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Introduction: Despite its recent reputation as prosocial neurohormone, the most important physiological role of oxytocin (OT) is stimulating uterine contractions. Though it is well known that plasma OT concentrations change drastically during delivery, it remains unexplored whether and how OT receptors in the maternal brain are activated. We examined whether the responses of cells in the central amygdala (CeA), an OT receptor-rich limbic site involved in pain and fear memory regulation, to exogenously applied OT analogue, Thr-Gly-OT (TGOT), vary depending on delivery. Methods: Intracellular Ca2+ dynamics of the CeA cells were visualized in brain slices from female rats at virgin (VG), during pregnancy term (PT) days 16–21, within 24 h after delivery (G0), and within 1–3 days after delivery (G3). The Ca2+ responses to 1 µM TGOT, 20 mM KCl (high K), and 300 µM ADP were compared. Results: We found that fraction of cells responding to TGOT, high K, and ADP differed significantly between the four delivery-associated terms. In particular, the fraction of cells responding to TGOT (TGOT responders) significantly increased from VG and PT at G0 and G3. Furthermore, the significant positive correlation between TGOT and high K response in TGOT and high K responders was reduced at G0, while that between TGOT and ADP responses in TGOT and ADP responders was increased at G0. Conclusion: These results indicate that the responses of CeA cells to an OT receptor agonist markedly change around delivery, which might play a role in controlling the labor-related pain and post-delivery emotional complications.

We developed a first-in-class proteolysis targeting chimera (PROTAC) for selective degradation of histone deacetylase 8 (HDAC8). The PROTAC induced degradation of HDAC8 without affecting the levels of other HDACs in cellular assays, and inhibited the growth of T-cell leukemia Jurkat cells more potently than a conventional HDAC8 inhibitor.

Supplemental Digital Content is Available in the Text. Activity of gamma-aminobutyric acid-ergic neurons in the right-side central amygdala determines ectopic mechanical allodynia in the bilateral hind limbs in rats with orofacial inflammation., Widespread or ectopic sensitization is a hallmark symptom of chronic pain, characterized by aberrantly enhanced pain sensitivity in multiple body regions remote from the site of original injury or inflammation. The central mechanism underlying widespread sensitization remains unidentified. The central nucleus of the amygdala (also called the central amygdala, CeA) is well situated for this role because it receives nociceptive information from diverse body sites and modulates pain sensitivity in various body regions. In this study, we examined the role of the CeA in a novel model of ectopic sensitization of rats. Injection of formalin into the left upper lip resulted in latent bilateral sensitization in the hind paw lasting >13 days in male Wistar rats. Chemogenetic inhibition of gamma–aminobutyric acid-ergic neurons or blockade of calcitonin gene-related peptide receptors in the right CeA, but not in the left, significantly attenuated this sensitization. Furthermore, chemogenetic excitation of gamma-aminobutyric acid-ergic neurons in the right CeA induced de novo bilateral hind paw sensitization in the rats without inflammation. These results indicate that the CeA neuronal activity determines hind paw tactile sensitivity in rats with remote inflammatory pain. They also suggest that the hind paw sensitization used in a large number of preclinical studies might not be simply a sign of the pain at the site of injury but rather a representation of the augmented CeA activity resulting from inflammation/pain in any part of the body or from activities of other brain regions, which has an active role of promoting defensive/protective behaviors to avoid further bodily damage.

The "nociplastic pain," a recently proposed novel mechanistic pain descriptor, is defined as pain occurring through altered nociception without nociceptor activation and nerve injury. Nociplastic pain is often characterized by widespread pain sensitization (WSP) in multiple body regions (Fitzcharles et al., 2021). As many patients with primary chronic pain would have nociplastic backgrounds, developing appropriate methods to evaluate drug effects against nociplastic pain in animal model is in great demand. Using two rat models with the WSP involving central amygdala (CeA) activation by orofacial inflammation or direct chemogenetic activation (Sugimoto et al., 2021), we examined whether widely used analgesics, acetaminophen (AcAph), pregabalin (PGB), and duloxetine (DLX) could attenuate the WSP. AcAph (100 or 200 mg/kg, i.p.) significantly elevated 50%-paw withdrawal threshold (PWT

Fat mass obesity-associated protein (FTO) is a DNA/RNA demethylase involved in the epigenetic regulation of various genes and is considered a therapeutic target for obesity, cancer, and neurological disorders. Here, we aimed to design novel FTO-selective inhibitors by merging fragments of previously reported FTO inhibitors. Among the synthesized analogues, compound 11b, which merges key fragments of Hz (3) and MA (4), inhibited FTO selectively over alkylation repair homologue 5 (ALKBH5), another DNA/RNA demethylase. Treatment of acute monocytic leukemia NOMO-1 cells with a prodrug of 11b decreased the viability of acute monocytic leukemia cells, increased the level of the FTO substrate N6-methyladenosine in mRNA, and induced upregulation of MYC and downregulation of RARA, which are FTO target genes. Thus, Hz (3)/MA (4) hybrid analogues represent an entry into a new class of FTO-selective inhibitors.

Chronic primary low back pain may be associated with hyperalgesia in uninjured tissues and with decreased pain inhibition. Previous studies have shown that the amygdala is involved in pain regulation and chronic pain, that neuronal activity in the amygdala is altered in models of persistent pain, and that the central nucleus of the right amygdala plays an active role in widespread hypersensitivity to noxious stimuli.Behavioral, electrophysiological, biochemical, and chemogenetic methods were used to examine the role of the central nucleus of the right amygdala in hypersensitivity to noxious stimuli in a rat model of chronic back pain induced by a local injection of Complete Freund Adjuvant (CFA) in paraspinal muscles.CFA produced chronic inflammation limited to the injected area. CFA-treated rats showed increased pain-like (liking) behaviors during the formalin test compared with controls. They also showed widespread mechanical hypersensitivity compared with controls, which persisted for 2 months. This widespread hypersensitivity was accompanied by altered activity of different types of right amygdala neurons, as shown by extracellular recordings. Plasmatic levels of IL-1β, IL-6, and TNF-α were not elevated after 1 or 2 months, indicating that persistent widespread hypersensitivity is not caused by persistent systemic inflammation. However, chemogenetic inhibition of GABAergic neurons in the right amygdala attenuated widespread mechanical hypersensitivity.These findings indicate that chronic widespread mechanical hypersensitivity in a model of chronic back pain can be attenuated by inhibiting GABAergic neurons of the right amygdala, and that widespread hypersensitivity is not maintained by chronic systemic inflammation.The amygdala is a key structure involved in pain perception and modulation. The present results indicate that the GABAergic neurons of its central nucleus are involved in widespread hypersensitivity to noxious stimuli in a rat model of chronic back pain. The inhibition of amygdala GABAergic neurons may be a potential target for future interventions in patients with chronic back pain.

The NAD+-dependent deacetylase SIRT2 represents an attractive target for drug development. Here, we designed and synthesized drug-like SIRT2-selective inhibitors based on an analysis of the putative binding modes of recently reported SIRT2-selective inhibitors and evaluated their SIRT2-inhibitory activity. This led us to develop a more drug-like diketopiperazine structure as a "hydrogen bond (H-bond) hunter" to target the substrate-binding site of SIRT2. Thioamide 53, a conjugate of diketopiperazine and 2-anilinobenzamide which is expected to occupy the "selectivity pocket" of SIRT2, exhibited potent SIRT2-selective inhibition. Inhibition of SIRT2 by 53 was mediated by the formation of a 53-ADP-ribose conjugate, suggesting that 53 is a mechanism-based inhibitor targeting the "selectivity pocket", substrate-binding site, and NAD+-binding site. Furthermore, 53 showed potent antiproliferative activity toward breast cancer cells and promoted neurite outgrowth of Neuro-2a cells. These findings should pave the way for the discovery of novel therapeutic agents for cancer and neurological disorders.

Background. Neuropsychological symptoms are common complications among patients with rheumatoid arthritis (RA), while it is largely unexplored how RA pathology spread to brain protected by blood-brain barrier (BBB). The sensory circumventricular organs (sCVOs) (brain regions lacking a blood–brain barrier) is the brain site that peripheral inflammatory signals, such as blood cytokines and chemokines, can directly access and modulate cell activities in the brain parenchyma. To determine whether microglia, resident immune cells in neuronal tissue, in the sCVOs can function as an interface between peripheral inflammation and brain under the autoimmune-arthritis conditions, we analyzed microglia in the sCVOs of a mouse model of collagen-induced arthritis (CIA).Methods. Microglial number and morphology were analyzed in the sCVOs of CIA and control mice (controls were administrated Freund’s adjuvant [FA] and/or saline). Immunostaining for ionized calcium-binding adaptor molecule-1 was performed at various disease phases: “pre-onset” (post-immunization day [PID] 21), ”establishment” (PID 35), and “chronic” (PID 56 and 84). Quantitative analyses on microglial number and morphology were performed, with principal component analysis used to classify microglia. Interleukin-1β (IL-1β) mRNA expression in microglia was also analyzed by multiple fluorescent in situ hybridization.Results. In the area postrema (AP), one of the sCVOs located in the medulla, microglia significantly increased in density (CIA, n = 15; FA, n = 6; saline: n = 10) with changes in morphology during the establishment and chronic phases. In other sCVOs (subfornical organs [SFO] and organum vasculosum laminae terminalis [OVLT]), microglial changes were not significant. In the AP microglia, non-subjective clustering classification of cell morphology (CIA, 1,256 cells; saline, 852 cells) showed that the proportion of microglia in a highly activated form was increased in the CIA group. Also, the density of IL-1β-positive microglia, a hallmark of functional activation, increased in the AP. These microglial changes in the AP persisted until the chronic phase.Conclusions. Our findings indicate that an increase and activation of microglia is sustained in the AP during chronic arthritis. This suggests that there is a direct physiological pathway linking peripheral arthritis to the brain through the AP.

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b, which was designed based on compound 1, degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1. These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.

It is well known that the posterior parietal cortex (PPC) and frontal motor cortices in primates preferentially control voluntary movements of contralateral limbs. The PPC of rats has been defined based on patterns of thalamic and cortical connectivity. The anatomical characteristics of this area suggest that it may be homologous to the PPC of primates. However, its functional roles in voluntary forelimb movements have not been well understood, particularly in the lateralization of motor limb representation; that is, the limb-specific activity representations for right and left forelimb movements. We examined functional spike activity of the PPC and two motor cortices, the primary motor cortex (M1) and the secondary motor cortex (M2), when head-fixed male rats performed right or left unilateral movements. Unlike primates, PPC neurons in rodents were found to preferentially represent ipsilateral forelimb movements, in contrast to the contralateral preference of M1 and M2 neurons. Consistent with these observations, optogenetic activation of PPC and motor cortices, respectively, evoked ipsilaterally and contralaterally biased forelimb movements. Finally, we examined the effects of optogenetic manipulation on task performance. PPC or M1 inhibition by optogenetic GABA release shifted the behavioral limb preference contralaterally or ipsilaterally, respectively. In addition, weak optogenetic PPC activation, which was insufficient to evoke motor responses by itself, shifted the preference ipsilaterally; although similar M1 activation showed no effects on task performance. These paradoxical observations suggest that the PPC plays evolutionarily different roles in forelimb control between primates and rodents.SIGNIFICANCE STATEMENTIn rodents, the primary and secondary motor cortices (M1 and M2, respectively) are involved in voluntary movements with contralateral preference. However, it remains unclear whether and how the posterior parietal cortex (PPC) participates in controlling multiple limb movements. We recorded functional activity from these areas using a behavioral task to monitor movements of the right and left forelimbs separately. PPC neurons preferentially represented ipsilateral forelimb movements and optogenetic PPC activation evoked ipsilaterally biased forelimb movements. Optogenetic PPC inhibition via GABA release shifted the behavioral limb preference contralaterally during task performance, whereas weak optogenetic PPC activation, which was insufficient to evoke motor responses by itself, shifted the preference ipsilaterally. Our findings suggest rodent PPC contributes to ipsilaterally biased motor response and/or planning.

Resumo Objetivo Analisar as interações observadas entre o técnico em enfermagem e a família do paciente hospitalizado, à luz dos pressupostos do Cuidado Centrado no Paciente e na Família e do Código de Ética dos Profissionais de Enfermagem. Métodos Estudo qualitativo, cujos referenciais teóricos foram os pressupostos do Cuidado Centrado no Paciente e na Família e o Código de Ética dos Profissionais de Enfermagem. Participaram nove técnicos em enfermagem das unidades de clínica médica de dois hospitais públicos do Estado de São Paulo. Os dados foram coletados por observação participante e analisados pela Análise Qualitativa de Conteúdo Convencional. Resultados As interações entre o técnico em enfermagem e os familiares foram limitadas no que se referiu à utilização dos pressupostos do Cuidado Centrado no Paciente e na Família e no cumprimento do que era preconizado pelo o Código de Ética dos Profissionais de Enfermagem, conforme revelaram as categorias: Não tratando os familiares com respeito e dignidade; Não compartilhando informação com os familiares; Não negociando a forma de participação e colaboração na prestação do cuidado. Conclusão É imprescindível a incorporação dos pressupostos do Cuidado Centrado no Paciente e na Família e de aspectos éticos relacionados à família preconizados pelo Código de Ética dos Profissionais de Enfermagem na formação e na vivência profissional do técnico em enfermagem, contribuindo para um cuidado de qualidade, ético e solidário. Resumen Objetivo Analizar las interacciones observadas entre el técnico en enfermería y la familia del paciente hospitalizado siguiendo los criterios de los objetivos de la Atención centrada en el Paciente y en la Familia, así como del Código de Ética de los Profesionales de Enfermería. Métodos Estudio cualitativo, cuyas referencias teóricas fueron los propósitos de la Atención centrada en el Paciente y en la Familia, así como del Código de Ética de los Profesionales de Enfermería. Participaron nueve técnicos en enfermería de las unidades de clínica médica de dos hospitales públicos del Estado de São Paulo. Los datos fueron recolectados por la observación participante y analizados por el Análisis Cualitativo de Contenido Convencional. Resultados Las interacciones entre el técnico en enfermería y los familiares estaban limitados en lo que se refiere a la utilización de los objetivos de la Atención Centrada en el Paciente y en la Familia y en el cumplimiento de lo recomendado por el Código de Ética de los Profesionales de Enfermería, según las categorías reveladas: no tratando a los familiares con respeto y dignidad; No compartiendo información con los familiares; No negociando la forma de participación y colaboración en la prestación de atención. Conclusión Se torna imprescindible la incorporación de los principios de la Atención Centrada en el paciente y la familia y de los aspectos éticos relacionados a la familia recomendado por el Código de Ética de los Profesionales de Enfermería en la formación y la experiencia profesional del técnico de enfermería, lo que contribuye a una atención de calidad, ética y solidaria. Abstract Objective Analyze the interactions observed between the nursing technician and the family of the hospitalized patient, in the light of the premises of Patient and Family-Centered Care and the Ethics Code of Nursing Professionals. Methods Qualitative study with the premises of Patient and Family-Centered Care and the Ethics Code of Nursing Professionals as the theoretical frameworks. The participants were nine nursing technicians from the medical clinical wards of two public hospitals in the State of São Paulo. The data were collected using participant observation and analyzed using Conventional Qualitative Content Analysis. Results The interactions between the nursing technician and the relatives were limited in terms of using the premises of Patient and Family-Centered Care and in complying with the recommendations of the Ethics Code of Nursing Professionals, as the following categories revealed: Not treating the family members with respect and dignity; Not sharing information with the family members; Not negotiating on how to participate and collaborate in the care provision. Conclusion It is fundamental to incorporate the premises of Patient and Family-Centered Care and the ethical aspects related to the family recommended in the Ethics Code of Nursing Professionals and in the professional experience of the nursing technician, contributing to high-quality, ethical and solidary care.

Rats are excellent animal models for experimental neuroscience. However, the application of optogenetics in rats has been hindered because of the limited number of established transgenic rat strains. To accomplish cell-type specific targeting of an optimized optogenetic molecular tool, we generated ROSA26/CAG-floxed STOP-ChRFR(C167A)-Venus BAC rats that conditionally express the step-function mutant channelrhodopsin ChRFR(C167A) under the control of extrinsic Cre recombinase. In primary cultured cortical neurons derived from this reporter rat, only Cre-positive cells expressing ChRFR(C167A) became bi-stable, that is, their excitability was enhanced by blue light and returned to the baseline by yellow~red light. In bigenic pups carrying the Phox2B-Cre driver, ChRFR(C167A) was specifically expressed in the rostral parafacial respiratory group (pFRG) in the medulla, where endogenous Phox2b immunoreactivity was detected. These neurons were sensitive to blue light with an increase in the firing frequency. Thus, this transgenic rat actuator/reporter system should facilitate optogenetic studies involving the effective in vivo manipulation of the activities of specific cell fractions using light of minimal intensity.

The role of the neuropeptide calcitonin gene‐related peptide (CGRP) is well established in nociceptive behaviors. CGRP is highly expressed in the projection pathway from the parabrachial nucleus to the laterocapsular region of the central amygdala (CeC), which plays a critical role in relaying nociceptive information. The CeC is a key structure in pain behavior because it integrates and modulates nociceptive information along with other sensory signals. Previous studies have demonstrated that blockade of the amygdalar CGRP‐signaling cascade attenuates nociceptive behaviors in pain models, while CGRP application facilitates amygdalar synaptic transmission and induces pain behaviors. Despite these lines of evidence, it remains unclear whether endogenous CGRP is involved in the development of nociceptive behaviors accompanied with amygdalar plasticity in a peripheral inflammation model in vivo. To directly address this, we utilized a previously generated CGRP knockout (KO) mouse to longitudinally study formalin‐induced plasticity and nociceptive behavior. We found that synaptic potentiation in the right PB‐CeC pathway that was observed in wild‐type mice was drastically attenuated in the CGRP KO mice 6 h post‐inflammation, when acute nociceptive behavior was no longer observed. Furthermore, the bilateral tactile allodynia 6 h post‐inflammation was significantly decreased in the CGRP KO mice. In contrast, the acute nociceptive behavior immediately after the formalin injection was reduced only at 20–25 min post‐injection in the CGRP KO mice. These results suggest that endogenous CGRP contributes to peripheral inflammation‐induced synaptic plasticity in the amygdala, and this plasticity may underlie the exaggerated nociception–emotion linkage in pain chronification.

Non-coding cis-regulatory elements are essential determinants of development, but their exact impacts on behavior and physiology in adults remain elusive. Cis-element-based transcriptional regulation is believed to be crucial for generating circadian rhythms in behavior and physiology. However, genetic evidence supporting this model is based on mutations in the protein-coding sequences of clock genes. Here, we report generation of mutant mice carrying a mutation only at the E′-box cis-element in the promoter region of the core clock gene Per2. The Per2 E′-box mutation abolishes sustainable molecular clock oscillations and renders circadian locomotor activity and body temperature rhythms unstable. Without the E′-box, Per2 messenger RNA and protein expression remain at mid-to-high levels. Our work delineates the Per2 E′-box as a critical nodal element for keeping sustainable cell-autonomous circadian oscillation and reveals the extent of the impact of the non-coding cis-element in daily maintenance of animal locomotor activity and body temperature rhythmicity., The circadian transcription factors BMAL1:CLOCK bind to E/E′-boxes in gene regulatory elements of their targets and facilitate rhythmic expression. Here, the authors mutate the Per2 promoter E’′-box in mice and observe that cell- and tissue-autonomous oscillations are dampened and that animals are less susceptible to jet lag.

A large majority of neurons in the superficial layer of the dorsal horn projects to the lateral parabrachial nucleus (LPB). LPB neurons then project to the capsular part of the central amygdala (CeA; CeC), a key structure underlying the nociception-emotion link. LPB-CeC synaptic transmission is enhanced in various pain models by using electrical stimulation of putative fibers of LPB origin in brain slices. However, this approach has limitations for examining direct monosynaptic connections devoid of directly stimulating fibers from other structures and local GABAergic neurons. To overcome these limitations, we infected the LPB of rats with an adeno-associated virus vector expressing channelrhodopsin-2 and prepared coronal and horizontal brain slices containing the amygdala. We found that blue light stimulation resulted in monosynaptic excitatory postsynaptic currents (EPSCs), with very small latency fluctuations, followed by a large polysynaptic inhibitory postsynaptic current in CeC neurons, regardless of the firing pattern type. Intraplantar formalin injection at 24 h before slice preparation significantly increased EPSC amplitude in late firing-type CeC neurons. These results indicate that direct monosynaptic glutamatergic inputs from the LPB not only excite CeC neurons but also regulate CeA network signaling through robust feed-forward inhibition, which is under plastic modulation in response to persistent inflammatory pain.

認定看護師教育課程 認知症看護認定看護師コース(以下、本教育課程)の教育実践を振り返り、今後の課題を検討した。今回、授業評価を実施した研修生20名の認知症看護経験年数は平均10.4±4.45年であり、本教育課程を受講した理由の大半は自己の学習ニーズ(16名)であった。研修生の本教育課程に対する期待には「臨床実践に沿った講義内容」があり、修了生による臨床に即した実践内容を含んだ授業の工夫が必要であると考えられた。研修生は「認知症ケアを自己の言語で伝えられるようになりたい」という目標を持つ者が多く、本教育課程で看護過程の展開技術を重視した学習プログラムはニーズに一致していた。研修生は自己の目標達成において病院実習の有効性を高く評価していたが、満足度は低い傾向を示した。特に、受講理由が施設長等の勧めである研修生にその傾向が認められた。よって、入学前に研修生が自己を振り返る課題を課し、本教育課程での学びのイメージを高めさせ、認定看護師の研修の質の向上を図ることが課題に挙げられた。, The purpose of the research was to look back upon the educational practice of the course for certified nurses in dementia nursing of the curriculum for of certified nurse education, (hereafter referred as to "this education course") and discuss tasks for future use. The average number of years of experience in dementia nursing for the 20 trainees of whom the class evaluation of this education course was implemented was 10.4±4.45, and the reason for attending this educational course was for the majority, a fulfillment of their own learning requirements (16 trainees). Their expectations for this educational course included the "contents of lectures consistent with clinical practice." Therefore, it was considered necessary to contrive the class in line with the clinical practice of those who have already completed this educational course. There were many trainees who had the target of "conveying dementia care in their own words," which showed that a learning program with emphasis on developing technology for the nursing process matched their needs. Although the trainees highly evaluated the eff ectiveness of hospital practice for their target achievement, they showed a low degree of satisfaction. This trend was significant among those who attended this educational course at the encouragement of the chief of their facility, in particular. Therefore, the benefit of indicating the tasks before they attend this educational course, in order to make them refl ect on themselves, enhance their image of learning in this educational course. Improving the quality of training for qualified nurses was also clarified., 8, KJ00010273219, その他, Others

Summary Objective Patients with epileptic spasms are at high risk for learning and memory impairment later in life. We examined whether synaptic plasticity is affected in the adult hippocampus, a structure responsible for learning and memory, using an animal model of epileptic spasms of unknown cause. Methods We produced a rat model of N-methyl-d-aspartate (NMDA)–induced spasms combined with prenatal betamethasone administration. In 6- to 11-week-old rats, we evaluated the long-term potentiation (LTP) and general properties of synaptic transmission in pyramidal neurons in the CA1 area of the hippocampus in brain slices. Results The magnitude of LTP by theta burst stimulation was significantly larger in adult rats with a history of infantile NMDA injections than in control rats and rats that received additional adrenocorticotropic hormone (ACTH) treatment. The frequency of spontaneous excitatory transmission, but not inhibitory transmission, was smaller in adult rats with a history of infantile NMDA injections. Significance This study is the first to provide a basis for the alteration of synaptic plasticity and transmission in a model of epileptic spasms of unknown cause. Postnatal NMDA treatment causing epileptic spasms–like aberrant episodes in the early stage of life in rats has a latent influence on various forms of synaptic plasticity in the hippocampus. Our results provide a novel insight into cognitive impairment that appears later in life in patients with a history of epileptic spasms.

Studies have suggested that sirtuin inhibition may have beneficial effects on several age-related diseases such as neurodegenerative disorders and cancer. Garcinia mangostana is a well-known tropical plant found mostly in South East Asia with several positive health effects. Some of its phytochemicals such as α-mangostin was found to be able to modulate sirtuin activity in mice and was implicated with inflammation, diabetes and obesity. However, comprehensive studies on sirtuin activity by the prenylated xanthones extracted from Garcinia mangostana have yet to be reported. The present study led to the discovery and identification of γ-mangostin as a potent and selective SIRT2 inhibitor. It was demonstrated that γ-mangostin was able to increase the α-tubulin acetylation in MDA-MD-231 and MCF-7 breast cancer cells. It was also found to possess potent antiproliferative activity against both cell lines. In addition, it was able to induce neurite outgrowth in the N2a cells.

In addition to the canonical spino-thalamo-cortical pathway, lines of recently accumulated anatomical and physiological evidence suggest that projections originating in nociception-specific neurons in lamina I of the dorsal horn or the spinal nucleus of the trigeminal nerve to the lateral parabrachial nucleus (LPB) and then to the central amygdala (CeA) play essential roles in the nociception-emotion link and its tightening in chronic pain. With recent advances in the artificial manipulation of central neuronal activity, such as those with optogenetics, it is now possible to address many unanswered questions regarding the molecular and cellular mechanisms underlying the plastic changes in this pathway and their role in the pain chronification process.

Nociceptive signals originating in the periphery are conveyed to the brain through specific afferent and ascending pathways. The spino-(trigemino-)parabrachio-amygdaloid pathway is one of the principal pathways mediating signals from nociception-specific ascending neurons to the central amygdala, a limbic structure involved in aversive signal-associated emotional responses, including the emotional aspects of pain. Recent studies suggest that the right and left central amygdala play distinct roles in the regulation of nociceptive responses. Using a latent formalin inflammatory pain model of the rat, we analyzed the right-left differences in synaptic potentiation at the synapses formed between the fibers from the lateral parabrachial nucleus and central amygdala neurons as well as those in the c-Fos expression in the lateral parabrachial nucleus, central amygdala, and the basolateral/lateral amygdala after formalin injection to either the right or left side of the rat upper lip. Although the single-sided formalin injection caused a significant bilateral increase in c-Fos-expressing neurons in the lateral parabrachial nucleus with slight projection-side dependence, the increase in the amplitude of postsynaptic excitatory currents and the number of c-Fos-expressing neurons in the central amygdala occurred predominantly on the right side regardless of the side of the inflammation. Although there was no significant correlation in the number of c-Fos-expressing neurons between the lateral parabrachial nucleus and central amygdala in the formalin-injected animals, these numbers were significantly correlated between the basolateral amygdala and central amygdala. It is thus concluded that the lateral parabrachial nucleus-central amygdala synaptic potentiation reported in various pain models is not a simple Hebbian plasticity in which raised inputs from the lateral parabrachial nucleus cause lateral parabrachial nucleus-central amygdala potentiation but rather an integrative and adaptive response involving specific mechanisms in the right central amygdala.

In addition to the canonical spino-thalamo-cortical pathway, lines of recently accumulated anatomical and physiological evidence suggest that projections originating in nociception-specific neurons in lamina I of the dorsal horn or the spinal nucleus of the trigeminal nerve to the lateral parabrachial nucleus (LPB) and then to the central amygdala (CeA) play essential roles in the nociception-emotion link and its tightening in chronic pain. With recent advances in the artificial manipulation of central neuronal activity, such as those with optogenetics, it is now possible to address many unanswered questions regarding the molecular and cellular mechanisms underlying the plastic changes in this pathway and their role in the pain chronification process.

Sulfonated nano-sized diamond powder (S-DP) was tested in a typical water-CPME (1:3, v/v) biphasic system and heated in a commercial monowave microwave oven to promote the dehydration of D-xylose into furfural as industrial platform molecule. This new heterogeneous catalyst with a propyl linker between the support and the sulfonyl group expressed remarkable sufficient hydrophilicity, affinity for D-xylose and catalytic activity in presence of NaCl. The solid can act as a strong acidic catalyst without detectable exchange between proton exclusively localized on the surface of the catalyst and sodium ion. It was also stable at 200 °C even after severe recycling treatment. The final optimized condition requires 10 wt% of the catalyst for a maximum furfural yield of 76% when the mixture is heated for 50 min in the current biphasic system.

Objective: To understand technical nursing students' meaning of interacting with family members of hospitalized children. Method: Symbolic Interactionism was used as the theoretical framework and Qualitative Content Analysis was the methodological procedure. A total of eight graduates from an institution situated in the city of Osasco, Sao Paulo state, participated in this study. Data were collected through semi-structured interviews. Results: A total of five representative themes were revealed: Dealing with difficult situations with family members; Perceiving oneself to be unprepared to interact with family members; Family members being a helpful tool; Developing strategies to obtain a good interaction with family members; and Teachers being facilitators of the interaction with family members. Final considerations: To be acquainted with this experience has led to the understanding of the need to include the theme of family care in the curriculum of the Technical Nursing Course. Additionally, the present study contributed to reflections on the importance of such knowledge for this population and to the development of future studies, as this theme has been scarcely explored in the literature. RESUMEN Objetivo: Comprender el significado de interactuar con los familiares del niño hospitalizado para el alumno del Curso Técnico en Enfermería. Método: Se utilizó Interaccionismo Simbólico como referencial teórico y Análisis Cualitativo de Contenido como procedimiento metodológico. Participaron ocho egresados de institución de Osasco/SP. Datos recolectados mediante entrevista semiestructurada. Resultados: Revelaron cinco temas representativos: interactuando con situaciones difíciles para los familiares; sintiéndose mal preparado para interactuar con familiares; familiares constituyendo herramienta de ayuda; desarrollando estrategias para obtener buena interacción con los familiares; profesores como facilitadores de la interacción con la familia. Consideraciones finales: Conocer esta experiencia permitió comprender la necesidad de inclusión de la temática relativa al cuidado de la familia en el currículo del Curso Técnico en Enfermería. Además, contribuyó a reflexiones sobre la importancia de tal conocimiento para dicho público y para realización de estudio futuros, pues consiste un asunto poco explorado en la literatura. RESUMO Objetivo: Compreender o significado de interagir com os familiares da criança hospitalizada para o aluno do Curso Técnico em Enfermagem. Método: Utilizou-se o Interacionismo Simbólico como referencial teórico e a Análise Qualitativa de Conteúdo como procedimento metodológico. Participaram oito egressos de uma instituição localizada em Osasco/SP, sendo os dados coletados por entrevista semiestruturada. Resultados: Revelaram cinco temas representativos: interagindo com situações difíceis com os familiares; percebendo-se despreparado para interagir com os familiares; familiares sendo uma ferramenta de ajuda; desenvolvendo estratégias para obter boa interação com os familiares; professores sendo facilitadores da interação com a família. Considerações finais: Conhecer essa vivência levou à compreensão da necessidade de inclusão da temática relativa ao cuidado à família na matriz curricular do Curso Técnico em Enfermagem. Além disso, contribuiu para reflexões sobre a importância desse conhecimento para esse público e para futura realização de novos estudos, pois trata-se de assunto pouco explorado na literatura.

Background Pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) are rare causes of pulmonary hypertension. Although diagnosis is based on pathological findings, an early diagnosis is crucial because of poor prognosis compared to other types of pulmonary hypertension. Furthermore, vasodilators may cause fatal pulmonary edema in patients with PVOD/PCH. This study aimed to identify specific characteristics for patients with PVOD/PCH to clinically diagnose PVOD/PCH. Methods Clinical data were obtained at baseline and were compared between 19 patients with PVOD/PCH and 55 patients with idiopathic/heritable pulmonary arterial hypertension. Receiver operating characteristic analyses were used to determine characteristics specific for patients with PVOD/PCH and a scoring system to diagnose PVOD/PCH was developed. Results Patients with PVOD/PCH had a smoking history and were predominantly male. Six-minute walk distance was significantly lower and oxygen desaturation was severe during the walk. Diffusion capacity of carbon monoxide was significantly low. Radiological findings included ground glass opacity on chest high-resolution computed tomography (CT) in all patients with PVOD/PCH, and thickened septal lines in 90% of the patients. Lung perfusion scintigraphy showed defect in >70% of the patients. Pulmonary edema after initiation of vasodilation therapy was frequently observed in PVOD/PCH patients. Based on these results, we identified nine important clinical characteristics and a novel scoring system was designed to clinically diagnose PVOD/PCH: male sex, smoking history, 6-minute walk distance Conclusions Our novel prediction rule for diagnosing PVOD/PCH may offer an early clinical diagnosis of these diseases.

Este estudo teve como objetivo compreender o significado atribuído pelo técnico em enfermagem à vivência de interagir com a família do paciente hospitalizado. Trata-se de uma pesquisa qualitativa, que utilizou como referencial teórico o Interacionismo Simbólico, e o metodológico, a Análise Qualitativa de Conteúdo. Participaram nove técnicos em enfermagem que atuavam nas unidades de clínica médica de dois hospitais públicos, sendo os dados coletados por entrevista semiestruturada e observação participante. Revelaram as dificuldades, ambiguidade e despreparo vivenciados pelos profissionais na interação com a família, embora reconheça sua importância, e a ausência de sua interação com conteúdo a respeito da temática, tanto no curso técnico como na vida profissional. Constatou-se que, na vivência com familiares, faltam-lhes conhecimento e habilidade para lidar com o cuidado da família, assim, necessitam de suporte teórico e prático para enfrentamento de tal situação.

The capsular part of the central amygdala (CeC) is called the "nociceptive amygdala," as it receives nociceptive information from various pathways, including monosynaptic input from the lateral part of the parabrachial nucleus (LPB), a major target of ascending neurons in the spinal and medullary dorsal horn. LPB-CeC synaptic transmission is mediated by glutamate but the fibers from the LPB also contain calcitonin gene-related peptide (CGRP) and the CeC is rich in CGRP-binding sites. CGRP might be released in response to strong nociception and activate these CGRP receptors. Though it has been shown that CGRP affects the excitatory postsynaptic current (EPSC) amplitude at this synapse in a manner sensitive to NMDA receptor (NMDA-R) blockers, the effect of CGRP on postsynaptic NMDA-R-mediated current recorded in isolation has never been directly examined. Thus, we evaluated the effects of CGRP on NMDA-R-mediated EPSCs that were pharmacologically isolated in brain slices from naive mice. CGRP significantly increased the amplitude of EPSCs mediated by NMDA-Rs in a manner dependent on protein kinase A activation, but not that mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, in concentration-dependent and antagonist-sensitive manners. This CGRP-induced potentiation of synaptic NMDA-R function would have a potent impact on the strengthening of the nociception-emotion link in persistent pain.