High Skin Research Articles

Perimarginal quadrangle dissection: Pushing the boundaries of neck dissection in gingivo-buccal complex cancer

ObjectivesPerimarginal nodes (PMN) lie in close relationship with marginal mandibular nerve (MMN), in the lymphatic drainage pathway of gingivo-buccal cancers (GBC), above the lower border of mandible and remain unaddressed in conventional neck dissection. We have aimed to define the boundaries of perimarginal node dissection, explore incidence of PMN metastasis and its correlation with histopathological characteristics. Materials and methodsA prospective study was conducted on 112 consecutive patients of GB carcinoma. PMN dissection was performed in an anatomically defined quadrangle. Prospective clinical characteristics included subsite, tumor and nodal stage, location of primary and clinical skin involvement. Histopathological characteristics analyzed included grade, size, pathological tumor, nodal stage, skin and/or bone involvement, depth of invasion, Brandwein Gensler histological risk score and lympho-vascular emboli. MMN function was graded at 3 and 6 months post-operatively. ResultsThe PMN were identified histologically in 75.89 % patients. 15.2 % patients harboured metastasis in PMN. 16.7 % patients had clinically occult metastasis with 11.7 % having isolated PMN metastasis. None of the pre-operative clinical factors was found to be significant in predicting incidence of metastasis. Higher nodal burden (p = 0.01) and pathological skin involvement (p = 0.03) were found statistically significant on multivariable analysis. At 6 months follow-up, none of the patients had any MMN functional deformity at rest. ConclusionThere is a high incidence of occult PMN metastasis from gingivo-buccal complex cancer. High nodal stage and pathological skin involvement are independent predictors for PMN metastasis. PMN dissection must be performed in all cases of GB cancer.

Skin Carotenoid Levels Are Associated with Demographic Factors, Body Size, and Fruit and Vegetable Intake in the Japanese Population.

This study aimed to determine the association between demographic factors, body size, and fruit and vegetable intake in the general population, focusing on individuals with both low and high skin carotenoid levels. This cross-sectional study was conducted during the 14th National Convention on the Promotion of Food and Nutrition Education (2019) in Yamanashi, Japan (a rural area) and the Open House 2019 at the National Institute of Biomedical Innovation, Health, and Nutrition in Tokyo, Japan (an urban area). Skin carotenoid measurements were conducted, and the participants were asked to fill out a self-administered questionnaire. The study population consisted of 492 Japanese individuals aged ≥16 years. The odds ratios (ORs) for low skin carotenoid levels were elevated in males, those who were overweight, and those who almost never consumed or consumed only one vegetable dish/day. Conversely, the ORs were lower in those living in Yamanashi, aged 30-39 and ≥70 years, and those who consumed fruit ≥1 time/week. For high skin carotenoid levels, the ORs were higher among those aged ≥70 years, living in Yamanashi, and those who consumed fruit ≥1 time/day or ≥5 vegetable dishes/day. Demographic factors, body size, and habitual fruit and vegetable intake may serve as indicators of skin carotenoid levels.

Improvements in edema and microcirculation in chronic venous insufficiency with Pycnogenol® or elastic compression.

Chronic venous insufficiency (CVI) is the consequence of venous valve reflux and/or venous flow obstruction and resulting venous hypertension in the lower extremities. The aim of this prospective supplement registry study was to evaluate the efficacy of compression stockings or Pycnogenol® in controlling symptoms and edema in CVI and their efficacy on microcirculatory parameters. Two comparable groups of 30 subjects with CVI were observed for 4 months. Elastic compression was less tolerated than Pycnogenol® with 12 subjects being unable to follow the compression routine. No side effects due to supplementation were observed; tolerability of the supplementation was optimal. Ambulatory venous pressure (AVP) and refilling time (RT) at inclusion indicated a significant increase in venous pressure and reflux (refilling time <16 seconds). AVP and RT did not change after 4 months. Microcirculatory and clinical measurements were comparable at inclusion between the 2 groups. After 4 months, skin resting flux (RF) and skin PO<inf>2</inf>-PCO<inf>2</inf> were significantly improved with Pycnogenol® compared to compression (P<0.05). The significant increase in skin PO<inf>2</inf> and the decrease in PCO<inf>2</inf> after Pycnogenol® intake were ascribed to the decrease in the abnormally high skin resting flux, a sign of better perfusion and skin nutritional supply. Pycnogenol® reduced leg volume, on average by 18.3% in the evening compared to 4.4% of reduction with compression (P<0.05) showing an important effect on edema. The venous Clinical Severity Score (VCSS) and the composite symptom score (CSS) decreased significantly in the Pycnogenol® group compared to compression, indicating a better improvement in microcirculatory perfusion and nutritional supply produced by the supplementation of Pycnogenol® in comparison with compression. Pycnogenol® significantly improved microcirculation and clinical symptoms in comparison with compression. The decrease in local oxidative stress (OS) at the distal perimalleolar region with Pycnogenol® was significant in comparison with compression (P<0.05). A lower local OS is an important metabolic indication of a better capillary perfusion with better nutritional exchanges. At the end of the registry study, four small ulcerations and skin breaks in four limbs (between 3 and 5 mm of maximum diameters) were observed in the compression group. No ulcerations or skin breaks were observed in the Pycnogenol® group. Pycnogenol® relieved edema, improved microcirculation in CVI patients and reduced stationary, interstitial fluid in comparison with compression. Most symptoms of CVI are associated with interstitial water retention; the presence of extra fluid in limb tissues alters perfusion and nutrient supply. Pycnogenol® supplementation reduced water and fluid accumulation in CVI limbs and improved microcirculation and local oxidative stress thus showing important anti-edema effects.

Viscoelastic Adhesive, Super-Conformable, and Semi-Flowable Liquid Metal Eutectogels for High-Fidelity Electrophysiological Monitoring.

Integrating gels with human skin through wearables provides unprecedented opportunities for health monitoring technology and artificial intelligence. However, most conductive hydrogels, organogels, and ionogels lack essential environmental stability, biocompatibility, and adhesion for reliable epidermal sensing. In this study, we have developed a liquid metal eutectogel simultaneously possessing superior viscoelasticity, semiflowability, and mechanical rigidity for low interfacial skin impedance, high skin adhesion, and durability. Liquid metal particles (LMPs) are employed to generate free radicals and gallium ions to accelerate the polymerization of acrylic acid monomers in a deep eutectic solvent (DES), obtaining highly viscoelastic polymer networks via physical cross-linking. In particular, graphene oxide (GO) is utilized to encapsulate the LMPs through a sonication-assisted electrostatic assembly to stabilize the LMPs in DES, which also enhances the mechanical toughness and regulates the rheological properties of the eutectogels. Our optimized semi-flowable eutectogel exhibits viscous fluid behavior at low shear rates, facilitating a highly conformable interface with hairy skin. Simultaneously, it demonstrates viscoelastic behavior at high shear rates, allowing for easy peel-off. These distinctive attributes enable the successful applications of on-skin adhesive strain sensing and high-fidelity human electrophysiological (EP) monitoring, showcasing the versatility of these ionically conductive liquid metal eutectogels in advanced personal health monitoring.

A scattering-foil free electron beam to increase dose rate for total skin electron therapy (TSET).

Electron beams are used at extended distances ranging between 300 to 700cm to uniformly cover the entirety of the patient's skin for total skin electron therapy (TSET). Even with electron beams utilizing the high dose rate total skin electron (HDTSe) mode from the Varian 23iX or TrueBeam accelerators, the dose rate is only 2500 cGy/min at source-to-surface distance (SSD)=100cm. At extended distances, the decrease in dose rate leads to long beam delivery times that can limit or even prevent the use of the treatment for patients who, in their weakened condition, may be unable to stand on their own for extended periods of time. Previously, to increase dose rate, a customized 6 MeV electron beam was created by removing the x-ray target, flattening filter, beam monitor chamber, and so forth. from the beam path (Chen, et at IJROBP 59, 2004) for TSET. Using this scattering-foil free (SFF) electron beam requires the treatment distance be extended to 700cm to achieve dose uniformity from the single beam. This room size requirement has limited the widespread use of the 6 MeV-SFF beam. This study explores an application of a dual-field technique with a 6 MeV-SFF beam to provide broad and uniform electron fields to reduce the treatment distances in order to overcome treatment room size limitations. The EGSnrc system was used to generate incident beams. Gantry angles between 6 MeV-SFF dual-fields were optimized to achieve the similar patient skin dose distribution resulting from a standard 6 MeV-HDTSe dual-field configuration. The patient skin dose comparisons were performed based on the patient treatment setup geometries using dose-volume-histograms. Similar dose coverage can be achieved between 6 MeV-SFF and 6 MeV-HDTSe beams by reducing gantry angles between dual-field geometries by 8° and 7° at treatment distances of 400 and 500cm, respectively. To achieve 95% mean dose to the first 5mm of skin depth in the torso area, the mean dose to depths of 5-10mm and 10-15mm below the skin surface was 74% (74%) and 49% (50%) of the prescribed dose when using 6 MeV-SFF (6 MeV-HDTSe) beam, respectively. The 6 MeV-SFF electron beam is feasible to provide similar TSET skin dose coverage at SSD ≥ 400cm using a dual-field technique. The dose rate of the 6 MeV-SFF beam is about 4 times that of current available 6 MeV-HDTSe beams at treatment distances of 400-500cm, which significantly shortens the treatment beam-on time and makes TSET available to patients in weakened conditions.

Perimarginal lymph node metastasis in gingivo-buccal complex carcinoma: Is it time to push the limits of neck dissection?.

6069 Background: Perimarginal nodes (PMN) are a group of perifacial lymph nodes that lie in close relationship with marginal mandibular nerve (MMN). They lie in the lymphatic drainage pathway of gingivo-buccal cancers (GBC), above the lower border of mandible which forms the superior limit of conventional neck dissection and thus remain unaddressed. With reported incidence of metastasis as high as 20.5%, we aimed to explore incidence of PMN metastasis in GBC, its correlation with histopathological tumor and nodal characteristics. Methods: A prospective study was conducted on 112 consecutive treatment naïve patients of GB squamous cell carcinoma. Patients with unresectable nodal disease, distant metastasis and prior radiotherapy or surgery to neck were excluded. PMN dissection was performed in the quadrangle bounded superiorly by the mandibular alveolar ridge, inferiorly by lower border of mandible, anteriorly by mental foramen and posteriorly by anterior border of masseter. On histopathological analysis, serial step sectioning and cytokeratin immunohistochemistry were performed. Prospective clinical characteristics analyzed were subsite, clinical tumor, nodal stage, location of primary and clinical skin involvement. PMN positivity was correlated with demographic, clinical, nodal status. Histopathological characteristics analyzed included tumor grade, pathological tumor, nodal stage, tumor size, skin and/or bone involvement, depth of invasion, Brandwein Gensler histological risk score and lympho-vascular emboli. MMN functional outcome was graded according to House-Brackman (HB) grading recorded at 3 and 6 months post-operatively. Results: Baseline characteristics are summarized in the table. The PMN were identified histologically in 75.89% (85/112) patients. Metastasis in these nodes were identified in 15.2% (17/112) patients. Our study revealed an occult PMN metastasis of 16.67% (13/78). None of the pre-operative clinical factors was found to be significant in predicting incidence of metastasis. Higher nodal burden (p=0.01) and pathological skin involvement (p=0.03) had statistically significant odds of having PMN metastasis on multivariable analysis. At 6 months follow-up, none of the patients had any MMN functional deformity at rest. Conclusions: There is a high incidence of occult PMN metastasis from gingivo-buccal complex cancer. High nodal stage and pathological skin involvement are independent adverse prognostic factors for PMN metastasis. The limits of conventional neck dissection should be expanded to include clearance of PMN in all cases of gingivo-buccal cancers. [Table: see text]

Upregulation of rate-limiting enzymes in cholesterol metabolism by PKCδ mediates endothelial apoptosis in diabetic wound healing

Diabetic foot ulcer (DFU) is a prevalent complication of diabetes that poses significant challenges in terms of treatment and management. It is characterized by heightened endothelial apoptosis and impaired angiogenesis. In this study, we aimed to investigate the role of protein kinase Cδ (PKCδ) in regulating endothelial apoptosis in diabetic wounds by promoting cholesterol biosynthesis. The expression of PKCδ was increased in human umbilical vascular endothelial cells (HUVECs) cultivated in high glucose medium and skin tissue isolated from diabetic mice. High glucose-induced HUVECs apoptosis was reduced by PKCδ inhibition with siRNA or rottlerin. RNA-seq identified two enzymes, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), as the downstream of PKCδ. PKCδ knockdown or inhibition suppressed the expression of HMGCS1 and HMGCR and lowered free cholesterol (FC) levels. Cholesterol restored high glucose-induced apoptosis in siRNA- or rottlerin-treated HUVECs. In vivo use of rosuvastatin calcium, an inhibitor of HMGCR, downregulated free cholesterol levels and accelerated the wound healing process. In conclusion, PKCδ expression in endothelial cells was activated by high glucose, which subsequently upregulates the expression of two enzymes catalyzing cholesterol biosynthesis, HMGCS1 and HMGCR. Enhanced cholesterol biosynthesis raises free cholesterol levels, promotes endothelial apoptosis, and finally delays wound healing.

Comparison of dual-plane micro-drop injection of botulinum toxin type A with two traditional methods for treating hypertrophic scars in the tension zone: A long-term clinical application study.

Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension. To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension. Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual-plane micro-drop injections, triamcinolone acetonide (TAC) suspension, and CO2 via fractional CO2 laser. Interventions were implemented in all three groups once a month for three consecutive sessions. After the final treatment, scarring was evaluated at 1, 3, 6, 12, and 24 months using the Patient and Observer Scar Assessment Scale (POSAS). The 3-month POSAS score for each scar indicator in the treatment groups was significantly lower than that in the preoperative groups (p < 0.001). The scar score in the TAC group decreased at 3 months and increased thereafter. For other groups, the scar score continually decreased at all time points according to the Patient Scar Assessment Scale. Based on the Observer Scar Assessment Scale, the scar score continuously decreased at all time points in the BTA group; in the TAC group, it decreased at 1 month and increased thereafter; and in the CO2 group, the scar score decreased at 3 months and subsequently stabilized. All three treatment methods were effective. However, the BTA group experienced a reduced risk of scar recurrence and maintained long-term treatment effects.

Identification of excessive contact pressures under hand orthosis based on finite element analysis.

Implicit magnitudes and distribution of excessive contact pressures under hand orthoses hinder clinicians from precisely adjusting them to relieve the pressures. To address this, contact pressure under a hand orthosis were analysed using finite element method. This paper proposed a method to numerically predict the relatively high magnitudes and critical distribution of contact pressures under hand orthosis through finite element analysis, to identify excessive contact pressure locations. The finite element model was established consisting of the hand, orthosis and bones. The hand and bones were assumed to be homogeneous and elastic bodies, and the orthosis was considered as an isotropic and elastic shell. Two predictions were conducted by assigning either low (fat) or high (skin) material stiffness to the hand model to attain the range of pressure magnitudes. An experiment was conducted to measure contact pressures at the predicted pressure locations. Identical pressure distributions were obtained from both predictions with relatively high pressure values disseminated at 12 anatomical locations. The highest magnitude was found at the thumb metacarpophalangeal joint with the maximum pressure range from 13 to 78 KPa. The measured values were within the predicted range of pressure magnitudes. Moreover, 6 excessive contact pressure locations were identified. The proposed method was verified by the measurement results. It renders understanding of interface conditions underneath the orthosis to inform clinicians regarding orthosis design and adjustment. It could also guide the development of 3D printed or sensorised orthosis by indicating optimal locations for perforations or pressure sensors.

Occupational skin cancer screening: Results of a cross‐sectional study at the city drainage company Munich

AbstractBackgroundSince skin cancer incidence and prevalence are rising steadily, the prevention of skin cancer has gained importance. People with high sun exposure at work are at special risk, and prevention measures by the employer may lower the risk, especially for keratinocyte carcinoma.ObjectivesThe aim of the study was to evaluate the results of a large‐scale skin cancer screening campaign at the city drainage company Munich where the cohort consisted mainly of outdoor workers.MethodsIn 2023, a skin cancer screening campaign was conducted at the city drainage company Munich. Sun exposure and protection measures of each participant were assessed using a questionnaire. Dermatologists identified clinical signs for sun damage and skin cancer by whole‐body skin examination.ResultsA total of 290 participants (72.8% male; mean age 43.7 ± 11.5 years) were enroled. 36.6% showed clinical signs of sun damage correlating with male gender, higher age, and more hours spent outdoors per day. Clinical examination revealed a suspect finding of skin cancer, a preliminary stage, or a lesion requiring clinical control to avoid skin cancer development in 19.3% of participants. Participants with atypical melanocytic lesions were mostly female and showed a high skin cancer awareness. This was concluded from the fewer signs of sun damage, a higher percentage of previous screening participation, and more regular self‐examination.ConclusionsWhole‐body examination for skin cancer screening at work is a valuable tool to encourage participation in this preventive measure. It may help identify people at risk either by clinical signs for sun damage or risk exposure which can be assessed with a simple questionnaire. Based on this result, the screening interval may be adopted individually.

Identification of the Wound Healing Activity Peptidome of Edible Bird's Nest Protein Hydrolysate and the In Silico Evaluation of Its Transport and Absorption Potential in Skin.

In this study, edible bird's nest (EBN) was proven to be a suitable source of bioactive peptides via enzymatic hydrolysis. The ultrafiltration component of the EBN peptides (EBNPs, Mw < 3 000 Da) could be responsible for moderate moisture retention and filaggrin synthesis. It was found that EBNP had a great capacity to protect HaCaT keratinocytes from DNA damage caused by UVB-irradiation and enhance wound healing by increasing the migratory and proliferative potential of cells. Furthermore, the external application of EBNP could effectively repair high glycolic acid concentration-induced skin burns in mice. A total of 1 188 peptides, predominantly the hydrophobic amino acids (e.g., Leu, Val, Tyr, Phe), were identified in the EBNP by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Molecular docking showed that hydrophobic tripeptides from EBNP had a good binding affinity to proton-dependent oligopeptide transporter PepT1. Our data indicated that the hydrophobic amino acid-rich EBNP plays an important role in skin wound healing.

P25 Identification of early changes in extracellular microRNA biomarkers of scleroderma for point-of-care diagnosis

Abstract Introduction and aims Scleroderma is a rare autoimmune disease, characterized by excessive extracellular matrix deposition leading to chronic inflammation and fibrosis. As a progressive disease initially affecting the skin, it presents similarly to Raynaud phenomenon, which delays diagnosis and treatment. Clinical diagnostic tests lack sensitivity, therefore novel Methods of detection and sensitive biomarkers are required to improve diagnosis rates. MicroRNAs are short, stable, noncoding RNAs, often present in the extracellular space, and can be sampled from interstitial skin fluid (ISF) through the employment of hydrogel microneedles. We aim to use this technique to improve upon current clinical gold standards of diagnosing scleroderma, at earlier stages of the disease. Methods In this study, we performed next-generation small-RNA sequencing on ISF from healthy individuals, patients prior to a clinical diagnosis of scleroderma [termed very early detection of systemic sclerosis (VEDOSS)], and patients with scleroderma classified as low and high skin score, identifying a panel of microRNA biomarkers for scleroderma diagnosis. Swellable hydrogel microneedles were manufactured in house, applied to excised human tissue and preclinical mouse models to demonstrate the ability to access and quantify extracellular microRNAs in ISF. Results Patients who received a VEDOSS diagnosis have increased ISF abundance of miR-379-5p and miR-125a-5p and decreased miR-30e-3p compared with healthy patients. miR-379-5p, miR-363-3p and miR-221-3p are sensitive to the progression of scleroderma and could be used to track the disease with improved sensitivity to autoantibodies in blood or where clinical practices usually require a skin biopsy. Using preclinical models of skin disease, we could differentiate between conditions, with higher sensitivity than blood sampling using our microneedle technology. Conclusions By identifying extracellular mircoRNAs, we have shown the potential use of these sensitive biomarkers in a liquid biopsy that can be applied at point-of-care. Peptide nucleic acids complementary to our microRNA biomarkers, will be used to provide real-time on-the-chip readouts of these ­biomarkers.

Interpretasi Rekahan Hydraulic Fracturing dengan Menggunakan Permodelan Simulator Fraccade Berdasarkan hasil Rock Properties Pada Sumur X Lapangan Y

Interpretation Fractures of Hydraulic fracturing with Fraccade Model Based on Rock Properties Results at Well X Field Y.Identifying fractures based on the results of Rock Properties purpose is to find out and get results during the identification process from the results of Hydraulic fracturing stimulation with the purpose of getting a conclusionwhether or not the operation is successful. Well X has several problems such as high skin and low permeability, because of that Hydraulic fracturing stimulation is the most effective action for this well.The method used is to select data data and the condition of well X to visualize the data results from Fraccade software V 5.4.1. And do calculations using Ms. Excel. The parameters that calculated in this Final Project include rock geometry, rock permeability, and wellbore damage. After identifying and interpreting the data using Fraccade V 5.4.1 software. The results show that not much different between manual calculation and Fraccade software.

Abstract PO5-18-05: Assessment of the Potential of Photon mini-GRID Therapy for Pre-operative Partial Breast Cancer Treatment

Abstract Purpose We propose a new spatially fractionated radiation therapy (SFRT) technique, called mini-GRID therapy, to reduce normal tissue toxicities in pre-operative partial breast cancer radiotherapy. Mini-GRID therapy, an optimized implementation of GRID therapy, utilizes very narrow beams (widths ~ 1-2 mm) which significantly increase normal tissue tolerances. The concept, proposed by our team in 2017 [1], has been successfully implemented at Hospital de Santiago de Compostela (Spain) showing excellent results in terms of brain toxicity reduction [2]. Profiting from this remarkable increase in tolerance, this study aims to evaluate the feasibility and efficacy of photon mini-GRID therapy for pre-operative partial breast cancer treatment. Methods Ten unbiased clinical cases were selected for the study, comparing photon mini-GRID therapy with conventional broad beam radiotherapy. Monte Carlo simulations (TOPAS v.3.6) were performed based on the mini-GRID therapy implementation (megavoltage X-rays, Varian flattening-filter-free LINAC) realized at the University Hospital in Santiago de Compostela. A mean dose of 24 Gy was delivered in the PTV using three photon mini-GRID arrays with mini beams of approximately 1.8x1.8 mm² at the isocenter. The study aimed to achieve better tumor coverage than conventional pre-operative radiotherapy while ensuring comparable skin toxicity. Valley doses, determining tissue-sparing effects, were compared against organs-at-risk (OARs) tolerance limits. Results The mini-GRID therapy treatments ensured partial tumor coverage and met the dose tolerance limits for all the considered OARs, the most challenging of all being the skin [3]. Peak-to-valley dose ratio (PVDR) in the skin was higher than 3.5 for all the considered patients. Compared to standard radiotherapy (SRT) plans, mini-GRID therapy significantly reduced mean doses to the lungs, heart, and chest wall in the studied cases. Conclusion In this proof-of-concept study, we evaluated photon mini-GRID therapy with megavoltage X-rays as an alternative treatment approach for pre-operative partial breast cancer irradiation, demonstrating its feasibility and straightforward implementation. Because of its high skin and normal tissue-sparing capacities, photon mini-GRID therapy has great potential to improve pre-operative treatment outcomes. Complementary studies and clinical validation are needed to fully establish the optimal protocols and assess long-term effects, but the results encourage the integration of photon mini-GRID therapy as a promising modality for breast cancer therapy.

Numerical parametric study of embedded geosynthetic-reinforced soil abutment

Three-dimensional numerical analysis was conducted to investigate the performance of embedded geosynthetic-reinforced soil abutments. The numerical model was validated using field-monitoring data. A parametric study was conducted to investigate the key factors affecting the performance of the embedded abutment under the working conditions, including the pile offset distance, pile diameter, pile spacing, and bridge load. The piles exhibited a retaining rather than a pushing effect in these cases due to the relatively high stiffness and negative skin friction of the piles, thus reducing the loads exerted on the facing wall. The lateral displacement of the facing wall significantly increased as the pile offset distance decreased mainly due to the reduced anchor length of the reinforcement and enhanced retaining effect of the piles. As the pile diameter increases, the deflection of the facing wall is constrained by factors such as increased bearing width, limited displacement, and enhanced retention effect of thepiles. This is an efficient way to increase the pile density near the abutment centerline to control thedeformation of the facing wall. An increase in the vertical bridge load resulted in a decrease in negative skin friction, leading to increased foundation settlement and lateral displacement of the facing wall.

Chikungunya-virus-specific CD4+ T cells are associated with chronic chikungunya viral arthritic disease in humans

Abstract Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus that causes recurrent outbreaks in tropical and subtropical regions of the world. In the first 2-7 days of infection, most individuals experience high fever, skin rash and joint pain and swelling. However, about 30-60% of the infected individuals, primarily middle-age females, develop debilitating chronic arthritis-like symptoms such as joint pain, muscle aches and edema. Despite ongoing treatment and vaccine development efforts, the immune responses to CHIKV in humans remain largely understudied. In this study, we tested peripheral blood mononuclear cells (PBMCs) collected from a cohort of 39 individuals diagnosed with CHIKV disease during the 2014-2015 epidemic in Colombia against pools of overlapping sequentially spanning the entire CHIKV genome. Using high-resolution spectral flow cytometry, we detected robust CHIKV-specific CD4+ T cell responses, but not CD8+ T cell responses in the periphery. Patients experiencing chronic symptoms displayed a significantly higher abundance of CHIKV-specific memory CD4+ T cells, compared to their recovered counterparts. Furthermore, these CD4+ T cells displayed a significantly lower Th1 phenotype but were enriched in the Th17 phenotype, with the predominant production of TNFɑ. Overall, our work demonstrates that CD4+ T cells play a pivotal role in the pathogenesis of CHIKV and provides insight into possible therapeutic options.

Transient skin friction behavior associated with hemisphere-based vortex ring collisions

Global and local transient skin friction variations resulting from a large-eddy simulation study on ReΓ0=3000 vortex rings colliding with surface-mounted hemispheres of hemisphere-to-vortex-ring diameter-ratios of 0.5≤D/d≤2 are investigated here. Skin friction distribution changes due to the approaching primary vortex ring, formation of secondary/tertiary vortex rings, subsequent mutual interactions between various vortex ring structures, and azimuthal instabilities are clarified with a view to better establish their relationships when the relative hemisphere size varies. Results show that the primary vortex ring produces the highest skin friction levels when it is close to or collides with the hemisphere/flat wall. Additionally, entrainment of wavy secondary/tertiary vortex rings leads to them entangling around the primary vortex ring and resulting in segmented skin friction regions at later stages of the collision process, regardless of the diameter-ratio. Unlike smaller hemispheres, the largest D/d=2 hemisphere here restricts all skin friction changes along its surface with the flat wall unaffected. It is also revealed here that while the diameter-ratio governs the global skin friction distributions, how secondary/tertiary vortex rings interact with the primary vortex ring and how azimuthal instabilities manifest and evolve for all the various vortex rings confer strong influences on the breaking-up and dissipation of regions with high skin friction levels.

Identification of Road Pavement Conditions in the Tanjung Balai City Road Section

Each region will try to increase its original income and the quality of existing infrastructure in that area. In order to realize this goal, quality infrastructure is needed to support economic development activities and good quality infrastructure. One of the infrastructure needed in this case is the road, where the intended road must have good conditions and quality so that it can function as it should. Where the condition of a good road is a road with good condition is a road with a completely flat pavement surface, no waves and no surface damage. For this reason, it is necessary to identify the condition of the pavement on existing roads in an area, so that the main goal of increasing income and infrastructure can be realized. One of the cities that can be used as a reference for identifying road pavement conditions is the City of Tanjung Balai, where the City of Tanjung Balai is located between 2°58′00″ North Latitude and 99°48′00″ East Longitude. Its area is 60.52 km2. The city of Tanjung Balai also has the longest bridge in the province of North Sumatra along ± 600 m which connects the city of Tanjung Balai with the villages of Sei Kepayang Kiri, Sei Kepayang Tengah to the upstream area in Sei Kepayang Kanan, Asahan district. Identification of road pavement conditions can be done using several methods, one of several methods that can be used is the PCI (Pavement Condition Index) method. Where this method is carried out by measuring the area of road surface damage, determining the level of damage to the road surface by looking at the Deduct Value chart, calculating level of damage occurs on the road surface (density), calculating Total Deduct Value (TDV), calculating Corrected Deduct Value (CDV), calculating PCI values and determining the level of the road, whether it is still feasible or not feasible. From the identification results it was found that on A. Rahman Road, there are several types of damage with varying levels of damage and the deduct value can be determined by looking at the graph, such as holes/potholes (low) damage, shoving with high damage, ravelling with high damage, basin cracks with high damage. Then on SMA 3 Road, there are several types of damage such as high crocodile skin cracks, patch damage with high damage levels, medium damage (medium) damage to basins. Next on Prof. Dr. Ir. Sutami / Education road there are types of holes / potholes (low) damage, grade depression with medium damage, patches with medium (medium) damage levels, ravelling with medium damage levels. And on Husni Thamrin Road, there are several types of damage such as holes/potholes (low) damage, basin cracks with high damage, ravelling with high damage levels. The results of this identification can be used as a reference for maintaining or improving the quality of existing roads in urban areas.

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Development of an Auraptene-Loaded Transdermal Formulation Using Non-ionic Sugar Ester Surfactants.

Auraptene (Aur) is a naturally occurring monoterpene coumarin ether that exhibits numerous therapeutic properties. Its high lipophilicity and low skin penetration, however, limit its potential application for local and transdermal delivery. Biocompatible non-ionic sugar esters (SEs) possess beneficial properties for the development of transdermal formulations in delivering pharmaceutically challenging molecules such as graphene and Aur. In the present study, we conducted a series of experiments to demonstrate the effect of several previously unstudied SEs on the skin permeation and distribution of Aur by preparing gel- and dispersion-type formulations. Skin permeation and deposition experiments were conducted using a Franz diffusion cell with rat skin as the membrane. The dispersion-type formulations prepared using SEs had higher entrapment efficiency, as well as better skin permeation and retention profiles. The dispersion-type formulation containing sucrose palmitate (sSP) exhibited the highest skin permeation over 8 h. Notably, the enhancement effects on Aur concentration in full-thickness skin after the application of the dispersion-type formulation was higher than those of the control formulation. These results indicated that the prepared formulation has potential for use in the transdermal delivery of Aur in pharmaceutical and cosmetic products.