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

Optimizing copy number variation analysis using genome-wide short sequence oligonucleotide arrays

The detection of copy number variants (CNV) by array-based platforms provides valuable insight into understanding human diversity. However, suboptimal study design and data processing negatively affect CNV assessment. We quantitatively evaluate their impact when short-sequence oligonucleotide arrays are applied (Affymetrix Genome-Wide Human SNP Array 6.0) by evaluating 42 HapMap samples for CNV detection. Several processing and segmentation strategies are implemented, and results are compared to CNV assessment obtained using an oligonucleotide array CGH platform designed to query CNVs at high resolution (Agilent). We quantitatively demonstrate that different reference models (e.g. single versus pooled sample reference) used to detect CNVs are a major source of inter-platform discrepancy (up to 30%) and that CNVs residing within segmental duplication regions (higher reference copy number) are significantly harder to detect (P < 0.0001). After adjusting Affymetrix data to mimic the Agilent experimental design (reference sample effect), we applied several common segmentation approaches and evaluated differential sensitivity and specificity for CNV detection, ranging 39–77% and 86–100% for non-segmental duplication regions, respectively, and 18–55% and 39–77% for segmental duplications. Our results are relevant to any array-based CNV study and provide guidelines to optimize performance based on study-specific objectives

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

Histopatološka analiza dišnih organa riba Channa striata izloženih zraku.

Effects of air exposure on the respiratory organs of Channa striata possessing bimodal respiration for exploitation of water (via gills and skin) as well as air (through air - breathing organs – suprabranchial chamber, ABOs) have been investigated. On air exposure the fish survived for 8 h. Following air exposure the fine, thin-walled blood capillaries (BLCs) at the surface of the ABO swelled and bulged out due to congestion when the blood came very close to air in the lumen. In the initial periods, mucous cells (MCs) of all three respiratory organs showed periodic fluctuations in their density and staining properties and stain for sulphated moieties known to hold an additional quantity of water. The sub-epithelial connective tissues of the ABO and skin also contained a large quantity of sulphated mucopolysaccharides. Subsequently, severe wear and tear and sloughing leading to haemorrhage took place from the skin. The outer cellular layers of the epidermis sloughed off. The density of sacciform-granulated cells (SGCs) increased and stained strongly with PAS technique (almost negative in controls). Air exposure also caused extensive damage in the gills. In the initial periods the BLCs showed severe congestion, causing extensive bulging and protrusion onto the surface. Later, the epithelial linings of gill filaments (PL) as well as respiratory lamellae (SL) were detached and lifted up. Subsequently, the neighbouring SL fused, causing decreased surface area, thereby reducing the efficiency of gills. The ladder-like arrangements of the pillar cells - blood capillaries (PLCs-BLCs) also collapsed. PAS-positive materials appeared within these PLCs. Subsequently, the BLCs dilated and showed congestion. The RBCs of gills also showed PAS staining. A thin layer of sulphated slime often covered the respiratory epithelia. Prior to death of the fish, the cells of the gills degenerated extensively. Thus, air exposure also prevented normal branchial respiration and the fish died due to anoxia and other physiological disorders.Istraženi su učinci izlaganja zraku dišnih organa ribe dvodihalice Channa striata koja za disanje koristi vodu (putem škrga i kože) ili zrak (putem organa zračnog disanja odnosno suprabranhijalne komore). Izložene zraku ribe su preživjele 8 sati. Nakon izloženosti zraku, nježne krvne kapilare tankih stijenki na površini organa zračnog disanja, odebljale su i izbočile se zbog kongestije kad je krv došla vrlo blizu zraku u lumenu organa. Sluznične stanice svih triju dišnih organa pokazivale su u početnim razdobljima povremeno kolebanje u gustoći i sposobnosti bojanja sulfatnih dijelova poznatih po zadržavanju dodatne količine vode. Subepitelno vezivno tkivo organa za zračno disanje i kože također je sadržavalo veliku količinu sulfatnih mukopolisaharida. Kao posljedica velike istrošenosti i ljuštenja javilo se krvarenje na koži. Vanjski slojevi stanica epidermisa su se ljuštili. Gustoća vrećastih zrnatih stanica se povećala i stanice su se snažno obojale PAS metodom (kontrola gotovo negativna). Izloženost zraku uzrokovala je i opsežna oštećenja škrga. Krvne kapilare su u početnom razdoblju bile zadebljane, nabubrene s izbočinama na površini. Kasnije su se bazalni epitel škržnih listića i dišni nabori odvojili i otkinuli. Potom su se susjedni dišni listići spojili dovodeći do smanjene površine, a time i do smanjene učinkovitosti škrga. Palisadni poredak stupčastih stanica krvnih kapilara također je propao. PAS pozitivni materijal pojavio se u stanicama škržnih listića. Nakon toga su se tanke stijenke krvnih kapilara proširile i zadebljale. Dišne stanice su se također obojale PAS metodom.Tanak sloj sulfatne sluzi često je prekrivao dišni epitel. Neposredno prije uginuća škržne stanice su degenerirale. Tako je izloženost zraku također spriječila normalno branhijalno disanje i ribe su uginule zbog nedostatka kisika i drugih fizioloških poremećaja

Procjena zagađenja vode cinkovim kloridom na osnovi patohistoloških nalaza dišnih organa ribe dvodihalice Channna striata (Bloch, 1797)

Sub-lethal toxicity of zinc chloride (11.5 ppm) on the respiratory organs of the Channa striata has been analysed. The mucous cells show periodic fluctuations in their number, size and staining properties elaborating larger quantities of sulphated mucopolysaccharides. The respiratory epithelium (RE) of the respiratory (secondary) lamellae (SL) of the gills shows periodic lifting with deformity of the lamellar elements, haemorrhages due to necrosis and sloughing off of the RE, followed by hyperplasia and fusion of neighbouring SL. Other prominent alterations include increased thickness of the RE and subsequent dismantling of the vascular elements. Fusion of SL reduces the surface area for gaseous exchange, causing impaired branchial respiration. The alterations in the suprabranchial chamber include protrusion of RBC-engorged minute vascular papillae on the floor of its lumen. This brings the blood nearer to the air in the lumen. Congestion of the sub-epithelial blood vessels of the respiratory organs, especially the suprabranchial chamber, takes place following exposure.Analizirana je subletalna toksičnost cinkova klorida (11,5 ppm) na dišne organe riba Channa striata. Sluznične stanice pokazivale su povremene promjene u broju, veličini i osobitostima bojanja s izraženom većom količinom sulfatnih mukopolisaharida. Epitel dišnih (sekundarnih) nabora škrga povremeno se otkidao što je dovelo do njihova oštećenja te krvarenja zbog nekroze i ljuštenja dišnog epitela s posljedičnom hiperplazijom i spajanjem susjednih dišnih listića. Druge promjene očitovale su se u vidu zadebljanja dišnog epitela i oštećenja krvožilja. Spajanje dišnih listića smanjilo je površinu za izmjenu plinova dovodeći do oslabljenog branhijalnog disanja. Promjene na suprabranhijalnoj komori dovele su do zadebljanja sićušnih papila na bazi lumena žila. Time se krv našla bliže zraku u lumenu. Nakon izloženosti došlo je do zadebljanja subepitelnih krvnih žila dišnih organa posebice suprabranhijalne komore

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