Real-world implementation and adaptation to local settings of first trimester preeclampsia screening in Italy: a systematic review

Background: Preeclampsia (PE) is a multisystem disease of pregnancy representing a major cause of maternal and perinatal morbidity and mortality. Early identification of pregnancies at risk of developing PE is crucial for implementing preventive strategies. The effective- ness of PE screening in the first trimester is widely recognized and endorsed by several guidelines, but unfortunately real-world im- plementation of this practice within local settings remains difficult. Methods: We performed a systematic review of the literature to un- derstand the critical issues hampering the implementation of PE screening procedures in Italy. All studies on first trimester PE screen- ing in the Italian population were eligible for inclusion. Key-concepts relevant for implementation of PE screening in Italy were extracted and analysed qualitatively. Results: Nine articles were selected and included. Lack of evidence concerning the topic of PE screening in Italy was shown. Major critical issues found encompassed health- care personnel education, training of sonographers, economic cov- erage for biochemical markers and adjustment of algorithms based on population characteristics. Conclusions: Identification and adapta- tion of specific protocols to local settings and population characteris- tics is critical for successful implementation of early PE screening in Italy. This process has the potential to improve pregnancy outcomes and to save valuable health-care resources, particularly scarce in the COVID-19 era. There is an urgent need for research studies on specific local populations focussing on subtle details capable of maximizing PE screening uptake. This action will likely potentiate PE screening implementation reducing the burden and the cost of perinatal and maternal complications

Effects of NSAIDs on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Trigeminal Ganglia

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to treat migraine, but the mechanisms of their effects in this pathology are not fully elucidated. The trigeminal ganglia and calcitonin gene-related peptide (CGRP) have been implicated in the pathophysiology of migraine. The release of CGRP and prostaglandin E 2 (PGE 2 ) from freshly isolated rat trigeminal ganglia was evaluated after oral administration of nimesulide, etoricoxib, and ketoprofen, NSAIDs with different pharmacological features. Thirty minutes after oral administration, nimesulide, 10 mg/Kg, decreased the GCRP release induced by an inflammatory soup, while the other NSAIDs were ineffective at this point in time. Two hours after oral nimesulide (5 and 10 mg/Kg) and ketoprofen (10 mg/Kg), but not of etoricoxib, a significant decrease in the CGRP release was observed. All drugs reduced PGE 2 , although with some differences in timing and doses, and the action on CGRP does not seem to be related to PGE 2 inhibition. The reduction of CGRP release from rat trigeminal ganglia after nimesulide and ketoprofen may help to explain the mechanism of action of NSAIDs in migraine. Since at 30 minutes only nimesulide was effective in reducing CGRP release, these results suggest that this NSAID may exert a particularly rapid effect in patients with migraine

Antagonism of the prokineticin system prevents and reverses allodynia and inflammation in a mouse model of diabetes

Neuropathic pain is a severe diabetes complication and its treatment is not satisfactory. It is associated with neuroinflammation-related events that participate in pain generation and chronicization. Prokineticins are a new family of chemokines that has emerged as critical players in immune system, inflammation and pain. We investigated the role of prokineticins and their receptors as modulators of neuropathic pain and inflammatory responses in experimental diabetes. In streptozotocin-induced-diabetes in mice, the time course expression of prokineticin and its receptors was evaluated in spinal cord and sciatic nerves, and correlated with mechanical allodynia. Spinal cord and sciatic nerve pro- and anti-inflammatory cytokines were measured as protein and mRNA, and spinal cord GluR subunits expression studied. The effect of preventive and therapeutic treatment with the prokineticin receptor antagonist PC1 on behavioural and biochemical parameters was evaluated. Peripheral immune activation was assessed measuring macrophage and T-helper cytokine production. An up-regulation of the Prokineticin system was present in spinal cord and nerves of diabetic mice, and correlated with allodynia. Therapeutic PC1 reversed allodynia while preventive treatment blocked its development. PC1 normalized prokineticin levels and prevented the up-regulation of GluN2B subunits in the spinal cord. The antagonist restored the pro-/anti-inflammatory cytokine balance altered in spinal cord and nerves and also reduced peripheral immune system activation in diabetic mice, decreasing macrophage proinflammatory cytokines and the T-helper 1 phenotype. The prokineticin system contributes to altered sensitivity in diabetic neuropathy and its inhibition blocked both allodynia and inflammatory events underlying disease

Contributions of implicit memory strategies to the rehabilitation of an amnesic patient: case report

Even severe amnesic patients usually are able to learn new information using implicit memory strategies. In the present study we describe our experience in the rehabilitation of an amnesic patient who had suffered cerebral anoxia. He was taught to use a computer text editor, enabling him to sheltered work. The training program lasted 14 weeks and was based on errorless learning and drilling practice techniques. The patient succeeded in all tasks, even though he could not remember accurately the training sessions. These results meet previous studies which point out that interaction between implicit and residual explicit memory can provide a basis new learning in amnesic patients. The domain-specific knowledge acquisition is demonstrating effectiveness in neuropsychological rehabilitation of brain injured patients.Mesmo pacientes severamente amnésticos são capazes de aprender informações novas, apoiados em estratégias de memória implícita. No presente estudo descrevemos uma experiência de reabilitação neuropsicológica, em que um paciente amnéstico, portador de lesão cerebral por anóxia, foi submetido a treino para uso de computador, visando sua capacitação semi-profissional. O treinamento teve duração de 14 semanas, e as técnicas de ensino utilizadas foram a prática repetitiva e a aprendizagem sem erros. O paciente obteve sucesso na realização das tarefas propostas, aprendendo a operar um editor de textos e mantendo o aprendizado após a passagem do tempo. Apesar disso, lembrava-se apenas vagamente da situação de aprendizagem. O presente estudo corrobora trabalhos anteriores que observam a interação entre mecanismos de memória implícita e resíduos de memória explícita operando na aquisição de conhecimentos em pacientes amnésticos. A aprendizagem de conhecimentos específicos vem se mostrando eficiente para a reabilitação de pacientes que sofreram lesões cerebrais.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsicobiologiaUNIFESP, EPM, Depto. de PsicobiologiaSciEL

Prokineticin System Is a Pharmacological Target to Counteract Pain and Its Comorbid Mood Alterations in an Osteoarthritis Murine Model

Osteoarthritis (OA) is the most prevalent joint disease associated with chronic pain. OA pain is often accompanied by mood disorders. We addressed the role of the Prokineticin (PK) system in pain and mood alterations in a mice OA model induced with monosodium iodoacetate (MIA). The effect of a PK antagonist (PC1) was compared to that of diclofenac. C57BL/6J male mice injected with MIA in the knee joint were characterized by allodynia, motor deficits, and fatigue. Twenty-eight days after MIA, in the knee joint, we measured high mRNA of PK2 and its receptor PKR1, pro-inflammatory cytokines, and MMP13. At the same time, in the sciatic nerve and spinal cord, we found increased levels of PK2, PKR1, IL-1β, and IL-6. These changes were in the presence of high GFAP and CD11b mRNA in the sciatic nerve and GFAP in the spinal cord. OA mice were also characterized by anxiety, depression, and neuroinflammation in the prefrontal cortex and hippocampus. In both stations, we found increased pro-inflammatory cytokines. In addition, PK upregulation and reactive astrogliosis in the hippocampus and microglia reactivity in the prefrontal cortex were detected. PC1 reduced joint inflammation and neuroinflammation in PNS and CNS and counteracted OA pain and emotional disturbances

Identification of Fetuses at Increased Risk of Trisomies in the First Trimester Using Axial Planes

Introduction: The measurement of nuchal translucency (NT) is crucial for assessing risk of aneuploidies in the first trimester. We investigate the ability of NT assessed by a transverse view of the fetal head to detect fetuses at increased risk of common aneuploidies at 11–13 weeks of gestation. Methods: We enrolled a nonconsecutive series of women who attended our outpatient clinic from January 2020 to April 2021 for aneuploidy screening by means of a first trimester combined test. All women were examined by operators certified by the Fetal Medicine Foundation. In each patient, NT measurements were obtained both from the median sagittal view and transverse view. We calculated the risk of aneuploidy using NT measurements obtained both with sagittal and axial scans, and then we compared the results. Results: A total of 1,023 women were enrolled. An excellent correlation was found between sagittal and transverse NT measurements. The sensitivity and specificity of the axial scan to identify fetuses that were deemed at risk of trisomy 21 using standard sagittal scans were 40/40 = 100.0% (95% confidence interval [CI]: 91.2–100.0) and 977/ 983 = 99.4% (95% CI: 98.7–99.7), respectively. The sensitivity and specificity of the axial scan to identify fetuses at risk of trisomy 13 or 18 were 16/16 = 100.0% (95% CI: 80.6–100.0) and 1,005/1,007 = 99.8% (95% CI: 99.3–99.9). Conclusions: When the sonogram, a part of combined test screening, is performed by an expert sonologist, axial views can reliably identify fetuses at increased risk of trisomies without an increase in false negative results

What is the impact of a novel MED12 variant on syndromic conotruncal heart defects? Analysis of case report on two male sibs

Background: Syndromic congenital heart disease accounts for 30% of cases and can be determined by genetic, environmental or multifactorial causes. In many cases the etiology remains uncertain. Many known genes are responsible for specific morphopathogenetic mechanisms during the development of the heart whose alteration can determine specific phenotypes of cardiac malformations. Case presentation: We report on two cases of association of conotruncal heart defect with facial dysmorphisms in sibs. In both cases the malformations' identification occurred by ultrasound in the prenatal period. It was followed by prenatal invasive diagnosis. The genetic analysis revealed no rearrangements in Array-CGH test, while gene panel sequencing identified a new hemizygous variant of uncertain significance (c.887G > A; p.Arg296Gln) in the MED12 gene, located on the X chromosome and inherited from the healthy mother. Conclusion: No other reports about the involvement of MED12 gene in syndromic conotruncal heart defects are actually available from the literature and the international genomic databases. This novel variant is a likely pathogenic variant of uncertain significance and it could broaden the spectrum of genes involved in the development of congenital heart diseases and the phenotypic range of MED12-related disorders

Elongation of the Hydrophobic Chain as a Molecular Switch:Discovery of Capsaicin Derivatives and Endogenous Lipids as Potent Transient Receptor Potential Vanilloid Channel 2 Antagonists

The transient receptor potential vanilloid type-2 (TRPV2) protein is a nonselective Ca2+ permeable channel member of the TRPV subfamily, still considered an orphan TRP channel due to the scarcity of available selective and potent pharmacological tools and endogenous modulators. Here we describe the discovery of novel synthetic long-chain capsaicin derivatives as potent TRPV2 antagonists in comparison to the totally inactive capsaicin, the role of their hydrophobic chain, and how the structure-activity relationships of such derivatives led, through a ligand-based approach, to the identification of endogenous long-chain fatty acid ethanolamides or primary amides acting as TRPV2 antagonists. Both synthetic and endogenous antagonists exhibited differential inhibition against known TRPV2 agonists characterized by distinct kinetic profiles. These findings represent the first example of both synthetic and naturally occurring TRPV2 modulators with efficacy in the submicromolar/low-micromolar range, which will be useful for clarifying the physiopathological roles of this receptor, its regulation, and its targeting in pathological conditions.We gratefully acknowledge financial support from Universitat de Lleida, Ministerio de Educación, Cultura y Deporte and Banco Santander (Programa UdL-Impuls). The authors are grateful to the Serveis Cientifictècnics (SCT) of the Universitat de Lleida for providing us with spectroscopic and chromatographic facilities. We acknowledge Dr. Alberto Minassi, Dipartimento di Scienze del Farmaco, Universitàdel Piemonte Orientale, Novara, Italy, for the kind gift of olvanil