The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network’s first protocol: deep phenotyping in three sub-Saharan African countries

Background: The PRECISE (PREgnancy Care Integrating translational Science, Everywhere) Network is a new and broadly-based group of research scientists and health advocates based in the UK, Africa and North America. Methods: This paper describes the protocol that underpins the clinical research activity of the Network, so that the investigators, and broader global health community, can have access to ‘deep phenotyping’ (social determinants of health, demographic and clinical parameters, placental biology and agnostic discovery biology) of women as they advance through pregnancy to the end of the puerperium, whether those pregnancies have normal outcomes or are complicated by one/more of the placental disorders of pregnancy (pregnancy hypertension, fetal growth restriction and stillbirth). Our clinical sites are in The Gambia (Farafenni), Kenya (Kilifi County), and Mozambique (Maputo Province). In each country, 50 non-pregnant women of reproductive age will be recruited each month for 1 year, to provide a final national sample size of 600; these women will provide culturally-, ethnically-, seasonallyand spatially-relevant control data with which to compare women with normal and complicated pregnancies. Between the three countries we will recruit ≈10,000 unselected pregnant women over 2 years. An estimated 1500 women will experience one/more placental complications over the same epoch. Importantly, as we will have accurate gestational age dating using the TraCer device, we will be able to discriminate between fetal growth restriction and preterm birth. Recruitment and follow-up will be primarily facility-based and will include women booking for antenatal care, subsequent visits in the third trimester, at time-of-disease, when relevant, during/ immediately after birth and 6 weeks after birth. Conclusions: To accelerate progress towards the women’s and children’s health-relevant Sustainable Development Goals, we need to understand how a variety of social, chronic disease, biomarker and pregnancy-specific determinants health interact to result in either a resilient or a compromised pregnancy for either mother or fetus/ newborn, or both. This protocol has been designed to create such a depth of understanding. We are seeking funding to maintain the cohort to better understand the implications of pregnancy complications for both maternal and child health

SARS-CoV-2 seroprevalence in pregnant women in Kilifi, Kenya from March 2020 to March 2022

BackgroundSeroprevalence studies are an alternative approach to estimating the extent of transmission of SARS-CoV-2 and the evolution of the pandemic in different geographical settings. We aimed to determine the SARS-CoV-2 seroprevalence from March 2020 to March 2022 in a rural and urban setting in Kilifi County, Kenya.MethodsWe obtained representative random samples of stored serum from a pregnancy cohort study for the period March 2020 to March 2022 and tested for antibodies against the spike protein using a qualitative SARS-CoV-2 ELISA kit (Wantai, total antibodies). All positive samples were retested for anti-SARS-CoV-2 anti-nucleocapsid antibodies (Euroimmun, ELISA kits, NCP, qualitative, IgG) and anti-spike protein antibodies (Euroimmun, ELISA kits, QuantiVac; quantitative, IgG).ResultsA total of 2,495 (of 4,703 available) samples were tested. There was an overall trend of increasing seropositivity from a low of 0% [95% CI 0–0.06] in March 2020 to a high of 89.4% [95% CI 83.36–93.82] in Feb 2022. Of the Wantai test-positive samples, 59.7% [95% CI 57.06–62.34] tested positive by the Euroimmun anti-SARS-CoV-2 NCP test and 37.4% [95% CI 34.83–40.04] tested positive by the Euroimmun anti-SARS-CoV-2 QuantiVac test. No differences were observed between the urban and rural hospital but villages adjacent to the major highway traversing the study area had a higher seroprevalence.ConclusionAnti-SARS-CoV-2 seroprevalence rose rapidly, with most of the population exposed to SARS-CoV-2 within 23 months of the first cases. The high cumulative seroprevalence suggests greater population exposure to SARS-CoV-2 than that reported from surveillance data

Sistemazioni di anfore per usi diversi nel Suburbio di Ostia

Sondaggi di scavo condotti negli anni 1999-2002 all’interno del parcheggio e della Stazione di Ostia Antica hanno portato alla scoperta di edifici connessi con la necropoli di Pianabella e con impianti abitativi ad essa preesistenti. Il comune denominatore di questi rinvenimenti è l’uso di anfore funzionali al drenaggio nel caso della struttura ad uso funerario, inserite su doppia fila a contenere la parete retrostante nello scavo presso la Stazione. In quest’ultimo caso, la disposizione consentiva di sfruttare una falda d’acqua mineralizzata tramite l’uso della ruota idraulica del tipo «a cassetta». Secondo la tipologia delle anfore di tipologia simile a quelle della zona vicina della Longarina, l’attività dell’impianto si colloca tra la seconda metà del I sec. a.C. e la prima metà del I sec. d.C. L’estensione e le modalità di sistemazione di questi ultimi ritrovamenti fa ipotizzare un grande intervento pubblico di risanamento del suolo probabilmente realizzato in età augustea.Amphorae placing for different uses in the Ostia suburb. Excavations conducted in the years 1999-2002 inside the station of Ostia Antica for the construction of a pedestrian underpass and for the creation of an external parking area, permitted the discovery of buildings connected with the necropolis of Pianabella and with housing systems. Both for the funerary structure and for the ditch with the remains of an hydraulic wheel pertinent to a villa, common is the use of amphorae functional to the drainage in the first case, and inserted vertically on double row to contain the wall behind in the second case; in this latter form, the disposal allowed to exploit a mineral water flap through the use of the «cassette» type hydraulic wheel. Following the typology of amphorae, similar to those in the close area of the Longarina, the activity of this disposal ranks between the second half of the first century B.C. and the first half of the first century A.D. Form and size of this disposal suggest a large and public intervention of drainage realized in the Augustan age

The afterlife of the Porticus Aemilia

I resti della Porticus Aemilia hanno caratterizzato nei secoli, insieme al Monte Testaccio e alle Mura Aureliane, il paesaggio della pianura subaventina, racchiuso tra le vie Florio, Branca, Rubattino e Vespucci. Tra il 2011 e il 2013, all’interno di un progetto di ricerca e valorizzazione coordinato dalla Soprintendenza, sono state effet-tuate tre campagne di scavo. Le indagini, in collaborazione con il KNIR, hanno permesso di acquisire nuovi dati sulla la vita e le modificazioni dell’edificio nel corso dei secoli. Secondo le fonti letterarie (Liv. 35.10.12; Liv. 41.27.8) nel 193 a.C. gli edili curuli M. Aemilius Lepidus e L. Aemilius Paulus promossero nell’area libera della Piana Subaventina, la realizzazione di un nuovo porto fluviale (Emporium) e di una grande costruzione ad esso connessa, la Porticus Aemilia; i lavori per l’edificazione di tale struttura si conclusero probabilmente attorno al 174 a.C. ad opera dei censori Q. Fulvius Flaccus e A. Postumius Albinus. Tradizionalmente identificato come edificio di stoccaggio, la Porticus è stata oggetto negli anni di altre proposte interpretative e funzionali, fra cui quella di struttura connessa ai controlli fiscali sugli approvvigionamenti e quella di darsena militare sul Tevere (Navalia). Lo scavo non ha incontrato i livelli repubblicani, probabilmente asportati in antico, ma ha potuto documentare l’architettura dell’edificio originari. La Porticus Aemilia venne interessata da ristrutturazioni, tra la fine del I d.C.-inizio del II sec. d.C. e il III d.C., volte a suddividere le navate in vani più piccoli, destinati probabilmente allo stoccaggio o ad attività manifatturiere. Tra la fine del IV d.C. e il VI d.C., la piana subaventina subì un processo di “ruralizzazione” e gli edifici furono progressivamente abbandonati. Anche la Porticus Aemilia subì lo stesso destino, come testimoniano i crolli rinvenuti nel corso degli scavi e le sepolture in anfora addossate alla struttura. Durante il lungo periodo di abbandono l’edificio, ridotto a rudere, si integrava nel paesaggio medievale e rinascimentale della piana, costituito prima da spazi rurali adibiti a orti e giardini suburbani e poi da vigneti e frutteti. Tra la fine del 1800 e il 1900, quando l’area subì un nuovo processo di edificazione con la costruzione del quartiere popolare, i resti della Porticus accolsero nel tempo una vetreria, di cui resta traccia nei molti reperti rinvenuti durante gli scavi, ma anche un deposito di acque minerali e persino una carrozzeria, cadendo nell’incuria e nel degrado fino al recente recupero. È parte del Museo Diffuso del Rione Testaccio, che comprende anche il Mercato di Testaccio e l’Emporium

Analysis of TAp73-Dependent Signaling via Omics Technologies

Transactivation-proficient (TA) p73 is a transcription factor belonging to the p53 family, which regulates a variety of biological processes, including neurogenesis, differentiation, apoptosis, and DNA damage checkpoint response. In the present study, we adopted multiple Omics approaches, based upon the simultaneous application of metabolomics, lipidomics, and proteomics, in order to dissect the intracellular pathways activated by p73. As cellular model, we utilized a clone of the human osteosarcoma SAOS-2 cell line that allows the expression of TAp73α in an inducible manner. We found that TAp73α promoted mitochondrial activity (accumulation of metabolic intermediates and up-regulation of proteins related to the Krebs cycle), boosted glutathione homeostasis, increased arginine–citrulline–NO metabolism, altered purine synthesis, and promoted the pentose phosphate pathway toward NADPH accumulation for reducing and biosynthetic purposes. Indeed, lipid metabolism was driven toward the accumulation and oxidation of long-chain fatty acids with pro-apoptotic potential. In parallel, the expression of TAp73α was accompanied by the dephosphorylation of key proteins of the mitotic spindle assembly checkpoint. In conclusion, the obtained results confirm existing evidence from transcriptomics analyses and suggest a role for TAp73α in the regulation of cellular metabolism, cell survival, and cell growth

Analysis of TAp73-Dependent Signaling via Omics Technologies

Transactivation-proficient (TA) p73 is a transcription factor belonging to the p53 family, which regulates a variety of biological processes, including neurogenesis, differentiation, apoptosis, and DNA damage checkpoint response. In the present study, we adopted multiple Omics approaches, based upon the simultaneous application of metabolomics, lipidomics, and proteomics, in order to dissect the intracellular pathways activated by p73. As cellular model, we utilized a clone of the human osteosarcoma SAOS-2 cell line that allows the expression of TAp73α in an inducible manner. We found that TAp73α promoted mitochondrial activity (accumulation of metabolic intermediates and up-regulation of proteins related to the Krebs cycle), boosted glutathione homeostasis, increased arginine–citrulline–NO metabolism, altered purine synthesis, and promoted the pentose phosphate pathway toward NADPH accumulation for reducing and biosynthetic purposes. Indeed, lipid metabolism was driven toward the accumulation and oxidation of long-chain fatty acids with pro-apoptotic potential. In parallel, the expression of TAp73α was accompanied by the dephosphorylation of key proteins of the mitotic spindle assembly checkpoint. In conclusion, the obtained results confirm existing evidence from transcriptomics analyses and suggest a role for TAp73α in the regulation of cellular metabolism, cell survival, and cell growth

Postpartum recovery after severe maternal morbidity in Kilifi, Kenya: a grounded theory of recovery trajectories beyond 42 days

Introduction The burden of severe maternal morbidity is highest in sub-Saharan Africa, and its relative contribution to maternal (ill) health may increase as maternal mortality continues to fall. Women’s perspective of their long-term recovery following severe morbidity beyond the standard 42-day postpartum period remains largely unexplored.Methods This woman-centred, grounded theory study was nested within the Pregnancy Care Integrating Translational Science Everywhere (PRECISE) study in Kilifi, Kenya. Purposive and theoretical sampling was used to recruit 20 women who experienced either a maternal near-miss event (n=11), potentially life-threatening condition (n=6) or no severe morbidity (n=3). Women were purposively selected between 6 and 36 months post partum at the time of interview to compare recovery trajectories. Using a constant comparative approach of line-by-line open codes, focused codes, super-categories and themes, we developed testable hypotheses of women’s postpartum recovery trajectories after severe maternal morbidity.Results Grounded in women’s accounts of their lived experience, we identify three phases of recovery following severe maternal morbidity: ‘loss’, ‘transition’ and ‘adaptation to a new normal’. These themes are supported by multiple, overlapping super-categories: loss of understanding of own health, functioning and autonomy; transition in women’s identity and relationships; and adaptation to a new physical, psychosocial and economic state. This recovery process is multidimensional, potentially cyclical and extends far beyond the standard 42-day postpartum period.Conclusion Women’s complex needs following severe maternal morbidity require a reconceptualisation of postpartum recovery as extending far beyond the standard 42-day postpartum period. Women’s accounts expose major deficiencies in the provision of postpartum and mental healthcare. Improved postpartum care provision at the primary healthcare level, with reach extended through community health workers, is essential to identify and treat chronic mental or physical health problems following severe maternal morbidity