URB447 Is Neuroprotective in Both Male and Female Rats after Neonatal Hypoxia-Ischemia and Enhances Neurogenesis in Females.

The need for new and effective treatments for neonates suffering from hypoxia-ischemia is urgent, as the only implemented therapy in clinics is therapeutic hypothermia, only effective in 50% of cases. Cannabinoids may modulate neuronal development and brain plasticity, but further investigation is needed to better describe their implication as a neurorestorative therapy after neonatal HI. The cannabinoid URB447, a CB1 antagonist/CB2 agonist, has previously been shown to reduce brain injury after HI, but it is not clear whether sex may affect its neuroprotective and/or neurorestorative effect. Here, URB447 strongly reduced brain infarct, improved neuropathological score, and augmented proliferative capacity and neurogenic response in the damaged hemisphere. When analyzing these effects by sex, URB447 ameliorated brain damage in both males and females, and enhanced cell proliferation and the number of neuroblasts only in females, thus suggesting a neuroprotective effect in males and a double neuroprotective/neurorestorative effect in females.

Cannabinoid-mediated Modulation of Oxidative Stress and Early Inflammatory Response after Hypoxia-Ischemia.

In the process of neonatal encephalopathy, oxidative stress and neuroinflammation have a prominent role after perinatal asphyxia. With the exception of therapeutic hypothermia, no therapeutic interventions are available in the clinical setting to target either the oxidative stress or inflammation, despite the high prevalence of neurological sequelae of this devastating condition. The endocannabinoid system (ECS), recently recognized as a widespread neuromodulatory system, plays an important role in the development of the central nervous system (CNS). This study aims to evaluate the potential effect of the cannabinoid (CB) agonist WIN 55,212-2 (WIN) on reactive oxygen species (ROS) and early inflammatory cytokine production after hypoxia-ischemia (HI) in fetal lambs. Hypoxic-ischemic animals were subjected to 60 min of HI by partial occlusion of the umbilical cord. A group of lambs received a single dose of 0.01 µg/kg WIN, whereas non-asphyctic animals served as controls. WIN reduced the widespread and notorious increase in inflammatory markers tumor necrosis factor (TNF)-α and interleukin (IL)-1ß and IL-6 induced by HI, a modulatory effect not observed for oxidative stress. Our study suggests that treatment with a low dose of WIN can alter the profile of pro-inflammatory cytokines 3 h after HI.

Role of Antioxidants in Neonatal Hypoxic-Ischemic Brain Injury: New Therapeutic Approaches.

Hypoxic-ischemic brain damage is an alarming health and economic problem in spite of the advances in neonatal care. It can cause mortality or detrimental neurological disorders such as cerebral palsy, motor impairment and cognitive deficits in neonates. When hypoxia-ischemia occurs, a multi-faceted cascade of events starts out, which can eventually cause cell death. Lower levels of oxygen due to reduced blood supply increase the production of reactive oxygen species, which leads to oxidative stress, a higher concentration of free cytosolic calcium and impaired mitochondrial function, triggering the activation of apoptotic pathways, DNA fragmentation and cell death. The high incidence of this type of lesion in newborns can be partly attributed to the fact that the developing brain is particularly vulnerable to oxidative stress. Since antioxidants can safely interact with free radicals and terminate that chain reaction before vital molecules are damaged, exogenous antioxidant therapy may have the potential to diminish cellular damage caused by hypoxia-ischemia. In this review, we focus on the neuroprotective effects of antioxidant treatments against perinatal hypoxic-ischemic brain injury, in the light of the most recent advances.

Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia-ischemia.

One of the most common causes of mortality and morbidity in children is perinatal hypoxia-ischemia (HI). In spite of the advances in neonatology, its incidence is not diminishing, generating a pediatric population that will require an extended amount of chronic care throughout their lifetime. For this reason, new and more effective neuroprotective strategies are urgently required, in order to minimize as much as possible the neurological consequences of this encephalopathy. In this sense, interest has grown in the neuroprotective possibilities of melatonin, as this hormone may help to maintain cell survival through the modulation of a wide range of physiological functions. Although some of the mechanisms by which melatonin is neuroprotective after neonatal asphyxia remain a subject of investigation, this review tries to summarize some of the most recent advances related with its use as a therapeutic drug against perinatal hypoxic-ischemic brain injury, supporting the high interest in this indoleamine as a future feasible strategy for cerebral asphyctic events.

Effects of Cannabidiol, Hypothermia, and Their Combination in Newborn Rats with Hypoxic-Ischemic Encephalopathy.

Therapeutic hypothermia is well established as a standard treatment for infants with hypoxic-ischemic (HI) encephalopathy but it is only partially effective. The potential for combination treatments to augment hypothermic neuroprotection has major relevance. Our aim was to assess the effects of treating newborn rats following HI injury with cannabidiol (CBD) at 0.1 or 1 mg/kg, i.p., in normothermic (37.5°C) and hypothermic (32.0°C) conditions, from 7 d of age (neonatal phase) to 37 d of age (juvenile phase). Placebo or CBD was administered at 0.5, 24, and 48 h after HI injury. Two sensorimotor (rotarod and cylinder rearing) and two cognitive (novel object recognition and T-maze) tests were conducted 30 d after HI. The extent of brain damage was determined by magnetic resonance imaging, histologic evaluation, magnetic resonance spectroscopy, amplitude-integrated electroencephalography, and Western blotting. At 37 d, the HI insult produced impairments in all neurobehavioral scores (cognitive and sensorimotor tests), brain activity (electroencephalography), neuropathological score (temporoparietal cortexes and CA1 layer of hippocampus), lesion volume, magnetic resonance biomarkers of brain injury (metabolic dysfunction, excitotoxicity, neural damage, and mitochondrial impairment), oxidative stress, and inflammation (TNFα). We observed that CBD or hypothermia (to a lesser extent than CBD) alone improved cognitive and motor functions, as well as brain activity. When used together, CBD and hypothermia ameliorated brain excitotoxicity, oxidative stress, and inflammation, reduced brain infarct volume, lessened the extent of histologic damage, and demonstrated additivity in some parameters. Thus, coadministration of CBD and hypothermia could complement each other in their specific mechanisms to provide neuroprotection.

New Insights into the Application of High-Pressure Processing and Storage Time and Temperature to Sliced Iberian Chorizo.

Producing dry-cured meats with relatively high aw and pH allows companies to cut costs to the detriment of microbial control. The purpose of this study was to evaluate for the first time the effect of High Processing Pressure (HPP) and storage temperature on the microbial counts, instrumental color, oxidation and sensory characteristics of sliced Iberian chorizo with high aw and pH. First, 600 MPa was applied for 480 s to sliced chorizo with aw: 0.88 and pH: 6.01, and the treated and untreated samples were stored at 4 or 20 °C for 90 or 180 days. HPP, storage time and storage at 20 °C were successful at decreasing the microbial counts that were initially high. HPP and the storage temperature had a limited detrimental effect, whereas the storage time had a marked adverse effect on oxidation and some sensory traits. Despite the high aw and pH, no safety issues arose initially or during the storage at 4 or 20 °C. In conclusion, for chorizo with high aw and pH favoring high microbial counts, HPP may be an effective hurdle without a noticeable detrimental effect, and the economically convenient storage at 20 °C might be beneficial despite causing moderate quality loss.

Magnesium sulfate treatment decreases the initial brain damage alterations produced after perinatal asphyxia in fetal lambs.

The aim of this work was to analyze the effect of MgSO(4) treatment in the brain after hypoxic-ischemic (HI) injury in premature fetal lambs. Injury was induced by partial occlusion of umbilical cord for 60 min, and then the preterm lambs (80-90% of gestation) were randomly assigned to one of the following groups: control group, in which the animals were managed by conventional mechanical ventilation for 3 hr; 3 hr postpartial cord occlusion (3-hr-PCO) group, in which injured animals were managed by ventilation and then sacrificed 3 hr after HI; and MgSO(4) group, in which animals received 400 mg/kg MgSO(4) for 20 min soon after HI was induced and were managed by ventilation for 3 hr. Brains were analyzed for apoptosis by TUNEL assay. Cell viability and intracellular state studies were assessed by flow cytometry. The delayed death index was significantly increased in the 3-hr-PCO group in comparison with control. Administration of MgSO(4) elicited a delay in cell death that was similar to that in the control group. The 3-hr-PCO group showed a significantly higher concentration of reactive oxygen species, mitochondrial damage, and intracellular calcium in comparison with control and MgSO(4) - treated groups. Our results suggest that MgSO(4) treatment might have potential therapeutic benefits after the HI event.

Pretreatment with the monoacylglycerol lipase inhibitor URB602 protects from the long-term consequences of neonatal hypoxic-ischemic brain injury in rats.

BACKGROUND: The endocannabinoids are emerging as natural brain protective substances that exert potentially beneficial effects in several neurological disorders by virtue of their hypothermic, immunomodulatory, vascular, antioxidant, and antiapoptotic actions. This study was undertaken to assess whether preventing the deactivation of the endocannabinoid 2-arachidonoylglycerol (2-AG) with the monoacylglycerol lipase (MAGL) inhibitor URB602 can provide neuroprotective effects in hypoxia-ischemia (HI)-induced brain injury. METHODS: URB602 was administered into the right lateral ventricle 30 min before 7-day-old pup rats were subjected to HI. The neuroprotective effect was evaluated on postnatal day (PN) 14 or at adulthood (PN80) using behavioral and histological analyses. Activated caspase-3 expression and propidium iodide labeling were assessed as indexes of apoptotic and necrotic cell death, respectively. RESULTS: Pretreatment with URB602 reduced apoptotic and necrotic cell death, as well as the infarct volume measured at PN14. At adulthood, URB602-treated HI animals performed better at the T-maze and the Morris maze, and also showed a significant reduction of brain damage. CONCLUSION: These results demonstrate that a pretreatment with URB602 significantly reduces brain damage and improves functional outcome, indicating that endocannabinoid-degrading enzymes may represent an important target for neuroprotection in neonatal ischemic brain injury.

"IH8U": confronting cyberbullying and exploring the use of cybertools in teen dating relationships.

Cyberbullying among adolescents has been a major focus of attention in mainstream media and has been documented to have many negative effects, as evidenced by several highly publicized suicides of teens who had been bullied online. The growing body of research about cyberbullying has rarely considered, however, the practice of cyberbullying between intimate partners. This article focuses on the frequency, types, and effect of cyberbullying between intimate partners in teen dating relationships. I examine the use of cybertools (electronic forms of communication) as mechanisms of power and control in relationships for both the target and the perpetrator. Suggested methods of prevention and intervention for adults working with teens who are experiencing cyberbullying in dating relationships are discussed.

Neonatal multiple organ failure after perinatal asphyxia.

Perinatal asphyxia is an event with far-reaching consequences that can lead not only to the development of neonatal encephalopathy, but also to multiple organ failure (MOF). This ailment may result from the redistribution of blood flow, which would preserve the perfusion of vital organs such as the heart, brain and adrenal glands at the expense of other organs. The objective of the study was to determine the incidence and aetiopathogenesis of failure in the organs most frequently involved in neonatal MOF following perinatal asphyxia. We conducted a systematic literature search in the PubMed, Scopus and Cochrane Library databases using the MeSH terms (ischemia AND hypoxia AND multiorgan dysfunction AND neonat*), (asphyxia AND multiorgan dysfunction AND neonat*) and (liver/kidney/digestive OR gastrointestinal/heart injury AND ischemia AND hypoxia AND neonat*). We selected clinical and preclinical studies published after 2000 and excluded case series, letters to the editor, cohort studies without comparison groups and abstracts. In this study, we found that MOF associated with perinatal asphyxia is a frequent phenomenon with a relevant impact on neonatal morbidity and mortality, as it can cause changes not only in the kidney, liver and gastrointestinal tract, but also cardiomyopathy if the ailment is protracted or severe.

The Endocannabinoid System as a Target for Neuroprotection/Neuroregeneration in Perinatal Hypoxic-Ischemic Brain Injury.

The endocannabinoid (EC) system is a complex cell-signaling system that participates in a vast number of biological processes since the prenatal period, including the development of the nervous system, brain plasticity, and circuit repair. This neuromodulatory system is also involved in the response to endogenous and environmental insults, being of special relevance in the prevention and/or treatment of vascular disorders, such as stroke and neuroprotection after neonatal brain injury. Perinatal hypoxia-ischemia leading to neonatal encephalopathy is a devastating condition with no therapeutic approach apart from moderate hypothermia, which is effective only in some cases. This overview, therefore, gives a current description of the main components of the EC system (including cannabinoid receptors, ligands, and related enzymes), to later analyze the EC system as a target for neonatal neuroprotection with a special focus on its neurogenic potential after hypoxic-ischemic brain injury.

Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs.

Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100ß protein and brain tissue percentage of TNFα(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 ± 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 ± 1.4 points). HI induced histological changes, and NSE and S100ß concentration and TNFα(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.

Asian in the Time of COVID-19: Creating a Social Work Agenda for Asian American and Pacific Islander Communities.

The health of Asian American and Pacific Islander (AAPI) communities remains an understudied area of racial/ethnic minority research in the United States, and even more so in the field of social work. The COVID-19 pandemic has highlighted how AAPI health and social welfare issues have not received adequate attention in social policy, social work practice, and research. Contrary to model minority myths, AAPIs are subject to racialized attitudes and discrimination, which have been associated with adverse physical and mental health outcomes, including increased anxiety, depression, and suicidality. Drawing from the theoretical framework of AsianCrit, which is grounded in critical race theory, authors analyze health disparities among AAPI communities as reflected in COVID-19 hospitalizations and fatalities, as well as increases in acts of anti-Asian racism and xenophobia. Better understanding health disparities of AAPI communities needs to be a key research issue for social workers in future years. The authors conclude by offering a short set of recommendations to improve social policy, social work practice, and research to more aptly address contemporary social issues impacting AAPI communities.

A Qualitative Evaluation of the Impacts of a Strength-based and Youth-driven Approach to Suicide Prevention in Rural and Minority Communities in Hawai'i.

Suicide is a serious public health issue, particularly for Native Hawaiians and Other Pacific Islander youth living in rural communities in Hawai'i. The Hawai'i's Caring Communities Initiative (HCCI) for Youth Suicide Prevention was implemented to address these concerns and used a strength-based, youthleadership approach to suicide prevention. A qualitative study was completed with youth leaders and adult community coordinators to evaluate the impacts of participating in HCCI. Participants included 9 adult community coordinators and 17 youth leaders ages 13-18 years. Coordinator interviews took place at a location of the interviewee's convenience, and youth leader focus groups were conducted at 1 of 6 rurally-based community organizations. A team of university staff members coded transcripts using a narrative approach and grouped codes into themes. Five themes emerged that fit with an adapted socio-ecological model framework, which included increased knowledge in suicide risk, pride in leadership identity, sense of positive relationships, positive affirmation from community members, and sustainability. Future efforts that focus on youth-related issues are encouraged to integrate a youth leadership model and preventive approach while considering implications such as long-term funding and capitalizing on community strengths and resources.

Relación entre la compresión maxilar y potencial impactación del canino superior: Scoping review

El canino maxilar permanente corresponde al segundo diente más frecuentemente impactado en el arco dental. La etiología de esta patología aún no está totalmente definida, sin embargo, investigadores plantean la deficiencia del ancho del hueso maxilar como una posible causa. Objetivo: Investigar la evidencia que asocia menores dimensiones transversales del maxilar a la ocurrencia de la impactación de caninos superiores y esclarecer la posible relación. Materiales y métodos: Se realizó una revisión sistemática exploratoria a partir de una búsqueda amplia de la literatura en bases de datos PubMed, Cochrane, EBSCO y Multibuscador UNAB. Los artículos fueron recopilados, identificados y filtrados según el diagrama de flujo de declaración PRISMA. Resultados: La búsqueda identificó 755 estudios, de los cuales 14 fueron incluidos. Los estudios varían en diseño, edad de estudio y métodos de diagnóstico. La mitad de los estudios reporta una asociación positiva entre compresión maxilar e impactación canina superior, mientras que la otra mitad una asociación negativa. Conclusiones: No hay evidencia suficiente para poder asociar compresión maxilar con impactación de caninos superiores. Estudios con métodos de diagnóstico rigurosos son necesarios para una mejor comprensión. No obstante, se enfatiza la importancia de un diagnóstico precoz, para garantizar mejores resultados y pronóstico más favorable.

The permanent maxillary canine is the second most frequently impacted tooth in the dental arch. The etiology of this disease is not completely defined, yet some researchers propose the deficiency of the width from the maxilla as a possible cause. Objective: To investigate available evidence correlating smaller transverse maxilla dimensions with the occurrence of potential impaction of upper canines and clarify the possible relation. Materials and methods: A systematic exploratory review was carried out based on comprehensive search of the literature in databases such as PubMed, Cochrane, EBSCO and UNAB multi search engine. The articles were compiled, identified and filtered systematically according to the PRISMA flow diagram. Results: Our search identified 755 studies, 14 of which were included. These studies vary in design, patients age, and methods for detection. Half of the studies show a positive correlation between maxillary compression and potential upper canine impaction, whereas the other half show a negative correlation. Conclusions: There is not enough evidence to link maxillary compression to upper canine impaction. Studies with rigorous diagnostic methods for detection are necessary for a better understanding of this relation. Nonetheless, the importance of early diagnosis must be emphasized to guarantee better results and a more favorable prognosis.

Hope, help, and healing: Culturally embedded approaches to suicide prevention, intervention and postvention services with native Hawaiian youth.

Suicide rates have reached their highest documented levels in the United States with the greatest increases among indigenous youth, including Native Hawaiians. Culturally informed, effective prevention and treatment services are needed now more than ever for Native communities to heal and flourish. Multicomponent prevention and service strategies rooted in indigenous values and approaches show the most promise. Native Hawaiian communities are united around a common goal of suicide prevention, intervention and postvention, linking cultural meanings to improve understanding and guide local efforts. This paper highlights important cultural values to consider when developing and implementing suicide prevention, intervention and postvention. Strategies build upon the strengths of Native Hawaiian youth and their respective communities. Native Hawaiian sayings anchor each level and serve to organize a set of culturally informed and culturally embedded programs and approaches along the continuum of prevention, intervention and postvention. Application of indigenization to suicide prevention enhances connections to people and place, inspiring hope among Native Hawaiian youth, their families and their communities. (PsycINFO Database Record

Comparison of two ELISA assays for anti-Sp100 determination.

Antibodies to Sp100 have been described not only in primary biliary cirrhosis (PBC), but also in other diseases. Two assays for detection of Sp100 levels by enzyme-linked immunosorbent assay (ELISA) have been compared in a cohort of patients from our area: (a) Sp100 kit produced by IMTEC, Immunodiagnostica GmbH, and (b) Quanta Lite Sp100 kit produced by INOVA Diagnostics. We analyze here the correlation between the two assays and compare their efficiency in diagnosing PBC. We also comment on the exceptions derived from reactivity with other diseases. We studied 78 sera by IIF with the typical multiple nuclear dots (MND) pattern from patients who suffered from PBC, hepatopathies different from PBC, systemic lupus erythematosus (SLE), other connective tissue diseases (CTD), skeletal diseases, lung diseases, hematological disorders, a miscellaneous group, and a healthy IIF negative control group. The tests work equally well despite their different quantification system: (a) it is based on a standard curve; and (b) it is based on a single-point antigen-specific calibration. Some discrepancies could be explained by differences in the immunodominant epitope used in the ELISA. The main finding of this study is that the presence of MND/Sp100-positive antibodies were detected not only in hepatic diseases, mainly PBC, but also in other clinical conditions, confirmed by both tests. Diagnosis of PBC must be established in the right clinical context, because other diseases recognizing the same epitope, mainly SLE, may also show high Sp100 levels. Sera from PBC patients with antimitochondrial antibodies (AMA) showed higher anti-Sp100 than the AMA-negative group.

Early cell death in the brain of fetal preterm lambs after hypoxic-ischemic injury.

The objective of the present study was to evaluate using premature fetal lambs the effect of cerebral hypoxia-ischemia induced by partial occlusion of the umbilical cord on the type of cell death which occurs in different brain regions and to ascertain some of the neural pathways which may underlie the associated pathologies. Lambs were sacrificed either immediately after a 1 h hypoxic-ischemic insult or 3 h later. Brains were fixed by perfusion and blocks of the different brain territories were processed for light microscopy (hematoxylin-eosin, Nissl staining), electron transmission microscopy and quantification of apoptosis by the TUNEL method. Other fixed brains were dissociated and labeled by nonyl acridine orange to determine mitochondrial integrity. Non-fixed brains were also used for membrane asymmetry studies, in which cell suspensions were analyzed by flow cytometry to quantify apoptosis. In both hypoxic-ischemic groups, necrotic-like neurons were observed mainly in the mesencephalon, pons, deep cerebellar nuclei and basal nuclei, whereas apoptotic cells were extensively found both in white and gray matter and were not limited to regions where necrotic neurons were present. The 3 h post-partial cord occlusion group, but not the 0 h group, showed a generalized alteration of cell membrane asymmetry and mitochondrial integrity as revealed by Annexin V/PI flow cytometry and nonyl acridine orange studies, respectively. Our results show that the apoptotic/necrotic patterns of cell death occurring early after hypoxic-ischemic injury are brain-region-specific and have distinct dynamics and suggest that therapeutic strategies aimed at rescuing cells from the effects of hypoxia/ischemia should be aimed at blocking the apoptotic components of brain damage.

Recent advances in cochlear hair cell regeneration-A promising opportunity for the treatment of age-related hearing loss.

The objective of this paper is to review current information regarding the treatment of age-related hearing loss by using cochlear hair cell regeneration. Recent advances in the regeneration of the inner ear, including the usefulness of stem cells, are also presented. Based on the current literature, cochlear cell regeneration may well be possible in the short term and cochlear gene therapy may also be useful for the treatment of hearing loss associated with ageing. The present review provide further insight into the pathogenesis of Inner Ear senescence and aged-related hearing loss and facilitate the development of therapeutic strategies to repair hair cells damaged by ageing. More research will be needed in order to translate them into an effective treatment for deafness linked to cochlear senescence in humans.

Antioxidant Treatments Recover the Alteration of Auditory-Evoked Potentials and Reduce Morphological Damage in the Inferior Colliculus after Perinatal Asphyxia in Rat.

Maturation of the auditory pathway is dependent on the central nervous system myelination and it can be affected by pathologies such as neonatal hypoxic ischemic (HI) encephalopathy. Our aim was to evaluate the functional integrity of the auditory pathway and to visualize, by histological and cellular methods, the damage to the brainstem using a neonatal rat model of HI brain injury. To carry out this morphofunctional evaluation, we studied the effects of the administration of the antioxidants nicotine, melatonin, resveratrol and docosahexaenoic acid after hypoxia-ischemia on the inferior colliculus and the auditory pathway. We found that the integrity of the auditory pathway in the brainstem was altered as a consequence of the HI insult. Thus, the auditory brainstem response (ABR) showed increased I-V and III-V wave latencies. At a histological level, HI altered the morphology of the inferior colliculus neurons, astrocytes and oligodendricytes, and at a molecular level, the mitochondria membrane potential and integrity was altered during the first hours after the HI and reactive oxygen species (ROS) activity is increased 12 h after the injury in the brainstem. Following antioxidant treatment, ABR interpeak latency intervals were restored and the body and brain weight was recovered as well as the morphology of the inferior colliculus that was similar to the control group. Our results support the hypothesis that antioxidant treatments have a protective effect on the functional changes of the auditory pathway and on the morphological damage which occurs after HI insult.