Mesenchymal stem cell-derived small extracellular vesicles alleviate the immunometabolic dysfunction in murine septic encephalopathy.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that results in high mortality and long-term sequela. The central nervous system (CNS) is susceptible to injury from infectious processes, which can lead to clinical symptoms of septic encephalopathy (SE). SE is linked to a profound energetic deficit associated with immune dysregulation. Here, we show that intravenous administration of adipose tissue mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) in septic mice improved disease outcomes by reducing SE clinical severity, restoring aerobic metabolism, and lowering pro-inflammatory cytokines in the cerebellum, a key region affected by SE. Our high throughput analysis showed that MSC-derived sEVs partially reversed sepsis-induced transcriptomic changes, highlighting the potential association of miRNA regulators in the cerebellum of MSC-derived sEV-treated mice with miRNAs identified in sEV cargo. MSC-derived sEVs could serve as a promising therapeutic agent in SE through their favorable immunometabolic properties.

Hypercapnia Causes Injury of the Cerebral Cortex and Cognitive Deficits in Newborn Piglets.

In critically ill newborns, exposure to hypercapnia (HC) is common and often accepted in neonatal intensive care units to prevent severe lung injury. However, as a "safe" range of arterial partial pressure of carbon dioxide levels in neonates has not been established, the potential impact of HC on the neurodevelopmental outcomes in these newborns remains a matter of concern. Here, in a newborn Yorkshire piglet model of either sex, we show that acute exposure to HC induced persistent cortical neuronal injury, associated cognitive and learning deficits, and long-term suppression of cortical electroencephalogram frequencies. HC induced a transient energy failure in cortical neurons, a persistent dysregulation of calcium-dependent proapoptotic signaling in the cerebral cortex, and activation of the apoptotic cascade, leading to nuclear deoxyribonucleic acid fragmentation. While neither 1 h of HC nor the rapid normalization of HC was associated with changes in cortical bioenergetics, rapid resuscitation resulted in a delayed onset of synaptosomal membrane lipid peroxidation, suggesting a dissociation between energy failure and the occurrence of synaptosomal lipid peroxidation. Even short durations of HC triggered biochemical responses at the subcellular level of the cortical neurons resulting in altered cortical activity and impaired neurobehavior. The deleterious effects of HC on the developing brain should be carefully considered as crucial elements of clinical decisions in the neonatal intensive care unit.

Parental attitudes towards vaccination against COVID-19 of children 5-11 years old in Greece.

RATIONALE: Vaccinating children against COVID-19 is critical to contain the ongoing pandemic. AIMS/OBJECTIVES: The aim of the present study was to assess parents' and caregivers' intention to vaccinate their 5-11 years old children against COVID-19 and to estimate the association between vaccination intention and sociodemographic, clinical and contextual factors. METHOD: We conducted a questionnaire-based survey on a convenience sample of parents in Patras, Western Greece. RESULTS: Out of 366 study participants, around 48% reported their intention to vaccinate their child. The main factors associated with positive attitudes were paediatrician recommendation, parental vaccination, and reliance on the healthcare providers for decision making. Of note, 80% of the 190 parents who did not intend to vaccinate their children would vaccinate them if the paediatrician recommended it. CONCLUSION: Interventions to further train healthcare professionals to establish rapport with parents, and to provide adequate information about vaccinations are crucial to address concerns related to COVID-19 vaccine benefits for children.

Peripheral subcutaneous stimulation for the treatment of intractable postherpetic neuralgia: two case reports and literature review.

Postherpetic neuralgia (PHN) is a common cause of chronic pain in the elderly. Antidepressants, anticonvulsants, and opioids may reduce discomfort in many patients, while others have pain intractable to all forms of therapy. We present a novel treatment approach for intractable PHN utilizing percutaneous peripheral nerve stimulation. Two cases are described in which an 80-year-old man and a 67-year-old woman with intractable PHN, lasting 2 and 10 years, respectively, were effectively treated with implantation of two octapolar leads in the lateral thoracic region. These cases suggest that peripheral nerve stimulation may offer an alternative treatment option for intractable pain associated with PHN especially in the elderly where treatment options are limited because of existing comorbidities.