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Severe craniofacial fractures may present different needs in treating intracranial lesions over facial injuries. This paper examines the results of our strategy, consisting of a single-stage combined neurosurgical-maxillofacial treatment. A retrospective review was conducted of 33 consecutive patients with complex fractures of the anterior cranial fossa and facial skeleton, who required elective surgery for craniofacial reconstruction. Patients who required emergency surgery for intracranial clots or penetrating wounds were excluded. In all cases, all or almost all the anterior skull-base was injured with compound fractures of the frontal sinus, the orbital roofs, the lamina cribrosa, and the planum sphenoidale. In all cases, the prioritization of treatment was carefully discussed, and surgical timing and strategy were agreed. There was 1 dead. Olfactory injuries were always found intraoperatively. There were no mucoceles, CSF-leak recurrences, cranial infections, or neurologic worsening. The functional and neurologic results were highly satisfactory. The one-stage surgical treatment of complex craniofacial fractures has numerous advantages, including the possibility of reducing facial fractures without the risk of CSF leaks. It also eliminates the need for repeated procedures in fragile patients, and the need to dismantle the facial reconstruction if the skull base repair is performed later. The main issue is the surgical timing, considering that the maxillofacial surgeon usually favors early facial repair, whereas the neurosurgeon generally prefers delayed manipulation of the contused frontal lobes. A timeframe of 10–14 days after trauma may be a good compromise for safe procedures with excellent neurologic and functional outcomes. [ABSTRACT FROM AUTHOR]

• Sex-based outcome of SARS-CoV-2 infection accounts for about 70 % of male deaths, despite similar susceptibility to infection. • TLR7/IFN-α axis in pDCs is crucial for B-cell activation and it is at the basis of dimorphic antibody response. • Dysregulated and unbalanced IFN-driven B cell response affects COVID-19 outcome in males. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, induces severe pneumonia mainly in elderly males. Epidemiological data clearly indicate sex-based differences in disease outcomes, with men accounting for about 70 % of deaths, despite similar susceptibility to infection. It is well known that females are endowed with higher capacity to produce antibodies, which correlates with viral clearance and disease resolution in the context of SARS-Cov-2 infection. Many X-linked immune genes escape X inactivation showing biallelic expression in female immune cells, particularly in plasmacytoid dendritic cells (pDCs). PDCs are more active in females and endowed with high capability to induce IFN-α-mediated B cell activation and differentiation into antibody-producing plasma cells throughout epigenetic mechanisms linked to trained immunity. Thus, we hypothesize that following SARS-CoV-2 infection, epigenetic modifications of X-linked genes involved in pDC-mediated type I IFN (IFN-I) signaling occurs more effectively in females, for inducing neutralizing antibody response as an immune correlate driving sex-biased disease outcome. [ABSTRACT FROM AUTHOR]

Immunotherapy is improving the prognosis and survival of cancer patients, but despite encouraging outcomes in different cancers, the majority of tumors are resistant to it, and the immunotherapy combinations are often accompanied by severe side effects. Here, we show that a periodic fasting-mimicking diet (FMD) can act on the tumor microenvironment and increase the efficacy of immunotherapy (anti-PD-L1 and anti-OX40) against the poorly immunogenic triple-negative breast tumors (TNBCs) by expanding early exhausted effector T cells, switching the cancer metabolism from glycolytic to respiratory, and reducing collagen deposition. Furthermore, FMD reduces the occurrence of immune-related adverse events (irAEs) by preventing the hyperactivation of the immune response. These results indicate that FMD cycles have the potential to enhance the efficacy of anti-cancer immune responses, expand the portion of tumors sensitive to immunotherapy, and reduce its side effects. [Display omitted] • FMD improves the efficacy of immunotherapy against triple-negative breast cancer • FMD increases the percentage of early exhausted effector T cells • FMD reduces intratumor collagen deposition, a poor-prognosis marker • FMD prevents immunotherapy side effects Cortellino et al. show that FMD sensitizes low-immunogenic and poorly responsive triple-negative breast cancer to immunotherapy, so it could be tested in a clinical trial in cancer patients to determine whether it improves their prognosis. Furthermore, the authors demonstrate that FMD reduces the adverse side effects associated with immunotherapy. [ABSTRACT FROM AUTHOR]

We examined the influence of an antecedent communication intervention on challenging behavior for three students with developmental disorders. Students were taught to request tangible items that were identified as reinforcers for challenging behavior in a prior functional analysis. Individual participant multielement and reversal designs were used to compare the effects of the antecedent communication intervention versus a no antecedent communication intervention condition. Immediately following the antecedent manipulations students were exposed to the tangible condition of the functional analysis. Results indicate that the antecedent communication intervention reduced challenging behavior in the subsequent tangible test condition for all three students. The importance of examining antecedent interventions to treat challenging behavior from a function analytic perspective is discussed. [Copyright &y& Elsevier]

Abstract: Joint attention is the act of sharing an experience of an object or event with another person. Individuals with autism often have deficits in this area. This review synthesizes 27 articles, involving interventions for individuals with autism, that measured joint attention as an outcome variable. Studies were analyzed and summarized in terms of: (a) joint attention as a collateral versus direct outcome, (b) participant characteristics, (c) study design, (d) intervention techniques, (e) types of joint attention measured, and (f) results. Interventions either directly targeted joint attention or measured joint attention as a collateral outcome. Most interventions used a combination of behavioral and developmental strategies. The results of these studies suggest that using play as a context, and training with natural communication partners may benefit generalization. Future research should address the relation between type of intervention and child characteristics, ensure that joint attention behaviors meet natural contingencies that serve the purpose of sharing attention, and continue to examine collateral outcomes of joint attention. [Copyright &y& Elsevier]

Abstract: Two children with autism who engaged in aggression and stereotypy were assessed using common analogue functional analysis procedures. Aggression was maintained by access to specific preferred items. Data on the rates of stereotypy and appropriate play were collected during an extended functional analysis tangible condition. These data reveal that once the child was given access to the items shown to be maintaining challenging behavior that these items were then used to engage in stereotypy. These results suggest a relationship between stereotypy and socially mediated challenging behavior. Potential modifications to standard functional analysis procedures designed to identify this relationship and the implications of this relationship for intervention design are discussed. [Copyright &y& Elsevier]

An estimated 50–90% of individuals with cocaine use disorder (CUD) also report using alcohol. Cocaine users report coabusing alcohol to 'self-medicate' against the negative emotional side effects of the cocaine 'crash', including the onset of anxiety. Thus, pharmaceutical strategies to treat CUD would ideally reduce the motivational properties of cocaine, alcohol, and their combination, as well as reduce the onset of anxiety during drug withdrawal. The hypothalamic orexin (hypocretin) neuropeptide system offers a promising target, as orexin neurons are critically involved in activating behavioral and physiological states to respond to both positive and negative motivators. Here, we seek to describe studies demonstrating efficacy of orexin receptor antagonists in reducing cocaine, alcohol- and stress-related behaviors, but note that these studies have largely focused on each of these phenomena in isolation. For orexin-based compounds to be viable in the clinical setting, we argue that it is imperative that their efficacy be tested in animal models that account for polysubstance use patterns. To begin to examine this, we present new data showing that rats' preferred level of cocaine intake is significantly increased following chronic homecage access to alcohol. We also report that cocaine intake and motivation are reduced by a selective orexin-1 receptor antagonist when rats have a history of cocaine + alcohol, but not a limited history of cocaine alone. In light of these proof-of-principle data, we outline what we believe to be the key priorities going forward with respect to further examining the orexin system in models of polysubstance use. This article is part of the special issue on Neurocircuitry Modulating Drug and Alcohol Abuse. • Most individuals with cocaine use disorder (CUD) also report using alcohol. • Alcohol protects against the onset of anxiety during cocaine withdrawal. • Orexin receptor antagonists reduce drug seeking and anxiety seeking. • These effects are stronger following cocaine + alcohol coadministration. • The orexin system is a promising candidate to treat polysubstance abuse. [ABSTRACT FROM AUTHOR]

Abstract: Hybrid organic–inorganic coatings based on thiol-ene systems were obtained by a UV-thermal dual-curing process. An improvement in mechanical properties and surface hardness was achieved because of the presence of the inorganic filler generated in situ via the sol–gel process. TEM analysis clearly evidenced the reduction of the nanosize dimensions of the inorganic silica domains by increasing the coupling agent content in the photocurable formulation. [Copyright &y& Elsevier]

This paper reports about a combined technology for soil remediation from PCBs using the thermal desorption technique coupled with the catalytic hydrogenation of recovered PCBs. The reactor is a bench scale rotating desorption furnace through which nitrogen is flushed and used as carrier gas of desorbed PCBs. The latter are condensed into an hexane or hexane–acetone (1:1 v/v) solution that is then hydrogenated using phosphate-supported Pd or Rh as catalyst. The analysis of the treated soil, under variable operative conditions (temperature and desorption time), shows that the total (99.8%) decontamination from PCBs occurs. The recovery yield of the desorbed PCBs is better than 75% and the subsequent hydrogenation reaches 63% of the collected PCBs in 5h or 100% in 12h. [Copyright &y& Elsevier]

Psychiatric disorders affect nearly 50% of individuals who have experienced a traumatic brain injury (TBI). Anhedonia is a major symptom of numerous psychiatric disorders and is a diagnostic criterion for depression. It has recently been appreciated that reinforcement may be separated into consummatory (hedonic), motivational and decisional components, all of which may be affected differently in disease. Although anhedonia is typically assessed using positive reinforcement, the importance of stress in psychopathology suggests the study of negative reinforcement (removal or avoidance of aversive events) may be equally important. The present study investigated positive and negative reinforcement following a rat model of mild TBI (mTBI) using lateral fluid percussion. Hedonic value and motivation for reinforcement was determined by behavioral economic analyses. Following mTBI, the hedonic value of avoiding foot shock was reduced. In contrast, the hedonic value of escaping foot shock or obtaining a sucrose pellet was not altered by mTBI. Moreover, motivation to avoid or escape foot shock or to acquire sucrose was not altered by mTBI. Our results suggest that individuals experiencing mTBI find avoidance of aversive events less reinforcing, and therefore are less apt to utilize proactive control of stress. [ABSTRACT FROM AUTHOR]

The transcription factor interferon regulatory factor-8 (IRF-8) is crucial for myeloid cell development and immune response and also acts as a tumor suppressor gene. Here, we analyzed the role of IRF-8 in the cross talk between melanoma cells and tumor-infiltrating leukocytes. B16-F10melanoma cells transplanted into IRF-8-deficient (IRF-8-/-) mice grow more rapidly, leading to higher numbers of lung metastasis, with respect to control animals. These events correlated with reduced dendritic cell and T cell infiltration, accumulation of myeloid-derived suppressor cells and a chemokine/chemokine receptor expression profile within the tumor microenvironment supporting tumor growth, angiogenesis, and metastasis. Noticeably, primary tumors developing in IRF-8-/- mice displayed a clear-cut inhibition of IRF-8 expression in melanoma cells. Injection of the demethylating agent 5-aza-2'-deoxycytidine into melanoma- bearing IRF-8 animals induced intratumoral IRF-8-/- expression and resulted in the re-establishment of a chemokine/chemokine receptor pattern favoring leukocyte infiltration and melanoma growth arrest. Importantly, intrinsic IRF-8 - expression was progressively down-modulated during melanoma growth in mice and in human metastatic melanoma cells with respect to primary tumors. Lastly, IRF-8 expression in melanoma cells was directly modulated by soluble factors, among which interleukin-27 (IL-27), released by immune cells from tumor-bearing mice. Collectively, these results underscore a key role of IRF-8 in the cross talk between melanoma and immune cells, thus revealing its critical function within the tumor microenvironment in regulating melanoma progression and invasiveness. [ABSTRACT FROM AUTHOR]

Abstract: Thirty years after the first isolation of the etiological agent of AIDS, the virus HIV-1 is still a major threat worldwide with millions of individuals currently infected. Although current combination therapies allow viral replication to be controlled, HIV-1 is not eradicated and persists in drug- and immune system-insensitive reservoirs and a cure is still lacking. Pathogens such as HIV-1 that cause chronic infections are able to adapt to the host in a manner that ensures long term residence and survival, via the evolution of numerous mechanisms that evade various aspects of the innate and adaptive immune response. One such mechanism is targeted to members of the interferon (IFN) regulatory factor (IRF) family of proteins. These transcription factors regulate a variety of biological processes including interferon induction, immune cell activation and downstream pattern recognition receptors (PRRs). HIV-1 renders IRFs harmless and hijacks them to its own advantage in order to facilitate its replication and evasion of immune responses. Type I interferon (IFN), the canonical antiviral innate response, can be induced in both acute and chronic HIV-1 infection in vivo, but in the majority of individuals this initial response is not protective and can contribute to disease progression. Type I IFN expression is largely inhibited in T cells and macrophages in order to successfully establish productive infection, whereas sustained IFN production by plasmacytoid dendritic cells is considered an important source of chronic immune activation, a hallmark to AIDS progression. [Copyright &y& Elsevier]

Abstract: Glycerol carbonate, synthesised via a non-phosgene route using glycerol and CO2 or urea in presence of a heterogeneous catalyst, was efficiently converted into a series of derivatives through the functionalization of the –OH moiety, using high yield, high selectivity synthetic routes not affecting the carbonate functionality. So, for example, glycerol carbonate was converted into epichlorohydrin, a product that has a large industrial application, under very mild conditions, using a two-step reaction with a 98% yield and 100% selectivity. The high yield and mild reaction conditions (very often close to the ambient conditions) make the environmentally friendly synthetic approach described in this work of potential applicative interest. All compounds prepared were fully characterized. [ABSTRACT FROM AUTHOR]

Abstract: We reviewed studies involving the treatment of elopement in individuals with developmental disabilities. Systematic searches of three electronic databases, journals, and reference lists identified 10 studies meeting the inclusion criteria. These studies were evaluated in terms of: (a) participants, (b) procedures used to assess elopement, (c) intervention procedures, (d) results of the intervention, and (e) certainty of evidence. Across the 10 studies, intervention was provided to a total of 53 participants aged 3–47 years. Assessment procedures included anecdotal staff reports, participant interviews, direct observation, and modified analog functional analysis. Intervention approaches included differential reinforcement, extinction, functional communication training, response blocking, non-contingent reinforcement, shaping, and scheduled exercise. Positive outcomes were reported in 80% of the reviewed studies. The evidence base suggests that function-based assessment (e.g. functional analysis procedures) and function-based treatments (e.g. functional communication training) may be most effective in the treatment of elopement in this population. Directions for future research are offered. [Copyright &y& Elsevier]