoro-femoral bypass grafting. Eight years later, almost 17 years after transplantation, this hyperlipidaemic patient was found to have an internal iliac origin stenosis proximal to the transplant kidney and also underwent successful angioplasty. In patients with functioning renal transplants, symptoms of arterial insufficiency in the ipsilateral leg should be investigated urgently because a proximal iliac stenosis potentially threatens graft survival.