Selective Cerebrospinal Fluid Hypothermia: Bioengineering Development and In Vivo Study of an Intraventricular Cooling Device (V-COOL)

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-022-01302-y.     

Morphologically Typical and Atypical B-Cell Chronic Lymphocytic Leukemias Display a Different Pattern of Surface Antigenic Density

Recent evidences suggest that B-cell chronic lymphocytic leukemia (B-CLL) may have heterogeneous biological and clinical features. Immunological phenotype may be useful for distinguishing these different forms of disease.

We used a quantitative flow cytometric approach to analyze the expression of several membrane molecules (CD19, CD20, CD22, CD23, CD11c, CD5, CD79b) commonly used to diagnose and characterize B-CLL in a choort of 84 consecutive B-CLL patients diagnosed according to morphological and immunological findings. We found that morphologically so-called “atypical” B-CLL displayed a significantly higher number of CD20 and CD22 molecules than typical forms. On the other hand, CD19 was found to be more expressed in typical B-CLL, although without reaching statistical significance. Finally, no difference was detected with respect to CD23, CD79b, CD11c and CD5 number of molecules/per cell between typical and atypical B-CLL. Other clinico-biological features, such as surface membrane immunoglobulin density, percentage of CD79b and FMC7 expression, peripheral blood lymphocytosis, trisomy 12 and advanced clinical stages were also found to be more frequent in atypical B-CLL. In conclusion, our data confirm the hypothesis that atypical B-CLL is a disease sustained by more mature B-cells, closely related but, at the same time, clearly distincted from neoplastic cells of typical B-CLL.     

Hygiene hypothesis and autoimmune diseases: A narrative review of clinical evidences and mechanisms

Since the start of the “modern era”, characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system.     

Gut Microbiota in Non-Alcoholic Fatty Liver Disease Patients with Inflammatory Bowel Diseases: A Complex Interplay

The intestinal microbiota represents the microbial community that colonizes the gastrointestinal tract and constitutes the most complex ecosystem present in nature. The main intestinal microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucromicrobia, with a clear predominance of the two phyla Firmicutes and Bacteroidetes which account for about 90% of the intestinal phyla. Intestinal microbiota alteration, or dysbiosis, has been proven to be involved in the development of various syndromes, such as non-alcoholic fatty liver disease, Crohn’s disease, and ulcerative colitis. The present review underlines the most recurrent changes in the intestinal microbiota of patients with NAFLD, Crohn’s disease, and ulcerative colitis.     

Resveratrol against Cervical Cancer: Evidence from In Vitro and In Vivo Studies

Cervical cancer affects many women worldwide, with more than 500,000 cases diagnosed and approximately 300,000 deaths each year. Resveratrol is a natural substance of the class of phytoalexins with a basic structure of stilbenes and has recently drawn scientific attention due to its anticancer properties. The purpose of this review is to examine the effectiveness of resveratrol against cervical cancer. All available in vitro and in vivo studies on cervical cancer were critically reviewed. Many studies utilizing cervical cancer cells in culture reported a reduction in proliferation, cell cycle arrest, and induction of apoptosis. Apart from apoptosis, induction of autophagy was seen in some studies. Importantly, many studies have shown a reduction in the HPV oncoproteins E6 and E7 and increased levels of the tumor suppressor p53 with resveratrol treatment. A few studies examined the effects of resveratrol administration in mice ectopic-xenografted with cervical cancer cells showing reduced tumor volume and weight. Overall, the scientific data show that resveratrol has the ability to target/inhibit certain signaling molecules (EGFR, VEGFR, PKC, JNK, ERK, NF-kB, and STAT3) involved in cervical cancer cell proliferation and survival. Further in vivo experiments and clinical studies are required to better understand the potential of resveratrol against cervical cancer.     

Rethinking Human Embryo Research Policies

It now seems technically feasible to culture human embryos beyond the “fourteen‐day limit,” which has the potential to increase scientific understanding of human development and perhaps improve infertility treatments. The fourteen‐day limit was adopted as a compromise but subsequently has been considered an ethical line. Does it remain relevant in light of technological advances permitting embryo maturation beyond it? Should it be changed and, if so, how and why? What justifications would be necessary to expand the limit, particularly given that doing so would violate some people's moral commitments regarding human embryos? Robust stakeholder engagement preceded adoption of the fourteen‐day limit and should arguably be part of efforts to reassess it. Such engagement could also consider the need for enhanced oversight of human embryo research. In the meantime, developing and implementing reliable oversight systems should help foster high‐quality research and public confidence in it.     

Tracheostomy in the COVID-19 pandemic

European Archives of Oto-Rhino-Laryngology - The role of tracheostomy in COVID-19-related ARDS is unknown. Nowadays, there is no clear indication regarding the timing of tracheostomy in these...     

Cell-based assays for the detection of MOG antibodies: a comparative study

Journal of Neurology - The detection of antibodies to myelin oligodendrocyte glycoprotein (MOG) is fundamental for the identification of MOG antibody-associated disorders (MOGAD), and the...