Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

[Carotid endarterectomy with placement of a PUR (polyurethane) patch]

In this study, 40 patients who underwent surgery for cerebro-vascular insufficiency were considered. Carotid endarterectomy was the procedure of choice in all of the patients; the arteriotomy was always closed using a PUR patch, a new material that, for its chemical and physical characteristics seems to be a good alternative to PTFE. All of the patients underwent surgery under loco-regional anesthesia, allowing a perioperative monitoring of the neurological status through the patient's active collaboration. During the postoperative period, non local or systemic pathology related to the use of the patch has been observed. During the short and half term follow-up, the patients underwent echo-Doppler of the supra-aortic trunks that didn't show either false aneurysms or thrombosis on the patch surface

Spermatozoan Morphology Of Brachidontes Darwinianus And Brachidontes Solisianus (bivalvia, Mytilidae) From The Southern Brazilian Coast

Numerous investigations have demonstrated the usefulness of sperm morphology in evaluating molluscan phylogeny. In this work we used transmission and scanning electron microscopy to study the structure of mature spermatozoa from two bivalves, Brachidontes darwinianus and Brachidontes solisianus, and compared them with those of other bivalves, particularly other mytilids. These two species have a wide geographic distribution and are particularly abundant in the intertidal zone of many rocky shores along the Brazilian coast, often in areas with strong water currents. B. darwinianus occurs from the state of Rio de Janeiro, Brazil, to Patagonia, in Argentina, whereas B. solisianus is distributed from Mexico to Uruguay. The spermatozoa of both species were of the primitive or ect-aquasperm form. In both species the spermatozoan head contained an spheroidal nucleus capped by a conical acrosome with an anterior extension. No actin was detected in the subacrosomal region. However, immunocytochemical staining identified actin throughout the nucleus of the sperm of both species. The chromatin was strongly electron-dense, homogenous and compact. The nuclei contained randomly distributed, electron-lucent regions formed by invaginations of the nuclear envelope. These invaginations were detected by E-PTA staining for glycoproteins at low pH. The mid-piece region consisted of five spherical mitochondria grouped in a ring around a pair of short cylindrical centrioles. The flagellum exhibited the typical 9+2 microtubule structure (9 double outer tubules + 2 single central tubules). These findings, together with conchological characteristics, can be used to distinguish between B. darwinianus and B. solisianus. The only marked difference in the morphology of spermatozoa from these two species was the longer anterior extension of the acrosomal vesicle in B. solisianus. This elongated acrosome may facilitate penetration of the jelly coat and cytoplasm of large oocytes and could increase the efficiency of fertilization. The resulting enhanced reproductive success could account for the wider geographic distribution of B. solisianus. © 2004 Balaban.462-3149158Berger, E.M., Population genetics of marine gastropods and bivalves (1983) The Mollusca, 6, pp. 563-596. , W.D. Russel-Hunter (ed.), Academic Press, LondonBernard, R.T.F., Hodgson, A.N., The fine structure of the sperm and spermatid differentiation in the brown mussel Perna perna (1985) South Afr. J. Zool., 20, pp. 5-9Bernard, R.T.F., Davies, B.R., Hodgson, A.N., Reproduction in a brackish-water mytilid: Gametogenesis and embryonic development (1988) The Veliger, 30, pp. 278-290Chichvarkhin, A.Y., Letter to the editor (2002) Mol. Phylogen. Evol., 22, pp. 330-332Distel, D.L., Phylogenetic relationships among Mytilidae (Bivalvia): 18S rRNA data suggest convergence in Mytilid body plans (2000) Mol. Phylogen. Evol., 15, pp. 25-33Eckelbarger, K.J., Bieler, R., Mikkelsen, P.M., Ultrastructure of sperm development and mature sperm morphology in three species of commensal bivalves (Mollusca: Galeommatoidea) (1990) J. Morphol., 205, pp. 63-75Ferreira, A.A., (2003) Estrutura, Ultra-estrutura e Citoquímica Da Espermatogênese, Dos Ductos e Ovidutos Do Lagarto Tropidurus itambere Durante O Ciclo Reprodutivo, , Doctoral Thesis, Unicamp, BrazilFoighil, D.O., Fine structure of Lasaea subviridis and Mysella tumida sperm (Bivalvia, Galeommatacea) (1985) Zoomorphology, 105, pp. 125-132Franzén, A., Sperm structure with regard to fertilization biology and phylogenetics (1977) Verh. Dtsch. Zool. Ges., pp. 123-138Franzén, A., Ultrastructural studies of spermatozoa in three bivalve species with notes on evolution of elongated sperm nucleus in primitive spermatozoa (1983) Gamete Res., 7, pp. 199-214Fricker, M., Hollinshead, M., White, N., Vaux, D., Interphase nuclei of many mammalian cell types contain deep, dynamic, tubular membrane-bound invaginations of the nuclear envelope (1997) J. Cell Biol., 136, pp. 531-544Garrido, O., Gallardo, C.S., Ultrastructure of sperms in bivalve molluscs of the Mytilidae family (1996) Invert. Reprod. Develop., 29, pp. 95-102Guerra, R., Campos, B., Esponda, P., Analysis of the spermatozoa of four bivalves with particular reference to the acrosome and plasma membrane glycoproteins (1994) J. Submicrosc. Cytol. Pathol., 26, pp. 489-495Gwo, J.C., Chang, H.H., Jong, K.J., Ultrastructure of the spermatozoa of the small abalone, Sulculus diversicolor supertexa (Mollusca, Gastropoda, Haliotidae) (1997) J. Submicrosc. Cytol. Pathol., 29, pp. 239-244Gwo, J.C., Yang, W.T., Sheu, Y.T., Cheng, H.Y., Spermatozoan morphology of four species of bivalve (Heterodonta, Veneridae) from Taiwan (2002) Tissue Cell, 34, pp. 39-43Healy, J.M., Spermiogenesis and spermatozoa in the relict bivalve genus Neotrigonia: Relevance to trigonioid relationships, particularly Unionoidea (1989) Mar. Biol., 103, pp. 75-85Healy, J.M., Sperm ultrastructure in the marine bivalve families Carditidae and Crassatellidae and its bearing on unification of the Crassatelloidea with the Carditoidea (1995) Zool. Scripta, 24, pp. 21-28Healy, J.M., Buckland-Nicks, J.A., Jamieson, B.G.M., Spermatozoal ultrastructure of spiny oysters (Spondylidae, Bivalvia) including a comparison with other bivalves (2001) Invert. Reprod. Develop., 40, pp. 27-37Ishikawa, M., Numamiya, T., (1988) Experiments on Development of Marine Invertebrates: Mollusca (Bivalvia), pp. 87-96. , Baiffuukan, TokyoJamieson, B.G.M., A biological classification of sperm types, with special reference to annelids and mollusks, and an example of spermiocladistics (1987) New Horizons in Sperm Cell Research, pp. 311-332. , H. Mohri (ed.), Japan Scientific Societies Press, Gordon and Breach Science, New YorkJohnson, N., Krebs, M., Boudreau, R., Giorgi, G., Legros, M., Larabell, C., Actin-filled nuclear invaginations indicate degree of cell de-differentiation (2003) Differentiation, 71, pp. 414-424Kafanov, A.I., Drozdov, A.L., Comparative sperm morphology and phylogenetic classification of recent Mytiloidea (Bivalvia) (1998) Malacologia, 39, pp. 129-139Komaru, A., Konishi, K., Ultrastructure of biflagellate spermatozoa in the freshwater clam, Corbicula leana (Prime) (1996) Invert. Reprod. Develop., 29, pp. 193-197Nalesso, R.C., Duarte, F.L., Mendes, E.G., Phenotypic plasticity in Brachidontes darwinianus (Bivalvia, Mytilidae) (1992) Rev. Brasil. Biol., 52, pp. 245-249Popham, J.D., Comparative morphometrics of the acrosomes of the sperms of "externally" and "internally" fertilizing sperms of the shipworms (Teredinidae, Bivalvia, Mollusca) (1974) Cell Tissue Res, 150, pp. 291-297Popham, J.D., Comparative spermatozoon morphology and bivalve phylogeny (1979) Malac. Rev., 12, pp. 1-20Reunov, A.A., Hodgson, A.N., Ultrastructure of the spermatozoa of five species of South African bivalves (Mollusca), and an examination of early spermatogenesis (1994) J. Morph., 219, pp. 275-283Rios, E.C., (1995) Seashells of Brazil, 2nd Ed., , Museu Oceanográfico da FURG, Rio Grande do SulRouse, G.W., Jamieson, B.G.M., An ultrastructural study of the spermatozoa of the polychaetes Eurythoe complanata (Amphinomidae), Clymenella laseroni and Micromaldane laseroni (Maldanidae) with definition of sperm types in relation to reproductive biology (1987) J. Submicrosc. Cytol., 19, pp. 573-584Seed, R., Factors influencing shell shape in the mussel Mytilus edulis (1968) J. Mar. Biol. Ass. UK, 48, pp. 561-584Souza, M., Oliveira, E., An ultrastructural study of Crassostrea angulata (Mollusca, Bivalvia) spermatogenesis (1994) Mar. Biol., 120, pp. 545-551Tanaka, M.O., Magalhães, C.A., Morphometric species recognition in Brachidontes darwinianus (Orbigny, 1846) e Brachidontes solisianus (Orbigny, 1846) (Bivalvia: Mytilidae) (1999) The Veliger, 42, pp. 267-27

Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

OBJECTIVE To evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia. DESIGN Randomised, double blind, placebo controlled trial. SETTING Referral hospital in Cape Town, South Africa. PARTICIPANTS 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks’ gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo. INTERVENTION 3 g of oral extended release metformin or placebo daily, in divided doses, until delivery. MAIN OUTCOME MEASURE The primary outcome was prolongation of gestation. RESULTS Of 180 participants, one woman delivered before taking any trial drug. The median time from randomisation to delivery was 17.7 days (interquartile range 5.4-29.4 days; n=89) in the metformin arm and 10.1 (3.7-24.1; n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39, 95% confidence interval 0.99 to 1.95; P=0.057). Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (interquartile range 5.4-28.7; n=76) days compared with 7.9 (3.0-22.2; n=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 95% confidence interval 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (interquartile range 4.8-28.8; n=40) days compared with 4.8 (2.5-15.4; n=61) days in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% confidence interval 1.14 to 2.88). Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ. In the metformin arm, birth weight increased non-significantly and length of stay decreased in the neonatal nursery. No serious adverse events related to trial drugs were observed, although diarrhoea was more common in the metformin arm. CONCLUSIONS This trial suggests that extended release metformin can prolong gestation in women with preterm preeclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible. TRIAL REGISTRATION Pan African Clinical Trial Registry PACTR201608001752102 https://pactr.samrc.ac.za/.Catherine A Cluver, Richard Hiscock, Eric H Decloedt, David R Hall, Sonja Schell, Ben W Mol, Fiona Brownfoot, Tu, uhevaha J Kaitu, u-Lino, Susan P Walker, Stephen Ton

Angiotensin II type 2 receptor mediates high fat diet-induced cardiomyocyte hypertrophy and hypercholesterolemia

Obesity is the major risk factor for several cardiovascular and metabolic disorders. Previous studies reported that deletion of Angiotensin II type 2 receptor (AT2R) protects against metabolic dysfunctions induced by high fat (HF) diet. However, the role of AT2R in obesity-induced cardiac hypertrophy remains unclear. Male AT2R knockout (AT2RKO) and wild type (AT2RWT) mice were fed with control or HF diet for 10 weeks. HF diet increased cardiac expression of AT2R in obese mice. Deletion of AT2R did not affect body weight gain, glucose intolerance and fat mass gain induced by HF feeding. However, loss of AT2R prevented HF diet-induced hypercholesterolemia and cardiac remodeling. Mechanistically, we found that pharmacological inhibition or knockdown of AT2R prevented leptin-induced cardiomyocyte hypertrophy in vitro. Collectively, our results suggest that AT2R is involved in obesity-induced cardiac hypertrophy

Can single-cell and spatial omics unravel the pathophysiology of pre-eclampsia?

Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality. Characterised by the onset of hypertension and proteinuria in the second half of pregnancy, it can lead to maternal end-organ injury such as cerebral ischemia and oedema, pulmonary oedema and renal failure, and potentially fatal outcomes for both mother and fetus. The causes of the different maternal end-organ phenotypes of pre-eclampsia and why some women develop pre-eclampsia condition early in pregnancy have yet to be elucidated. Omics methods include proteomics, genomics, metabolomics, transcriptomics. These omics techniques, previously mostly used on bulk tissue and individually, are increasingly available at a single cellular level and can be combined with each other. Multi-omics techniques on a single-cell or spatial level provide us with a powerful tool to understand the pathophysiology of pre-eclampsia. This review will explore the status of omics methods and how they can and could contribute to understanding the pathophysiology of pre-eclampsia