cAMP Activation Research Articles

Leisure and cultural identity: an empirical study based on root-seeking summer camp for ethnic Chinese new generation

This study examines the role of root-seeking summer camps in enhancing Chinese cultural identity among the new ethnic Chinese generation (ECNG) amidst the challenges of globalization. Semi-structured interviews with thirty campers revealed that ECNG often lack clear ethnic consciousness, experience conflict in community relationships, and have limited opportunities for traditional cultural experiences. The study found that summer camps exert both intrinsic and extrinsic influences on campers. Intrinsically, they facilitate the internalization of leisure motivation, foster a deepened leisure experience, and promote strengthened leisure interactions. Extrinsically, they provide opportunities for leisure education and cultural immersion. Through this synergy, summer camps enhance the cultural identification of ECNG. However, the study also noted that course enjoyment and teaching staff behavior could influence perceptions of the camp. This study contributes to understanding the relationship between leisure and identity, explaining how summer camp activities enhance ECNG’s cultural identity, and offering insights for governments and agencies.

Novel Protocol for the Use of Advanced Hybrid Closed-Loop System in Adolescents Engaged in Contact Sports.

Managing exercise remains challenging for adolescent athletes with type 1 diabetes (T1D), especially in contact sports. Even the use of hybrid closed loops can cause problems due to the need to disconnect the pump during some training or competitions. This study evaluated the efficacy of a novel protocol for the use of an Advanced Hybrid Closed-Loop System in adolescent football players with T1D during a sports camp. Eleven boys aged 14.9 years (25-75th percentile: 14-15.5), with a diabetes duration of 5.7 years (5.2-7) and regular training schedules in junior football leagues, participated in the study. They started AHCL (MiniMed780G, Medtronic) therapy a month before a week-long sports camp and were observed during the sports camp and the preceding week. Daily camp activities included two 1.5-hour training sessions. Protocol included a 90-minute temporary target of 150 mg/dL before and insulin pump disconnection during training. Physical activity was tracked using wGT3X-BT Actigraph monitors. The camp provided conditions of demanding physical activity (6.6[6-6.9] hours/day of moderate-to-vigorous intensity). After starting AHCL, the average participant time spent in the target glucose range (70-180mg/dL) was 79.34±8.46%, and no significant change was observed during the camp (mean difference +0.79±8.24%, p=0.7581). Median glucose levels dropped by 10.91±12.08mg/dL (p=0.0134), and time in the tight target range increased by 11.41±11.60% (p=0.0008) without increasing the time below range (<70mg/dL) or glycemic variability. During the camp, daily insulin dose and basal/bolus ratio remained comparable with baseline, but the relative amount of automated bolus insulin decreased by 14.24±4.65% (p<0.0001). The predefined regimen, including a temporary target before and disconnection of AHCL during football training, was safe and may provide satisfactory glucose control in active adolescents with T1D. This protocol could be adapted for use in other intensive contact sports.

Glucagon-like Peptide 1 Receptor Agonists in Cardio-Oncology: Pathophysiology of Cardiometabolic Outcomes in Cancer Patients.

Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88. In this narrative review, we highlight the biochemical properties of GLP-1 RA through a deep analysis of the clinical and preclinical evidence of the primary prevention of cardiomyopathies. The overall picture of this review encourages the study of GLP-1 RA in cancer patients with type-2 diabetes, as a potential primary prevention strategy against heart failure and atherosclerosis.

Total Physical Response In English Camp For New Students Of Lombok Business Academy

One of the innovative approaches to enhance students' confidence in communicating using English is through English Camp activities. This research is an effort the director of the Lombok Business Academy (AKBIL) and Lecturers of the Faculty of Culture, Management, and Business (FBMB), especially Lecturers in the English Education Study Program. This research is also a form of follow-up to the collaboration carried out by AKBIL and FBMB. AKBIL New Students need to be given motivation and confidence in speaking English through English Camp activities. English Camp is intended as a fun learning activity that is carried out indoors/outdoors which lasts for 3 days. Through these activities, students have gained an understanding of basic theories in communicating using English. The method used in this study is a qualitative method, a data collection technique carried out by the author through literature studies, observations, interviews, and questionnaires. Literature studies are used to help authors find relevant information related to English Camp. Observation is used to directly observe the participants' activities and dynamics during the English camp. Interviews were conducted by the author to participants to find out the success of event planning. The analysis of this interview data includes three activity flows, namely data reduction, data presentation, and conclusion drawn. The questionnaire was used to determine the success of the English Camp 2024 event planning, in collecting data through the dissemination of the author's questionnaire using the Likert Scale.

An Effective Interprofessional Collaboration to Support African Refugee Students' Oral and Written Language and Social Integration

Purpose: Two faculty members collaborated to advance educational equity by providing a summer camp experience to prevent summer learning loss for African refugee students in preschool through high school. Both faculty members educate university students in graduate programs, one for students aiming to become educators of English to Speakers of Other Languages and the other for speech-language pathology students. Method: Speech-language pathology graduate students provided supports for oral and written language within Tier 1 of a multitiered systems of support framework during camp. Interventions were provided within the context of the camp activities, rooted in the constructs of contextualized intervention, implicit learning, and feedback-free learning. The speech-language pathology students collaborated with the faculty members, camp director, community members, and the campers. Results: The speech-language pathology students learned to provide language support in natural environments, analyze writing, recognize strengths and areas for growth in multilingual learners, establish rapport with individuals from cultural and linguistic backgrounds that differ from their own, collaborate with other professionals, and build campers' confidence and self-esteem. The campers expanded their vocabulary, syntactic, and narrative production and developed teamwork, collaboration, and leadership. Conclusions: This program can be a model for others aiming to collaborate to advance educational equity. Speech-language pathologists have an important role in collaborating with colleagues from other disciplines to provide programs for language and literacy support, even when the students do not have underlying language disorder.

PET imaging in rat brain shows opposite effects of acute and chronic alcohol exposure on phosphodiesterase-4B, an indirect biomarker of cAMP activity.

The cyclic adenosine monophosphate (cAMP) cascade is thought to play an important role in regulating alcohol-dependent behaviors, with potentially opposite effects following acute versus chronic administration. Phosphodiesterase 4 (PDE4) is the primary brain enzyme that metabolizes cAMP, thereby terminating its signal. Radioligand binding to PDE4 serves as an indirect biomarker of cAMP activity, as cAMP-protein kinase A (PKA)-mediated phosphorylation of PDE4 increases its affinity for radioligand binding ~10-fold. Of the four PDE4 subtypes, PDE4B polymorphisms are known to be strongly associated with alcohol and substance use disorders. This study imaged rats with the PDE4B-preferring positron emission tomography (PET) radioligand [18F]PF-06445974 following acute and chronic ethanol administration, aiming to explore the potential of PDE4B PET imaging for future human studies. Compared to the control group treated with saline, acute alcohol administration (i.p. ethanol 0.5 g/kg) significantly increased whole brain uptake of [18F]PF-06445974 as early as 30 minutes post-exposure. This effect persisted at 2 hours, peaked at 4 hours, and diminished at 6 hours and 24 hours post-exposure. In contrast, in a rat model of alcohol dependence, [18F]PF-06445974 brain uptake was significantly reduced at 5 hours post-exposure and was normalized by 3 days. This reduction may reflect long-term adaptation to repeated alcohol-induced activation of cAMP signaling with chronic exposure. Taken together, the results suggest that PET imaging of PDE4B in individuals with alcohol use disorder (AUD) should be considered in conjunction with ongoing trials of PDE4 inhibitors to treat alcohol withdrawal and reduce alcohol consumption.

Monkey bars and medical masks: a photo-voice study of children’s playground safety in British Columbia, Canada

ABSTRACT Children’s perspectives on their outdoor play safety can provide unique insight into what activities and environments are injurious for them. In this study, we conducted photo-elicitation interviews with 13 children (7 girls, 6 boys) from low- to mid-income communities who were between the ages of 9- to 13-years-old. The goal of the study was to examine their perspectives of outdoor play safety around urban playgrounds over a two-week period while they participated in day camp activities. Our thematic content analysis resulted in three themes: (1) fear of falling; (2) illness prevention; and (3) need for excitement. Our findings suggest children’s perception of safe play may be shaped by exposure to sanitary practices throughout the COVID-19 pandemic. Further, findings demonstrate children can experience tensions in participating in desirable play that is exciting, novel, and challenging, while fearing they could fall from higher structures that afford them with these opportunities.

Abstract Mo070: Metabolic Syndrome Alters cAMP Homeostasis and Contractile Function of Cardiomyocytes

Approximately one third of the population in the US has metabolic syndrome (MetS), a condition associated with increased risk for coronary artery disease and myocardial infarction. But whether MetS alters properties of the myocardium before the occurrence of ischemic insults remains to be fully elucidated. For this purpose, MetS was induced in C57Bl/6 female mice with a dietary paradigm recapitulating Western-style alimentary habits in humans. Animals on regular chow were used as control (Ctrl). Cardiac function was assessed by echocardiography and myocytes were studied under field stimulation, following enzymatic dissociation. From 3-12 months on the diet, MetS mice had increased body weight, impaired glucose metabolism, augmented left ventricular (LV) mass, but preserved cardiac function, with respect to Ctrl mice. Using ECGs, heart rate variability was attenuated in MetS mice, suggesting that metabolic disorders alter cardiac sympathovagal balance. At the cellular level, LV myocytes from MetS mice had increased volume (+24%), enhanced fractional cell shortening (+42%), and faster kinetics of relaxation (-27%), with respect to Ctrl myocytes. Because cAMP and protein Kinase A (PKA) modulates myocardial contractility upon activation of G-protein coupled receptors, including beta-adrenergic receptors (B-AR), levels of these molecules were assessed by ELISA assay. Consistent with enhanced cell shortening and faster relaxation, levels of cAMP and PKA activity were, respectively, 1.8-fold and 1.9-fold larger in MetS myocytes, in comparison to Ctrl cells. Interestingly, inhibition of PKA with H-89 reduced cell shortening (-30%) and delayed kinetics of relaxation (+50%) in MetS myocytes but had no major effects on Ctrl cells. To establish the contribution of the cAMP/PKA signaling in the functional behavior of the heart with MetS, mice were treated with the B-AR blocker propranolol. Under this condition, MetS mice had reduced ejection fraction and impaired indices of diastolic function, with respect to Ctrl animals. Interestingly, myocytes obtained from Ctrl and MetS mice treated with the B-AR blocker had comparable cell shortening and kinetics of relaxation. Collectively, these results indicate that metabolic syndrome alters the functional properties of the myocytes and heart by affecting cAMP homeostasis. These properties may increase myocardial oxygen demand predisposing the heart to ischemic insults.

Functional characterization of follicle-stimulating hormone and luteinizing hormone receptors in cloudy catshark, Scyliorhinus torazame

The follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) in cloudy catshark were cloned, and recombinant FSHR and LHR were expressed for characterization. Ventral lobe extract (VLE) from the pituitary contains homologous FSH and LH, and it stimulated the cAMP signaling of FSHR and LHR dose-dependently. Two transcript variants of LHR (LHR-L with exon 10 and LHR-S without) were identified, and LHR-S was the dominant form with higher basal cAMP activity without VLE stimulation. Among various developmental stages of follicles, FSHR expression was mainly associated with the pre-vitellogenic and early white follicles. When follicles were recruited into vitellogenesis, the expression of FSHR decreased while of LHR was upregulated reciprocally, suggesting that LHR may also be responsible for the control of vitellogenesis in chondrichthyans. The expression of LHR-L was upregulated among maturing follicles before ovulation, indicating LHR-L could have a specific role in receiving the LH surge signal for final maturation. Plasma LH-like activity was transiently increased prior to the progesterone (P4)-surge and testosterone-drop at the beginning of P4-phase, supporting a pituitary control of follicle-maturation via LH signaling in chondrichthyans. The expression of follicular LHR was downregulated during the P4-phase when LH-like activity was high, indicating that the LH-dependent downregulation of LHR is conserved in chondrichthyans as it is in other vertebrate lineages. (213 words)

A Critical Functional Missense Mutation (T117M) in Sheep MC4R Gene Significantly Leads to Gain-of-Function.

The melanocortin 4 receptor (MC4R) gene plays a central role in regulating energy homeostasis and food intake in livestock, thereby affecting their economic worth and growth. In a previous study, the p.T117M mutation in the sheep MC4R gene, which leads to the transition of threonine to methionine, was found to affect the body weight at six months and the average daily gain in Hu sheep. However, there are still limited studies on the frequency of the sheep p.T117M missense mutation globally, and the underlying cellular mechanism remains elusive. Therefore, this study first used WGS to investigate the distribution of the MC4R gene p.T117M mutation in 652 individuals across 22 breeds worldwide. The results showed that the mutation frequency was higher in European breeds compared with Chinese sheep breeds, particularly in Poll Dorset sheep (mutation frequency > 0.5). The p.T117M mutation occurs in the first extracellular loop of MC4R. Mechanistically, the basal activity of the mutated receptor is significantly increased. Specifically, upon treatment with α-MSH and ACTH ligands, the cAMP and MAPK/ERK signaling activation of M117 MC4R is enhanced. These results indicate that the T117M mutation may change the function of the gene by increasing the constitutive activity and signaling activation of cAMP and MAPK/ERK, and, thus, may regulate the growth traits of sheep. In conclusion, this study delved into the global distribution and underlying cellular mechanisms of the T117M mutation of the MC4R gene, establishing a scientific foundation for breeding sheep with superior growth, thereby contributing to the advancement of the sheep industry.

CUMP elicits interendothelial gap formation during Pseudomonas aeruginosa infection.

Pseudomonas aeruginosa utilizesa type 3 secretion system to intoxicate host cells with the nucleotidyl cyclase ExoY. After activation by its host cell cofactor, filamentous actin, ExoY produces purine and pyrimidine cyclic nucleotides, including cAMP, cGMP, and cUMP. ExoY-generated cyclic nucleotides promote interendothelial gap formation, impair motility, and arrest cell growth. The disruptive activities of cAMP and cGMP during the P. aeruginosa infection are established; however, little is known about the function of cUMP. Here, we tested the hypothesis that cUMP contributes to endothelial cell barrier disruption during P. aeruginosa infection. Using a membrane permeable cUMP analog, cUMP-AM, we revealed that during infection with catalytically inactive ExoY, cUMP promotes interendothelial gap formation in cultured pulmonary microvascular endothelial cells (PMVECs) and contributes to increased filtration coefficient in the isolated perfused lung. These findings indicate that cUMP contributes to endothelial permeability during P. aeruginosa lung infection.NEW & NOTEWORTHY During pneumonia, bacteria utilizea virulence arsenal to communicate with host cells. The Pseudomonas aeruginosa T3SS directly introduces virulence molecules into the host cell cytoplasm. These molecules are enzymes that trigger interkingdom communication. One of the exoenzymes is a nucleotidyl cyclase that produces noncanonical cyclic nucleotides like cUMP. Little is known about how cUMP acts in the cell. Here we found that cUMP instigates pulmonary edema during Pseudomonas aeruginosa infection of the lung.

Graded control of Purkinje cell outputs by cAMP through opposing actions on axonal action potential and transmitter release.

All-or-none signalling by action potentials (APs) in neuronal axons is pivotal for the precisely timed and identical size of outputs to multiple distant targets. However, technical limitations with respect to measuring the signalling in small intact axons have hindered the evaluation of high-fidelity signal propagation. Here, using direct recordings from axonal trunks and/or terminals of cerebellar Purkinje cells in slice and culture, we demonstrate that the timing and amplitude of axonal outputs are gradually modulated by cAMP depending on the length of axon. During the propagation in long axon, APs were attenuated and slowed in conduction by cAMP via specifically decreasing axonal Na+ currents. Consequently, the Ca2+ influx and transmitter release at distal boutons are reduced by cAMP, counteracting its direct facilitating effect on release machinery as observed at various CNS synapses. Together, our tour de force functional dissection has unveiled the axonal distance-dependent graded control of output timing and strength by intracellular signalling. KEY POINTS: The information processing in the nervous system has been classically thought to rely on the axonal faithful and high-speed conduction of action potentials (APs). We demonstrate that the strength and timing of axonal outputs are weakened and delayed, respectively, by cytoplasmic cAMP depending on the axonal length in cerebellar Purkinje cells (PCs). Direct axonal patch clamp recordings uncovered axon-specific attenuation of APs by cAMP through reduction of axonal Na+ currents. cAMP directly augments transmitter release at PC terminals without changing presynaptic Ca2+ influx or readily releasable pool of vesicles, although the extent is weaker compared to other CNS synapses. Two opposite actions of cAMP on PC axons, AP attenuation and release augmentation, together give rise to graded control of synaptic outputs in a manner dependent on the axonal length.

The Guidelines for Enhancing Knowledge and Proficiency in Food Decoration Skills: RMUTP

The purpose of this study was to examine the level of knowledge and skills related to food decoration, and to identify consistent study activities for each academic year in the food service industry's student program through correspondence analysis. The population was 304 people. The results demonstrated a high level of knowledge and behavioral learning in the area of artistic skills. An analysis of the correlation between the academic year and activities aimed at enhancing knowledge, skills, and creativity in the art of food decoration revealed that the 1st year students engaged in activities related to analyzing food decoration design, the 2nd year students focused on the fundamentals of food decoration, the 3rd year students explored visual elements and art principles in food design and decoration, and the 4th year students assessed their ability to design food decorations before class. Activities to enhance art skills involved 1st year students participating in exhibitions, 2nd year students participating in artificial decoration activities, and 3rd and 4th year students participating in culinary workshops and learning about food decoration techniques. Activities to enhance creativity involved the 1st and 2nd students creating images from points, the 3rd students participating in art camp activities, and the 4th students learning how to add value to food through plating and photography.

CAMP-independent DNA binding of the CRP family protein DdrI from Deinococcus radiodurans.

The cAMP receptor proteins (CRPs) play a critical role in bacterial environmental adaptation by regulating global gene expression levels via cAMP binding. Here, we report the structure of DdrI, a CRP family protein from Deinococcus radiodurans. Combined with biochemical, kinetic, and molecular dynamics simulations analyses, our results indicate that DdrI adopts a DNA-binding conformation in the absence of cAMP and can form stable complexes with the target DNA sequence of classical CRPs. Further analysis revealed that the high-affinity cAMP binding pocket of DdrI is partially filled with Tyr113-Arg55-Glu65 sidechains, mimicking the anti-cAMP-mediated allosteric transition. Moreover, the second syn-cAMP binding site of DdrI at the protein-DNA interface is more negatively charged compared to that of classical CRPs, and manganese ions can enhance its DNA binding affinity. DdrI can also bind to a target sequence that mimics another transcription factor, DdrO, suggesting potential cross-talk between these two transcription factors. These findings reveal a class of CRPs that are independent of cAMP activation and provide valuable insights into the environmental adaptation mechanisms of D. radiodurans.IMPORTANCEBacteria need to respond to environmental changes at the gene transcriptional level, which is critical for their evolution, virulence, and industrial applications. The cAMP receptor protein (CRP) of Escherichia coli (ecCRP) senses changes in intracellular cAMP levels and is a classic example of allosteric effects in textbooks. However, the structures and biochemical activities of CRPs are not generally conserved and there exist different mechanisms. In this study, we found that the proposed CRP from Deinococcus radiodurans, DdrI, exhibited DNA binding ability independent of cAMP binding and adopted an apo structure resembling the activated CRP. Manganese can enhance the DNA binding of DdrI while allowing some degree of freedom for its target sequence. These results suggest that CRPs can evolve to become a class of cAMP-independent global regulators, enabling bacteria to adapt to different environments according to their characteristics. The first-discovered CRP family member, ecCRP (or CAP) may well not be typical of the family and be very different to the ancestral CRP-family transcription factor.

The effectiveness of active rehabilitation camp on wheelchair users’ self-esteem

Background: The Active Rehabilitation Camps (ARC) provide access to comprehensive rehabilitation. The main goal is to provide wheelchair users achieving the maximum possible independence in performing activities of daily living, to help them accept a new lifestyle, as well as comprehensive rehabilitation in the social and vocational fields. Higher self-esteem in wheelchair users help them overcome barriers in everyday living, increase initiative, improve their mental health and well-being.Aims of the study: The aim of the research was to evaluate the impact of Active Rehabilitation Camps on self-esteem of wheelchair users.Material and methods: 95 adult wheelchair users aged 18 to 75 took part in the study. 92 participants were included in the analysis (31 women and 61 men). The research tool was a questionnaire including first part with personal data and a second part - an international and validated questionnaire the Rosenberg Self-Esteem Scale (RSES). All participants filled the questionnaire at the beginning of the ARC and after two-week camp.Results: The results showed a significant improvement in self-esteem among participant after camps, total self-esteem according to RSES increased from 28.32 4.99 before a camp, to 30.8 4.85 after a camp (p<0.0001). Our results showed that apart from general self-esteem, SE in such domains as “on the whole, I am satisfied with myself”, “I am able to do things as well as most other people” or “I take a positive attitude towards myself” increased significantly after the ARC (p<0.001).Conclusions: The activities of the Active Rehabilitation Camp including access to physical activity, health-promoting education, experience exchange and integration of wheelchair users, increase the level of self-esteem of Active Rehabilitation Camp participants. Systematic physical activities, social and emotional support, as well as appropriate education should be provided in everyday rehabilitation among wheelchair users to improve their self-esteem and everyday life functioning.

Business Camp: MSME Financial Management in West Sumatra

Financial management is the heart of a business. Many businesses fail and eventually go bankrupt due to poor financial management. Quality products and services with sound financial management will be helpful with thorough financial planning. Empowering MSMEs is one of the government's commitments. Universities have a role in helping the government in empowering MSMEs. Therefore, Andalas University has organized various programs to carry out this role. One of the programs organized by Andalas University is the Business Camp activity. Business Camp activities consist of several types of empowerment material, including MSME financial management. First Business Camp activities with Financial Management material were conducted online using the Zoom Meeting Application. The activity was held on Saturday, 28 October 2023. The main participants in this activity were MSME owners whom Andalas University accompanied. However, this activity did not close the opportunity for other MSMEs who want to join. Therefore, as many as 80 participants had taken part in this activity. The result of this activity was the motivation for MSMEs to separate their financial books first so that sound financial management can be carried out. This activity is essential to carry out so that MSME businesses can become businesses that continue to grow.

Fast and Fun: A Pilot Feasibility Study Using Dual Joystick-Operated Ride-on Toys for Upper Extremity Rehabilitation in Children with Hemiplegia

Aim Our study investigates the feasibility and utility of implementing a dual joystick-operated ride-on-toy navigation training (RNT) program within a 3-week intensive camp based on principles of modified constraint-induced movement therapy and bimanual training, to improve upper extremity (UE) function in children with unilateral cerebral palsy (UCP). Methods We employed a single-group pretest posttest, mixed methods study design. Eleven 4-to-10-year-old children with UCP received RNT as part of camp activities. Sessions required children to use both arms together for navigation and completing gross and fine motor UE challenges. We collected exit questionnaires from children, caregivers, and clinicians to assess the feasibility, acceptance, enjoyment, and perceived efficacy of RNT. Videos of training sessions were coded using Datavyu behavioral coding software to assess children’s facial expressions and affective states, indicative of their level of engagement during intervention sessions. Results We found high levels of child engagement during RNT sessions based on video data and stakeholder feedback. The RNT program was smoothly integrated into the camp. Stakeholders acknowledged the highly motivating nature of RNT. When combined with other camp activities, the program led to stakeholder-reported improvements in bimanual skills and spontaneous daily use of the affected UE. Conclusions Our pilot study provides promising evidence for using joystick-operated ride-on toys as engaging therapy adjuncts. Our findings call for future studies to systematically assess the efficacy of these devices in improving UE function among children with UCP.

Joystick-Operated Ride-On Toy Navigation Training for Children With Hemiplegic Cerebral Palsy: A Pilot Study.

Children with hemiplegic cerebral palsy (HCP) require intensive task-oriented training to make meaningful gains in affected upper extremity (UE) motor function. To evaluate the acceptability and utility of single joystick-operated ride-on toy (ROT) navigation training incorporated into a modified constraint-induced movement therapy (CIMT) camp for children with HCP. Single group pretest-posttest design. Three-wk structured CIMT camp. Eleven children with HCP between ages 3 and 14 yr. Children received group-based CIMT for 6 hr/day, 5 days/wk, for 3 wk. As part of camp activities, children also received ROT navigation training for 20 to 30 min/day, 5 days/wk, for 3 wk. We assessed children's acceptance of ROT training by monitoring adherence and evaluating child engagement (affect and attention) during training sessions. The effects of ROT training combined with other camp activities on children's affected UE motor function were also assessed with the standardized Quality of Upper Extremity Skills Test (QUEST) and training-specific measures of ROT maneuvering accuracy. Children demonstrated high levels of training adherence, positive affect, and task-appropriate attention across weeks. Positive engagement during ROT sessions was correlated with independent navigation. We also found medium- to large-sized improvements in QUEST scores and toy-maneuvering capabilities after the combined program. Our pilot data support the use of joystick-operated ROTs as child-friendly therapy adjuncts that can be incorporated into intensive UE training programs to improve adherence and motivation in therapy programs, boost treatment dosing, and promote affected UE motor function in children with HCP. Plain-Language Summary: This pilot study offers promising evidence that supports the use of modified single joystick-operated ride-on toys (ROTs) for children with hemiplegic cerebral palsy (HCP). The study used ROTs as one of several interventions that were part of a constraint-induced movement therapy (CIMT) camp program for children with HCP. The ROTs boosted children's motivation, their engagement with and adherence to training, and their practice in using their affected upper extremity (UE) for goal-directed activities in their natural settings. ROTs are accessible, age-appropriate, and easy-to-use devices for both occupational therapy clinicians and families to encourage children to use their affected UEs by challenging their perceptual, motor-planning, problem-solving, and movement-control skills in an enjoyable and engaging way. ROTs can be used within and outside conventional rehabilitation settings.

EGFR inhibition with erlotinib induces membrane accumulation of aquaporin-2 via PDK1 and RSK activation

In the canonical aquaporin-2 (AQP2) signaling pathway, vasopressin (VP) binds to its V2 receptor, which in turn activates adenylate cyclase and protein kinase A (PKA), resulting in AQP2 S256 phosphorylation and accumulation of AQP2 in the membrane. The epidermal growth factor receptor (EGFR) inhibitor erlotinib also increases AQP2 S256 phosphorylation and membrane accumulation, yet it does not increase cAMP or PKA activity. We hypothesize that the ribosomal s6 kinase (RSK), a downstream effector in the EGFR-MAPK/ERK pathway, is the terminal kinase phosphorylating AQP2 in this novel PKA-independent pathway activated by erlotinib, and that the phosphoinositide dependent kinase-1 (PDK1), a well-established activator of RSK, is indispensable for erlotinib-induced AQP2 activation. Using our LLC-AQP2 cell model, we show that erlotinib-induced AQP2 membrane accumulation and S256 phosphorylation are abolished by the specific RSK inhibitor BI-D1870. RSK knockdown with siRNA also blocked AQP2 S256 phosphorylation and membrane accumulation, as did RSK knockout with CRISPR/cas9 editing. Next, rat kidney slices were incubated in Hank’s buffer with or without BI-D1870 and treated with erlotinib. BI-D1870 inhibited AQP2 membrane accumulation in collecting duct principal cells, supporting the relevance of this pathway in kidney cells in situ. An in-vitro kinase assay using purified proteins demonstrated that RSK directly phosphorylates AQP2 at the S256 residue. Additionally, erlotinib consistently increased phosphorylation of RSK T359, a residue associated with RSK’s active state. In canonical RSK activation, a phosphorylation cascade results in PDK1 binding to and activating RSK. We found that PDK1 inhibition with an experimental compound PS-222 also blocked erlotinib-induced AQP2 membrane accumulation and S256 phosphorylation. This implicates PDK1 along with RSK in the novel erlotinib-induced pathway of AQP2 traffcking. Our data show that RSK and PDK1 are terminal effectors in the novel, PKA-independent pathway of AQP2 activation induced by erlotinib. Further elaboration of this new non-canonical pathway promises to uncover potential pharmacological targets for the treatment of water balance disorders. This work was supported by the National Institutes of Health (NIH) grant DK096586 (D. Brown). P. W. Cheung was supported was supported by NIH K-award DK115901. Richard Babicz is the recipient of the Ben J Lipps Research Fellowship (American Society of Nephrology). Additional support for the Program in Membrane Biology Microscopy Core came from the Boston Area Diabetes and Endocrinology Research Center (DK057521) and the Massachusetts General Hospital (MGH) Center for the Study of Inflammatory Bowel Disease (DK043351). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

캠핑활동의 지각된 위험과 참여동기가 태도와 행동의도에 미치는 영향

Purpose - The camping market in China has demonstrated consistent growth in recent years, with a continued expansion observed. Particularly, following the COVID-19 pandemic, heightened concern for safety during leisure activities has become prevalent among individuals. This study aimed to ascertain the motivational factors driving Chinese individuals to engage in camping activities, and assess the influence of perceived risk on camper attitudes and behavioral intentions. Design/Methodology/Approach - Data analysis encompassed a sample of 258 sets collected from campers that visited three campsites situated in Qinhuangdao, China. Findings - The findings revealed that all perceived risk factors associated with camping activities significantly impacted individual attitudes. Furthermore, among the motivating factors for participation, aspects such as affinity for nature and escapism from daily routines were identified as influential in attitudes toward camping activities. The study confirmed a substantial relationship between the attitude toward camping activities and behavioral intentions. Research Implications - The outcomes underscore the necessity for camping operators to furnish campers with strategies to manage risks and educational initiatives encompassing safe camping practices and emergency protocols. Consequently, this study offers insights into the future trajectory of the camping industry, emphasizing the imperative of amalgamating safety measures with a rich natural experience.