Modulation of prefrontal couplings by prior belief-related responses in ventromedial prefrontal cortex.

Humans and other animals can maintain constant payoffs in an uncertain environment by steadily re-evaluating and flexibly adjusting current strategy, which largely depends on the interactions between the prefrontal cortex (PFC) and mediodorsal thalamus (MD). While the ventromedial PFC (vmPFC) represents the level of uncertainty (i.e., prior belief about external states), it remains unclear how the brain recruits the PFC-MD network to re-evaluate decision strategy based on the uncertainty. Here, we leverage non-linear dynamic causal modeling on fMRI data to test how prior belief-dependent activity in vmPFC gates the information flow in the PFC-MD network when individuals switch their decision strategy. We show that the prior belief-related responses in vmPFC had a modulatory influence on the connections from dorsolateral PFC (dlPFC) to both, lateral orbitofrontal (lOFC) and MD. Bayesian parameter averaging revealed that only the connection from the dlPFC to lOFC surpassed the significant threshold, which indicates that the weaker the prior belief, the less was the inhibitory influence of the vmPFC on the strength of effective connections from dlPFC to lOFC. These findings suggest that the vmPFC acts as a gatekeeper for the recruitment of processing resources to re-evaluate the decision strategy in situations of high uncertainty.

Human orbitofrontal cortex signals decision outcomes to sensory cortex during behavioral adaptations.

The ability to respond flexibly to an ever-changing environment relies on the orbitofrontal cortex (OFC). However, how the OFC associates sensory information with predicted outcomes to enable flexible sensory learning in humans remains elusive. Here, we combine a probabilistic tactile reversal learning task with functional magnetic resonance imaging (fMRI) to investigate how lateral OFC (lOFC) interacts with the primary somatosensory cortex (S1) to guide flexible tactile learning in humans. fMRI results reveal that lOFC and S1 exhibit distinct task-dependent engagement: while the lOFC responds transiently to unexpected outcomes immediately following reversals, S1 is persistently engaged during re-learning. Unlike the contralateral stimulus-selective S1, activity in ipsilateral S1 mirrors the outcomes of behavior during re-learning, closely related to top-down signals from lOFC. These findings suggest that lOFC contributes to teaching signals to dynamically update representations in sensory areas, which implement computations critical for adaptive behavior.

Analogous cognitive strategies for tactile learning in the rodent and human brain.

Evolution has molded individual species' sensory capacities and abilities. In rodents, who mostly inhabit dark tunnels and burrows, the whisker-based somatosensory system has developed as the dominant sensory modality, essential for environmental exploration and spatial navigation. In contrast, humans rely more on visual and auditory inputs when collecting information from their surrounding sensory space in everyday life. As a result of such species-specific differences in sensory dominance, cognitive relevance and capacities, the evidence for analogous sensory-cognitive mechanisms across species remains sparse. However, recent research in rodents and humans yielded surprisingly comparable processing rules for detecting tactile stimuli, integrating touch information into percepts, and goal-directed rule learning. Here, we review how the brain, across species, harnesses such processing rules to establish decision-making during tactile learning, following canonical circuits from the thalamus and the primary somatosensory cortex up to the frontal cortex. We discuss concordances between empirical and computational evidence from micro- and mesoscopic circuit studies in rodents to findings from macroscopic imaging in humans. Furthermore, we discuss the relevance and challenges for future cross-species research in addressing mutual context-dependent evaluation processes underpinning perceptual learning.

Thalamic regulation of frontal interactions in human cognitive flexibility.

Interactions across frontal cortex are critical for cognition. Animal studies suggest a role for mediodorsal thalamus (MD) in these interactions, but the computations performed and direct relevance to human decision making are unclear. Here, inspired by animal work, we extended a neural model of an executive frontal-MD network and trained it on a human decision-making task for which neuroimaging data were collected. Using a biologically-plausible learning rule, we found that the model MD thalamus compressed its cortical inputs (dorsolateral prefrontal cortex, dlPFC) underlying stimulus-response representations. Through direct feedback to dlPFC, this thalamic operation efficiently partitioned cortical activity patterns and enhanced task switching across different contingencies. To account for interactions with other frontal regions, we expanded the model to compute higher-order strategy signals outside dlPFC, and found that the MD offered a more efficient route for such signals to switch dlPFC activity patterns. Human fMRI data provided evidence that the MD engaged in feedback to dlPFC, and had a role in routing orbitofrontal cortex inputs when subjects switched behavioral strategy. Collectively, our findings contribute to the emerging evidence for thalamic regulation of frontal interactions in the human brain.

Adapting the ACMG/AMP variant classification framework: A perspective from the ClinGen Hemoglobinopathy Variant Curation Expert Panel.

Accurate and consistent interpretation of sequence variants is integral to the delivery of safe and reliable diagnostic genetic services. To standardize the interpretation process, in 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published a joint guideline based on a set of shared standards for the classification of variants in Mendelian diseases. The generality of these standards and their subjective interpretation between laboratories has prompted efforts to reduce discordance of variant classifications, with a focus on the expert specification of the ACMG/AMP guidelines for individual genes or diseases. Herein, we describe our experience as a ClinGen Variant Curation Expert Panel to adapt the ACMG/AMP criteria for the classification of variants in three globin genes (HBB, HBA2, and HBA1) related to recessively inherited hemoglobinopathies, including five evidence categories, as use cases demonstrating the process of specification and the underlying rationale.

Progressive gray matter hypertrophy with severity stages of insomnia disorder and its relevance for mood symptoms.

OBJECTIVE: To investigate the gray matter (GM) alterations in patients with insomnia disorder (ID) at different severity stages and the relationship between GM alterations and sleep, mood, and cognitive measures. METHODS: One hundred one ID patients and 63 healthy controls (HC) were included. Each patient underwent structural MRI and completed sleep-, mood-, and cognitive-related questionnaires. The ID patients were further grouped into subthreshold insomnia (SI) group and clinical insomnia (CI) group. We investigated changes in GM volumes in ID patients via diffeomorphic anatomical registration through exponentiated lie algebra voxel-based morphometry (DARTEL-VBM). We first compared voxel-wise differences in GM volumes between the HC group and the ID group. Analysis of variance was performed on individual GM maps in the SI, CI, and HC groups to further investigate the effects of different stages of ID severity on GM volumes. Multiple regression was used to model the relationship between altered GM volumes in SI and CI groups and clinical measures. RESULTS: GM hypertrophies in the left anterior and middle cingulate gyrus, right middle and inferior temporal gyrus, and right cerebellum Crus II were detected in ID. Increased GM volume in the right middle temporal gyrus was detected in the SI group, whereas all three regions in the CI group. Regression analysis showed that mood- and cognitive-related measures had a positive correlation with GM volumes, while sleep-related measures had a negative correlation with GM volumes in the CI group. CONCLUSIONS: Our findings of the progressively increased GM volumes in ID suggest that a hypertrophic cortical morphological mechanism may underlie the altered neuroanatomy induced by insomnia. KEY POINTS: • Insomnia-induced GM hypertrophies in the cingulate gyrus, temporal gyrus, and cerebellum Crus II. • The middle temporal gyrus was early detectable in the SI group. • The increased GM volumes in the CI group were correlated with clinical measures.

Sharing and caring: The impact of social support on quality of life and health outcomes in hematopoietic stem cell transplantation.

BACKGROUND: Social support is crucial for successful recovery after hematopoietic stem cell transplantation (HSCT) and has the potential to affect patient quality of life (QOL) and health outcomes. However, there are limited data on the relationship between a patient's perception of his or her social support and these outcomes. METHODS: The authors conducted a secondary analysis of 250 autologous and allogeneic HSCT recipients enrolled in 2 supportive care trials at Massachusetts General Hospital from April 2011 through February 2016. They assessed social support as a patient's perception of his or her social well-being via the social well-being subscale of the Functional Assessment of Cancer Therapy. The authors used multivariate regression analyses to examine the relationship between pretransplant social well-being and QOL (Functional Assessment of Cancer Therapy-Treatment Outcome Index), psychological distress (Hospital Anxiety and Depression Scale), posttraumatic stress disorder [PTSD] symptoms (PTSD Checklist), fatigue (Functional Assessment of Cancer Therapy-Fatigue), and health care utilization (hospitalizations and days alive and out of the hospital) 6 months after HSCT. RESULTS: Participants were on average 56.4 years old (SD, 13.3 years); 44% (n = 110) and 56% (n = 140) received autologous and allogeneic HSCT, respectively. Greater pre-HSCT social well-being was associated with higher QOL (B = 0.10; 95% CI, 0.06-0.13; P < .001), lower psychological distress (B = -0.21; 95% CI, -0.29 to -0.12; P < .001), and lower PTSD symptoms (B = -0.12; 95% CI, -0.19 to -0.06; P < .001). Pre-HSCT social well-being was not significantly associated with fatigue or health care utilization 6 months after HSCT. CONCLUSIONS: Patients with higher pre-HSCT perceptions of their social support reported better QOL and lower psychological distress 6 months after HSCT. These findings underscore the potential for social support as a modifiable target for future supportive care interventions to improve the QOL and care of HSCT recipients.

Stimulus transformation into motor action: Dynamic graph analysis reveals a posterior-to-anterior shift in brain network communication of older subjects.

Cognitive performance slows down with increasing age. This includes cognitive processes that are essential for the performance of a motor act, such as the slowing down in response to an external stimulus. The objective of this study was to identify aging-associated functional changes in the brain networks that are involved in the transformation of external stimuli into motor action. To investigate this topic, we employed dynamic graphs based on phase-locking of Electroencephalography signals recorded from healthy younger and older subjects while performing a simple visually-cued finger-tapping task. The network analysis yielded specific age-related network structures varying in time in the low frequencies (2-7 Hz), which are closely connected to stimulus processing, movement initiation and execution in both age groups. The networks in older subjects, however, contained several additional, particularly interhemispheric, connections and showed an overall increased coupling density. Cluster analyses revealed reduced variability of the subnetworks in older subjects, particularly during movement preparation. In younger subjects, occipital, parietal, sensorimotor and central regions were-temporally arranged in this order-heavily involved in hub nodes. Whereas in older subjects, a hub in frontal regions preceded the noticeably delayed occurrence of sensorimotor hubs, indicating different neural information processing in older subjects. All observed changes in brain network organization, which are based on neural synchronization in the low frequencies, provide a possible neural mechanism underlying previous fMRI data, which report an overactivation, especially in the prefrontal and pre-motor areas, associated with a loss of hemispheric lateralization in older subjects.

Intention to seek professional help for depression and its associated factors among elderly patients in Tenkera Health Clinic, Melaka, Malaysia

@#Background: Prevalence of mental disorders such as depression in the elderly is rising with the ageing population. This study is aimed to determine the prevalence of depression, their intention to seek help and the factors associated to seek professional help among elderly patients in a primary care clinic. Methods: This was a cross-sectional with systematic sampling conducted from June to December 2019 in Tengkera Health Clinic (THC). Patient Health Questionnaire9 (PHQ-9), socioeconomic data and a dichotomous yes-no response for intention to seek help was collected from 273 elderly patients attending the outpatient clinic. Results: The prevalence of elderly depression at THC was 10.3% and the prevalence of intention to seek professional help for depression among elderly patients at Tengkera Health Clinic was 27.5%. Factors that were associated with intention to seek professional help for depression were prior experience of seeking professional help, adjusted OR 3.45[95%CI (1.41-8.48)] and education level of the respondents- secondary education, adjusted OR 3.10 [95%CI (1.01-9.53)] comparing with no formal education; tertiary education, adjusted OR 4.66 [95%CI (1.08-20.04)] comparing with no formal education. Conclusion: The prevalence of elderly depression was high while the prevalence of intention to seek professional help for depression in the sample population was low. Primary care physicians play a vital role in identifying elderly patients with low education level for screening and treatment as well as promoting awareness and breaking down barriers and stigma towards mental illness.

Bacillus megaterium: a Potential and an Efficient Bio-Degrader of Polystyrene

Abstract This research has been conducted to investigate the biodegradation of polystyrene (PS) by isolated strain Bacillus megaterium from Zophobas morio's. The viability and metabolic activity of Bacillus megaterium utilizing emulsified PS in liquid carbon free basal medium as sole carbon source was confirmed using redox probe 2,3,5-triphenyltetrazolium chloride (TTC). Bacillus megaterium showed prominent result with TTC, which forms red colored insoluble TPF (triphenyl formazan) within four to seven days. The formation of TPF confirmed the metabolism activity of the cell using PS as source of carbon. The biodegradation activity of Bacillus megaterium on PS film was also confirmed by FTIR analysis, the result showed changes in functional groups due to microbial activities. FESEM analysis was carried out on the PS surface, revealing the formation of bacterial biofilm as well as occurrence of porosity and fragility of the bacterial deteriorate surface compared to control. Overall, the identification of plastic degrading bacteria (PDB) will become a fundamental platform promoting more in-depth research for optimal plastic waste management to switch from the conventional landfilling to enzymatic biodegradation. In the long run, it is to regulate the current global plastic waste accumulation on Earth which poses potent ecological threat.

What to do in an oncology department to face the new COVID-19 era challenges?

Italy was the first European country to be hit by COVID-19 pandemic. As a consequence, Italian oncologists had to guarantee essential treatments although minimizing exposure to the virus, and accidental infection, of patients and healthcare professionals. As Department of Medical Oncology of the University Hospital of Udine, in this short report, we describe the measures that we have taken, and gradually updated, since February 26, 2020. All accesses to our Oncology facilities are currently regulated by entrance check-points where patients are screened for infections following dedicated algorithms. Up to date, after 6 weeks of systematic execution of swabs no physician, nurse or other individual of the staff has been found positive to COVID-19. Only one patient admitted for therapy has been identified as COVID-19 positive. The aim of our work is to propose a model, made up of a set of operative procedures, that may be adopted by all the oncologists that daily struggle to guarantee safety and care in Oncology during this COVID-19 emergency.

Innovation in Chinese internet companies: A meta-frontier analysis.

The innovation of a particular company benefits the whole industry when innovation technology transfers to others. Similarly, the development and innovation in internet companies influence the development and innovation of the industry. This investigation has applied a unique approach of meta-frontier analysis to estimate and analyze the innovation in internet companies in China. A unique dataset of Chinese internet companies from 2000 to 2017 has been utilized to estimate and compare the innovation over the period of study. The change in technology gap ratio (TGR) and a shift in production function have translated into innovation which was overlooked by previous studies. It is found that the production function of internet companies is moving upward in the presence of external factors such as smartphones invention, mobile internet, mobile payments, and artificial intelligence, etc. Consequently, a sudden increase in TGR is captured due to the innovation of some companies. Hence, the average TE of the industry falls caused by the increased distance of other companies form industry production function. However, the innovation advantage defused when other companies start imitating and the average TE elevates. A steady increase in the TGR index revealed that the continuous innovation-based growth of some companies lifting the production frontier upward. This provides the opportunity for other companies to imitate and provides continuous growth in the industry. This study provides a novel methodological approach to measure innovation and also provide practical implication by empirical estimation of innovation in Chinese internet companies.

A response-locking protocol to boost sensitivity for fMRI-based neurochronometry.

The timeline of brain-wide neural activity relative to a behavioral event is crucial when decoding the neural implementation of a cognitive process. Yet, fMRI assesses neural processes indirectly via delayed and regionally variable hemodynamics. This method-inherent temporal distortion impacts the interpretation of behavior-linked neural timing. Here we describe a novel behavioral protocol that aims at disentangling the BOLD dynamics of the pre- and post-response periods in response time tasks. We tested this response-locking protocol in a perceptual decision-making (random dot) task. Increasing perceptual difficulty produced expected activity increases over a broad network involving the lateral/medial prefrontal cortex and the anterior insula. However, response-locking revealed a previously unreported functional dissociation within this network. preSMA and anterior premotor cortex (prePMV) showed post-response activity modulations while anterior insula and anterior cingulate cortex did not. Furthermore, post-response BOLD activity at preSMA showed a modulation in timing but not amplitude while this pattern was reversed at prePMV. These timeline dissociations with response-locking thus revealed three functionally distinct sub-networks in what was seemingly one shared distributed network modulated by perceptual difficulty. These findings suggest that our novel response-locked protocol could boost the timing-related sensitivity of fMRI.

Modulations of Insular Projections by Prior Belief Mediate the Precision of Prediction Error during Tactile Learning.

Awareness for surprising sensory events is shaped by prior belief inferred from past experience. Here, we combined hierarchical Bayesian modeling with fMRI on an associative learning task in 28 male human participants to characterize the effect of the prior belief of tactile events on connections mediating the outcome of perceptual decisions. Activity in anterior insular cortex (AIC), premotor cortex (PMd), and inferior parietal lobule (IPL) were modulated by prior belief on unexpected targets compared with expected targets. On expected targets, prior belief decreased the connection strength from AIC to IPL, whereas it increased the connection strength from AIC to PMd when targets were unexpected. Individual differences in the modulatory strength of prior belief on insular projections correlated with the precision that increases the influence of prediction errors on belief updating. These results suggest complementary effects of prior belief on insular-frontoparietal projections mediating the precision of prediction during probabilistic tactile learning.SIGNIFICANCE STATEMENT In a probabilistic environment, the prior belief of sensory events can be inferred from past experiences. How this prior belief modulates effective brain connectivity for updating expectations for future decision-making remains unexplored. Combining hierarchical Bayesian modeling with fMRI, we show that during tactile associative learning, prior expectations modulate connections originating in the anterior insula cortex and targeting salience-related and attention-related frontoparietal areas (i.e., parietal and premotor cortex). These connections seem to be involved in updating evidence based on the precision of ascending inputs to guide future decision-making.

Confidence in Decision-Making during Probabilistic Tactile Learning Related to Distinct Thalamo-Prefrontal Pathways.

The flexibility in adjusting the decision strategy from trial to trial is a prerequisite for learning in a probabilistic environment. Corresponding neural underpinnings remain largely unexplored. In the present study, 28 male humans were engaged in an associative learning task, in which they had to learn the changing probabilistic strengths of tactile sample stimuli. Combining functional magnetic resonance imaging with computational modeling, we show that an unchanged decision strategy over successively presented trials related to weakened functional connectivity between ventralmedial prefrontal cortex (vmPFC) and left secondary somatosensory cortex. The weaker the connection strength, the faster participants indicated their choice. If the decision strategy remained unchanged, participant's decision confidence (i.e., prior belief) was related to functional connectivity between vmPFC and right pulvinar. While adjusting the decision strategy, we instead found confidence-related connections between left orbitofrontal cortex and left thalamic mediodorsal nucleus. The stronger the participant's prior belief, the weaker the connection strengths. Together, these findings suggest that distinct thalamo-prefrontal pathways encode the confidence in keeping or changing the decision strategy during probabilistic learning. Low confidence in the decision strategy demands more thalamo-prefrontal processing resources, which is in-line with the theoretical accounts of the free-energy principle.

Multimodal psychosocial intervention for family caregivers of patients undergoing hematopoietic stem cell transplantation: A randomized clinical trial.

BACKGROUND: Caregivers of patients undergoing hematopoietic stem cell transplantation (HCT) experience an immense caregiving burden before, during, and after HCT. METHODS: We conducted an unblinded, randomized trial of a psychosocial intervention (BMT-CARE) for caregivers of patients undergoing autologous and allogeneic HCT at Massachusetts General Hospital. Caregivers were randomly assigned to BMT-CARE or usual care. BMT-CARE was tailored to the HCT trajectory and integrated treatment-related education and self-care with cognitive-behavioral skills to promote coping. Caregivers assigned to BMT-CARE met with a trained interventionist (a psychologist or a social worker) in person, via telephone, or via videoconferencing for 6 sessions starting before HCT and continuing up to day +60 after HCT. The primary endpoint was feasibility, which was defined as at least 60% of eligible caregivers enrolling and completing 50% or more of the intervention sessions. We assesed caregiver quality of life (QOL; Caregiver Oncology Quality of Life Questionnaire), caregiving burden (Caregiver Reaction Assessment), psychological distress (Hospital Anxiety and Depression Scale), self-efficacy (Cancer Self-Efficacy Scale-Transplant), and coping (Measures of Current Status) at baseline and 30 and 60 days after HCT. We used mixed linear effect models to assess the effect of BMT-CARE on outcomes longitudinally. RESULTS: We enrolled 72.5% of eligible caregivers (100 of 138), and 80% attended 50% or more of the intervention sessions. Caregivers randomized to BMT-CARE reported improved QOL (B = 6.11; 95% CI, 3.50-8.71; P < .001), reduced caregiving burden (B = -6.02; 95% CI, -8.49 to -3.55; P < .001), lower anxiety (B = -2.18; 95% CI, -3.07 to -1.28; P < .001) and depression symptoms (B = -1.23; 95% CI, -1.92 to -0.54; P < .001), and improved self-efficacy (B = 7.22; 95% CI, 2.40-12.03; P = .003) and coping skills (B = 4.83; 95% CI, 3.04-6.94; P < .001) in comparison with the usual-care group. CONCLUSIONS: A brief multimodal psychosocial intervention tailored for caregivers of HCT recipients is feasible and may improve QOL, mood, coping, and self-efficacy while reducing the caregiving burden during the acute HCT period.

A Rare Case of Neurenteric Cyst of Spinal Cord with Thoracic Vertebra Fusion Successfully Managed with Spinal Cyst Excision and Posterior Instrumentation Surgery

@#The incidence of neurenteric cyst (NC) is rare amongst spine tumors. It is most often asymptomatic but may present with sensory and motor symptoms. When associated with thoracic vertebra fusion it is not reported before, this complicates the placement of pedicle screw during posterior instrumentation. Herein, we report a case of thoracic spinal neurenteric cyst in a 40-year-old man that presents with chronic back pain, left lower limb weakness and numbness. Elective excision of NC over T6-T7 with laminectomy and multilevel posterior instrumentation was successfully performed with significant improvement of the symptoms. Neurenteric cyst is a rare spinal cord lesion which may cause permanent neurological sequalae. Complete surgical excision with spine fixation in this case provides good long-term outcome.

Rare morbidity of permanent quadriplegia caused by neurenteric cyst of the cervical cord.

The incidence of neurenteric cyst (NC) is rare, accounting for 0.3%-1.3% of all spine tumors. The occurrence of quadriplegia caused by NC is even scarcer. Herein we report on a young girl with a rare NC over the C2-C5 spinal cord, which led to the morbidity of permanent quadriplegia despite early surgical intervention. This case highlights the rare morbidity of cervical cord NC presenting with permanent quadriplegia that failed to respond despite early surgical excision.

Freely chosen and instructed actions are terminated by different neural mechanisms revealed by kinematics-informed EEG.

Neurophysiological accounts of human volition are dominated by debates on the origin of voluntary choices but the neural consequences that follow such choices remain poorly understood. For instance, could one predict whether or not an action was chosen voluntarily based only on how that action is motorically executed? We investigated this possibility by integrating scalp electroencephalograms and index-finger accelerometer recordings acquired while people chose between pressing a left or right button either freely or as instructed by a visual cue. Even though freely selected and instructed actions were executed with equal vigor, the timing of the movement to release the button was comparatively delayed for freely selected actions. This chronometric difference was six-times larger for the ß-oscillations over the sensorimotor cortex that characteristically accompany an action's termination. This surprising modulation of an action's termination by volition was traceable to volition-modulated differences in how the competing yet non-selected action was represented and regulated.

Rabbit as an Animal Model for Pharmacokinetics Studies of Enteric Capsule Contains Recombinant Human Keratinocyte Growth Factor Loaded Chitosan Nanoparticles.

BACKGROUND: Recombinant human keratinocyte growth factor (rHuKGF) has gained considerable attention by researchers as epithelial cells proliferating agent. Moreover, intravenous truncated rHuKGF (palifermin) has been approved by Food and Drug Administration (FDA) to treat and prevent chemotherapy-induced oral mucositis and small intestine ulceration. The labile structure and short circulation time of rHuKGF in-vivo are the main obstacles that reduce the oral bioactivity and dosage of such proteins at the target site. OBJECTIVE: Formulation of methacrylic acid-methyl methacrylate copolymer-coated capsules filled with chitosan nanoparticles loaded with rHuKGF for oral delivery. METHODS: We report on chitosan nanoparticles (CNPs) with diameter < 200 nm, prepared by ionic gelation, loaded with rHuKGF and filled in methacrylic acid-methyl methacrylate copolymercoated capsules for oral delivery. The pharmacokinetic parameters were determined based on the serum levels of rHuKGF, following a single intravenous (IV) or oral dosages using a rabbit model. Furthermore, fluorescent microscope imaging was conducted to investigate the cellular uptake of the rhodamine-labelled rHuKGF-loaded nanoparticles. The proliferation effect of the formulation on FHs 74 Int cells was studied as well by MTT assay. RESULTS: The mucoadhesive and absorption enhancement properties of chitosan and the protective effect of methacrylic acid-methyl methacrylate copolymer against rHuKGF release at the stomach, low pH, were combined to promote and ensure rHuKGF intestinal delivery and increase serum levels of rHuKGF. In addition, in-vitro studies revealed the protein bioactivity since rHuKGFloaded CNPs significantly increased the proliferation of FHs 74 Int cells. CONCLUSION: The study revealed that oral administration of rHuKGF-loaded CNPs in methacrylic acid-methyl methacrylate copolymer-coated capsules is practically alternative to the IV administration since the absolute bioavailability of the orally administered rHuKGF-loaded CNPs, using the rabbit as animal model, was 69%. Fluorescent microscope imaging revealed that rhodaminelabelled rHuKGF-loaded CNPs were taken up by FHs 74 Int cells, after 6 hours' incubation time, followed by increase in the proliferation rate.