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A man in his 70s with rheumatoid arthritis presented with seizures and coma and was transferred to our emergency department. Two months prior to admission, he started to take tofacitinib 10 mg/day. On admission, we noted a rash with a blister on the forehead, and herpes zoster was diagnosed. Cerebrospinal fluid examination suggested meningitis. An MRI of the brain showed no abnormality. Based on these findings, he was suspected with herpes zoster meningitis. We discontinued tofacitinib and treated the patient with intravenous acyclovir for 2 weeks. He regained complete consciousness, but right forehead skin lesion, severe vision loss in the right eye and right facial nerve paralysis remained as sequelae. Six weeks after admission, we restarted tofacitinib with oral valaciclovir as antiviral prophylaxis. Two years after admission, we administered Shingrix, an adjuvant recombinant vaccine for herpes zoster, and discontinued oral valaciclovir.

Agriculture sector of Saudi Arabia is growing swiftly and tomato is an important crop cultivated mostly under green houses. Unfortunately, it is facing severe infestation due to divers mite species. Present study, relates to evaluation of toxicity of oxamyl against two phytophagous mites; Aculops lycopersici and Tetranychus urticae, isolated from tomato plants suffering from infestation. Simultaneous effect of oxamyl on two predatory mites; Neosiulus cucumeris and Euseius scutalis, was also evaluated. Three concentrations of oxamyl; half of the recommended dose (HRD), recommended dose (RD) and double recommended dose (DRD), were used against each mite specie to observe mortality within seven days as compared to the control. Significant mortality of 97.91% and 93.92% was observed in A. lycopersici and T. urticae, respectively at RD. In case of predatory mites; N. cucumeris and E. scutalis, mortality was 60.61% and 64.48%, respectively, under same conditions. Mortality of mites observed at HRD was insignificant and there was negligible increase in mortality at DRD. Oxamyl being less toxic to predatory mites and significantly mortal to phytophagous mites is recommended as a tool to as a tool to achieve biological control parallel to pesticidal effect.

Skin cancer is a life threatening disease and has caused significant loss to human health across the globe. Its prevalence has been increasing every year and is one of the common malignancies in case of organ transplant recipients of which 95% constitute the basal cell and squamous cell carcinomas. Around the 20th century, sunlight has proven to be the major cause of skin cancer. The prime factor that is responsible for causing skin cancer is the UV radiations. A novel hypothesis by US scientists stated that the cutaneous melanoma was mainly due to the recurrent exposure to the sun, whereas keratinocyte cancer occurred due to progressive accumulation of sun exposure. Management of skin cancer has been done via various approaches such as cryotherapy, radiotherapy, photodynamic therapy etc. Radiotherapy has proven to treat skin cancers to some extent after the discovery of X-rays, but the indication are uncertain since it depends upon the type of tumour and surgical treatment that is required for the patient. Due to various limitations of skin cancer treatment and increased severity, there is a requirement of cost effective, novel and efficient treatment. Various nanocarriers such as SLNs, magnetic nanoparticles, gold nanoparticles, carbon nanotubes etc have been the potential carriers in the management and prognosis of both non-melanoma and melanoma skin cancer. To extract the results, various research and review database along with patent reports have been studied and information has been compiled. A review also discuss about the role of various nanocarriers in the treatment and diagnosis of skin cancer.

Objective Chronic skin wounds are one of the most devastating complications in diabetic patients due to the formation of advanced glycation end products (AGEs) resulting from non-enzymatic glycation of proteins and lipids in hyperglycemia. AGEs, upon binding their receptors (RAGEs), trigger pro-inflammatory signals that impair wound healing in diabetes and contribute to the pathology of chronic skin wounds. Approach We previously developed a recombinant fusion protein containing the binding domain of RAGE (vRAGE) linked to elastin-like polypeptides (ELPs) that acts as a competitive inhibitor of AGEs, and another ELP fusion protein containing stromal cell-derived factor 1 (SDF1) that promotes revascularization. Herein, we report the effects of protein coacervates incorporating both vRAGE-ELP and SDF1-ELP on wound healing in an in vitro diabetes-mimicking cell culture system, and in in vivo in full-thickness wounds on diabetic mice. Results The combination of vRAGE-ELP and SDF1-ELP increased cell metabolic activity in AGE-stimulated endothelial cells, promoted in vitro tube formation and accelerated healing in an in vitro cell migration assay. When used in a single topical application on full-thickness excisional skin wounds in diabetic mice, wound closure in the combination groups reached almost 100% on post-wounding day 35, compared to 62% and 85% on the same days in animals treated with fibrin gel control and vehicle control consisting of ELP alone. Innovation To our knowledge, this is the first study that attempts to reverse the AGE-RAGE-mediated signaling as well as to promote cell proliferation and vascularization in one single treatment. Conclusion The co-delivery of vRAGE-ELP and SDF1-ELP has potential for the treatment of diabetic wounds.

OBJECTIVE The mechanisms of action of high-frequency stimulation (HFS) are unknown. We investigated the possible mechanism of subthreshold superexcitability of HFS on the excitability of the peripheral nerve. MATERIALS AND METHODS The ulnar nerve was stimulated at the wrist in six healthy participants with a single (control) stimulus, and the responses were compared with the responses to a continuous train of 5 seconds at frequencies of 500 Hz, 2.5 kHz, 5 kHz, and 10 kHz. Threshold intensity for compound muscle action potential (CMAP) was defined as intensity producing a 100-μV amplitude in ten sequential trials and "subthreshold" as 10% below the CMAP threshold. HFS threshold was defined as stimulation intensity eliciting visible tetanic contraction. RESULTS Comparing the threshold of single pulse stimulation for eliciting CMAP vs threshold for HFS response and pooling data at different frequencies (500 Hz-10 kHz) revealed a significant difference (p = 0.00015). This difference was most obvious at 10 kHz, with a mean value for threshold reduction of 42.2%. CONCLUSIONS HFS with a stimulation intensity below the threshold for a single pulse induces axonal superexcitability if applied in a train. It can activate the peripheral nerve and produce a tetanic muscle response. Subthreshold superexcitability may allow new insights into the mechanism of HFS.

A 73-year-old man presented to the emergency department with lethargy and influenza-like symptoms. Incidentally, prominent blue sclera and blue-grey skin discolouration to the periorbital skin, pinnae, neck, upper and lower limbs, hands, feet, fingernails and toenails were noted. His general practitioner (GP) had previously ceased amiodarone, believing it to be the causative agent. A literature search confirms the side effects were likely due to minocycline, which the patient had been taking for 10 years. Long-term minocycline use is associated with scleral and skin hyperpigmentation, with no apparent adverse effect on ocular structure or function. The pigmentation may reverse with cessation of minocycline, or it may be permanent. Amiodarone may also cause skin hyperpigmentation, but scleral pigmentation is not a known association. This case report explores the side effect profiles of these two drugs, and highlights the potential for confusion regarding causative agents when used concurrently.

Few cases of programmed death-ligand 1 inhibitor-induced scleroderma have been reported and their clinical features remain unpublished. Optimal management is, therefore, unknown and an autoantibody association has yet to be identified. We present the case of a female in her 60s who developed skin thickening after starting atezolizumab for metastatic non-small cell lung cancer. Skin biopsy 7 months after symptom onset showed histological changes consistent with scleroderma. Anti-PM/SCL-75 antibody was positive. Atezolizumab was discontinued and treatment was started with mycophenolate mofetil. After 5 months, she experienced mild improvement in skin thickening. Earlier identification of this complication may limit morbidity in this disease process, which otherwise has limited treatment options. In suspected cases, obtaining scleroderma-associated autoantibodies may help with earlier diagnosis.

Significance: Skin inevitably heals with the formation of a fibrotic scar. Patients affected by skin scarring suffer from long-term psychological and physical burdens. Recent Advances: Since the di...

Scrub typhus is a disease endemic to the Indian subcontinent caused by the obligate intracellular pleomorphic organism, Orientia tsutsugamushi. Scrub typhus, among other acute febrile illnesses, manifests as prodromal symptoms of fever, malaise, myalgia and anorexia followed by a distinct maculopapular rash, hepatosplenomegaly and lymphadenopathy. We report the case of a patient presenting to tertiary care hospital in southern India in 2021 who developed a rare cutaneous vasculitis secondary to infection with Orientia tsutsugamushi. After performing the Weil-Felix test, a diagnostic titre of >1:640 against OXK was obtained. Furthermore, a skin biopsy was carried out which confirmed the diagnosis of leukocytoclastic vasculitis. The patient was treated with doxycycline and showed drastic improvement in his symptoms. Keywords: Scrub Typhus, Rickettsia; Vasculitis; Doxycycline; India.

Objectives: To support rational decision-making on spinal cord stimulation (SCS), a European expert panel developed an educational e-health tool using the RAND/University of California at Los Angeles Appropriateness Method. This retrospective study aimed to determine the applicability and validity of the tool using data from patients for whom SCS had been considered. Materials and Methods: A total of 12 European implant centers retrieved data from 25 to 50 consecutive patients for whom SCS was considered in 2018–2019. For each patient, data were captured on the clinical and psychosocial variables included in the e-health tool, center decisions on SCS, and patient outcomes. Patient outcomes included global perception of effect by the patient and observer, and pain reduction (numeric pain rating scale) at six-month follow-up. Results: In total, 483 patients were included, of whom 133 received a direct implant, 258 received an implant after a positive trial, 32 had a negative trial, and 60 did not receive SCS for reasons other than a negative trial. The most frequent indication was persistent spinal pain syndrome type 1 and type 2 (74%), followed by neuropathic pain syndromes (13%), complex regional pain syndrome (12%), and ischemic pain syndromes (0.8%). Data on the clinical and psychosocial variables were complete for 95% and 93% of patients, respectively, and missing data did not have a significant impact on the study outcomes. In patients who had received SCS, panel recommendations were significantly associated with patient outcomes (p < 0.001 for all measures). Substantial improvement ranged from 25% if the e-health tool outcome was “not recommended” to 83% if SCS was “strongly recommended”. In patients who underwent a trial (N = 290), there was 3% of trial failure when SCS was ”strongly recommended” vs 46% when SCS was ”not recommended”. Conclusions: Retrospective application of the e-health tool on patient data showed a strong relationship between the panel recommendations and both SCS trial results and treatment outcomes.

Background Chronic wounds are of many etiologies and difficult to treat. Many commercial products to manage such wounds are available, which claim to have good outcomes. Aim of this study was to compare the efficacy of Ionic Silver Solution and Super Oxidized Solution in the management of chronic wounds. Methods Patients with chronic wounds were randomly placed in two groups-Group A (Ionic Silver Solution) and Group B (Super Oxidized Solution) with 30 patients each. The dressings were continued until the wound healed completely or the wound was ready for a definitive procedure. Wound parameters were recorded as per Bates Jensen Wound Assessment Tool (BJWAT) Score. Results FIfty patients completed the study. The scores were compared at the initiation and endpoint of treatment. The pretreatment total for BJWAT was 916 and 924 in group A and group B respectively, which was not statistically significant. Post-treatment improvement was noticed in both the groups and the score decreased to 510 and 675 in group A and group B respectively (p = 0.001). Ionic Silver Solution and Super Oxidized Solution both were found to be effective in improving the overall wound condition. However, Ionic Silver Solution was found to be more effective than Super Oxidized Solution in the healing of chronic wounds. Complete healing was noticed in a small number (6%) of patients. These agents can therefore best prepare the wounds for early surgical intervention. Conclusion Both the agents were found to be safe and useful in the management of chronic wounds. However, Ionic Silver Solution was found to be more effective than the super oxidized solution in this study.

Objectives To assess the currently available evidence regarding associations between spinal cord stimulator (SCS) lead type, clinical indications for device placement, and interference between SCSs and cardiac pacemakers (CPMs)/implantable cardioverter-defibrillators (ICDs). Study design Review of case reports and original research studies assessing the interference between SCS and CPM/ICD. Materials and methods PubMed and Cochrane databases were searched for articles commenting on the interference between SCS and CPM/ICD. The search criteria which generated the greatest number of relevant studies was (spinal cord stimulator AND [pacemaker OR implantable cardioverter defibrillator]). Additional, empiric review was conducted using JSTOR, ScienceDirect, and EBSCOhost databases; however, no additional eligible studies were identified. Data were extracted, summarized into tables, and quantitatively analyzed using LibreTexts and MedCalc software. Results There was no statistically significant interference observed between SCS and CPM/ICD devices in patients regardless of indication for SCS placement and SCS lead polarity. Limitations Limited by variability of patient cases and variability in maximum frequency and amplitude of SCS devices tried in individual cases. Also limited by small sample size and the absence of a standard definition for device interference across studies. Conclusions Interference between cardiac devices and SCSs is a rare occurrence. As there are currently no published guidelines, devices should be interrogated on a case-by-case basis in the SCS trial period (if implanted after cardiac device), during permanent implantation, and during scheduled follow-up visits. Peri-operative testing should include increasing the SCS settings to maximally tolerated levels with cardiac device set at its maximum sensitivity.

The aim of this paper is to have comparative analysis of open loop control provided for solar panel and the non isolated control provided for solar panel. Solar current and Voltage for the designed panel was determined and the maximum voltage and current are determined for the designed panel. Maximum efficient processing system has been determined by accounting two controllers for the designed solar panel.

Solar cell layers technology has achieved global standing in the solar cell layers deposition process, and it covers the innovative methods and techniques in significant applications. Recent solar cell layers technology has an advanced interest in a refined approach to enhance performance and highlights the importance of recent proficient procedures for manufacturing. For example, the application is used to search for novel materials for solar cells' layers to clarify the current energy crisis. The technological process and various types of solar cells depend on climate change. Among them, layers of solar cells and silicon wafer solar cells are very encouraging. Solar cell layers technology has led to solar cells being a more reasonable active option in design and production. The productivities facilitated by new solar cells still need to be enhanced for the various processes involved in the additional enhancement from Copper Indium Gallium Selenide (CIGS) microfilms to solar cell crystal structure dye-sensitized solar cells. The hydrophobic coating works as an anti-dust coating, enhancing efficiency and decreasing the cost of cleaning solar cells. In Saudi Arabia Majmaah City, most solar projects are in dry regions, where the dusty weather reduces solar cell efficiency. Therefore, combining these two properties and applying an anti-reflective and superhydrophobic coating will increase solar cell efficiency by 20%. Solar cells' crystal structure results are substituted with layers or new materials to balance environmental impact and toxic nature.

Background The skin barrier is important in the pathogenesis of atopic dermatitis and stratum corneum lipids have a critical role. Skin surface lipids have been largely overlooked but also contribute to barrier function. An untargeted approach was used to compare the skin surface lipids from atopic and non-atopic West Highland White terrier dogs (WHWT). Objectives The primary hypothesis was that a difference in the lipidome would exist. The secondary hypothesis was that affected and unaffected skin lipids would differ. Animals and methods This prospective, cross-sectional, case-controlled study included thirty-nine privately owned WHWTs. Dogs were assigned to one of four disease status groups based on strict criteria. Samples for lipid analysis were collected from the skin surface of unaffected and affected sites. Lipid analysis was by untargeted liquid chromatography/mass spectrometry and utilised lipid identification software packages. Principle component analysis (PCA) and partial least-squares discriminant analysis (sPLS-DA) statistical methods analysed the association between the relative lipid abundance and disease status and affected and unaffected skin. Results Samples for lipid analysis found 421 lipid soluble features of which ten lipids were positively identified. Statistical analysis could not distinguish between non-atopic and atopic dogs but did reveal a statistically significant difference in the lipid profiles from affected and non-affected skin irrespective of disease status. Conclusions A large array of unidentified lipids from the skin surface were found with a difference between affected and unaffected skin unrelated to disease status. Investigation into the lipidome of the skin surface is an emerging area of research with clinical and therapeutic applications.

Introduction. Early activation of the innate immune response as a compensatory mechanism can lead to the damage of vessels and their dysfunction. This enables the development and progression of cognitive dysfunction, alteration of cerebral microcirculation, thus makes the onset of age-related neurodegenerative diseases possible. Inflammasomes of NLRP3 play the important role as far as they are triggers of the inflammatory process in age-related chronic neurodegenerative diseases. Objectives. To study the development of social and cognitive impairments in aging NLRP3 knockout animals. Material and methods. The experimental group was NLRP3 knockout (NLRP3-/-) male mice of the line B6.129S6-Nlrp3tm1Bhk / JJ) aged 12 months (n=10); control group – C57BL/6.SJL male mice aged 12 months (n=10). Neurobehavioral testing: “open field” test, “X-maze” test, “light-dark box”, three-chamber social test, and “five-trial social memory” test. Results. In the “open field” test, when the social object appeared, NLRP3-/- animals spent less time at the center of the field I in comparison with the animals of the C57BL/6 line (p=0.013). NLRP3-/- animals spent more time in the black chamber compared to the animals in the control group (p=0.037) in the “light-dark box” test. In the “three-chamber social” test NLRP3-/- animals spent the same time both with the new and the already familiar social object (p=0.885). In the “five-trial social memory” test NLRP3-/- animals did not demonstrate reduction of interest towards individuals of the opposite sex in the fourth attempt compared to the first attempt. Conclusion. NLRP3-/- mice have the increased levels of anxiety and inhibition, disruption of memory, and destructive changes in the field of social contacts and interactions. This indicates a disorder in the sphere of emotional behavior, as well as social memory, №2 (2018)

Objective To evaluate the role of disease-modifying anti-rheumatic drugs (DMARDs) on wound healing outcomes of patients with autoimmune disease at our tertiary wound care center. Approach Retrospective review of patients presenting to our wound care center between 2014 and 2018 with both chronic wounds and a history of inflammatory disease. Patient demographics, comorbid conditions, and progression to complete wound healing were compared between those taking DMARDs or not at the time of wound onset. The study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Results 58 patients with a total of 296 wounds were retrospectively reviewed. Patients were taking at least one DMARD at wound onset in 217 (73.3%) of these wounds. The average number of DMARDs at wound onset was 1.5 (SD 1.2). 210 wounds progressed to heal (70.9%) with a median time to healing of 229.5 days (IQR 71.0-490.0). Of the 210 wounds that healed, patients taking at least one DMARD had a significantly shorter time to healing relative to patients who were not on any DMARDs (median 190.5 vs 340.0 days, p=0.0156). Innovation Characterizing wound healing outcomes at a tertiary hospital with a dedicated wound care center and analyzing the role of DMARDs in wound healing progression. Conclusions Chronic wounds are notoriously challenging to treat in the setting of autoimmune disease. The median time to healing in the studied cohort was 229.5 days, which is alarming when compared to patients with non-infected diabetic foot ulcers, who take a median time to heal of 30.8 days at our institution.10.

Abstract: Probiotics are defined as “live microorganisms that confer a health benefit on the host when administered adequately.” In recent years, the cosmetic industry has tried to develop many products classified as probiotics. They can exert their benefits at the skin level because of their favorite properties, and they could prevent and treat skin diseases and represent an emerging area for skin health. The antibacterial and immunomodulatory properties make them promising candidates to target skin disorders including acne, psoriasis, and atopic dermatitis and aid wound healing. The scientific reports show that specific probiotic strains can modulate cutaneous microflora, skin immune system, lipid barrier, and skin health preservation. This review summarizes the most relevant evidence from scientific literature concerning potential topical applications of probiotics in dermatology. Altogether, the evidence reported here affords the possibility of designing new strategies based on a topical approach to prevent and treat cutaneous disorders.

Erythema nodosum (EN) is a poly-etiological disease with an acute flow that is characterized by symmetric emergence of painful nodules often in pretibial areas. A twenty-month-old male child was admitted to hospital for evaluation of the eruptive skin changes in the lower extremities and forearms. The disease began 10 days before getting febricity and loose stools. The laboratory analysis showed an elevated erythrocyte sedimentation rate and leukocytosis. Blood cultures demonstrated the presence of coagulase-negative Staphylococcus, while Proteus vulgaris was isolated in urine cultures. After initiation of the empiric antibiotic therapy and then, the targeted antibiotic therapy according to the antibiogram, there was a significant improvement in a general condition and regression of cutaneous lesions. Erythema nodosum in the present case, is the result of staphylococcal bacteremia although Proteus vulgaris cannot be excluded as a cause.

It is necessary to develop a new strategy for treatment of lung cancer since it is the main cause of cancer death. Tanshinone IIA (Tan IIA), an active ingredient of a commonly used traditional Chinese herb Salvia miltiorrhiza, provides a new direction to develop a new strategy for the treatment. It has been found that Tan IIA could inhibit lung cancer in vitro and in vivo by inducing autophagic apoptosis. Tan IIA increased apoptotic cells and the expression of cleaved caspase 3 and cleaved caspase 9, decreased B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio in human non-small cell lung cancer (NSCLC) cell lines, which was promoted by an autophagy activator Rapamycin, and weaken by autophagy inhibitor 3-methyladenine (3-MA). In addition, Tan IIA induced more autophagosomes, up-regulated light chain 3β (LC-3B) I and LC-3B II conversion and less sequestosome 1 (SQSTM1/p62) expression, which cannot be weakened by the caspase 3 antagonist. Moreover, overexpression of LC-3B gene (LC3B) and downregulation of autophagic gene 5 (ATG5) further confirmed that Tan IIA induced autophagic apoptosis in NSCLC cell lines. Beclin-1 gene (BECN1) overexpression and silence attenuated the effects of Tan IIA, suggesting autophagic apoptosis that Tan IIA induced was dependent on Beclin-1. Overall, our study demonstrated a new treatment mechanism of Tan IIA and suggested that Tan IIA is a potential new anti-cancer therapeutic option.

Significance: Nonhealing wounds are a significant burden for the health care system all over the world. Existing treatment options are not enough to promote healing, highlighting the urgent need for improved therapies. In addition, the current advancements in tissue-engineered skin constructs and stem cell-based therapies are facing significant hurdles due to the absence of a renewable source of functional cells. Recent Advances: Induced pluripotent stem cell technology (iPSC) is emerging as a novel tool to develop the next generation of personalized medicine for the treatment of chronic wounds. The iPSC provides unlimited access to various skin cells to generate complex personalized three-dimensional skin constructs for disease modeling and autologous grafts. Furthermore, the iPSC-based therapies can target distinct wound healing phases and have shown accelerating wound closure by enhancing angiogenesis, cell migration, tissue regeneration, and modulating inflammation. Critical Issues: Since the last decade, iPSC has been revolutionizing the field of wound healing and skin tissue engineering. Despite the current progress, safety and heterogeneity among iPSC lines are still major hurdles in addition to the lack of large animal studies. These challenges need to be addressed before translating an iPSC-based therapy to the clinic. Future Directions: Future considerations should be given to performing large animal studies to check the safety and efficiency of iPSC-based therapy in a wound healing setup. Furthermore, strategies should be developed to overcome variation between hiPSC lines, develop an efficient manufacturing process for iPSC-derived products, and generate complex skin constructs with vasculature and skin appendages.

Leukocytoclastic vasculitis is a rare cutaneous manifestation in multiple myeloma and only twenty cases have been described to date. We report an unusual case with kappa IgA multiple myeloma in a 63 years old woman presented with leukocytoclastic vasculitis type of digital necrosis and leg ulcer. The vasculitis seems to be paraneoplastic as skin lesions regressed following multiple myeloma treatment.

Fin clips (complete fin removal) or punch marks (stamping of a hole) in fins or operculum are quick and inexpensive methods to identify individuals or groups of fish. This study evaluated the retention of 6 mm diameter punch marks on the operculum, caudal (upper and lower lobes), dorsal, pelvic, and anal fins, and fin clips on adipose, pectoral, pelvic, dorsal and anal fins of rainbow trout Oncorhynchus mykiss for 279 days. Growth and survival were not significantly different among fish with the different mark types or locations. At the end of the experiment, 100% of adipose clips, 97% of pectoral and anal fin clips, and 93% of dorsal clips and pelvic fin clips were retained. Retention of punch marks was 57% and 50% for the lower and upper caudal fin lobe locations respectively, 23% for the dorsal fin, and 3% for the operculum. No pelvic or anal fin punch marks were identified at the end of the trial. Significant differences in retention among the treatment groups did not occur until 125 days post marking, after which all fin clip treatments had significantly greater retention than pelvic and dorsal punch marks. Beyond 244 days, fin clips outperformed all punch mark locations.

Lichens, algae and fungi-based symbiotic associations, are sources of many important secondary metabolites, such as antibiotics, anti-inflammatory, antioxidants, and anticancer agents. Wide range of experiments based on in vivo and in vitro studies revealed that lichens are a rich treasure of anti-cancer compounds. Lichen extracts and isolated lichen compounds can interact with all biological entities currently identified to be responsible for tumor development. The critical ways to control the cancer development include induction of cell cycle arrests, blocking communication of growth factors, activation of anti-tumor immunity, inhibition of tumor-friendly inflammation, inhibition of tumor metastasis, and suppressing chromosome dysfunction. Also, lichen-based compounds induce the killing of cells by the process of apoptosis, autophagy, and necrosis, that inturn positively modulates metabolic networks of cells against uncontrolled cell division. Many lichen-based compounds have proven to possess potential anti-cancer activity against a wide range of cancer cells, either alone or in conjunction with other anti-cancer compounds. This review primarily emphasizes on an updated account of the repository of secondary metabolites reported in lichens. Besides, we discuss the anti-cancer potential and possible mechanism of the most frequently reported secondary metabolites derived from lichens.

Introduction: The general objective was to determine the epidemiological, clinical, paraclinical, therapeutic and evolutionary aspects of connectivitis in the dermatology department of the CHU Aristide Le Dantec. Patients and methods: This was a retrospective and descriptive study conducted in the Dermatology Department of the University Hospital Center (UHC) Aristide Le Dantec (HALD) of Dakar between January 2009 and December 2019. Their diagnoses were retained according to the international criteria validated in the course of connectivites Results: We identified 290 cases of connectivitis. Systemic scleroderma was the most frequent in 34.42% (n=94), followed by systemic lupus in 25.86% (n=75), mixed connectivities in 22,06% (n=64) and dermatomyositis in 19,32% (n=56). Cancer was associated with dermatomyositis in 11 cases and with systemic scleroderma in 3 cases. The mean age of our patients was 38.23 years. The sex ratio was 4.2 and the mean duration of evolution was 25 months. Dermatological manifestations were constant, found in all patients. In systemic lupus, they were dominated by discoid lupus lesions found in 40% and hypochromic spots (86%) in systemic scleroderma. In dermatomyositis, skin lesions were dominated by periorbital erythroedema (66.07%). Joint manifestations were found in 56.89% of cases (n= 165), muscular manifestations in 41.37% of cases (n= 120) and pleuropulmonary manifestations in 31.3% of cases (n=91). Neuropsychiatric manifestations were noted in 5.17% of cases (n=15). All our patients were treated with corticosteroid therapy and 12.06% of them had received immunosuppressive treatment, the most commonly used molecules being methotrexate (3.44%) and cyclophosphamide (8.27%). Hydroxychloroquine was prescribed in 59.31% of patients, while D-penicillamine was prescribed in 42.06% of patients, 100% of whom were treated for systemic scleroderma. The main complications encountered were infectious complications in 83 cases (28.6%). Visceral complications, a type of visceral insufficiency, were noted in 4.13% of cases. Conclusion: Our study demonstrates the frequency of connectivitis in the dermatology department. Its particularity was the predominance of systemic scleroderma over lupus which was classically the first connectivite in dermatology services. The delay in diagnosis noted is correlated with visceral attacks; hence the importance of a better knowledge of these affections for an early management.

The present study was aimed to evaluate the protective effects of Hydroethanolic Murraya koenigii leaves extract (HEMKLE) against DMBA/TPA-induced angiogenesis, hepatotoxicity and renal toxicity during skin carcinogenesis in mice. For the study, male LACA mice were divided into four groups: Group I (C), Group II (DMBA/TPA), Group III (HEMKLE), and Group IV (HEMKLE+DMBA/TPA). 7, 12-dimethylbenz(a) anthracene (DMBA), and 12-O-tetradecanoyl phorbol-13-acetate (TPA) were applied on the depilated skin of the mice to raise skin tumors in Group II and Group IV. The chemopreventive response of HEMKLE was evident by histoarchitectural and morphometric analysis of skin/tumors in Group IV (HEMKLE+DMBA/TPA). In addition, HEMKLE administration also decreased the mRNA and protein expression of HIF-1α, HMOX-1, VEGF, bFGF, and ANGPT-2 in Group IV (HEMKLE+DMBA/TPA) when compared to Group II (DMBA/TPA) that suggest its anti-angiogenic effect. Moreover, HEMKLE administration protected the liver and kidney tissues from damages incurred during skin carcinogenesis as evident through histological analysis, assessment of ROS and LPO levels, assessment of liver and kidney function markers (viz., SGOT, SGPT, D-bilirubin, T-bilirubin, ALP, urea, creatinine and BUN) and activities of the antioxidant enzymes in Group IV (HEMKLE +DMBA/TPA) when compared to Group II (DMBA/TPA). The outcome of the present study showed that HEMKLE administration markedly alleviated the angiogenesis and also showed the protective effects against damages incurred in liver and kidney tissues during skin carcinogenesis. However, further extensive studies are needed to explore the efficacy of HEMKLE on metastasis before going to human trials.

A novel thermal-constant blood-feeder covered with a perforated film and using pig blood was developed for rearing Aedes aegypti (L.) (Diptera: Culicidae). The perforated film was used as a substitute for the membrane or parafilm that is normally used in conventional blood-feeders to prevent the mosquitoes from directly contacting the blood. The efficiency of this perforated blood feeder was assessed by using live mice and comparing the engorgement rate of female mosquitoes and their demographic parameters. In a no-choice test, no significant differences were observed in the engorgement rates and fecundity between females fed on perforated feeders containing pig blood and those fed on live mice. In a three-minute-long free-choice test, the accumulated engorgement rate was significantly higher in mosquitoes feeding on the perforated feeders than in those feeding on live mice. The demographic characteristics indicated that mosquitoes fed on the perforated feeder containing pig blood had a higher immature survival rate and prolonged adult male and female longevity. Although a lower intrinsic rate of increase and lower finite rate of increase were observed when female adults fed on the perforated feeder, computer projection of the population growth was comparable using both blood sources. Massrearing analysis showed that the perforated blood feeder was much more cost-effective than using live mice. These results demonstrate that the perforated blood feeder containing pig blood is more effective and cost efficient than using live mice for maintaining and mass rearing of mosquitoes in the laboratory.

Sarcoptes scabiei is the causative agent of a highly contagious skin disease in humans and more than 100 mammals. Here, we reported the first chromosome-level reference genome of S. scabiei isolated from rabbits, with a contig N50 size of 5.92 Mb, a total assembled length of 57.30 Mb, ∼12.65% repetitive sequences and 9333 predicted protein-coding genes. The phylogenetic tree based on 1338 shared high-confidence single-copy orthologous genes estimated that the mammalian ectoparasite S. scabiei and the plant-feeding mite Tetranychus urticae separated ∼340 million years ago. Both neighbour-joining tree and principal component analysis of 20 mite populations isolated from four hosts (humans, pigs, dogs and rabbits) distributed in three countries (China, Australia and the USA) consistently supported genetic subdivisions according to host species rather than geographical location. The demographic history of S. scabiei reconstructed by multiple sequentially Markovian coalescent analysis suggested that S. scabiei isolated from rabbits, humans, dogs and pigs diverged ∼5000 years ago. Investigation of the homeobox (Hox) genes revealed that S. scabiei contains 8 of 10 canonical Hox genes that are present in the arthropod ancestor, and the absence of the Abd-A gene may correlate with the long gap between their front and back legs. Comparative genomics demonstrated that genes specific to scabies mites were mainly enriched in nutrition digestive systems, whereas genes in the families that involved detoxification (cytochrome P450, carboxyl/cholinesterases and the ATP-binding cassette transporter C group) were extremely contracted compared with that of other mites analysed in this study. Selective sweep analysis of mite populations from various pairs of two out of the four host species revealed that the strongest selective sweep signals were mainly enriched in cysteine-type peptidase activity and apoptosis. The results provided clues for the mechanisms of S. scabiei adaptation to a permanent parasitic lifestyle and knowledge that would enable further control of this highly contagious skin disease.

Abstract: Vitiligo is an acquired, chronic, and progressive depigmentation or hypopigmentation, characterized by the destruction of melanocytes, and occurrence of white patches or macules in the skin, mucosal surface of eyes, and ears. Melanocytes are the melanin pigment producing cells of the skin which are destroyed in pathological conditions called vitiligo. Approximately, 0.5 - 2.0% of the population is suffering from vitiligo, and a higher prevalence rate up to 8.8% has been reported in India. It is caused by various pathogenic factors like genetic predisposition, hyperimmune activation, increased oxidative stress, and alteration in neuropeptides level. Genetic research has revealed a multi-genetic inheritance that exhibits an overlap with other autoimmune disorders. However, melanocytes specific genes are also affected (such as DDR1, XBP1, NLRP1, PTPN22, COMT, FOXP3, ACE, APE, GSTP1, TLR, SOD, and CTLA-4). The numbers of therapeutic options are employed for the treatment of vitiligo. The topical corticosteroids and immunomodulators are currently in practice for the management of vitiligo. Phototherapies alone, and in combinations with other approaches are used in those patients who do not respond to the topical treatment. The main focus of this review is on the etiopathological factors, pharmacological management (phototherapy, topical, systemic and surgical therapy), and herbal drugs use to treat vitiligo.

Chronic, non-healing, dermal wounds form a worldwide medical problem with limited and inadequate treatment options and high societal burden and costs. With the advent of regenerative therapies exploiting extracellular matrix (ECM) components, its efficacy to augment wound healing is to be explored. This systematic review was performed to assess and compare the current therapeutic efficacy of ECM hydrogels on dermal wound healing. The electronic databases of Embase, Medline Ovid, and Cochrane Central were searched for in vivo and clinical studies on the therapeutic effect of ECM-composed hydrogels on dermal wound healing (April 13, 2021). Two reviewers selected studies independently. Studies were assessed based on ECM content, ECM hydrogel composition, additives, and wound healing outcomes, such as wound size, angiogenesis, and complications. Of the 2102 publications, 9 rodent-based studies were included while clinical studies were not published at the time of the search. Procedures to decellularize tissue or cultured cells and subsequently generate hydrogels were highly variable and in demand of standardization. ECM hydrogels with or without additives reduced wound size and also seem to enhance angiogenesis. Serious complications were not reported. To date, preclinical studies preclude to draw firm conclusions on the efficacy and working mechanism of ECM-derived hydrogels on dermal wound healing. The use of ECM hydrogels can be considered safe. Standardization of decellularization protocols and implementation of quality and cytotoxicity controls will enable obtaining a generic and comparable ECM product. Impact statementExtracellular matrix (ECM)-based hydrogels are biocompatible and harbor growth factors that can instruct tissue healing. Their application is a novelty in (pre)clinical wound healing treatment. This systematic review provides an overview of the current evidence for ECM hydrogels in enhancing wound healing and an extensive overview of the decellularization procedures used. Lastly, challenges and future directions to standardize decellularization procedures and implement quality controls are proposed.

There are different types of skin diseases due to chronic injuries that impede the natural healing process of the skin. Tissue engineering has focused on the development of bioengineered skin or skin substitutes that cover the wound, providing the necessary care to restore the functionality of injured skin. There are two types of substitutes: acellular skin substitutes, which offer a low response to the body, and cellular skin substitutes (CSSs), which incorporate living cells and appear as a great alternative in the treatment of skin injuries due to their greater interaction and integration with the rest of the body. For the development of a CSS, it is necessary to select the most suitable biomaterials, cell components, and methodology of biofabrication for the wound to be treated. Moreover, these CSSs are immature substitutes that must undergo a maturing process in specific bioreactors, guaranteeing their functionality. The bioreactor simulates the natural state of maturation of the skin by controlling parameters such as temperature, pressure, or humidity, allowing a homogeneous maturation of the CSSs in an aseptic environment. The use of bioreactors not only contributes to the maturation of the CSSs but also offers a new way of obtaining large sections of skin substitutes or natural skin from small portions acquired from the patient, donor, or substitute. Based on the innovation of this technology and the need to develop efficient CSSs, this work offers an update on bioreactor technology in the field of skin regeneration. Impact Statement The manufacture of functional cellular skin substitutes (CSSs) is one of the current goals in the field of tissue engineering to improve the treatment of chronic skin injuries, thus favoring skin repair and regeneration. The main advances in the development of innovative and effective CSSs are largely focused on the selection of more adequate cellular components, biomaterials, and biofabrication techniques to be used in their biofabrication. However, the maturation of CSSs should be an essential step in obtaining a functional substitute capable of replacing the native skin. The sequential procedure from the design of the CSS to its maturation process will be reviewed. In the context of the manufacturing of novel CSSs, different technologies to biofabricate functional structures and how their maturation can be carried out by specific devices are addressed, as well as key challenges facing the design and development of CSSs.