1. Structured Hysteroscopic Evaluation of Endometrium in Women With Postmenopausal Bleeding
Margit Dueholm, Ina Marie D Hjorth, Peter Secher, Annemette Jørgensen, Gitte Ørtoft J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1215-24. doi: 10.1016/j.jmig.2015.06.018. Epub 2015 Jun 30.
Study objective: To evaluate visual pattern parameters obtained with hysteroscopy for the prediction of endometrial cancer, to evaluate observer variation of these parameters, and to present a scoring system of the parameters for the prediction of malignancy compared with subjective evaluation. Design: A prospective controlled study (Canadian Task Force classification II-1). Setting: A university clinic. Patients: One hundred forty-nine consecutive women with postmenopausal bleeding and an endometrium thickness ≥ 5 mm. Sixty-one (41%) had endometrial cancer. Forty-six of 149 women were referred based on suspected malignancy. Interventions: Endometrial pattern characteristics for endometrial cancer were evaluated in hysteroscopic video clips. The reference standard was pathologic evaluation of resectoscopic samples or hysterectomy. Using multivariate logistic regression, image parameters were correlated with the presence of endometrial cancer. A scoring system of visual parameters for the prediction of malignancy was compared with subjective evaluation of malignancy. Measurements and main results: A score for lesion surface, necrosis, and vessels had an area under the curve (AUC) of 0.89, 0.89, and 0.87, respectively. A hysteroscopic cancer (HYCA) scoring system based on unsmooth lesion surface, papillary projections, surface necrosis, "candy floss" necrosis, white hyperintense spots, irregular branching vessels, and irregular distribution of irregular vessels was able to predict cancer (AUC = 0.964) with higher accuracy than subjective evaluation (AUC = 0.859, p < .01). At a score value ≥ 3, sensitivity was 89% and specificity was 92% with moderate agreement between observers (kappa = 0.56 [0.42-0.71]). Conclusion: A systematic pattern evaluation of optimal parameters by a HYCA scoring system based on systematically defined terms may increase accuracy in the diagnosis of endometrial cancer and should be further elaborated and external validity tested in unselected women with postmenopausal bleeding.
2. Isolation and characterization of hypophosphite--resistant mutants of Escherichia coli: identification of the FocA protein, encoded by the pfl operon, as a putative formate transporter
B Suppmann, G Sawers Mol Microbiol. 1994 Mar;11(5):965-82. doi: 10.1111/j.1365-2958.1994.tb00375.x.
Hypophosphite was used as a toxic analogue to identify genes whose products have a putative function in the transport of formate. Two Tn10-derived insertion mutants were identified that exhibited increased resistance to high concentrations of hypophosphite in the culture medium. The transposon was located in the identical position in the focA (formate channel; previously termed orf) gene of the pfl operon in both mutants. A defined chromosomal focA nonsense mutant, which showed minimal polarity effects on pfl gene expression, had the same phenotype as the insertion mutants. Results obtained using a hycA-lacZ fusion to monitor changes in the intracellular formate concentration in a focA mutant indicated that the level of formate inside the cell was elevated compared with the wild type. Moreover, it could be shown that there was a corresponding reduction of approximately 50% in the amount of formate excreted by a focA mutant into the culture medium. Taken together, these results indicate that formate accumulates in anaerobic cells which do not have a functional focA gene product and that one function of FocA may be to export formate from the cell. A further significant result was that hypophosphite could substitute for formate in activating hycA gene expression. This hypophosphite-dependent activation of hycA gene expression was reduced 10-fold in a focA null mutant, suggesting that hypophosphite must first enter the cell before it can act as a signal to activate hycA expression. By analogy, these data suggest that focA may also be functional in the import of formate into anaerobic Escherichia coli cells. Site-specific mutagenesis identified the translation initiation codon of focA as a GUG. Therefore, the FocA polypeptide has a molecular weight of 30,958. FocA shows significant similarity at both the primary and secondary structural levels with the NirC protein of E. coli and the FdhC protein of Methanobacterium formicicum. All three proteins are predicted to be integral membrane proteins. A detailed in vivo TnphoA mutagenesis study predicted that FocA has six membrane-spanning segments.
3. What Changes for Young Carers? A Qualitative Evaluation of the Impact of Dedicated Support Provision for Young Carers
Daniel Phelps Child Adolesc Social Work J. 2021;38(5):547-558. doi: 10.1007/s10560-021-00790-9. Epub 2021 Sep 14.
In 2016, the Children's Commissioner for England reported that the most frequent provision for young carers (YCs) comes from dedicated YC services. This study formed one part of a three-year evaluation of support for YCs and their families provided by the Hampshire YCs Alliance (HYCA), a county-wide collaboration of ten YC services in the UK. It set out to explore the following primary questions; (a) what are the most important changes that the YC services made to YCs and their families? (b) what is it about the services that creates those changes? Semi-structured interviews were carried out in 2017, with YCs aged 9-17 (n = 8), their parents (n = 5), HYCA staff (n = 6) and professionals from other stakeholder organisations (n = 5) and a thematic analysis was undertaken. Reflecting previous research that YCs and their families have a broad range of needs, findings also reveal how YC services support them through a diverse range of interventions. Support led to a diverse range of positive changes for YCs and their families. A number of service features that facilitate change for YCs, as well as 'key dynamics' important in facilitating change were identified. These findings have led to a conceptual framework of how YC services facilitate change for YCs and are important for understanding the impact these dedicated services can make to the lives of YCs and how they facilitate change. Together they have implications for the development and commissioning of interventions for YCs and families and how service providers promote their support provision.