An Enchanted Modern: Urban Cultivation in Shanghai

China is in the midst of the fastest and largest process of urbanization in history. Alongside the dynamism of the region’s hyperdense cities however are alarming levels of air pollution, recurrent stories of toxic food, contaminated waterways and intensifying popular protests concerning polluting factories and plants. Issues surrounding a sustainable urban ecology have thus become paramount in the construction of Asia’s metropolitan future. This paper, which focuses particularly on the Shanghai region, suggests that the ideas and practices of ‘cultivation’ might be of value in the creation and imagination of a future ecological metropolis. We examine self-cultivation concretely, as a set of situated embodied practices in specific places and specific historical conditions. We also explore the abstract conceptual idea, by looking at how the modern philosopher Mou Zongsan, articulated the idea of ‘cultivation’ as a guide for life. Ultimately, we are interested in how the embodied cultural practices of cultivation can be harnessed as a strategy of re-enchantment, with the power to reconfigure urban nature in the Chinese megacity of the 21st century

Thalassemia and the heartquake

On May 2012 the city of Ferrara and the surrounding region were hit by several earthquakes. We had the chance to observe the behavior of one thalassemic heart during the shocks, because of a 24-h electrocardiogram recording had been put in place a few hours before the shocks

Mitophagy in Cardiovascular Diseases

Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic‐ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic‐ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate‐to‐severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third‐level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic‐ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life

Utilizzo della melatonina come neuroprotettore dell'encefalopatia ipossico ischemica neonatale e identificazione di un possibile biomarker

INTRODUZIONE L’encefalopatia ipossico ischemica (EII) ha un’incidenza di 3-5x1000 nati vivi e può comportare paralisi cerebrale, disabilità intellettive severe e deficit cognitivi minori. L’ipotermia terapeutica (HT) rappresenta il trattamento di scelta dell’EII moderato-severa, tuttavia la letteratura dimostra che anche i neonati con EII lieve non trattati con HT sono a rischio di esiti neurologici a breve e lungo termine. La melatonina agisce in sinergia all'HT ed è una buona candidata come neuroprotettore per i suoi effetti di scavenger dei radicali liberi, blocco della cascata eccitotossica e modulazione dell’infiammazione. L’evento ipossico comporta la morte neuronale per apoptosi e necrosi, tuttavia è stato documentato anche un aumento dell’espressione di autofagia e mitofagia nei nuclei della base, talami, corteccia e ippocampo dei neonati asfittici. L'autofagia consente la rimozione o iI riciclaggio di componenti danneggiati o non più necessari per sostenere l’omeostasi cellulare e Atg5 è essenziale nella sua regolazione. Nel caso dei mitocondri, la mitofagia è responsabile della rimozione degli organelli non funzionanti e Parkin contrassegna i mitocondri pronti per essere digeriti. MELPRO studio prospettico multicentrico randomizzato non farmacologico, in doppio cieco in fase di reclutamento. Il progetto valuta sia gli effetti neuroprotettivi della melatonina associata all'HT, sia i suoi effetti sul processo di autofagia e mitofagia. PAZIENTI E METODI Verranno reclutati 100 neonati con EII moderato-severa. Attualmente sono stati randomizzati 24 neonati nel gruppo HT+placebo e 19 nel gruppo HT+melatonina. E’ somministrata melatonina (10 mg/kg), o placebo, per os per 5 giorni consecutivi. I livelli di Parkin e Atg5 vengono misurati nella prima settimana di vita nei 2 gruppi. Durante l’HT viene registrato l’EEG o aEEG e a 5-7 giorni di vita viene eseguita la RM encefalo con spettroscopia. I pazienti entrano in un programma di follow up eseguito con le scale Bayley III fino a 2 anni di età. RISULTATI L’analisi statistica è stata eseguita su 43 pazienti. Il follow up neuroevolutivo non è ancora disponibile. Dai primi dati la melatonina sembra prolungare l’effetto dell’HT mantenendo costante il processo di mitofagia. AGAIN studio prospettico, multicentrico. Vengono valutati l’autofagia e la mitofagia nei neonati con acidosi metabolica alla nascita e/o EII lieve che non soddisfano i criteri per l’HT. PAZIENTI E METODI Sono stati reclutatati i neonati con acidosi metabolica alla nascita e/o EII lieve non sottoposti a HT e sono stati eseguiti, nella prima settimana di vita, i dosaggi di Atg5 e Parkin per confrontarli con volontari sani e con neonati con EII severa sottoposta a HT. RISULTATI Le concentrazioni plasmatiche di Parkin sono risultate statisticamente differenti nei 3 gruppi e correlano con la severità dell’insulto ipossico ischemico. I neonati con EII severa hanno livelli di Parkin molto maggiori rispetto ai controlli sani e alle EII lievi e alla nascita correla con i lattati ed è inversamente proporzionale al pH arterioso. Inoltre, nel tempo, è risultato un incremento significativo di Parkin dell’81% nelle acidosi metaboliche alla nascita rispetto al 27% dei neonati sottoposti a HT. Atg5 è risultato significativamente più elevato nelle asfissie severe rispetto alle EII lievi e ai controlli sani. CONCLUSIONI Anche se il risultato non è definitivo, sembra che la melatonina prolunghi l’effetto dell’HT mantenendo elevati i livelli di mitofagia a 5 e 7 giorni. Parkin potrebbe essere un biomarker promettente per la sua correlazione con la severità dell’insulto ipossico e per il suo andamento nel tempo. Questo studio è stato disegnato per valutare l’effetto neuroprotettivo della melatonina, per comprenderne il meccanismo e l’effetto sul metabolismo cellulare. I risultati devono essere confermati co un ampio campione e maggiori trials clinici.INTRODUCTION Hypoxic-Ischemic Encephalopathy (HIE) occurs in 3-5x1000 births with consequences as cerebral palsy, severe intellectual disabilities and minor behavioral and cognitive deficits risk. The gold standard for moderate-severe HIE is hypothermic treatment (HT), but emerging evidences suggest that infants with mild HIE not qualified for HT have an increased risk for neurodevelopmental impairment. Melatonin potentially acts in synergy with HT and is a good candidate for neuroprotection due to protective effects, including reactive oxygen species scavenging, excitotoxic cascade blockade and neuroinflammatory pathways modulation. Neuronal injury is caused by apoptotic and necrotic death, however, increased expression of autophagy and mitophagy has been detected in the basal ganglia, thalamus, cortex and hippocampus of asphyxiated newborns. Autophagy removes and recycles unnecessary and dysfunctional elements to sustain cellular energetic requirements. Atg5 is essential to downregulate autophagy activation. In the case of mitochondria, mitophagy removes the ones tagged as dysfunctional; Parkin marks mitochondria as ready to be digested. MELPRO Multicenter, randomized, double-blind, placebo-controlled trial in the recruiting phase. This project evaluates the neuroprotective properties and both the clinical and the molecular effects of melatonin with HT to the neuropsychological development and the autophagy and mitophagy. METHODS Is a trial on 100 neonates with moderate to severe HIE. Babies are randomized into placebo/hHT group (currently n=24) and melatonin/HT group (n=19). Newborns receive 5 daily enteral doses of melatonin (10 mg/kg) or placebo. Mitophagy and autophagy levels are measured during the first week of life in the 2 HIE groups. aEEG monitoring is performed during HT and re-warming. Brain MRI and Spectroscopy are performed between day 5 and 7. The infants will enter in a neurodevelopmental follow-up program using the Bayley Scales III until 2 years of age. RESULTS Melatonin group maintained higher level of Parking than placebo group at 5 and 7 days. However, data are incomplete and statistical analysis considered 43 babies with HIE. The neurological follow up is not yet available. AGAIN Multicenter, prospective study to evaluate the autophagy and mitophagy processes in newborns with metabolic acidosis at birth and/or mild HIE not qualified for HT. METHODS Infants with metabolic acidosis at birth and evidence of mild HIE not qualified for HT were recruited to evaluate plasma autophagy and mitophagy during the first week of life. Plasmatic changes were compared to healthy control and severe HIE. RESULTS Plasma concentrations of Parkin were statistically different among study groups and correlate with the severity of hypoxic insult at birth. Severe HIE had significantly higher levels of Parkin when compared to mild HIE and healthy neonates. At birth Parkin is significantly and inversely correlated with the arterial pH and directly proportional to lactates. In addition, over time, Parkin showed an 81% increase in mild HIE cohort compared to the 27% in the severe HT-treated pool. Severe HIE had significantly higher levels of Atg5 when compared to mild HIE and healthy neonates. CONCLUSIONS Literature reported that melatonin with HT improves the neurodevelopmental outcome. In this study melatonin with HT maintained higher the levels of Parking than placebo at 5-7 days. Data are incompleted as recruitment is ongoing. Parkin seems to be a promising biomarker both in correlation with the severity of the hypoxic insult at birth and in its ability to significantly and constantly increase over time in mild to severe HIE. This study has been drawn to evaluate the improvement of melatonin towards neurodevelopmental outcome in asphyxiated infants, however, to understand its molecular mechanisms on the brain and cellular metabolism, data must be confirmed with a larger sample size and more clinical trials

An Enchanted Modern: Urban Cultivation in Shanghai

China is in the midst of the fastest and largest process of urbanisation in history. Alongside the dynamism of the region's hyperdense cities, however, are alarming levels of air pollution, recurrent stories of toxic food, contaminated waterways and intensifying popular protests concerning polluting factories and plants. Issues surrounding a sustainable urban ecology have thus become paramount in the construction of Asia’s metropolitan future. This paper, which focuses particularly on the Shanghai region, suggests that the ideas and practices of "cultivation" might be of value in the creation and imagination of a future ecological metropolis. We examine self-cultivation concretely, as a set of situated embodied practices in specific places and specific historical conditions. We also explore the abstract conceptual idea, by looking at how the modern philosopher Mou Zongsan articulated the idea of "cultivation" as a guide for life. Ultimately, we are interested in how the embodied cultural practices of cultivation can be harnessed as a strategy of re-enchantment, with the power to reconfigure urban nature in the Chinese megacity of the 21st century

Universal Head Ultrasound Screening in Full-term Neonates: A Retrospective Analysis of 6771 Infants

Background Full-term neonates may have asymptomatic cranial injuries at birth and head ultrasound screening could be useful for early diagnosis. The aim of this study was to assess the prevalence and type of intracranial abnormalities and the usefulness of head ultrasound screening in these infants. Methods Head ultrasound screening was performed on all full-term neonates (gestational age between 37 and 42 weeks), born at Sant'Anna University Hospital of Ferrara, Italy, from June 1, 2008 through May 31, 2013. Ultrasound findings were categorized into three groups: normal, minor, and major anomalies. Results All full-term neonates (6771) born at our hospital underwent head ultrasound screening. One hundred fourteen of 6771 (1.7%) presented ultrasound abnormalities, whereas 6657 were normal or exhibited insignificant findings. In 101 of 114 (88.6%), abnormalities were minor, and only 13 infants had major abnormalities (0.19% of all full-term newborns). All neonates with major abnormalities presented with either microcephaly or abnormal neurological evaluations. Only one individual with major abnormalities was detected exclusively by ultrasound. Conclusions The number of significant anomalies detected by head ultrasound screening in asymptomatic full-term neonates born during the study period was low. Therefore, there is no indication for routine general head ultrasound screening in these patients. However, even if low, in neonates who have neurological abnormalities, risk factors or suspected brain malformations, head ultrasound screening may play an important role in the early diagnosis of intracranial anomalies

Use of Ketamine in a Newborn With Refractory Status Epilepticus: A Case Report

BACKGROUND: Brain malformations represent a major cause of refractory seizures. Standardized protocols to treat status epilepticus of newborn are not available in the literature. PATIENT: We present a case report of use of ketamine administered to a late preterm with Pierre Robin sequence, lissencephaly, polymicrogyria, and severe epilepsy. RESULTS: The infusion of ketamine permitted resolution of status epilepticus, cardiorespiratory stabilization, and improved parental care for 15 days. No significant side effects were noted. CONCLUSION: In the literature there are few studies regarding the use of ketamine for refractory status epilepticus, and only in nine of these described the use of, ketamine in children (2 months-18 years). This is the first report to document the effective use of ketamine in the newborn with status epilepticus

Amplitude-integrated EEG recorded at 32 weeks postconceptional age. Correlation with MRI at term

Objective The study aims to establish the role of late aEEG (scored by Burdjalov) in predicting brain maturation as well as abnormalities evaluated at term equivalent age (TEA) by brain MRI. Methods 91 infants born before 30 wks gestation underwent an aEEG monitoring at 32 wks postconceptional age (PCA). aEEG, was correlated with TEA MRI, scored by Kidokoro. Results A significant correlation between the aEEG score and the MRI scores was found. The same results were obtained for the aEEG continuity score; cyclicity and bandwidth scores were associated with grey matter and cerebellar MRI items. Moreover, a correlation between aEEG and cEEG recorded both at 32 and 40 wks PCA, was found. Conclusions aEEG monitoring can be predictive of MRI findings at TEA, suggesting that it could be implemented as a useful tool to support ultrasound to help identify neonates who will benefit from early intervention services