Use of an immunocapture device to detect cytokine release in discrete brain regions

Production of proinflammatory cytokines in the central nervous system is a key process in the neuroinflammatory response to trauma,infection,and neurodegenerative diseases(Kumar,2019).These intercellular signaling molecules play multiple roles in the immune response in the central nervous system including the orchestration of the sickness response to innate immune perturbations in the brain(Dantzer et al.,2008).

Education Programs for Invasive Procedures Involving Nurses: A Scoping Review

Background: Implementing invasive procedures is an important part of patient management by clinical nurses;however, there are gaps between nurses’ actual knowledge and skills and expected professional care capacity. Purpose: This scoping review aimed to map the existing literature related to recent institution-provided educational programs for invasive procedures involving clinical nurses. This study seeks to understand the contents of educational programs and the methods for assessing educational effects. Methods: This scoping review was completed using the following four databases: PubMed (MEDLINE), Embase, Cochrane Library, and Emcare for the period 2000-2022. We included studies that used all forms of educational approaches (e.g., didactic lectures, hands-on training, or on-the-job training). This scoping review considered peer-reviewed publications published in English using quantitative, qualitative, or mixed approaches. A total of 83 studies underwent in the final analysis. Results and Conclusion: A combination of didactic lectures and hands-on training was provided as an educational program in most studies. Contrary to our prediction, educational interventions with advanced technologies such as VR are extremely rare, suggesting that the effectiveness of advanced technologies in learning invasive procedures should be examined to facilitate and retain educational effects more efficiently in future studies. Regarding the assessment of educational effects, nurses’ cognitive (i.e., theoretical knowledge about procedures), psychomotor (i.e., implementing procedures), and psychological aspects (e.g., confidence and self-efficacy in procedures) were evaluated using questionnaires and observational methods. While most studies used a one-group pretest-posttest design, the ratio of randomized controlled trials (RCT) was relatively low. Thus, an RCT design should be introduced in future studies to test the validity of the developed educational program more accurately.

Expression of nesfatin-1/NUCB2 in rodent digestive system

AIM: To observe the regional distributions and morphological features of nesfatin-1/nucleobindin-2 (NUCB2) immunoreactive (IR) cells in the rodent digestive system. METHODS: Paraffin-embedded sections of seven organs (pancreas, stomach, duodenum, esophagus, liver, small intestine and colon) dissected from sprague-dawley (SD) rats and institute of Cancer Research (ICR) mice were prepared. The regional distributions of nesfatin-1/NUCB2 IR cells were observed by immunohistochemical staining. The morphological features of the nesfatin-1/NUCB2 IR cells were evaluated by hematoxylin and eosin (HE) staining. Fresh tissues of the seven organs were prepared for Western blotting to analyze the relative protein levels of NUCB2 in each organ.RESULTS: Immunohistochemical staining showed that the nesfatin-1/NUCB2 IR cells were localized in the central part of the pancreatic islets, the lower third and middle portion of the gastric mucosal gland, and the submucous layer of the duodenum in SD rats and ICR mice. HE staining revealed that the morphological features of nesfatin-1/NUCB2 IR cells were mainly islet cells in the pancreas, endocrine cells in the stomach, and Brunner’s glands in the duodenum. Western blotting revealed that NUCB2 protein expression was higher in the pancreas, stomach and duodenum than in the esophagus, liver, small intestine and colon (P = 0.000). CONCLUSION: Nesfatin-1/NUCB2 IR cells are expressed in the pancreas, stomach and duodenum in rodents. These cells may play an important role in the physiological regulation of carbohydrate metabolism, gastrointestinal function and nutrient absorption.

Increased virulence of the oral microbiome in oral squamous cell carcinoma revealed by metatranscriptome analyses

Oral squamous cell carcinoma(OSCC) is the most prevalent and most commonly studied oral cancer. However, there is a void regarding the role that the oral microbiome may play in OSCC. Although the relationship between microbial community composition and OSCC has been thoroughly investigated, microbial profiles of the human microbiome in cancer are understudied. Here we performed a small pilot study of community-wide metatranscriptome analysis to profile mRNA expression in the entire oral microbiome in OSCC to reveal molecular functions associated with this disease. Fusobacteria showed a statistically significantly higher number of transcripts at tumour sites and tumour-adjacent sites of cancer patients compared to the healthy controls analysed. Regardless of the community composition, specific metabolic signatures were consistently found in disease. Activities such as iron ion transport, tryptophanase activity, peptidase activities and superoxide dismutase were over-represented in tumour and tumour-adjacent samples when compared to the healthy controls. The expression of putative virulence factors in the oral communities associated with OSCC showed that activities related to capsule biosynthesis, flagellum synthesis and assembly, chemotaxis, iron transport, haemolysins and adhesins were upregulated at tumour sites. Moreover, activities associated with protection against reactive nitrogen intermediates, chemotaxis, flagellar and capsule biosynthesis were also upregulated in non-tumour sites of cancer patients. Although they are preliminary, our results further suggest that Fusobacteria may be the leading phylogenetic group responsible for the increase in expression of virulence factors in the oral microbiome of OSCC patients.

Metabolic cost of level,uphill,and downhill running in highly cushioned shoes with carbon-fiber plates

Background:Compared to conventional racing shoes,Nike Vaporfly 4% running shoes reduce the metabolic cost of level treadmill running by4%.The reduction is attributed to their lightweight,highly compliant,and resilient midsole foam and a midsole-embedded curved carbon-fiber plate.We investigated whether these shoes also could reduce the metabolic cost of moderate uphill(+3°) and downhill(-3°) grades.We tested the null hypothesis that,compared to conventional racing shoes,highly cushioned shoes with carbon-fiber plates would impart the same ~4%metabolic power(W/kg) savings during uphill and downhill running as they do during level running.Methods:After familiarization,16 competitive male runners performed six 5-min trials(2 shoes × 3 grades) in 2 Nike marathon racing-shoe models(Streak 6 and Vaporfly 4%) on a level,uphill(+3°),and downhill(-3°) treadmill at 13 km/h(3.61 m/s).We measured submaximal oxygen uptake and carbon dioxide production during Minutes 4-5 and calculated metabolic power(W/kg) for each shoe model and grade combination.Results:Compared to the conventional shoes(Streak 6),the metabolic power in the Vaporfly 4% shoes was 3.83%(level),2.82%(uphill),and2.70%(downhill)less(all p <0.001).The percent of change in metabolic power for uphill running was less compared to level running(p=0.04;effect size(ES)=0.561) but was not statistically different between downhill and level running(p=0.17;ES=0.356).Conclusion:On a running course with uphill and downhill sections,the metabolic savings and hence performance enhancement provided by Vaporfly 4% shoes would likely be slightly less overall,compared to the savings on a perfectly level race course.

Exploring the Possibility of Virtual Reality in Nursing Skills Education: A Preliminary Study Using a First-Person Video

Background: While demonstration videos from a third-person perspective have traditionally been used as teaching materials for nursing skills, first-person videos allow observers to experience how nursing educators move and what they see. In this pilot study, a first-person demonstration video for tracheostomy suctioning skills was shown to participants via a virtual reality (VR) head-mounted display (HMD), which we referred to as a VR teaching material (VR-TM). In an intervention experiment, we investigated the effects of the VR-TM on participants’ performance on the skill assessment test. Additionally, usability of the VR-TM was evaluated by questionnaire ratings. Methods: Thirty-six participants (nursing students) were assigned to three groups in the experiment: 1) VR group: the participants that viewed the VR-TM, 2) TR group: the participants that viewed a traditional demonstration video from a third-person perspective, and 3) NO group: the participants that received no intervention. Score changes in the skill assessments of participants before the intervention (pre-test) and after the intervention (post-test) were analyzed. After the experiment, all participants completed a faculty-designed questionnaire about the VR-TM usability. Results: The questionnaire ratings indicated that the participants evaluated the VR-TM favorably in terms of skill understanding and motivation to practice the skill. However, one-third of participants reported mild discomfort during the VR-TM. In regards to score changes in the skill assessment test, no significant difference between the VR and TR groups was identified, though the two groups produced greater score changes compared to the NO group. Conclusion: The combination of first-person video and the HMD might be promising as a teaching material for nursing skills, though further improvements are necessary.

Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States

BACKGROUND Helicobacter pylori(H.pylori),a bacterium that infects approximately half of the world’s population,is associated with various gastrointestinal diseases,including peptic ulcers,non-ulcer dyspepsia,gastric adenocarcinoma,and gastric lymphoma.As the burden of antibiotic resistance increases,the need for new adjunct therapies designed to facilitate H.pylori eradication and reduce negative distal outcomes associated with infection has become more pressing.Characterization of the interactions between H.pylori,the fecal microbiome,and fecal fatty acid metabolism,as well as the mechanisms underlying these interactions,may offer new therapeutic approaches.AIM To characterize the gut microbiome and metabolome in H.pylori patients in a socioeconomically challenged and underprivileged inner-city community.METHODS Stool samples from 19 H.pylori patients and 16 control subjects were analyzed.16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2.Alpha and beta diversity analyses were performed in QIIME 2.Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry,which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters.Multi-dimensional scaling(MDS)was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates.RESULTS Fecal microbiome analysis showed that alpha diversity was lowest in H.pylori patients over 40 years of age compared to control subjects of similar age group.Beta diversity analysis of the samples revealed significant differences in microbial community structure between H.pylori patients and control subjects across all ages.Thirty-eight and six taxa had lower and higher relative abundance in H.pylori patients,respectively.Taxa that were enriched in H.pylori patients included Atopobium,Gemellaceae,Micrococcaceae,Gemellales and Rothia(R.mucilaginosa).Notably,relative abundance of the phylum Verrucomicrobia was decreased in H.pylori patients compared to control subjects.Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets.Stool samples from H.pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids(PUFAs)22:4n6,22:5n3,20:3n6 and 22:2n6,while decreases were noted in other fatty acids including the PUFA 18:3n6.The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis.CONCLUSION This exploratory study demonstrates H.pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism.Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.

Breath-based meditation: A mechanism to restore the physiological and cognitive reserves for optimal human performance

Stress can be associated with many physiologicalchanges resulting in significant decrements in human performance.Due to growing interests in alternative and complementary medicine by Westerners,many of the traditions and holistic yogic breathing practices today are being utilized as a measure for healthier lifestyles.These state-of-the-art practices can have a significant impact on common mental health conditions such as depression and generalized anxiety disorder.However,the potential of yogic breathing on optimizing human performance and overall well-being is not well known.Breathing techniques such as alternate nostril,Sudarshan Kriya and bhastrika utilizes rhythmic breathing to guide practitioners into a deep meditative state of relaxation and promote self-awareness.Furthermore,yogic breathing is physiologically stimulating and can be described as a natural"technological"solution to optimize human performance which can be categorized into:(1)cognitive function(i.e.,mind,vigilance);and(2)physical performance(i.e.,cardiorespiratory,metabolism,exercise,whole body).Based on previous studies,we postulate that daily practice of breathing meditation techniques play a significant role in preserving the compensatory mechanisms available to sustain physiological function.This preservation of physiological function may help to offset the time associated with reaching a threshold for clinical expression of chronic state(i.e.,hypertension,depression,dementia)or acute state(i.e.,massive hemorrhage,panic attic)of medical conditions.However,additional rigorous biomedical research is needed to evaluate the physiological mechanisms of various forms of meditation(i.e.,breath-based,mantra,mindfulness)on human performance.These efforts will help to define how compensatory reserve mechanisms of cardiovascular and immune systems are modulated by breath-based meditation.While it has been suggested that breath-based meditation is easier for beginning practitioners when compared to other forms of meditation more research is needed to elucidate these observations.A breath-based meditation sequence suchas Sudarshan Kriya has the potential to help develop an individual’s self-awareness and support better integration of the brain(i.e.,mind)with other organ systems(i.e.,body)for enhanced human performance.

Pyruvate-fortified resuscitation stabilizes cardiac electrical activity and energy metabolism during hypovolemia

AIM: To test the hypothesis that fluid resuscitation with Ringer's solution enriched with pyruvate(PR), a physiological antioxidant and energy substrate, affords protection of myocardial metabolism and electrophysiological performance superior to lactated Ringer's(LR) during hypovolemia and hindlimb ischemia-reperfusion.METHODS: Male domestic goats(25-30 kg) were exsanguinated to a mean arterial pressure of 48 ± 1 mm Hg. Right hindlimb ischemia was imposed for 90 min by applying a tourniquet and femoral crossclamp. LR or PR, infused iv, delivered 0.05 mmol/kg per minute L-lactate or pyruvate, respectively, from 30 min hindlimb ischemia until 30 min post-ischemia. Time controls(TC) underwent neither hemorrhage, hindlimb ischemia nor resuscitation. Goats were sacrificed and left ventricular myocardium biopsied at 90 min fluid resuscitation(n = 6 per group) or 3.5 h later(n = 9 LR, 10 PR, 8 TC).RESULTS: Myocardial 8-isoprostane content, phosphocreatine phosphorylation potential, creatine kinase activity, and heart rate-adjusted QT interval(QTc) vari- ability were evaluated at 90 min resuscitation and 3.5 h post-resuscitation. PR sharply lowered pro-arrhythmic QTc variability vs LR(P < 0.05); this effect persisted 3.5 h post-resuscitation. PR lowered myocardial 8-isoprostane content, a product of oxidative stress, by 39 and 37% during and 3.5 h after resuscitation, respectively, vs LR. Creatine kinase activity fell 42% post-LR vs TC(P < 0.05), but was stable post-PR(P < 0.02 vs post-LR). PR doubled phosphocreatine phosphorylation potential, a measure of ATP free energy state, vs TC and LR(P < 0.05); this energetic enhancement persisted 3.5 h post-resuscitation.CONCLUSION: By augmenting myocardial energy state and protecting creatine kinase activity, pyruvateenriched resuscitation stabilized cardiac electrical function during central hypovolemia and hindlimb ischemiareperfusion.

Modeling cardiac arrest and resuscitation in the domestic pig

Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca2+ overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation(CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.

超重和肥胖者的血管内皮NAD(P)H氧化酶-p47^(phox)表达增加并有内皮氧化应激的证据

背景：肥胖可改变一些分子的血管内皮细胞蛋白表达（VECPE），从而影响对动脉粥样硬化的易感性。方法和结果：研究对象为无其他临床疾病、肥胖程度不同的108例男女性受试者（体重指数18．4～36．7kg／m^2；总体脂肪5．8～55．0kg；腰围63．0～122．9em），用定量免疫荧光法检测其血管内皮细胞。所有3种肥胖状况的表达方式均与氧化酶亚单位NAD（P）H氧化酶-p47[部分相关系数（rpart）=0．22～0．24，所有P〈0．05]和抗氧化酶过氧化氢酶（rpart=0．71～0．75，所有P〈0．001）的VECPE呈正相关。

Walking for health during pregnancy:A literature review and considerations for future research

Walking is the most commonly chosen type of physical activity(PA)during pregnancy and provides several health benefits to both mother and child.National initiatives have promoted the importance of walking in general,but little emphasis is directed toward pregnant women,the majority of whom are insufficiently active.Pregnant women face a variety of dynamic barriers to a physically active lifestyle,some of which are more commonly experienced during specific times throughout the pregnancy experience.Walking is unique in that it appears resistant to a number of these barriers that limit other types of PA participation,and it can be meaningfully integrated into some transportation and occupational activities when leisure-time options are unavailable.Preliminary intervention work suggests that walking programs can be effectively adopted into a typical pregnancy lifestyle.However,a great deal of work remains to administer successful pregnancy walking interventions,including developing and using validated methods of PA and walking assessment.This narrative review discusses the unique advantages of walking during pregnancy,provides recommendations for future intervention work,and outlines the need for pregnancy-focused community walking initiatives.Standard search procedures were followed to determine sources from the literature specific to walking during pregnancy for use in each section of this review.

Direction without speed information process in the human brain: a magnetoencephalographic study using random dots apparent motion stimulus

Apparent motion stimulus induces visual perception of smooth motion even though there is no speed information. We examined whether human brain response as measured by magnetoencephalography carries direction information in the visually presented apparent motion of a randomdot pattern in a similar manner as continuous motions that have speed and direction information. Although there was no significant effect of motion direction on the peak response latency and amplitude, mutual information entropy (IE) significantly increased after the motion onset at approximately 36 ms after the response latency in 41% of the evaluations. Detailed analysis of the data from five subjects who participated in both the present apparent motion and our previous coherent motion studies revealed that the maximum IE latency (delay) for apparent motion was significantly longer than that for coherent motion, although the mean maximum IE was the same. The results indicate that direction is represented in the response waveform evoked by apparent motion but the manner is different from that for coherent motion probably due to the distinct neural processes engaged only for the apparent motion perception. We consider that direction and speed can be processed separately in the human brain because direction information was generated without speed information for the perception of apparent motion.

The role of Nkx3.2 in chondrogenesis

Transcription factor, Nkx3.2, is a member of the NK family of developmental genes and is expressed during embryogenesis in a variety of mammalian model organisms, including chicken and mouse. It was first identified in Drosophila as the Bagpipe （bap） gene, where it has been demonstrated to be essential during formation of the midgut musculature. However, mammalian homolog Nkx3.2 has been shown to play a significant role in axial and limb skeletogenesis; in particular, the human skeletal disease, spondylo-megaepiphyseal-metaphyseal dysplasia （SMMD）, is associated with mutations of the Nkx3.2 gene. In this review, we highlight the role of Nkx3.2 during musculoskeletal development, with an emphasis on the factor＇s role in determining chondrogenic cell fate and its subsequent role in endochondral ossification and chondrocyte survival.

Nasal cytology with emphasis on mast cells can improve the diagnosis and treatment of chronic rhinosinusitis

Objective:Chronic rhinosinusitis (CRS) involves inflammation of the nasal and para-nasal mucosa.Due to its heterogeneous nature,unknown pathogenesis,and high recurrence rate,effective treatment is difficult.Nasal cytology is presently not a part of the routine diagnosis or treatment decision for CRS.Data sources:A literature search was performed for published papers in English between January 1990 and June 2019 using MEDLINE.Study sdection:Terms used were chronic rhinosinusids,eosinophils,etiology,immunopathology,inflammation,mast cells,nasal cytology,polyps,and treatment.Both reviews and original articles were collected and studied.Results:There is no standard nasal fluid,mucus sampling,or staining techniques for identifying inflammatory cell types.Results were divergent from different countries.Moreover,the main focus of these papers on the cells in nasal washings was eosinophils,with infrequent mentioning of other cell types that may imply different etiology and pathology.The heterogeneous cell profile of CRS and the role of mast cells have been unappreciated due to the lack of specific immunohistochemical technique or study of its unique mediators.Conclusions:Nasal cytology could help distinguish the type and the activation state of inflammatory cells.Thus it can help in providing a clearer picture of CRS pathogenesis,identifying different patient groups,and developing effective treatments.

Effects of temperature and hydric environment on survival of the Panamanian Golden Frog infected with a pathogenic chytrid fungus

Considerable controversy exists concerning whether or not climate changes(particularly global warming)are causing outbreaks of a lethal amphibian pathogen,the chytrid fungus Batrachochytrium dendrobatidis(Longcore,Pessier&D.K.Nichols 1999).In the present study,groups of Panamanian golden frogs(Atelopus zeteki Dunn,1993),a critically endangered amphibian thought to be nearly extinct in Panama,were exposed to varying dosages of zoospores of Batrachochytrium dendrobatidis,temperatures and hydric environments in order to learn whether this species is susceptible to this pathogen and,if so,how environmental factors affect survival.This pathogen proved to be highly lethal for A.zeteki.Frogs exposed to a dosage of 100 Bd zoospores survived significantly(P<0.0001)longer than those that had been exposed to 104 or 106 zoospores.Exposed frogs housed at 23℃survived significantly(P<0.0001)longer than those that were housed at 17℃.Exposed frogs held in dry conditions survived significantly longer than those in wet conditions(P<0.0001).As a laboratory study,these results do not directly test hypotheses about the relation between climate change and the decline of these frogs in the field,but they inform the discussion about how environmental conditions can have an impact on the interaction between a susceptible amphibian and this pathogen.These data do not support the contention that rising global temperatures are necessary to cause the death of amphibians infected with this pathogen because the pathogen was equally lethal at 17 as at 23℃,and frogs at the warmer temperature lived significantly longer than those at the cooler one.

Small molecule activation of the neurotrophin hepatocyte growth factor to treat Alzheimer disease

Alzheimer's disease(AD)is a neurodegenerative disease characterized by progressive neuron loses in memory-related brain structures.Five drugs have been approved by the FDA to treat Alzheimer's disease;however,these drugs have failed to modify or significantly slow disease progression.New therapies are needed to delay the course of this disease and hopefully prevent further neuron losses.This review describes available AD drugs and several novel approaches presently being investigated.We next describe relevant biomarkers and urge greater research interest in the potential utilization of neurotrophic agents to treat AD.Neurotrophins such as nerve growth factor,brain-derived neurotrophic factor and hepatocyte growth factor(HGF)are capable of stimulating dendritic arborization,synaptogenesis,stem cell differentiation,neurogenesis,and decreases in neuroinflammation,oxidative stress-induced damage and neurotoxicity due to a wide range of cellular insults.We present the strategy of utilizing small molecule analogs specifically designed to penetrate the blood-brain barrier and facilitate dimerization and activation of the HGF/Met receptor system.These molecules have been shown to encourage the formation of new functional synaptic connections,induce long-term potentiation and augment memory consolidation and retrieval in animal models of AD.Such molecules may be appropriate for use at the first indication of mild cognitive impairment,and perhaps prophylactically in those individuals who are most likely to develop dementia due to genetic,health,behavioral and life-style predisposing factors.