Search

The negative influence of professional hierarchies between health cadres can silence nurse-midwives and junior medical staff,6 and may even demotivate personnel from participating in MPDSR. Maternal and perinatal death surveillance and response (MPDSR) is a health systems process entailing the continuous cycle of identification, notification and review of maternal and perinatal deaths (Surveillance), followed by actions to improve service delivery and quality of care (Response).1 Before the coronavirus disease 2019 (COVID-19) pandemic, there were an estimated 4.6 million maternal and neonatal deaths and stillbirths each year.2 During the pandemic, maternal and perinatal health outcomes have worsened, especially in low- and middle-income countries,3 highlighting the urgent need to galvanise MPDSR to end preventable mortality and strengthen health systems. Overcoming the blame culture that currently impedes MPDSR implementation requires action at all levels of the health system. 1 Therefore, dual national prioritisation on the value of systems learning and quality improvement that MPDSR encompasses needs to be matched with political priority for health system investment to implement I response i , deliver improved health outcomes and reduce the number of preventable deaths. [Extracted from the article]

Perinatal mental health disorders are a significant contributor to morbidity and mortality in childbearing women. The World Health Organization recommends all women be screened for mental health disorders postnatally and have diagnostic and management services available. There are, however, currently no global indicators in use which measure the status and progress of perinatal mental health. The aim of this scoping review was to identify existing perinatal mental health indicators and propose a core set which could be used at a global level. We used the Global Perinatal Mental Health Theory of Change as the conceptual framework. We found 25 indicators for PMH aligned with the Global Perinatal Mental Health Theory of Change, which were condensed to form a core set of nine indicators These core indicators include the proportion of women with depression, anxiety, post-traumatic stress disorder, psychosis, or adjustment disorders in the perinatal period; the proportion of women screened for these services; the proportion who have access to services following a positive diagnosis; and, the proportion of healthcare providers trained to provide mental health care. This review forms part of the foundational work for the development of a global monitoring framework which would be able to monitor progress towards the provision of universal high quality perinatal mental health care., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Layton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self-limiting edema due to temporary increase in vascular permeability. HAE with normal C1 esterase inhibitor (C1INH) activity includes the form with mutations in the F12 gene encoding for coagulation factor XII (FXII-HAE) causing an overproduction of bradykinin (BK) leading to angioedema attack. BK binding to B2 receptors (BK2R) leads to an activation of phospholipase C (PLC) and subsequent generation of second messengers: diacylglycerols (DAGs) and possibly the endocannabinoids (eCBs), 2-arachidonoylglycerol (2-AG) and anandamide (AEA), and eCB-related N-acylethanolamines [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)]. To date, there are no data on the role of these lipid mediators in FXII-HAE., Methods: Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII-HAE and 40 sex- and age-matched healthy individuals., Results: Plasma PLC activity was increased in FXII-HAE patients compared to controls. Concentrations of DAG 18:1-20:4, a lipid second messenger produced by PLC, were higher in FXII-HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2-AG were altered in FXII-HAE. AEA and OEA were decreased in FXII-HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH-HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls., Conclusions: BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII-HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII-HAE, and provide new potential biomarkers and therapeutic targets., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Neutrophils (polymorphonuclear leukocytes, PMNs) are the most abundant subtype of white blood cells and are among the main actors in the inflammatory response. Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting both the axial and peripheral joints. Typically associated with psoriasis, PsA can also affect multiple systems and organs, including the nails and entheses. Despite the involvement of PMNs in PsA, their specific role in the disease remains poorly understood. This study aimed to characterize the biological functions of PMNs and neutrophil-related mediators in PsA patients., Materials and Methods: 31 PsA patients and 22 healthy controls (HCs) were prospectively recruited. PMNs were isolated from peripheral blood and subjected to in vitro stimulation with lipopolysaccharide (LPS), N-Formylmethionyl-leucyl-phenylalanine (fMLP), tumor necrosis factor (TNF), phorbol 12-myristate 13-acetate (PMA), or control medium. Highly purified peripheral blood PMNs (>99%) were evaluated for activation status, reactive oxygen species (ROS) production, phagocytic activity, granular enzyme and neutrophil extracellular traps (NETs) release. Serum levels of matrix metalloproteinase-9 (MMP-9), myeloperoxidase (MPO), TNF, interleukin 23 (IL-23), and interleukin 17 (IL-17) were measured by ELISA. Serum Citrullinated histone H3 (CitH3) was measured as a NET biomarker., Results: Activated PMNs from PsA patients displayed reduced activation, decreased ROS production, and impaired phagocytic activity upon stimulation with TNF, compared to HCs. PMNs from PsA patients also displayed reduced granular enzyme (MPO) and NET release. Serum analyses revealed elevated levels of MMP-9, MPO, TNF, IL-23, IL-17, and CitH3 in PsA patients compared to HCs. Serum CitH3 levels positively correlated with MPO and TNF concentrations, and IL-17 concentrations were positively correlated with IL-23 levels in PsA patients. These findings indicate that PMNs from PsA patients show reduced in vitro activation and function, and an increased presence of neutrophil-derived mediators (MMP-9, MPO, TNF, IL-23, IL-17, and CitH3) in their serum., Conclusions: Taken together, our findings suggest that PMNs from PsA patients exhibit an "exhausted" phenotype, highlighting their plasticity and multifaceted roles in PsA pathophysiology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Modestino, Tumminelli, Mormile, Cristinziano, Ventrici, Trocchia, Ferrara, Palestra, Loffredo, Marone, Rossi, de Paulis and Galdiero.)

Historically, countries have primarily relied on policy rather than legislation to implement Maternal and Perinatal Death Surveillance and Response systems (MPDSR). However, evidence shows significant disparities in how MPDSR is implemented among different countries. In this article, we argue for the importance of establishing MPDSR systems mandated by law and aligned with the country's constitutional provisions, regional and international human rights obligations, and public health commitments. We highlight how a "no blame" approach can be regulated to provide a balance between confidentiality of the system and access to justice and remedies., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Introduction: The Janus kinase (JAK) family includes four cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3, and TYK2) constitutively bound to several cytokine receptors. JAKs phosphorylate downstream signal transducers and activators of transcription (STAT). JAK-STAT5 pathways play a critical role in basophil and mast cell activation. Previous studies have demonstrated that inhibitors of JAK-STAT pathway blocked the activation of mast cells and basophils., Methods: In this study, we investigated the in vitro effects of ruxolitinib, a JAK1/2 inhibitor, on IgE- and IL-3-mediated release of mediators from human basophils, as well as substance P-induced mediator release from skin mast cells (HSMCs)., Results: Ruxolitinib concentration-dependently inhibited IgE-mediated release of preformed (histamine) and de novo synthesized mediators (leukotriene C 4 ) from human basophils. Ruxolitinib also inhibited anti-IgE- and IL-3-mediated cytokine (IL-4 and IL-13) release from basophils, as well as the secretion of preformed mediators (histamine, tryptase, and chymase) from substance P-activated HSMCs., Discussion: These results indicate that ruxolitinib, inhibiting the release of several mediators from human basophils and mast cells, is a potential candidate for the treatment of inflammatory disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Poto, Cristinziano, Criscuolo, Strisciuglio, Palestra, Lagnese, Di Salvatore, Marone, Spadaro, Loffredo and Varricchi.)

The innate immune system, composed of neutrophils, basophils, eosinophils, myeloid-derived suppressor cells (MDSCs), macrophages, dendritic cells (DCs), mast cells (MCs), and innate lymphoid cells (ILCs), is the first line of defense. Growing evidence demonstrates the crucial role of innate immunity in tumor initiation and progression. Several studies support the idea that innate immunity, through the release of pro- and/or anti-inflammatory cytokines and tumor growth factors, plays a significant role in the pathogenesis, progression, and prognosis of cutaneous malignant melanoma (MM). Cutaneous melanoma is the most common skin cancer, with an incidence that rapidly increased in recent decades. Melanoma is a highly immunogenic tumor, due to its high mutational burden. The metastatic form retains a high mortality. The advent of immunotherapy revolutionized the therapeutic approach to this tumor and significantly ameliorated the patients' clinical outcome. In this review, we will recapitulate the multiple roles of innate immune cells in melanoma and the related implications for immunotherapy.

IBD is an uncontrolled inflammatory condition of the gastrointestinal tract, which mainly manifests in two forms: ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis of IBD appears to be associated with an abnormal response of innate and adaptive immune cells. Innate immunity cells, such as macrophages, mast cells, and granulocytes, can produce proinflammatory (e.g., TNF-α) and oxidative stress (ROS) mediators promoting intestinal damage, and their abnormal responses can induce an imbalance in adaptive immunity, leading to the production of inflammatory cytokines that increase innate immune damage, abate intestinal barrier functions, and aggravate inflammation. Considering that Ca 2+ signalling plays a key role in a plethora of cellular functions, this review has the purpose of deepening the potential Ca 2+ involvement in IBD pathogenesis.

Background: Macrophages are the predominant immune cells in the human lung and play a central role in airway inflammation, including asthma and chronic obstructive pulmonary disease (COPD). Thymic stromal lymphopoietin (TSLP), a pleiotropic cytokine mainly expressed by bronchial epithelial cells, plays a key role in asthma and COPD pathobiology. TSLP exists in two variants: the long form (lfTSLP) and a shorter TSLP isoform (sfTSLP). We aimed to localize TSLP in human lung macrophages (HLMs) and investigate the mechanisms of its release from these cells. We also evaluated the effects of the two variants of TSLP on the release of angiogenic factor from HLMs., Methods: We employed immunofluorescence and Western blot to localize intracellular TSLP in HLMs purified from human lung parenchyma. HLMs were activated by T2-high (IL-4, IL-13) and T2-low (lipopolysaccharide: LPS) immunological stimuli., Results: TSLP was detected in HLMs and subcellularly localized in the cytoplasm. IL-4 and LPS induced TSLP release from HLMs. Preincubation of macrophages with brefeldin A, known to disrupt the Golgi apparatus, inhibited TSLP release induced by LPS and IL-4. lfTSLP concentration-dependently induced the release of vascular endothelial growth factor-A (VEGF-A), the most potent angiogenic factor, from HLMs. sfTSLP neither activated nor interfered with the activating property of lfTSLP on macrophages., Conclusions: Our results highlight a novel immunologic circuit between HLMs and TSLP. Given the central role of macrophages in airway inflammation, this autocrine loop holds potential translational relevance in understanding innovative aspects of the pathobiology of asthma and chronic inflammatory lung disorders., Competing Interests: Declaration of competing interest These authors declare that they have no conflicts of interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Thymic stromal lymphopoietin (TSLP), mainly expressed by epithelial cells, plays a central role in asthma. In humans, TSLP exists in two variants: the long form TSLP (lfTSLP) and a shorter TSLP isoform (sfTSLP). Macrophages (HLMs) and mast cells (HLMCs) are in close proximity in the human lung and play key roles in asthma. We evaluated the early proteolytic effects of tryptase and chymase released by HLMCs on TSLP by mass spectrometry. We also investigated whether TSLP and its fragments generated by these enzymes induce angiogenic factor release from HLMs. Mass spectrometry (MS) allowed the identification of TSLP cleavage sites caused by tryptase and chymase. Recombinant human TSLP treated with recombinant tryptase showed the production of 1-97 and 98-132 fragments. Recombinant chymase treatment of TSLP generated two peptides, 1-36 and 37-132. lfTSLP induced the release of VEGF-A, the most potent angiogenic factor, from HLMs. By contrast, the four TSLP fragments generated by tryptase and chymase failed to activate HLMs. Long-term TSLP incubation with furin generated two peptides devoid of activating property on HLMs. These results unveil an intricate interplay between mast cell-derived proteases and TSLP. These findings have potential relevance in understanding novel aspects of asthma pathobiology.

Mastocytosis is a heterogeneous disease associated to uncontrolled proliferation and increased density of mast cells in different organs. This clonal disorder is related to gain-of-function pathogenic variants of the c-kit gene that encodes for KIT (CD117) expressed on mast cell membrane. Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine, which plays a key role in allergic disorders and several cancers. TSLP is a survival and activating factor for human mast cells through the engagement of the TSLP receptor. Activated human mast cells release several preformed mediators, including tryptase. Increased mast cell-derived tryptase is a diagnostic biomarker of mastocytosis. In this study, we found that in these patients serum concentrations of TSLP were lower than healthy donors. There was an inverse correlation between TSLP and tryptase concentrations in mastocytosis. Incubation of human recombinant TSLP with sera from patients with mastocytosis, containing increasing concentrations of tryptase, concentration-dependently decreased TSLP immunoreactivity. Similarly, recombinant β-tryptase reduced the immunoreactivity of recombinant TSLP, inducing the formation of a cleavage product of approximately 10 kDa. Collectively, these results indicate that TSLP is a substrate for human mast cell tryptase and highlight a novel loop involving these mediators in mastocytosis., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: While there has been a decline in maternal and perinatal mortality, deaths remain high in sub-Saharan Africa and Asia. With the sustainable development goals (SDGs) targets to reduce maternal and perinatal mortality, more needs to be done to accelerate progress and improve survival. Maternal and perinatal death surveillance and response (MPDSR) is a strategy to identify the clinical and social circumstances that contribute to maternal and perinatal deaths. Through MPDSR, an active surveillance and response cycle is established by bringing together different stakeholders to review and address these social and clinical factors. Community engagement in MPDSR provides a strong basis for collective action to address social factors and quality of care issues that contribute to maternal and perinatal deaths. Studies have shown that community members can support identification and reporting of maternal and/or perinatal deaths. Skilled care at birth has been increasing globally, but there are still gaps in quality of care. Through MPDSR, community members can collaborate with health workers to improve quality of care. But we do not know how community engagement in MPDSR works in practice; for whom it works and what aspects work (or do not work) and why. This realist review answers the question: which strategies of community engagement in MPDSR produce which outcomes in which contexts? Methods : For this realist review, we will identify published and grey literature by searching relevant databases for articles. We will include papers published from 2004 in all languages and from all countries. We have set up an advisory group drawn from academia, international organizations, and practitioners of both MPDSR and community engagement to guide the process. Conclusion: This protocol and the subsequent realist review will use theoretical approaches from the community engagement literature to generate theory on community engagement in MPDSR. Prospero registration number :  CRD42022345216., Competing Interests: No competing interests were disclosed., (Copyright: © 2023 Mbuo M et al.)

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease.

COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily, but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding of spike protein to ACE2 on the host cells. The virus uses the protease TMPRSS2 as an entry activator. Human lung macrophages (HLMs) are the most abundant immune cells in the lung and fulfill a variety of specialized functions mediated by the production of cytokines and chemokines. The aim of this project was to investigate the effects of spike protein on HLM activation and the expression of ACE2 and TMPRSS2 in HLMs. Spike protein induced CXCL8, IL-6, TNF-α, and IL-1β release from HLMs; promoted efficient phagocytosis; and induced dysfunction of intracellular Ca 2+ concentration by increasing lysosomal Ca 2+ content in HLMs. Microscopy experiments revealed that HLM tracking was affected by spike protein activation. Finally, HLMs constitutively expressed mRNAs for ACE2 and TMPRSS2. In conclusion, during SARS-CoV-2 infection, macrophages seem to play a key role in lung injury, resulting in immunological dysfunction and respiratory disease.

High levels of human group IIA secreted phospholipase A 2 (hGIIA) have been associated with various inflammatory disease conditions. We have recently shown that hGIIA activity and concentration are increased in the plasma of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) and negatively correlate with C1-INH plasma activity. In this study, we analyzed whether the presence of both hGIIA and C1-INH impairs their respective function on immune cells. hGIIA, but not recombinant and plasma-derived C1-INH, stimulates the production of IL-6, CXCL8, and TNF-α from peripheral blood mononuclear cells (PBMCs). PBMC activation mediated by hGIIA is blocked by RO032107A, a specific hGIIA inhibitor. Interestingly, C1-INH inhibits the hGIIA-induced production of IL-6, TNF-α, and CXCL8, while it does not affect hGIIA enzymatic activity. On the other hand, hGIIA reduces the capacity of C1-INH at inhibiting C1-esterase activity. Spectroscopic and molecular docking studies suggest a possible interaction between hGIIA and C1-INH but further experiments are needed to confirm this hypothesis. Together, these results provide evidence for a new interplay between hGIIA and C1-INH, which may be important in the pathophysiology of hereditary angioedema., (© 2022. The Author(s).)

Data from national health information systems are essential for routinely tracking progress, programmatic decision-making and to improve quality of services. Understanding the data elements captured in patient registers which are building blocks of national HMIS indicators, enables us to standardize data collection and measurement of key indicators for tracking progress towards achieving maternal and newborn health goals. This analysis was done through a review of antenatal care (ANC), childbirth and postnatal care (PNC) registers from 21 countries across five geographic regions. Between July and October 2020, country-based maternal and newborn experts, implementing agencies, program managers, and ministry of health personnel were asked to share the registers in use. Both paper-based and electronic registers were obtained. Twenty ANC registers, eighteen childbirth and thirteen PNC were available and analyzed. Both longitudinal and cross-sectional ANC and PNC registers were obtained, while the childbirth registers included in the analysis were all cross-sectional. Fifty-five percent (11/20) ANC registers and 54% (7/13) PNC registers were longitudinal. In four countries, the registers were electronic, while the rest were paper-based (17 countries). Sub-analysis of registers from four countries (Ghana, Kenya, Nigeria, and Zambia) where the 2017/2018 and 2019/2020 registers were available showed that the latest versions included 21/27 (78%) of data elements that are critical in the computation of key maternal and newborn care indicators. This analysis highlights some areas in where there are data gaps in data on pregnancy and childbirth. Program managers and health workers should use data gathered routinely to monitor the performance of their national health system and to guide the continuous improvement of health care services for women and newborns. The findings can help to inform the standardization of pregnancy and childbirth registers, and provide information for other countries seeking to introduce indicators in their health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kabue et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: An emerging body of evidence indicates an association between anthropogenic particulate matter (PM) and neurodegeneration. Although the historical focus of PM toxicity has been on the cardiopulmonary system, ultrafine PM particles can also exert detrimental effects in the brain. However, only a few studies are available on the harmful interaction between PM and CNS and on the putative pathomechanisms. Methods: Ultrafine PM particles with a diameter < 0.1 μm (PM0.1) and nanoparticles < 20 nm (NP20) were sampled in a lab-scale combustion system. Their effect on cell tracking in the space was studied by time-lapse and high-content microscopy in NSC-34 motor neurons while pHrodo™ Green conjugates were used to detect PM endocytosis. Western blotting analysis was used to quantify protein expression of lysosomal channels (i.e., TRPML1 and TPC2) and autophagy markers. Current-clamp electrophysiology and Fura2-video imaging techniques were used to measure membrane potential, intracellular Ca2+ homeostasis and TRPML1 activity in NSC-34 cells exposed to PM0.1 and NP20. Results: NP20, but not PM0.1, reduced NSC-34 motor neuron movement in the space. Furthermore, NP20 was able to shift membrane potential of motor neurons toward more depolarizing values. PM0.1 and NP20 were able to enter into the cells by endocytosis and exerted mitochondrial toxicity with the consequent stimulation of ROS production. This latter event was sufficient to determine the hyperactivation of the lysosomal channel TRPML1. Consequently, both LC3-II and p62 protein expression increased after 48 h of exposure together with AMPK activation, suggesting an engulfment of autophagy. The antioxidant molecule Trolox restored TRPML1 function and autophagy. Conclusions: Restoring TRPML1 function by an antioxidant agent may be considered a protective mechanism able to reestablish autophagy flux in motor neurons exposed to nanoparticles.

The anthropogenic particulate matter (PM), suspended air dust that can be inhaled by humans and deposited in the lungs, is one of the main pollutants in the industrialized cities atmosphere. Recent studies have shown that PM has adverse effects on respiratory diseases. These effects are mainly due to the ultrafine particles (PM0.1, PM < 100 nm), which, thanks to their PM size, are efficiently deposited in nasal, tracheobronchial, and alveolar regions. Pulmonary macrophages are a heterogeneous cell population distributed in different lung compartments, whose role in inflammatory response to injury is of particular relevance. In this study, we investigated the effect of PM0.1 on Human Lung Macrophages (HLMs) activation evaluated as proinflammatory cytokines and chemokine release, Reactive Oxygen Species (ROS) production and intracellular Ca 2+ concentration ([Ca 2+ ] i ). Furthermore, PM0.1, after removal of organic fraction, was fractionated in nanoparticles both smaller (NP20) and bigger (NP100) than 20 nm by a properlydeveloped analytical protocol, allowed isolating their individual contribution. Interestingly, while PM0.1 and NP20 induced stimulatory effects on HLM cytokines release, NP100 had not effect. In particular, PM0.1 induced IL-6, IL-1β, TNF-α, but not CXCL8, release from HLMs. Moreover, PM0.1, NP20 and NP100 did not induce β-glucuronidase release, a preformed mediator contained in HLMs. The long time necessary for cytokines release (18 h) suggested that PM0.1 and NP20 could induce ex-novo production of the tested mediators. Accordingly, after 6 h of incubation, PM0.1 and NP20 induced mRNA expression of IL-6, TNF-α and IL-1β. Moreover, NP20 induced ROS production and [Ca 2+ ] i increase in a time-dependent manner, without producing cytotoxicity. Collectively, the present data highlight the main proinflammatory role of NP20 among PM fractions. This is particularly of concern because this fraction is not currently covered by legal limits as it is not easily measured at the exhausts by the available technical methodologies, suggesting that it is mandatory to search for new monitoring techniques and strategies for limiting NP20 formation., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation, predominantly affecting the lung parenchyma and peripheral airways, that results in progressive and irreversible airflow obstruction. COPD development is promoted by persistent pulmonary inflammation in response to several stimuli (e.g., cigarette smoke, bacterial and viral infections, air pollution, etc.). Angiogenesis, the formation of new blood vessels, and lymphangiogenesis, the formation of new lymphatic vessels, are features of airway inflammation in COPD. There is compelling evidence that effector cells of inflammation (lung-resident macrophages and mast cells and infiltrating neutrophils, eosinophils, basophils, lymphocytes, etc.) are major sources of a vast array of angiogenic (e.g., vascular endothelial growth factor-A (VEGF-A), angiopoietins) and/or lymphangiogenic factors (VEGF-C, -D). Further, structural cells, including bronchial and alveolar epithelial cells, endothelial cells, fibroblasts/myofibroblasts, and airway smooth muscle cells, can contribute to inflammation and angiogenesis in COPD. Although there is evidence that alterations of angiogenesis and, to a lesser extent, lymphangiogenesis, are associated with COPD, there are still many unanswered questions.

Background: Maternal and perinatal death surveillance and response (MPDSR) is a system of identifying, analysing and learning lessons from such deaths in order to respond and prevent future deaths, and has been recommended by WHO and implemented in many low-and-middle income settings in recent years. However, there is limited documentation of experience with MPDSR in humanitarian settings. A meeting on MPDSR in humanitarian settings was convened by WHO, UNICEF, CDC and Save the Children, UNFPA and UNHCR on 17th-18th October 2019, informed by semi-structured interviews with a range of professionals, including expert attendees., Consultation Findings: Interviewees revealed significant obstacles to full implementation of the MPDSR process in humanitarian settings. Many obstacles were familiar to low resource settings in general but were amplified in the context of a humanitarian crisis, such as overburdened services, disincentives to reporting, accountability gaps, a blame approach, and politicisation of mortality. Factors more unique to humanitarian contexts included concerns about health worker security and moral distress. There are varying levels of institutionalisation and implementation capacity for MPDSR within humanitarian organisations. It is suggested that if poorly implemented, particularly with a punitive or blame approach, MPDSR may be counterproductive. Nevertheless, successes in MPDSR were described whereby the process led to concrete actions to prevent deaths, and where death reviews have led to improved understanding of complex and rectifiable contextual factors leading to deaths in humanitarian settings., Conclusions: Despite the challenges, examples exist where the lessons learnt from MPDSR processes have led to improved access and quality of care in humanitarian contexts, including successful advocacy. An adapted approach is required to ensure feasibility, with varying implementation being possible in different phases of crises. There is a need for guidance on MPDSR in humanitarian contexts, and for greater documentation and learning from experiences., (© 2022. The Author(s).)

On 9 March 2020, Italy passed the Prime Minister's Decree n. 648, establishing urgent measures to contain the transmission of COVID-19 and prevent biological hazards, including very restrictive interventions on public Holy Masses and funerals. Italy banned burial procedures based (i) on the recent acknowledgment about the virus environmental stability as well as (ii) its national civil contingency plan. Hence, only the cremation process is admitted for COVID-19 deaths. Viewing of the body is permitted only for mourners, which are allowed to perform the prayer at the closing of the coffin and the prayer at the tomb (cf. Rite of Succession, first part n. 3 and n. 5). The dead cannot be buried in their personal clothes; however, priests have been authorized to put the family clothes on top of the corpse, as if they were dressed. Burying personal items is also illegal. The dignity of the dead, their cultural and religious traditions, and their families should be always respected and protected. Among all the threats, COVID-19 epidemic in Italy revealed the fragility of human beings under enforced isolation and, for the first time, the painful deprivation of families to accompany their loved ones to the last farewell. Ethics poses new challenges in times of epidemics., (Copyright © 2020 Ussai, Armocida, Formenti, Palestra, Calvi and Missoni.)

Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author) and declare no conflicts of interest.

Study Objective: To investigate the reasons for discontinuation of the last contraceptive method used among adolescent women with a current unintended pregnancy., Design: Demographic and health, cross-sectional, surveys., Setting: Thirty-five low- and middle-income countries., Participants: We selected 2173 girls aged 15-19 years with a current unintended pregnancy, using a multistage cluster random sampling method., Interventions: A questionnaire administered by trained interviewers, which included sociodemographic as well as individual maternal and contraceptive history, was used to collect data., Main Outcome Measures: The prevalence of contraception utilization and the contribution of each reason for contraceptive discontinuation before the current unintended pregnancies., Results: Almost three-quarters of adolescent women were not using any contraception before the current unintended pregnancy, and less than 1 in 100 was using a long-acting modern method. Among girls who last used a traditional method, 111/150 (74.0%) discontinued because of failure. Among girls who last used a long-acting modern method, 7/11 (63.6%) discontinued because of health concerns and side effects., Conclusion: This study highlights that approximately 80.0% of adolescent women with an unintended pregnancy in 35 low- and middle-income countries were either nonusers or using traditional methods. An additional 20.4% were using a short-acting modern method. Long-acting methods would have prevented the overwhelming majority of unintended pregnancies, including the vast numbers from contraceptive failure., (Copyright © 2019 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance., Methods: In this observational, multicenter, nationwide study, children (age 1 month-12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and <13 years; and (3) written informed consent. Children were subdivided into three groups: ≤3 years, >3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses., Results: Two hundred fifty-nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month-12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy., Significance: In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Array comparative genomic hybridization is now a powerful tool to investigate patients with multiple congenital abnormalities and intellectual/motor impairment, and genomic imbalances are identified in a growing number of children with intellectual disability. Deletions in the 17p13.1 region have been reported in patients with dysmorphic features and developmental delay but a consistent phenotype has yet to emerge. Here, we report on the diagnosis of a 17p13.1 microdeletion of 829 kb in an 8-year-old girl presenting with profound cognitive disability, psychomotor delay, facial dysmorphisms, and refractory epilepsy. This deletion comprises 44 genes, including 8 OMIM morbid genes. We discuss genetic, clinical, and epileptic features comparing our patient with those previously reported in the literature., (© 2013 Wiley Periodicals, Inc.)