Exploring Digital Dermatology: An Analysis of Ichthyosis Content on TikTok.

Background TikTok is among the most popular social media sites, and its utilization for health information is growing each day. The present study assesses the popularity and quality of the top 100 most-liked videos on TikTok tagged with "#ichthyosis." This study aims to do so by assessing contributions from physician, and nonphysician sources (such as from patients) to guide healthcare professionals interested in leveraging this platform for public health.  Methodology A cross-sectional analysis of the top 100 most-liked videos tagged with "#ichythosis" on TikTok as of January 3, 2024, was conducted. The parameters assessed for this study include observable characteristics, content type, and whether the creator was a physician or nonphysician. The quality of the content was measured using the DISCERN scale.  Results Based on these results, 14 of the top 100 videos were posted by physicians with 1,912,975 as the mean number of views. There were 86 videos posted by nonphysician creators averaging 2,675,341 views. Videos posted by nonphysician creators had a higher average number of views, number of likes, and number of comments but less average saves. Videos made by physicians and educational content had the highest average DISCERN scores, whereas nonphysician, awareness, and personal experience content had the lowest average DISCERN scores.  Conclusions Physicians are deemed trustworthy, reliable sources of healthcare-related information on TikTok. This study emphasizes the importance of physicians continuing to provide reliable, evidence-based health information on social media platforms such as TikTok.

Effect of SARS-CoV-2 and Toxoplasma gondii co-infection on IFN-γ and TNF-α expression and its impact on disease severity.

The symptomatology of COVID-19 is dependent on the immune status and the cytokine response of the host. The cytokine level of the host is influenced by the presence of chronic persistent or latent infections with co-pathogens. Parasitic diseases are known to induce host immune-modulation which may impact the response to co-infection. Toxoplasmosis is a widespread protozoal infection that remains quiescent in its latent form to be re-activated during states of immune depression. Clinical data on the relation between toxoplasmosis and COVID-19 cytokine profile and symptomatology are still insufficient. Seventy-nine subjects were included in this study. Patients were diagnosed with COVID-19 by PCR. Serological testing for toxoplasmosis was performed by the detection of anti-Toxoplasma IgG antibodies, in addition to IgG avidity testing. IFN-γ and TNF-α levels were determined by RT-PCR. Among patients diagnosed with COVID-19, 67.1% were seronegative for anti-Toxoplasma IgG, while 32.9% were seropositive. High avidity was found in 10 cases (40% of seropositive cases), 4 of whom required ICU administration, while low avidity was found in 15 cases (60%), 7 of which were administered to the ICU. TNF-α and INF-γ levels were significantly higher in COVID-19 patients than in healthy control subjects. No significant association was found between the seroprevalence of toxoplasmosis and the presence of COVID-19 and its severity. Cytokines were significantly higher in both seropositive and seronegative COVID-19 patients than in their control counterparts. The high prevalence of toxoplasmosis merits further exploration of its relation to COVID-19 by mass studies.

Serum selenium status in Egyptians patients who had Graves' disease with and without ophthalmopathy.

Selenium is efficient in reducing the progression of active Graves' orbitopathy and improving life quality. The impact of mending relative deficiency of selenium on improving Graves' orbitopathy is not known, due to the lack of previous measurement of baseline levels of selenium. The study object was to determine whether serum selenium levels are lower in patients with Graves' ophthalmopathy (GO) disease in comparison with those without ophthalmopathy. This prospective case control study was conducted between 2019 and 2021 at the endocrine and ophthalmology clinics, Ain Shams University, Cairo. The study included a total of 75 subjects, 50 patients with Graves' disease (GD) and 25 subjects as a control group. Of the GD patients, 25 had Graves' orbitopathy. Serum selenium concentrations were measured in each group. The mean level of serum selenium was significantly lower in patients with Graves' orbitopathy (16.6 ± 7.5 ng/ml) than in patients with Graves' disease (42.9 ± 8.2 ng/ml) (p < 0.001). Mean selenium levels were reduced with increasing severity of GO, as selenium level was 30-55 ng/ml in GD, 21-28 ng/ml in mild GO, 18-22 ng/ml in moderate GO and 5-16 ng/ml in severe GO (p < 0.001). In conclusion, serum selenium levels were lower in GO patients compared with GD patients in an Egyptian population. Low selenium levels may be a risk factor for ophthalmopathy in Graves' disease patients.

Efficacy of parsley seed-supplemented bread in improving serum osteopontin level and renal health in obese women: A nutritional intervention study.

BACKGROUND: Obesity is a global epidemic and a major contributor to chronic kidney disease worldwide. This interventional study aimed to evaluate the effects of a unique parsley seed bread and a healthy balanced diet on serum osteopontin level and renal function in obese women. METHODS: A total of 85 obese women (BMI, 35.68 ± 0.47 kg/m2) participated in an 8-week nutritional intervention comprising two phases. In the first phase, participants consumed 100 g of ground parsley seed bread along with a healthy balanced low caloric regimen for four weeks. In the second phase, Baladi bread was substituted for the supplement, providing an equal caloric intake, for another four weeks. Relevant Anthropometric measurements, blood pressure, dietary recall, and biochemical parameters (osteopontin, IL-1ß, IL-10, kidney functions, and lipid parameters) were assessed before and after each intervention phase. RESULTS: Following the initial intervention phase, there were significant improvements in all recorded mean anthropometric parameters (p ≤ 0.001). Lipid parameters and risk factors also significantly decreased (p < 0.05), while osteopontin, creatinine, and IL-1ß levels decreased significantly. eGFR, creatinine clearance, IL-10 increased. However, these improved values returned to elevated levels after the omission of the supplement in the second phase. There was a significant negative correlation between osteopontin and creatinine, creatinine clearance, and IL-10. CONCLUSION: The combined effect of the novel parsley seed-based intervention and a healthy balanced low-calorie regimen demonstrated improvements in osteopontin level associated with renal disorders, and inflammation, in addition to dyslipidemia in obese women. This suggests a promising approach for improving and protecting kidney disorders.

Blindness influences emotional authenticity perception in voices: Behavioral and ERP evidence.

The ability to distinguish spontaneous from volitional emotional expressions is an important social skill. How do blind individuals perceive emotional authenticity? Unlike sighted individuals, they cannot rely on facial and body language cues, relying instead on vocal cues alone. Here, we combined behavioral and ERP measures to investigate authenticity perception in laughter and crying in individuals with early- or late-blindness onset. Early-blind, late-blind, and sighted control participants (n = 17 per group, N = 51) completed authenticity and emotion discrimination tasks while EEG data were recorded. The stimuli consisted of laughs and cries that were either spontaneous or volitional. The ERP analysis focused on the N1, P2, and late positive potential (LPP). Behaviorally, early-blind participants showed intact authenticity perception, but late-blind participants performed worse than controls. There were no group differences in the emotion discrimination task. In brain responses, all groups were sensitive to laughter authenticity at the P2 stage, and to crying authenticity at the early LPP stage. Nevertheless, only early-blind participants were sensitive to crying authenticity at the N1 and middle LPP stages, and to laughter authenticity at the early LPP stage. Furthermore, early-blind and sighted participants were more sensitive than late-blind ones to crying authenticity at the P2 and late LPP stages. Altogether, these findings suggest that early blindness relates to facilitated brain processing of authenticity in voices, both at early sensory and late cognitive-evaluative stages. Late-onset blindness, in contrast, relates to decreased sensitivity to authenticity at behavioral and brain levels.

Cysteine Enrichment Mediates Co-Option of Uricase in Reptilian Skin and Transition to Uricotelism.

Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property that we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with the transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with ß-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.

Utility of the 4C ISARIC mortality score in hospitalized COVID-19 patients at a large tertiary Saudi Arabian center.

Background: The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) 4C mortality score has been used before as a valuable tool for predicting mortality in COVID-19 patients. We aimed to address the utility of the 4C score in a well-defined Saudi population with COVID-19 admitted to a large tertiary referral hospital in Saudi Arabia. Methods: A retrospective study was conducted that included all adults COVID­19 patients admitted to the Armed Forces Hospital Southern Region (AFHSR), between January 2021 and September 2022. The receiver operating characteristic (ROC) curve depicted the diagnostic performance of the 4C Score for mortality prediction. Results: A total of 1,853 patients were enrolled. The ROC curve of the 4C score had an area under the curve of 0.73 (95% CI: 0.702-0.758), p<0.001. The sensitivity and specificity with scores >8 were 80% and 58%, respectively, the positive and negative predictive values were 28% and 93%, respectively. Three hundred and sixteen (17.1%), 638 (34.4%), 814 (43.9%), and 85 (4.6%) patients had low, intermediate, high, and very high values, respectively. There were significant differences between survivors and non-survivors with regard to all variables used in the calculation of the 4C score. Multivariable logistic regression analysis revealed that all components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Conclusions: Our data support previous international and Saudi studies that the 4C mortality score is a reliable tool with good sensitivity and specificity in the mortality prediction of COVID-19 patients. All components of the 4C score, except gender and O2 saturation, were independent significant predictors of mortality. Within the 4C score, odds ratios increased proportionately with an increase in the score value. Future multi-center prospective studies are warranted.

Cerebrospinal Fluid Lactate as a Differential Biomarker for Bacterial and Viral Meningitis.

Meningitis is a critical public health problem demanding immediate diagnosis and effective treatment due to high mortality rates. Cerebrospinal Fluid (CSF) lactate concentration is a promising test to distinguish bacterial from viral meningitis. This study aimed to assess the performance and usefulness of CSF lactate as a biomarker to differentiate between bacterial and viral meningitis, and to determine its optimal level to differentiate between them. This prospective study included 50 patients, presented to Abbassia Fever Hospital with clinical findings consistent with meningitis. Patients were divided into two groups: Group1 included 30 patients with bacterial meningitis. Group 2 included 20 patients with viral meningitis. CSF lactate and other conventional CSF parameters were recorded. For CSF culture, Streptococcus pneumoniae was identified in 53.3% of the bacterial meningitis group. The polymerase chain reaction (PCR) indicated that S. pneumoniae was present in 26/50 (52%) and 3/50 (6%) patients were PCR negative. Among bacterial meningitis patients, S. pneumoniae was the most pervasive organism 26/30 (86.7%). The mean CSF lactate level was 9.3 mmol/l ±5.0 (2.2-17.6). There was a statistically significant strong agreement (Kappa=0.957) between types of meningitis diagnosed by PCR, culture, and CSF lactate at cutoff level of 7.2 mmol/L. This cutoff value was the best to differentiate between bacterial and viral meningitis. The validity of CSF lactate as a differentiating tool showed sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 100%, 100%, and 90.9%, respectively. In conclusion, CSF lactate could be a valuable, sensitive, specific, and rapid marker for identifying the most dangerous bacterial causes of CNS infection, especially S. pneumoniae. CSF lactate can be routinely used as an early biochemical warning marker and a useful point-of-care test. CSF lactate at cutoff level of >7.2 mmol/L can accurately detect S. pneumoniae, the most prevalent organism in Egypt.

Determination of amphetamines, opioids, cocaine metabolites and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol in urine using biocompatible solid-phase microextraction and ultra-performance LC-MS/MS.

Background: Workplace drug testing primarily relies on urine analysis, targeting multiple compounds with varying physicochemical characteristics. Biocompatible solid-phase microextraction (BioSPME) is a miniaturized solid-phase extraction technique that enables the simultaneous extraction and preconcentration of analytes directly from the biological matrix. Methods: The BioSPME procedure consisted of the sequential extraction of 50-µl urine samples using LC Tips C18 in basic and acidic pH, followed by desorption with methanol and n-hexane, respectively. The extracts were analyzed by ultra-performance LC-MS/MS. Results: Intra-day precision was 1.2-8.6% and inter-day precision was 1.8-14.2%. Accuracy was 96.8-107.4%. The extraction yields were 62.8-109.4%. The matrix effects were -3.98% to 1%. Conclusion: BioSPME shows promise as an alternative method for preparing urine samples prior to drug measurement by ultra-performance LC-MS/MS.

Impact of viral co-infection on clinical outcomes and mortality of COVID-19 patients: a study from Saudi Arabia.

Background: In COVID-19 patients undetected co-infections may have severe clinical implications associated with prolonged hospitalization, ICU admission, and mortality. Therefore, we aimed to investigate the impact of viral coinfections on the outcomes of hospitalized patients with COVID-19 in a large tertiary Saudi Arabian Hospital. Methods: A total of 178 adult patients with confirmed SARS-CoV-2 who were hospitalized at the Armed Forces Hospital Southern Region (AFHSR), Saudi Arabia, from March 1st to June 30th 2022, were enrolled. Real-time PCR for the detection of viral co­infections was carried out. Cases (SARS-CoV-2 with viral coinfections) and control (SARS-CoV-2 mono-infection) groups were compared. Results: 12/178 (7%) of enrolled COVID-19 patients had viral coinfections. 82/178 (46%) of patients were males. 58% of patients had comorbidities. During the study period, 4/12 (33%) and 21/166 (13%) cases and control patients died, p=0.047, respectively. Duration of hospitalization was the only significant independent factor associated with SARS-CoV-2 coinfections, OR 1.140, 95% CI 1.020-1.274, p=0.021. Conclusions: The findings of this study from a large tertiary Saudi Arabian Center revealed a prevalence of 7% for SARS-CoV-2 viral coinfections. SARS-CoV-2 coinfected patients had a significantly prolonged duration of hospitalization and higher mortality than those with SARS-CoV-2 alone. Future studies are needed.

Memory footprint: Predictors of flashbulb and event memories of the 2016 Euro Cup final.

Two years after Portugal won the UEFA European Championship, we examined what the Portuguese remember of this momentous occasion. We investigated if flashbulb memories (FBMs) and event memories (EMs) were determined by distinct factors, and whether EM was a predictor of FBM. Participants responded to an online questionnaire about their FBM, EM and set of predictors. Structural equation modeling revealed that FBM and EM were associated with different pathways. Interest in football predicted importance which triggered emotional intensity which predicted personal rehearsal, a direct determinant of FBMs. On the other pathway, interest determined knowledge about football, the main predictor of EMs. Importantly, EM was a causal determinant of FBM which shows that the memory trace for the original event enhances memory for the reception context. The findings suggests that even though the two types of memories are determined by independent factors, they interact very closely.

Attention and emotion shape self-voice prioritization in speech processing.

Both self-voice and emotional speech are salient signals that are prioritized in perception. Surprisingly, self-voice perception has been investigated to a lesser extent than the self-face. Therefore, it remains to be clarified whether self-voice prioritization is boosted by emotion, and whether self-relevance and emotion interact differently when attention is focused on who is speaking vs. what is being said. Thirty participants listened to 210 prerecorded words spoken in one's own or an unfamiliar voice and differing in emotional valence in two tasks, manipulating the attention focus on either speaker identity or speech emotion. Event-related potentials (ERP) of the electroencephalogram (EEG) informed on the temporal dynamics of self-relevance, emotion, and attention effects. Words spoken in one's own voice elicited a larger N1 and Late Positive Potential (LPP), but smaller N400. Identity and emotion interactively modulated the P2 (self-positivity bias) and LPP (self-negativity bias). Attention to speaker identity modulated more strongly ERP responses within 600 ms post-word onset (N1, P2, N400), whereas attention to speech emotion altered the late component (LPP). However, attention did not modulate the interaction of self-relevance and emotion. These findings suggest that the self-voice is prioritized for neural processing at early sensory stages, and that both emotion and attention shape self-voice prioritization in speech processing. They also confirm involuntary processing of salient signals (self-relevance and emotion) even in situations in which attention is deliberately directed away from those cues. These findings have important implications for a better understanding of symptoms thought to arise from aberrant self-voice monitoring such as auditory verbal hallucinations.

Single-dose pharmacokinetics, safety, and tolerability of the dual endothelin receptor antagonist aprocitentan in subjects with moderate hepatic impairment.

The effect of moderate hepatic impairment on the pharmacokinetics (PK), safety, and tolerability of the dual endothelin receptor antagonist aprocitentan was clinically investigated as 25% of aprocitentan is cleared through the liver. Aprocitentan is in clinical development for the treatment of resistant hypertension. This was an open-label, Phase 1 study. Subjects were recruited in two groups (i.e., moderate hepatic impairment (Child-Pugh B; n = 8) and matched healthy subjects (n = 9) and received a single oral dose of 25 mg aprocitentan. Thereafter, they were observed for 14 days. Due to personal reasons one healthy subject discontinued the study. The PK of aprocitentan were similar between subjects with moderate hepatic impairment and healthy subjects, with maximum plasma concentrations (Cmax) reached at 4.0 h. There was no difference in Cmax, indicated by the geometric means ratio (90% confidence interval) of 1.03 (0.86-1.24). There was a lower apparent clearance, a similar apparent volume of distribution, a longer terminal half-life (56.4 h vs 48.3 h in healthy subjects), and an increase in area under the curve from zero to infinity of 23% in moderate hepatically impaired subjects compared to healthy subjects. There were no differences observed in plasma protein binding (range 98.7-99.0%). Aprocitentan was well tolerated, and headache was the only adverse event reported by one subject. In conclusion, there were no clinically relevant differences in PK between subjects with moderate hepatic impairment and healthy subjects. Based on these results, aprocitentan can be administered in subjects with mild and moderate hepatic impairment and dose adjustment is not required.Clinical Trial Registration ClinicalTrials.gov NCT04252495.

The time course of emotional authenticity detection in nonverbal vocalizations.

Previous research has documented perceptual and brain differences between spontaneous and volitional emotional vocalizations. However, the time course of emotional authenticity processing remains unclear. We used event-related potentials (ERPs) to address this question, and we focused on the processing of laughter and crying. We additionally tested whether the neural encoding of authenticity is influenced by attention, by manipulating task focus (authenticity versus emotional category) and visual condition (with versus without visual deprivation). ERPs were recorded from 43 participants while they listened to vocalizations and evaluated their authenticity (volitional versus spontaneous) or emotional meaning (sad versus amused). Twenty-two of the participants were blindfolded and tested in a dark room, and 21 were tested in standard visual conditions. As compared to volitional vocalizations, spontaneous ones were associated with reduced N1 amplitude in the case of laughter, and increased P2 in the case of crying. At later cognitive processing stages, more positive amplitudes were observed for spontaneous (versus volitional) laughs and cries (1000-1400 msec), with earlier effects for laughs (700-1000 msec). Visual condition affected brain responses to emotional authenticity at early (P2 range) and late processing stages (middle and late LPP ranges). Task focus did not influence neural responses to authenticity. Our findings suggest that authenticity information is encoded early and automatically during vocal emotional processing. They also point to a potentially faster encoding of authenticity in laughter compared to crying.

The perceived salience of vocal emotions is dampened in non-clinical auditory verbal hallucinations.

Introduction: Auditory verbal hallucinations (AVH) are a cardinal symptom of schizophrenia but are also reported in the general population without need for psychiatric care. Previous evidence suggests that AVH may reflect an imbalance of prior expectation and sensory information, and that altered salience processing is characteristic of both psychotic and non-clinical voice hearers. However, it remains to be shown how such an imbalance affects the categorisation of vocal emotions in perceptual ambiguity.Methods: Neutral and emotional nonverbal vocalisations were morphed along two continua differing in valence (anger; pleasure), each including 11 morphing steps at intervals of 10%. College students (N = 234) differing in AVH proneness (measured with the Launay-Slade Hallucination Scale) evaluated the emotional quality of the vocalisations.Results: Increased AVH proneness was associated with more frequent categorisation of ambiguous vocalisations as 'neutral', irrespective of valence. Similarly, the perceptual boundary for emotional classification was shifted by AVH proneness: participants needed more emotional information to categorise a voice as emotional.Conclusions: These findings suggest that emotional salience in vocalisations is dampened as a function of increased AVH proneness. This could be related to changes in the acoustic representations of emotions or reflect top-down expectations of less salient information in the social environment.

Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model.

AIMS: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs (i) in the pathologically remodelled heart using an (ii) implantable multi-LED device for (iii) in vivo closed-chest, local illumination. METHODS AND RESULTS: In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place 3 weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin or Citrine for control experiments. At 8-10 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination. CONCLUSION: Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion.

Idiopathic Hypereosinophilic Syndrome Presenting With Embolic Stroke.

Hypereosinophilic syndrome is a rare condition characterized by eosinophilia associated with organ damage, most commonly affecting the skin, lung, gastrointestinal, cardiovascular and central nervous system. The idiopathic form is characterized by the absence of other conditions associated with hypereosinophilia such as allergies, infectious, hematological, immunological, endocrine or neoplasm diseases. The authors present a clinical case of a 70-year-old man with no relevant history, who went to the emergency department for neurological deficits and nonspecific chest pain. Laboratory tests revealed marked eosinophilia, elevation of cardiac enzymes with normal electrocardiogram. Computed tomography of the head showed multiple bilateral ischemic lesions. Upon further investigation for the cerebrovascular disease, transesophageal echocardiogram showed a thrombus at the aortic arch, as a probable embolic source. Despite anticoagulant therapy and corticosteroids, the patient's status deteriorated, with multiple successive ischemic strokes and worsening neurological deficits. After a thorough investigation, the diagnosis of idiopathic eosinophilia was established.

α4/α9 Integrins Coordinate Epithelial Cell Migration Through Local Suppression of MAP Kinase Signaling Pathways.

Adhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function as intracellular biochemical signaling platforms to enable cells to respond to changing extracellular cues. The α4ß1 and α9ß1 integrins are both expressed in basal keratinocytes, share some common ECM ligands, and have been shown to promote wound healing in vitro and in vivo. However, their roles in maintaining epidermal homeostasis and relative contributions to pathological processes in the skin remain unclear. We found that α4ß1 and α9ß1 occupied distinct regions in monolayers of a basal keratinocyte cell line (NEB-1). During collective cell migration (CCM), α4 and α9 integrins co-localized along the leading edge. Pharmacological inhibition of α4ß1 and α9ß1 integrins increased keratinocyte proliferation and induced a dramatic change in cytoskeletal remodeling and FA rearrangement, detrimentally affecting CCM. Further analysis revealed that α4ß1/α9ß1 integrins suppress extracellular signal-regulated kinase (ERK1/2) activity to control migration through the regulation of downstream kinases including Mitogen and Stress Activated Kinase 1 (MSK1). This work demonstrates the roles of α4ß1 and α9ß1 in regulating migration in response to damage cues.

Effect of mast cell stabilization on angiogenesis in primary and secondary experimental Trichinella spiralis infection.

BACKGROUND: Mast cells are known to affect the primary and secondary immune responses against parasites, and this effect is partially mediated through the release of pro-angiogenic mediators. The aim of this study was to explore the effect of the mast cell stabilizer (MCS), ketotifen, with and without albendazole, an anti-parasitic prescription medicine, on the inflammatory response against Trichinella spiralis, with the overall aim to investigate its effect on angiogenesis accompanying nurse cell formation. METHODS: The effect of ketotifen and albendazole was explored in eight groups of female BALB/c mice. Four groups were sensitized with a small dose of T. spiralis larvae. The drug regimen was then applied to both sensitized (challenged) and non-sensitized mice. The parasite load was assessed by histopathological examination of the small intestine and muscle tissue, and angiogenesis was assessed by immunohistochemistry to determine the expression of vascular endothelial growth factor (VEGF). RESULTS: Sensitized mice showed a significantly lower parasite load and a more pronounced inflammatory response than mice receiving a single infective dose of T. spiralis larvae. All treated groups showed a significant reduction in parasite count compared to the control groups (groups IAa and IBa), reaching approximately an 98.8% reduction in adult parasite count in the sensitized group treated with albendazole (groups IIAb and IIBb). MCS significantly decreased the parasite count during both the intestinal or muscular phases, reduced tissue inflammation, and decreased local VEGF expression, both in the non-sensitized and sensitized groups. CONCLUSION: Sensitization with a low dose of T. spiralis larvae was found to confer a partial protective immunity against re-infection and to positively affect the study outcomes, thus underlining the importance of vaccination, but after extensive studies. The anti-angiogenic effect of MCS protects against larval encystation during the muscle phase. The anti-angiogenic potential of albendazole suggests that the action of this anti-helminthic during trichinellosis is not confined to structural damage to the parasite cuticle but includes an effect on host immunopathological response.