Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking. To this aim, preclinical studies can be really helpful to longitudinally study behavioural alterations resembling human symptoms and to investigate the underlying neurobiological correlates. In this regard, the BTBR T+ Itpr3tf/J (BTBR) mice are an inbred mouse strain that exhibits a pattern of behaviours well resembling human ASD-like behavioural features. In this study, the BTBR mice model was used to investigate neurochemical and biomolecular alterations, regarding Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), together with GABAergic, glutamatergic, cholinergic, dopaminergic and noradrenergic neurotransmissions and their metabolites in four different brain areas, i.e. prefrontal cortex, hippocampus, amygdala and hypothalamus. In our results, BTBR strain reported decreased noradrenaline, acetylcholine and GABA levels in prefrontal cortex, while hippocampal measurements showed reduced NGF and BDNF expression levels, together with GABA levels. Concerning hypothalamus, no differences were retrieved. As regarding amygdala, we found reduced dopamine levels, accompanied by increased dopamine metabolites in BTBR mice, together with decreased acetylcholine, NGF and GABA levels and enhanced glutamate content. Taken together, our data showed that the BTBR ASD model, beyond its face validity, is a useful tool to untangle neurotransmission alterations that could be underpinned to the heterogeneous ASD-like behaviours, highlighting the crucial role played by amygdala.

Increased stress vulnerability in the offspring of socially isolated rats: Behavioural, neurochemical and redox dysfunctions.

Stressful events during pregnancy impact on the progeny neurodevelopment. However, little is known about preconceptional stress effects. The rat social isolation represents an animal model of chronic stress inducing a variety of dysfunctions. Moreover, social deprivation during adolescence interferes with key neurodevelopmental processes. Here, we investigated the development of behavioural, neurochemical and redox alterations in the male offspring of socially isolated female rats before pregnancy, reared in group (GRP) or in social isolation (ISO) from weaning until young-adulthood. To this aim, females were reared in GRP or in ISO conditions, from PND21 to PND70, when they were mated. Their male offspring was housed in GRP or ISO conditions through adolescence and until PND70, when passive avoidance-PA, novel object recognition-NOR and open field-OF tests were performed. Levels of noradrenaline (NA), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), glutamate (GLU) and GABA were assessed in the prefrontal cortex (PFC). Moreover, cortical ROS levels were quantified, as well as NF-kB and the NADPH oxidase NOX2 expression, redox status (expressed as GSH:GSSG ratio) and SOD1 amount. A significant decrease of the latency time in the PA was observed in the offspring of ISO females. In the NOR test, while a significant increase in the exploratory activity towards the novel object was observed in the offspring of GRP females, no significant differences were found in the offspring of ISO females. No significant differences were found in the OF test among experimental groups. Theoffspring of ISO females showed increased NA and 5-HIAA levels, whereas in the offspring persistently housed in isolation condition from weaninguntil adulthood, we detected reduced 5-HT levels and ehnanced 5-HIAA amount. No significant changes in GLU concentrations were detected, while decreased GABA content was observed in the offspring of ISO females exposed to social isolation. Increased ROS levels as well as reduced NF-κB, NOX2 expression were detected in the offspring of ISO females. This was accompanied by reduced redox status and enhanced SOD1 levels. In conclusion, our results suggest that female exposure to chronic social stress before pregnancy might have a profound influence on the offspring neurodevelopment in terms of cognitive, neurochemical and redox-related alterations, identifying this specific time window for possible preventive and therapeutic strategies.

Relationship of microvascular density on histological and immunohistochemical features in endometrioid adenocarcinomas of the uterus: experimental study.

The most common malignant tumors of the uterus are endometrioid adenocarcinomas (EA). Their prognosis depends on the qualitative characteristics of the neoplastic cells and their stroma. The neovascularization of EA tissues and level of microvascular density (MVD) influence tumor progression. Our study aims to establish the relationship between MVD in EA tissue and the histological and immunohistochemical features of tumors. Materials and methods: The authors studied 30 cases of endometrial ЕА and compared their histological and immunohistochemical characteristics with the MVD of tumor tissues. Results: Our study indicated that MVD in EA tissue depends on the grade of the tumors and their FIGO stage. Increased MVD was correlated with a depression of E-cadherin and PR expression and enhanced expression of VEGF and Ki-67. MVD enhancement during VEGF overexpression is a manifestation of the functional activity of these proteins. The increase in MVD was accompanied by more frequent metastasis of the EA to the lymph nodes. Conclusion: EA progression is accompanied by qualitative and quantitative variations of parenchymal and stromal patterns of tumors. Dedifferentiation of EA leads to overexpression of VEGF, which becomes diffuse in tumors cells, resulting in an increase of adenocarcinomas' MVD and their metastatic potential. Correlations between histological and immunohistochemical features of EAs indicate the synchronicity of the occurrence and progression of morphological and immunological anaplasia, which can be used in predicting the course of the disease.

The Use of Cardioprotective Devices and Strategies in Patients Undergoing Percutaneous Procedures and Cardiac Surgery.

In the United States, about one million people are seen to visit the operating theater for cardiac surgery annually. However, nearly half of these visits result in complications such as renal, neurological, and cardiac injury of varying degrees. Historically, many mechanisms and approaches have been explored in attempts to reduce injuries associated with cardiac surgery and percutaneous procedures. Devices such as cardioplegia, mechanical circulatory support, and other methods have shown promising results in managing and preventing life-threatening cardiac-surgery-related outcomes such as heart failure and cardiogenic shock. Comparably, cardioprotective devices such as TandemHeart, Impella family devices, and venoarterial extracorporeal membrane oxygenation (VA-ECMO) have also been proven to show significant cardioprotection through mechanical support. However, their use as interventional agents in the prevention of hemodynamic changes due to cardiac surgery or percutaneous interventions has been correlated with adverse effects. This can lead to a rebound increased risk of mortality in high-risk patients who undergo cardiac surgery. Further research is necessary to delineate and stratify patients into appropriate cardioprotective device groups. Furthermore, the use of one device over another in terms of efficacy remains controversial and further research is necessary to assess device potential in different settings. Clinical research is also needed regarding novel strategies and targets, such as transcutaneous vagus stimulation and supersaturated oxygen therapy, aimed at reducing mortality among high-risk cardiac surgery patients. This review explores the recent advances regarding the use of cardioprotective devices in patients undergoing percutaneous procedures and cardiac surgery.

Lung Metastases to the Heart with Atypical Clinical Manifestations of Cardiac Failure.

The heart is a rare site of cancer metastases, even from the most common malignancies, such as lung cancer. Cardiac metastases may lead to myocardial dysfunction. This report presents a case of lung cancer metastases to the left ventricular myocardium that clinically manifested as atypical symptoms of cardiac dysfunction. The metastases were not revealed until after the patient died. Posthumously, the anamnesis, autopsy results, and morphological examination were evaluated. We demonstrated that the atypical symptoms of cardiac dysfunction were caused by occult (undiagnosed) metastases of lung cancer cells to the heart. The doctors did not consider this variant as possible metastatic lung cancer, because the patient had been treated radically one year earlier.

Appraising war's impacts on neurosurgical delivery in Ukraine.

The conflict in Ukraine, which started when Russia invaded and violated its sovereignty, has led to the country's worst war since the annexation of Crimea in 2014. The war has resulted in a significant number of casualties, displaced millions of people, and damaged the healthcare system, which was already struggling before the conflict. The neurosurgical field, in particular, has been severely affected, with infrastructure and healthcare systems routinely demolished or interrupted in conflict zones, making fundamental medical operations unavailable to victims of armed conflict. As a result, neurosurgeons have been compelled to conduct surgeries outside of their areas of competence, in makeshift settings or under challenging conditions, with limited access to materials and equipment. The war has also severely damaged specialised neurosurgery facilities, causing a severe shortage of crucial supplies and equipment. To address the challenges facing neurosurgery care in Ukraine, it is essential to rebuild and repair the damaged neurosurgical centres and provide them with the necessary equipment and supplies to successfully administer neurosurgical treatments. Training programs for neurosurgeons and other medical specialists must also be organised to manage complex neurosurgical problems under difficult conditions.

NeuroVerse: neurosurgery in the era of Metaverse and other technological breakthroughs.

The tremendous evolution in modern technology has led to a paradigm shift in neurosurgery. The latest advancements such as augmented reality, virtual reality, and mobile applications have been incorporated into neurosurgical practice. NeuroVerse, representing the application of the metaverse in neurosurgery, brings enormous potential to neurology and neurosurgery. Implementation of NeuroVerse could potentially elevate neurosurgical and interventional procedures, enhance medical visits and patient care, and reshape neurosurgical training. However, it is also vital to consider the challenges that may be associated with its implementation, such as privacy issues, cybersecurity breaches, ethical concerns, and widening of existing healthcare inequalities. NeuroVerse adds phenomenal dimensions to the neurosurgical environment for patients, doctors, and trainees, and represents an incomparable advancement in the delivery of medicine. Therefore, more research is needed to encourage widespread use of the metaverse in healthcare, particularly focusing on the areas of morality and credibility. Although the metaverse is expected to expand rapidly during and after the COVID-19 pandemic, it remains to be seen whether it represents an emerging technology that will revolutionize our society and healthcare or simply an immature condition of the future.

Increased rhinovirus/enterovirus infections including Ev-D68 in the United States, a challenge for healthcare providers amidst influenza virus infection and the COVID-19 pandemic.

In March 2020, WHO declared SARS-CoV-2 a global pandemic and lockdowns were enforced in most of the United States. Self-protective measures and travel restrictions were implemented, and schools/universities initiated online learning. Consequently, the global incidence and hospitalization rates of seasonal respiratory infections decreased significantly up to early 2021. Despite the decrease in hospitalization rates due to respiratory illnesses other than Covid-19, hospitals and healthcare providers faced huge stressors regarding workload dueto the pandemic. Furthermore, higher vaccination rates across the United States decreased non pharmaceutical interventions (NPI) implementation increasing the risk of major seasonal viral outbreaks. This editorial discusses the increased Rhinovirus/Enterovirus infections in the United States, challenges faced by healthcare providers and provides recommendations to address the issue.

Social isolation from early life induces anxiety-like behaviors in adult rats: Relation to neuroendocrine and neurochemical dysfunctions.

Subjects suffering from psychosis frequently experience anxiety. However, mechanisms underlying this comorbidity remain still unclear. We investigated whether neurochemical and neuroendocrine dysfunctions were involved in the development of anxiety-like behavior in a rodent model of psychotic-like symptoms, obtained by exposing male rats to social isolation rearing from postnatal day 21 to postnatal day 70. In the elevated zero maze test, isolated rats showed a significant reduction in the time spent in the open arms, as well as an increase in the time spent in the closed arms, compared to controls. An increased grooming time in the open field test was also observed in isolated animals. Isolation-induced anxiety-like behavior was accompanied by a decrease of plasmatic oxytocin, prolactin, ghrelin and melatonin levels, whereas plasmatic amount of Neuropeptide S was not altered. Social isolation also caused a reduction of noradrenaline, serotonin and GABA levels, together with an increase of serotonin turnover and glutamate levels in the amygdala of isolated animals. No significant differences were found in noradrenaline and serotonin levels, as well as in serotonin turnover in hippocampus, while glutamate amount was increased and GABA levels were reduced in isolated rats. Furthermore, there was a reduction in plasmatic serotonin content, and an increase in plasmatic kynurenine levels following social isolation, while no significant changes in serotonin turnover were observed. Taken together, our data provide novel insights in the neurobiological alterations underlying the comorbidity between psychosis and anxiety, and open new perspectives for multi-target therapies acting on both neurochemical and neuroendocrine pathways. DATA AVAILABILITY STATEMENT: The data presented in this study are available on request from the corresponding author.

Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment.

Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.

Approaching COVID-19 with epidemiological genomic surveillance and the sustainability of biodiversity informatics in Africa.

COVID-19 is an acute respiratory illness caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). The first case was reported in Africa on February 14, 2020 and has surged to 11 million as of July 2022, with 43% and 30% of cases in Southern and Northern Africa. Current epidemiological data demonstrate heterogeneity in transmission and patient outcomes in Africa. However, the burden of infectious diseases such as malaria creates a significant burden on public health resources that are dedicated to COVID-19 surveillance, testing, and vaccination access. Several control measures, such as the SHEF2 model, encompassed Africa's most effective preventive measure. With the help of international collaborations and partnerships, Africa's pandemic preparedness employs effective risk-management strategies to monitor patients at home and build the financial capacity and human resources needed to combat COVID-19 transmission. However, the lack of safe sanitation and inaccessible drinking water, coupled with the financial consequences of lockdowns, makes it challenging to prevent the transmission and contraction of COVID-19. The overwhelming burden on contact tracers due to an already strained healthcare system will hurt epidemiological tracing and swift counter-measures. With the rise in variants, African countries must adopt genomic surveillance and prioritize funding for biodiversity informatics.