Aspirin and low-molecular weight heparin combination therapy effectively prevents recurrent miscarriage in hyperhomocysteinemic women.

The management of recurrent pregnancy loss (RPL) still remains a great challenge, and women with polycystic ovarian syndrome (PCOS) are at a greater risk for spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has become an accepted treatment option for women with RPL; however, the subgroup of women, who are likely to respond to LMWH, has not been precisely identified. The present study evaluated the efficacy of LMWH with reference to PCOS and associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin resistance (IR) and obesity. This prospective observational study was conducted at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with history of 2 or more consecutive first trimester abortions were screened and 336 were selected for the study. The selected patients were initially divided on the basis of presence or absence of PCOS, while subsequent stratification was based on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one conception cycle and aspirin-LMWH combined anticoagulant therapy for the immediate next conception cycle, if the first treated cycle was unsuccessful. Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy salvage following aspirin therapy was 43.15%, which was mostly represented by normohomocysteinemic women, while the salvage rate was lower in the HHcy populations irrespective of the presence or absence of PCOS, IR, or obesity. By contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the aspirin-failed cases. Logistic regression analyses showed that HHcy remained a significant factor in predicting salvage rates in the PCOS, IR, and obese subpopulations controlled for other confounding factors. With regard to pregnancy salvage, combined anticoagulant therapy with aspirin and LMWH conferred added benefit to those with HHcy phenotype

A novel sialylation site on Neisseria gonorrhoeae lipooligosaccharide links heptose II lactose expression with pathogenicity [preprint]

Sialylation of lacto-N-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for mAb 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac)-containing media enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOS of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and a MS11 mutant with only lactose from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6-linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with mAb 2C7; mAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. mAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose in vivo. Our findings reiterate the candidacy of the 2C7 epitope as a vaccine antigen and mAb 2C7 as an immunotherapeutic antibody

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract: Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes

Neonatal mortality risk of vulnerable newborns : A descriptive analysis of subnational, population-based birth cohorts for 238 143 live births in low- and middle-income settings from 2000 to 2017

Objective: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). Design: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. Setting: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. Population: Live birth neonates. Methods: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. Main Outcome Measures: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. Results: There were 238 143 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.8, interquartile range [IQR] 2.0–3.2), PT + LGA (median RR 7.3, IQR 2.3–10.4), PT + AGA (median RR 6.0, IQR 4.4–13.2) and PT + SGA (median RR 10.4, IQR 8.6–13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. Conclusions: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.Peer reviewe

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

An unusual groin mass. Seminal vesicle abscess: a case report

The rare pathology of seminal vesicle abscess is usually diagnosed with computerised tomography scan and confirmed with transrectal ultrasound. We report a recently encountered case where diagnosis proved difficult owing to the non-specific clinical presentation

Supervised segmentation of RTI appearance attributes for change detection on cultural heritage surfaces

International audienceThis paper proposes a supervised segmentation method for detecting surface changes based on appearance attributes, focusing on cultural heritage metal surfaces. Reflectance Transformation Imaging (RTI) reconstruction coefficients (PTM and HSH) are explored for tracking changes over time on different data sets. Each acquisition is normalised to ensure the method's robustness, allowing consecutive acquisitions with different RTI acquisition parameters. The proposed method requires expert labelling on groups of pixels representing individual classes. Afterward, the surface appearance is identified over time based on the estimated discriminant model. After segmentation, each detected category is assigned to a single colour to present the results with a user-friendly colourmap visualisation. The method is user-dependent; the labelling of the pixels must be accurately defined based on the research question. The results were evaluated based on human expertise in the conservation-restoration field and are considered ground truth in this work. A case study with visibly segmentable characteristics was used to prove the concept and evaluate the invariance of the proposed method. Comparison with the segmentation of the visible characteristics shows very accurate segmentation for HSH (99%) and lower for PTM (80%), which is influenced by surface rotation. The method was tested on metal surfaces undergoing accelerated corrosion or cleaning treatments. The results were promising for tracking changes based on segmentation. Equally promising is the possibility of qualitative quantifying the degree of change by counting the change of a selected class of pixels. PTM and HSH results are comparable in cases of mat surfaces; however, in high specular surfaces, HSH seems to provide more detailed information and, therefore, can better depict the surface characteristics. Limitations of the application are related to the possibility of identifying surface characteristics that do not exhibit topographic changes or significant reflectance differentiation

n-alkylamino analogs of Vitamin K3: Electrochemical, DFT and anticancer activity of their oxidized and one electron reduced form

Synthesis, characterization and anticancer activity of reduced form of n-alkylamino analogs of Vitamin K3 (1Na to 8Na) are undertaken. Molecular structure and molecular association of oxidized form of 2-ethylamino-3-methyl-1,4-naphthoquinone (2) and 2-hexylamino-3-methyl-1,4-naphthoquinone (6) were studied by single crystal X-ray analysis. 2 crystallize in monoclinic C2/c and 6 in P21 space group. The reduced form of eight homologated analogs of 2-(n-alkylamino)-3-methyl-1,4-naphthoquinone (1Na to 8Na) were synthesized using sodium metal as reductant at 0 °C in methanol. The formations of naphthosemiquinone radical in 1 to 6 have been confirmed from their EPR spectra. Polycrystalline powder X-band EPR spectra of 1 to 6 shows signals ∼2.0020 ± 0.0026 at 133 K. Anticancer activity of 2-(n-alkylamino)-3-methyl-1,4-naphthoquinone (1Na to 8Na) and one electron reduced forms have been evaluated against breast cancer (HeLa) cell line, 1 and 1Na showed promising anticancer activity

Food Habits of the Red Panda, Ailurus Fulgens in the Singhalila National Park, Darjeeling, India

Volume: 98Start Page: 224End Page: 23

Segmentation of change in surface geometry analysis for cultural heritage applications

This work proposes a change-based segmentation method for applications to cultural heritage (CH) imaging to perform monitoring and assess changes at each surface point. It can be used as a support or component of the 3D sensors to analyze surface geometry changes. In this research, we proposed a new method to identify surface changes employing segmentation based on 3D geometrical data acquired at different time intervals. The geometrical comparison was performed by calculating point-to-point Euclidean distances for each pair of surface points between the target and source geometry models. Four other methods for local distance measurement were proposed and tested. In the segmentation method, we analyze the local histograms of the distances between the measuring points of the source and target models. Then the parameters of these histograms are determined, and predefined classes are assigned to target surface points. The proposed methodology was evaluated by considering two different case studies of restoration issues on CH surfaces and monitoring them over time. The results were presented with a colormap visualization for each category of the detected change in the analysis. The proposed segmentation method will help in the field of conservation and restoration for the documentation and quantification of geometrical surface change information. This analysis can help in decision-making for the assessment of damage and potential prevention of further damage, and the interpretation of measurement results