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Fungal keratitis is a severe corneal infection characterized by suppurative and ulcerative lesions. Aspergillus fumigatus is a common cause of fungal keratitis. Antifungal drugs, such as natamycin, are currently the first-line treatment for fungal keratitis, but their ineffectiveness leads to blindness and perforation. Additionally, the development of fungal resistance makes treating fungal keratitis significantly more challenging. The present study used platelet-derived biomaterial (PDB) to manage A. fumigatus keratitis in the animal model. Freezing and thawing processes were used to prepare PDB, and then A. fumigatus keratitis was induced in the mice. Topical administration of PDB, natamycin, and plasma was performed; quantitative real-time PCR (qPCR) and histopathologic examination (HE) were used to assess the inhibitory effect of the mentioned compounds against fungal keratitis. The qPCR results showed that PDB significantly decreased the count of A. fumigatus compared to the control group (P-value ≤ 5). Natamycin also remarkably reduced the count of fungi in comparison to the untreated animal, but its inhibitory effect was not better than PDB (P-value > 5). The findings of HE also demonstrated that treatment with PDB and natamycin decreased the fungal loads in the corneal tissue. However, plasma did not show a significant inhibitory effect against A. fumigatus. PDB is intrinsically safe and free of any infections or allergic responses; additionally, this compound has a potential role in decreasing the burden of A. fumigatus and treating fungal keratitis. Therefore, scientists should consider PDB an applicable approach to managing fungal keratitis and an alternative to conventional antifungal agents. [ABSTRACT FROM AUTHOR]

BackgroundBiofilms are bacterial communities that can protect them against external factors, including antibiotics. In this study, silver nanoparticles (AgNPs) were formed by modifying AgNPs with C-phycocyanin (Ag-Pc) to inhibit the growth of carbapenem-resistant Pseudomonas aeruginosa (CR P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) and destroy biofilm of these bacteria.MethodsThe AgNPs were prepared with the green synthesis method, and Pc was used to stabilize the AgNPs. The Ag-Pc’s antibacterial and antibiofilm effects were evaluated using the Microbroth dilution method and microtiter plate assay. The inhibitory effect of Ag-Pc on the expression of biofilm-related genes was evaluated by real-time PCR. Moreover, the MTT assay was used to assess the Ag-Pc toxicity.ResultsThe Ag-Pc minimum inhibitory concentration (MIC) was 7.4 μg/mL for CR P. aeruginosa and MRSA. Pc did not show antibacterial effects against any of the strains. Ag-Pc suppressed biofilm formation and destroyed matured biofilm in both bacteria more efficiently than the AgNPs (P< 0.05). The expression of all genes was not significantly reduced in the presence of synthesized nanoparticles. Finally, the MTT assay results did not show toxicity against a murine fibroblast cell line (L929) at MIC concentration.ConclusionThe present study showed the promising potential of Pc for improving the antibacterial and antibiofilm function of AgNPs and inhibiting drug-resistant bacteria. Therefore, Ag-Pc nanoparticles can be considered a promising therapeutic approach for the managing of the bacterial biofilm.

Purpose: evaluation of the role of combined injection of triamcinolone acetonide with 5 Fluorouracil in treatment of the enlarged extraocular muscles secondary to chronic non-specific non-infectious inflammation. Methods: injection of 0.1 ml of triamcinolone acetonide 40 mg/ml and 0.1 ml of 5 Fluorouracil 50 mg/ml in the enlarged extraocular muscles secondary to chronic non-specific non-infectious inflammation in 6 patients, after the confirmation of the histopathological diagnosis of these patients by revising their medical records. Results: There was a significant improvement in the visual acuity, in addition to a significant improvement also in the clinical and the radiological features in the patients who were consented for the trial of the new injection protocol. However, there was failure of clinical and radiological improvement in one case presented with sever fibrosis. There was a significant absence of the side effects in all patients except for one patient that reported discomfort near the inner canthus. Conclusion: The new protocol of the treatment is a promising modality that can be used in the chronic non-infectious inflammation without extensive fibrosis. [ABSTRACT FROM AUTHOR]

A case report published in the International Journal of Dermatology discusses the potential use of topical tirbanibulin ointment 1% as a new treatment for recalcitrant plantar warts. The report highlights the challenges of treating plantar warts and the need for innovative approaches. Tirbanibulin, an inhibitor of tubulin polymerization, has shown promising results in inducing apoptosis in rapidly dividing cells infected by HPV. The case study describes the successful treatment of a large plantar wart with tirbanibulin cream, suggesting the need for further research to establish its efficacy and safety profile. [Extracted from the article]

Myotonic dystrophy type 1 (DM1), the most common form of adult muscular dystrophy, is caused by an abnormal expansion of CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The expanded repeats of the DMPK mRNA form hairpin structures in vitro, which cause misregulation and/or sequestration of proteins including the splicing regulator muscleblind-like 1 (MBNL1). In turn, misregulation and sequestration of such proteins result in the aberrant alternative splicing of diverse mRNAs and underlie, at least in part, DM1 pathogenesis. It has been previously shown that disaggregating RNA foci repletes free MBNL1, rescues DM1 spliceopathy, and alleviates associated symptoms such as myotonia. Using an FDA-approved drug library, we have screened for a reduction of CUG foci in patient muscle cells and identified the HDAC inhibitor, vorinostat, as an inhibitor of foci formation; SERCA1 (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) spliceopathy was also improved by vorinostat treatment. Vorinostat treatment in a mouse model of DM1 (human skeletal actin–long repeat; HSALR) improved several spliceopathies, reduced muscle central nucleation, and restored chloride channel levels at the sarcolemma. Our in vitro and in vivo evidence showing amelioration of several DM1 disease markers marks vorinostat as a promising novel DM1 therapy. [ABSTRACT FROM AUTHOR]

Background: Alopecia areata is a common and unpleasant illness that manifests as abrupt, circular patches of complete hair loss that heal scar-free. For most individuals with patchy alopecia areata, intralesional or topical corticosteroids are regarded the first therapeutic option due to their relative safety and convenience; nevertheless, there is limited evidence for their efficacy. Objective: Review of the literature on New Treatment Strategies in Management of Alopecia Areata. Methods: We looked for data on New Treatment Strategies and Alopecia Areata, treatment in medical journals and databases like PubMed, Google Scholar, and Science Direct. However, only the most recent or extensive study was taken into account between November 2002 and December 2021. References from related works were also evaluated by the writers. There are not enough resources to translate documents into languages other than English, hence those documents have been ignored. It was generally agreed that documents such as unpublished manuscripts, oral presentations, conference abstracts, and dissertations did not qualify as legitimate scientific study. Conclusion: When a ligand attaches to their specific cytokine receptor, janus kinases (JAKs) can phosphorylate signal transducers and activators of transcription (STATs). Hair regrowth is facilitated by oral formulations because they are simple to ingest. Tofacitinib comes in 5-mg and 11-mg doses and can be taken once or twice day. Treatment options for alopecia areata of the scalp are limited, but the 308-nm excimer laser has proven to be helpful in restoring hair growth in affected areas. [ABSTRACT FROM AUTHOR]

Paola Galozzi, Sara Bindoli, Andrea Doria, Paolo Sfriso Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, ItalyCorrespondence: Paola Galozzi, Rheumatology Unit, Department of Medicine DIMED, University of Padova, via Giustiniani, 2, Padova, 35128, Italy, Tel +39 049 821 8654, Email paola.galozzi@unipd.itAbstract: Adult-onset Still’s disease (AOSD) is a rare multifactorial autoinflammatory disorder of unknown etiology, characterized by an excessive release of cytokines triggered by dysregulated inflammation and articular and systemic manifestations. The clinical spectrum of AOSD ranges from self-limiting forms with mild symptoms to life-threatening cases and presents clinical and biological similarities with the juvenile form (sJIA). Nowadays, the advances in biologic agents no longer limit the treatment to NSAIDs, glucocorticoids, or conventional synthetic DMARDs. The blockade of IL-1 and IL-6 is effective in the treatment of systemic and articular inflammation of AOSD patients; however, novel compounds with different properties and targets are now available and others are being studied. In this review, starting from the pathogenesis of AOSD, we summarized the current and emerging biological therapies, possible effective agents for achieving AOSD control and remission.Keywords: biologics, AOSD, IL-1 inhibitors, IL-6 inhibitors, small molecules, new treatment

Abstract Background Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. Methods Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. Results All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P

Simple Summary: Current cancer treatment strategies such as surgery, chemotherapy, and radiotherapy, have significant drawbacks. There is a need for a breakthrough approach to cancer treatment. Bacteriocin, an antimicrobial peptide, has shown several anticancer properties in vitro. Therefore, this article reviews the effect of bacteriocin on cancer cells and how bacteriocins affect cancer cells in vitro. This article aims to promote additional bacteriocin research, particularly in vivo studies, to fully understand the potential of bacteriocin as a cancer treatment agent. Cancer is regarded as one of the most common and leading causes of death. Despite the availability of conventional treatments against cancer cells, current treatments are not the optimal treatment for cancer as they possess the possibility of causing various unwanted side effects to the body. As a result, this prompts a search for an alternative treatment without exhibiting any additional side effects. One of the promising novel therapeutic candidates against cancer is an antimicrobial peptide produced by bacteria called bacteriocin. It is a non-toxic peptide that is reported to exhibit potency against cancer cell lines. Experimental studies have outlined the therapeutic potential of bacteriocin against various cancer cell lines. In this review article, the paper focuses on the various bacteriocins and their cytotoxic effects, mode of action and efficacies as therapeutic agents against various cancer cell lines. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus and Staphylococcus epidermidis are associated with life-threatening infections. Despite the best medical care, these infections frequently occur due to antibiotic resistance and the formation of biofilms of these two bacteria (i.e., clusters of bacteria embedded in a matrix). As a consequence, there is an urgent need for effective anti-biofilm treatments. Here, we describe the antibacterial properties of a combination treatment of diethyldithiocarbamate (DDC) and copper ions (Cu+2) and their low toxicity in vitro and in vivo. The antibacterial activity of DDC and Cu+2 was assessed in vitro against both planktonic and biofilm cultures of S. aureus and S. epidermidis using viability assays, microscopy, and attachment assays. Cytotoxicity of DDC and Cu+2 (DDC-Cu+2) was determined using a human fibroblast cell line. In vivo antimicrobial activity and toxicity were monitored in Galleria mellonella larvae. DDC-Cu+2 concentrations of 8 µg/ml DDC and 32 µg/ml Cu+2 resulted in over 80% MRSA and S. epidermidis biofilm killing, showed synergistic and additive effects in both planktonic and biofilm cultures of S. aureus and S. epidermidis, and synergized multiple antibiotics. DDC-Cu+2 inhibited MRSA and S. epidermidis attachment and biofilm formation in the xCELLigence and Bioflux systems. In vitro and in vivo toxicity of DDC, Cu+2 and DDC-Cu+2 resulted in > 70% fibroblast viability and > 90% G. mellonella survival. Treatment with DDC-Cu+2 significantly increased the survival of infected larvae (87% survival of infected, treated larvae vs. 47% survival of infected, untreated larvae, p < 0.001). Therefore, DDC-Cu+2 is a promising new antimicrobial with activity against planktonic and biofilm cultures of S. epidermidis and S. aureus and low cytotoxicity in vitro. This gives us high confidence to progress to mammalian animal studies, testing the antimicrobial efficacy and safety of DDC-Cu2+. [ABSTRACT FROM AUTHOR]

Background: Biofilms are bacterial communities that can protect them against external factors, including antibiotics. In this study, silver nanoparticles (AgNPs) were formed by modifying AgNPs with C-phycocyanin (Ag-Pc) to inhibit the growth of carbapenem-resistant Pseudomonas aeruginosa (CR P. aeruginosa ) and methicillin-resistant Staphylococcus aureus (MRSA) and destroy biofilm of these bacteria., Methods: The AgNPs were prepared with the green synthesis method, and Pc was used to stabilize the AgNPs. The Ag-Pc's antibacterial and antibiofilm effects were evaluated using the Microbroth dilution method and microtiter plate assay. The inhibitory effect of Ag-Pc on the expression of biofilm-related genes was evaluated by real-time PCR. Moreover, the MTT assay was used to assess the Ag-Pc toxicity., Results: The Ag-Pc minimum inhibitory concentration (MIC) was 7.4 μg/mL for CR P. aeruginosa and MRSA. Pc did not show antibacterial effects against any of the strains. Ag-Pc suppressed biofilm formation and destroyed matured biofilm in both bacteria more efficiently than the AgNPs (P< 0.05). The expression of all genes was not significantly reduced in the presence of synthesized nanoparticles. Finally, the MTT assay results did not show toxicity against a murine fibroblast cell line (L929) at MIC concentration., Conclusion: The present study showed the promising potential of Pc for improving the antibacterial and antibiofilm function of AgNPs and inhibiting drug-resistant bacteria. Therefore, Ag-Pc nanoparticles can be considered a promising therapeutic approach for the managing of the bacterial biofilm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Chegini, Shariati, Alikhani, Safaiee, Rajaeih, Arabestani and Azizi.)

The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms' resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, a-terpineol, ß-pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABCtransported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goalwill be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds. [ABSTRACT FROM AUTHOR]

Background & Objective: Multiple sclerosis (MS) is an inflammatory neurological disorder that affects the central nervous system (CNS) and causes individuals to experience a variety of cognitive and physical problems. As proven by two decades of clinical experience with immunomodulatory therapies for MS, the disease progresses and relapses through several immunological pathways. New medicines aimed at remyelination and neurodegeneration are being developed; however, they need stronger evidence before being introduced into routine clinical care. The purpose of this study was a thorough assessment of MS immunopathology and predictive biomarkers. Methods: Immunotherapy, immunopathogenesis, and prognostic biomarkers were all parts of the search method. Only publications in English were considered for inclusion in the study. For that purpose, we went through the current state of knowledge around MS immunopathology and related biomarkers. Immunology, as well as the identification of increased inflammation as an important component of neurodegeneration, shaped our understanding of this disease aetiology. The relevant sources examined covered the years 2015-2021. Conclusion: We found biomarkers in the cerebrospinal fluid and blood that might be used for the prediction and diagnosis of MS, as well as for measuring treatment response and adverse effects. Many variables, including the role of some infectious organisms and the impact of environmental and social factors, might contribute to the immunological dysfunctions seen in MS. Patients with MS may benefit from better therapy options if a better understanding of MS biomarkers and immune response mechanisms would be obtained. [ABSTRACT FROM AUTHOR]

The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms’ resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, β–pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.

Background: Cell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19. Methods: Patients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed. Results: All safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005). Conclusions: For the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients. Trial registration: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287. IRCT, IRCT20180619040147N6. Registered 04/01/2021. [ABSTRACT FROM AUTHOR]

Introduction: Regular Astigmatism is one of the most common problems for the eye; it makes a patient unable to see things clearly. Therefore, the aim of the study estimates the incidence of regular astigmatism among age group (10-32) years by using physical exerciser in the college of health and medical technology. We perform therapeutic exercises in an applied scientific way to activate the towed eye muscles by the pulled during treatment sessions to get rid of regular astigmatism and improve vision without the use of glasses or surgery to patients. Materials and Method: The method used in this study was a cross-sectional analysis of 100 cases (51 males) (49 females) with different types of astigmatism through physical exercise. The data analysed using the SPSS package program. Results: We found the compound astigmatism (58%) is higher than simple astigmatism (33%), as well as the compound astigmatism is higher than mixed astigmatism (13%). Also, we found to improve in (90%) patients treatment for continuous exercise as requested by the therapist. Conclusion: This study that most patients of Astigmatism were compound and improvement in 90% of cases treatment by physical exercise and did not need to use any glasses to read during the examination and get 'Visual Acuity' VA=6/6. [ABSTRACT FROM AUTHOR]

Vitiligo is a relatively common disorder characterized by areas of depigmented skin. It may be associated with social stigma and adversely affects the quality of life. Although many treatment options are available, none is curable. The search continues for an effective therapeutic option. New targeted options include biologics and other immunomodulatory agents, with varying degrees of evidence. We have discussed briefly the therapeutic options with special emphasis on the newer immunomodulatory agents. We undertook a comprehensive English literature search across multiple databases such as PubMed, SCOPUS, EMBASE, MEDLINE, and Cochrane using keywords (alone and in combination) and MeSH items such as "vitiligo," "treatment," "recent," and "immunomodulators" to obtain several relevant articles, priority being given to prospective randomized controlled trials. We scanned all the relevant articles and summarized them to obtain the latest information about the treatment of this condition to prepare the current article. [ABSTRACT FROM AUTHOR]

Hansen’s disease is an important public health problem and it is one of the important cause of disability in patients with nonhealing trophic ulcer in Hansen’s disease, and also the long-term management of these trophic ulcers works out to be very costly. Reduction in the healing time would be a major step in the rehabilitation of these patients. Authors hereby present one such case of chronic plantar ulcer in Hansen’s patient which was refractory to standard treatment like oral and topical antibiotics and daily dressings for more than six years. Hence, Platelet Rich Fibrin Matrix (PRFM) was applied along with adequate rest using Plaster of Paris (POP) cast. The wound was opened and the dried PRFM was cleared from the bed of the wound after 10 days. Procedure was repeated every third week. This led to dramatic healing of the ulcer with a reduction in wound diameter with no noticeable side-effects.

Uveitis is a spectrum of inflammatory disorders characterized by ocular inflammation and is one of the leading causes of preventable visual loss. The main aim of the treatment of uveitis is to control the inflammation, prevent recurrences of the disease and preserve vision while minimizing the adverse effects associated with the therapeutic agents. Initial management of uveitis relies heavily on the use of corticosteroids. However, monotherapy with high‐dose corticosteroids is associated with side effects and cannot be maintained long term. Therefore, steroid‐sparing agents are needed to decrease the burden of steroid therapy. Currently, the therapeutic approach for non‐infectious uveitis (NIU) consists of a step‐ladder strategy with the first‐line option being corticosteroids in various formulations followed by the use of first‐, second‐ and third‐line agents in cases with suboptimal steroid response. Unfortunately, the agents currently at our disposal have limitations such as having a narrow therapeutic window along with their own individual potential side‐effect profiles. Therefore, research has been targeted to identify newer drugs as well as new uses for older drugs that target specific pathways in the inflammatory response. Such efforts are made in order to provide targeted and safer therapy with reduced side effects and greater efficacy. Several specially designed molecular antibodies are currently in various phases of investigations that can potentially halt the inflammation in patients with NIU. In the review, we have provided a comprehensive overview of the current and upcoming therapeutic options for patients with NIU. [ABSTRACT FROM AUTHOR]

Introduction: Farnesoid X nuclear receptor is involved in the regulation of lipid and glucose metabolism, though mainly in the homeostasis of bile acids. Indeed, the agonists of farnesoid X nuclear receptor represent promising drugs. Areas covered: Obeticholic acid, a novel semisynthetic analogue of the naturally occurring bile acid, has led to encouraging preliminary results in both cholestatic and metabolic liver disease. In patients with primary biliary cholangitis, obeticholic acid determines a significant biochemical improvement although the effects on liver fibrosis are lacking. Obeticholic acid has been suggested for the treatment of nonalcoholic liver disease with good laboratory results. In cirrhotic animal models, the drug seems to reduce both portal hypertension and gut bacterial translocation. Expert commentary: The use of obeticholic acid for the treatment of primary biliary cholangitis shows satisfying results. However, some open questions remain unresolved. Herein, we provide an overview of the current knowledge about the use of obeticholic acid in the field of nonviral chronic liver diseases. We tried to give a global point of view using a translational approach. [ABSTRACT FROM AUTHOR]

Eribulin is a synthetic analog of halichondrin B belonging to microtubule-targeted agents with a distinct mechanism of inhibition of microtubule dynamics. This molecule has multiple nonmitotic effects on tumor biology, exhibiting effects on epithelial-mesenchimal transition and tumor vasculature. We review here preclinical and clinical studies on eribulin. The mitotic and nonmitotic effects together with its favorable safety profile make eribulin a unique drug with high potential in the treatment of metastatic breast cancer. The new emphasis of eribulin mechanism of action on vascular remodeling, microenvironment modifications and reversal of epithelial-mesenchimal transition paves the way to rethinking the use of the drug in an immunological perspective. [ABSTRACT FROM AUTHOR]

A lecture with topic "Reattach: introduction of a new schema therapy" was held on September 14, 2015 at the Faculty of Philosophy. It was organized under the auspices of The Macedonian Scientific Society for Autism. The lecture started at 10 am with the presentation by the President of MSSA Dr. Vladimir Trajkovski, who warmly welcomed the guests. There were 50 participants among which parents, professionals from different areas and students. He introduced the presenter Dr. Paula Weerkamp - Bartholomeus, who is a school psychologist. Dr. Paula Weerkamp - Bartholomeus has gained a lot of experience in the last 26 years with intensive work and education at the universities in Holland in the fields of psychology and special education and rehabilitation. Dr. Paula Weerkamp – Bartholomeus began the presentation of her work "Reattach: introduction of a new schema therapy", which is a multimodal approach for adults and children who suffer from different functional disabilities, as well as neuropsychological dysfunction. This treatment, despite the fact that it is used as a schema therapy, shows promising implementation in the treatment of people with autism.

The author found some taxonomic issues during the compilation of China Plant Catalogue Volume 1(3)(Liliaceae-Dilleniaceae), the authorities of two species from Liliaceae were wrongly treated and used, and we found it was necessary to explain and give new treatment for the two taxa. As a result, the incorrect later isonym, Lilium concolor var. pulchellum(Fisch.)Regel adopted in Flora Reipublicae Popularis Sinicae, should be corrected to Lilium concolor var. pulchellum (Fisch.)Baker. Tricyrtis pilosa Wall., adopted in Flora of China, should be replaced by Tricyrtis maculata(D. Don)J. F. Macbr., which is based on Compsoa maculata D. Don. [ABSTRACT FROM AUTHOR]

Primarye systemic AL amyloidosis is a rare hematologic disorder. The majority of the therapeutic guidelines are based on phase II studies or on retrospective comparisons and case series. Our study aimed to describe all the cases of primary AL amyloidosis reported in 2 military hospitals and to make a comparison between standard melphalan-dexamethasone protocol and new agents in first-line treatment of patients with this disease. We conducted a retrospective, descriptive and multicentric study of all patients with AL amyloidosis whose data were collected during the period July 2009-June 2016. Twenty five patients were enrolled in the study (12 patients treated with melphalan-dexamethasone and 13 with bortezomibbased protocol or lenalidomide-based protocol). There was no significant difference in the epidemiological, clinical and prognostic features between the 2 groups. After a median follow up of 40 months, median overall survival was 54 months in the melphalan-dexamethasone-treated group and 60 months in the new therapies-treated group (P = 0.98). Progression-free survival was 18 months in the standard treatment group vs 11 months in the 2nd group (p = 0.08). In our small case series we haven't found a superiority of the new therapies compared to the standard protocol. This result should be confirmed by a true prospective study, mainly because of the cost of these new molecules that are not always accessible, especially in developing countries. [ABSTRACT FROM AUTHOR]

Myelofibrosis (MF) is the most severe among the classical Philadelphia-negative myeloproliferative neoplasms that also include essential thrombocytemia and polycythemia vera. Myelofibrosis is characterized by numerous genetic lesions, often variously associated with each other, and by an aggressive clinical phenotype leading to severely reduced survival. Also, the inflammatory microenvironment plays a key role in disease initiation and progression. Because of the complexity of its pathogenesis and the variability of clinical features, MF is a disease that requires a personalized approach and remains orphan of curative treatments besides allogeneic transplantation. JAK2 inhibitors have marked a remarkable progress, because they alleviate systemic symptoms and reduce splenomegaly but have a limited effect on survival, on mutation load, and on marrow fibrosis. Here, we review the main contributing factors to MF pathogenesis and prognosis, focusing on how these factors relate to therapeutic choices. We discuss results from ongoing studies of JAK2 inhibitors and report on new therapeutic strategies that proved effective in early preclinical and clinical trials, including combination treatments, antifibrotic agents, and telomerase inhibitors. [ABSTRACT FROM AUTHOR]

Aims: To test the safety of new buprenorphine oral lyophilisate wafer ("bup-lyo") versus standard sub-lingual buprenorphine ("bup-SL").Design: Randomised (2:1) open-label study; opioid-dependent subjects; subsequent partial cross-over.Settings: Specialised clinical trials facility and addictions treatment facility.Participants: Opioid-dependent subjects (n = 36) commencing buprenorphine maintenance (personalised dose-titration) including patients co-using alcohol, cocaine and benzodiazepines (below thresholds).Measurements: Respiratory function (respiratory rate, pulse-oximetry); medication hold and dose adequacy; opiate withdrawal signs and symptoms; tablet disintegration times; treatment retention. Pharmacokinetics (PK) for plasma buprenorphine and norbuprenorphine (n = 11).Findings: Oral lyophilised buprenorphine ("bup-lyo") completely dissolved within 2 min for 58 vs. 5% for "bup-SL." Dose titration resulted in similar maintenance dosing (10.8 vs. 9.6 mg). There were no significant between-group differences in opiate-withdrawal phenomena, craving, adequacy of "hold," respiratory function. No serious adverse events (AEs), nor "severe" AEs, although more AEs and Treatment-Emergent AEs with "bup-lyo" (mostly "mild"). PK found greater bioavailability of buprenorphine with "bup-lyo" (but not norbuprenorphine).Conclusions: Orally disintegrating buprenorphine oral lyophilisate wafer disintegrated rapidly. No increased respiratory depression was found and clinically no difference between medications was observed. PK found substantially increased bioavailability of buprenorphine (but not of nor-buprenorphine) with "bup-lyo" relative to "bup-SL." In supervised dosing contexts, rapidly disintegrating formulations may enable wider buprenorphine prescribing. [ABSTRACT FROM AUTHOR]

Hansen's disease is an important public health problem and it is one of the important cause of disability in patients with nonhealing trophic ulcer in Hansen's disease, and also the long-term management of these trophic ulcers works out to be very costly. Reduction in the healing time would be a major step in the rehabilitation of these patients. Here, authors hereby present one such case of chronic plantar ulcer in Hansen's patient which was refractory to standard treatment like oral and topical antibiotics and daily dressings for more than six years. Hence, Platelet Rich Fibrin Matrix (PRFM) was applied along with adequate rest using Plaster of Paris (POP) cast. The wound was opened and the dried PRFM was cleared from the bed of the wound after 10 days. Procedure was repeated every third week. This led to dramatic healing of the ulcer with a reduction in wound diameter with no noticeable side-effects. [ABSTRACT FROM AUTHOR]

Background: Macrophages play a key role in all environmental conditions surrounding pregnancy. Coating of autologous red blood cells (RBCs) with polyclonal antibodies to Rh(D) antigen may result in an immunomodulation and improved outcome in Rh(D) positive women with recurrent pregnancy loss (RPL)., Methods: A total of 60 Rh(D) positive women (age 23 to 45 years) with a history of RPL and ineffective treatment with low molecular weight heparin (LMWH) and/or aspirin were included in this retrospective study. In addition to this treatment, Anti-D (300 μg) was given subcutaneously to each woman either prior to pregnancy and/or two times within 12 weeks of gestation., Results: Treatment with Anti-D in non-responders to heparin/aspirin resulted in successful pregnancies in 67% of all cases. The remaining women had only aborts (23%) or did not become pregnant (10%). None of the treated women has developed anemia due to this treatment or any other significant adverse reaction. The rate of successful pregnancies does not appear to be influenced by the administration of: Anti-D prior to pregnancy, age, thrombophilia or previous alive births., Conclusion: The improved outcome following the administration of Anti-D in women with RPL might be explained by immune modulations induced by different immune reactions including polarization of decidual macrophages. The results obtained in this study clearly indicate that Anti-D is safe and highly effective in treatment of Rh(D) positive women with RPL. However, further studies are required to support our results and to find out the optimal dose and timing of Anti-D administration.

Age-related macular degeneration (AMD) is the most common cause of visual loss in older populations in developed countries. In the pathogenesis of AMD, there are wide spectrum in which photoreceptors, retinal pigment epithelium and choroidal sheet take part. Many different factors including genetic factors as well as environmental factors are accused for the etiology. Confirming the importance of oxidative stress, complement pathway, end-toxin products of visual cycle in the pathogenesis of dry type AMD has led to development of novel therapeutic agents in this disease. This article reviews recently developed molecules that are subjected to experimental and clinical trials for the treatment of dry type AMD in addition to ongoing treatment modalities. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED), keratoconjunctivitis sicca or dysfunctional tear syndrome, is the most prevalent ophthalmic disease which affects a substantial segment of people worldwide with increasing frequency. It is considered a multifactorial disease of the ocular surface and tear film, characterized by a variation of signs and symptoms. The symptoms range from mild to severe itching, burning, irritation, eye fatigue, and ocular inflammation that may lead to potential damage to the cornea, conjunctiva and even vision loss. Correspondingly, depending on the different manifestations and pathophysiology, the treatment must be tailored specifically to each patient by targeting the specific mechanisms implicated in their disease. Currently, there are several medical products and techniques available or under investigation for the treatment of DED. The present article focused on the pathophysiology of DED, the new diagnostic approach and the recently developed drug delivery systems or devices reducing the progress of the disease and treating the causes. [Display omitted] [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Numerous scientific publications have confirmed that percutaneous laser thermal ablation ( LTA) represents a possible therapeutic option in selected patients with benign thyroid nodules. A study was carried out to evaluate the feasibility of adopting the LTA technique to treat benign thyroid nodules in a teaching and research hospital in northern Italy. Methods A cost analysis from a company's perspective determined the impact of adoption of the new technique on the overall Hospital budget, considering currently available equipment, infrastructure and personnel, equipment costs and treatment tariffs. Results The cost analysis shows that, strictly from an economic point of view, any provision of the LTA technique will result as a loss on the Hospital's balance sheet. However, it does not estimate the extent of the impact on the overall budget because it did not evaluate the savings that such a technique would make with respect to alternative therapeutic treatments. Therefore, the Hospital policy management decided to extend the current agreement with a private authorized health care structure that already carries out LTA. Also, although difficult to express in economic terms, this new technique would undoubtedly raise the profile and enhance the reputation of the Hospital. Conclusions Using the new technique in these patients could cut costs for the entire regional health care system, widen the experience of the Hospital's endocrinology team and offer the potential for the procedure also to be provided by operators on a freelance basis within the Hospital. [ABSTRACT FROM AUTHOR]

Background: Pilonidal sinus is a common condition often managed with invasive surgery associated with a significant morbidity and often a prolonged recovery time. Fibrin glue has been used in our institution as an alternative to conventional surgery. The purpose of this study was to perform a service evaluation of patient satisfaction and recovery following fibrin glue treatment for pilonidal sinus. Methods: All pilonidal glue procedures for a single surgeon were identified from theatre and consultant diary records from March 2007 to September 2011. A questionnaire was sent by post to all patients. Patient satisfaction, time to return to normal activities, the need for further procedures and whether they would recommend a glue procedure to a friend were evaluated. Results: Ninety-three patients were identified, accounting for a total of 119 glue procedures and 57/93 responses were received (61 %). The median age of respondents was 26 (17-70) years. Seventy-nine per cent ( n = 45) were satisfied, pleased or very pleased with the result of their procedure. Fifty-four per cent ( n = 31) were back to normal activities within a week with a further 17 % ( n = 10) back to normal activities within 2 weeks. Seventy-four per cent ( n = 42) required no further treatment. Of the 15 patients requiring a further procedure, 3 went on to have a repeat glue treatment which resulted in complete healing. Eighty-two per cent ( n = 47) would recommend a glue procedure to a friend. Conclusions: Fibrin gluing for pilonidal sinus should be considered as first-line treatment for most pilonidal sinuses. It has a high level of patient satisfaction and allows a rapid return to normal activities in this group of patients of working age. [ABSTRACT FROM AUTHOR]

Abstract: Background: The number of patients with mitochondrial fatty acid oxidation (FAO) disorders is recently becoming larger with the spread of newborn mass screening. Despite the advances in metabolic and molecular characterization of FAO disorders, the therapeutic studies are still limited. It was reported recently that bezafibrate (BEZ), an agonist of peroxisome proliferating activator receptor (PPAR), can restore FAO activity in cells from carnitine palmitoyltransferase-2 (CPT2) and very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiencies as well as clinical symptoms in the adult patients. Methods: In this study, the therapeutic effect of BEZ was determined by in vitro probe acylcarnitine (IVP) assay using cultured fibroblasts and tandem mass spectrometry on various FAO disorders. The clinical trial of BEZ treatment for a boy with the intermediate form of glutaric acidemia type 2 (GA2) was also performed. Results: The effect of BEZ was proven in cells from various FAO disorders including GA2, deficiencies of VLCAD, medium‐chain acyl-CoA dehydrogenase, CPT2, carnitine acylcarnitine translocase and trifunctional protein, by the IVP assay. The aberrantly elevated long- or medium-chain acylcarnitines that are characteristic for each FAO disorder were clearly corrected by the presence of BEZ (0.4mmol/L) in culture medium. Moreover, daily administration of BEZ in a 2-year-old boy with GA2 dramatically improved his motor and cognitive skills, accompanied by sustained reduction of C4, C8, C10 and C12 acylcarnitines in blood, and normalized the urinary organic acid profile. No major adverse effects have been observed. Conclusion: These results indicate that BEZ could be a new treatment option for FAO disorders. [Copyright &y& Elsevier]

Febuxostat, a novel, orally administered, potent, non-purine analogue, xanthine oxidase / xanthine dehydrogenase inhibitor in the management of hyperuricemia in patients with gout & chronic tophaceous gout. It completely inhibits activity of xanthine oxidase enzyme by obstructing substrate binding but has minimal effects on activity of other enzymes in purine metabolism. It inhibits both oxidized and reduced forms of xanthine oxidase. Febuxostat is more potent than allopurinol in inhibiting xanthine oxidase. Recommended dosage in hyperuricemia and gout is 40 mg or 80 mg OD. Febuxostat, at a daily dose of 80 mg or 120 mg, was more effective than allopurinol at the commonly used fixed daily dose of 300 mg in lowering serum urate, significant number of patients achieves target levels of serum uric acid (< 6 mg/dl) with febuxostat as compared to allopurinol and uric acid ↓ effect is sustained with febuxostat. No dose adjustments are required in hepatic impairment, renal impairment or elderly patient. [ABSTRACT FROM AUTHOR]

OBJECTIVE Brain damage is universal in the rare survivor of unwitnessed cardiac arrest. Non-pulsatile-controlled cerebral reperfusion offsets this damage, but may simultaneously cause brain oedema when delivered at the required the high mean perfusion pressure. This study analyses pulsatile perfusion first in control pigs and then using controlled reperfusion after prolonged normothermic brain ischaemia (simulating unwitnessed arrest) to determine if it might provide a better method of delivery for brain reperfusion. METHODS Initial baseline studies during isolated brain perfusion in 12 pigs (six non-pulsatile and six pulsatile) examined high (750 cc/min) then low (450 cc/min) fixed flow before and after transient (30 s) ischaemia, while measuring brain vascular resistance and oxygen metabolism. Twelve subsequent pigs underwent 30 min of normothermic global brain ischaemia followed by either uncontrolled reperfusion with regular blood (n = 6) or pulsatile-controlled reperfusion (n = 6) before unclamping brain inflow vessels. Functional neurological deficit score (NDS; score: 0, normal; 500, brain death) was evaluated 24 h post-reperfusion. RESULTS High baseline flow rates with pulsatile and non-pulsatile perfusion before and after transient ischaemia maintained normal arterial pressures (90–100 mmHg), surface oxygen levels IN Vivo Optical Spectroscopy (INVOS) and oxygen uptake. In contrast, oxygen uptake fell after 30 s ischaemia at 450 cc/min non-pulsatile flow, but improved following pulsatile perfusion, despite its delivery at lower mean cerebral pressure. Uncontrolled (normal blood) reperfusion after 30 min of prolonged ischaemia, caused negligible INVOS O2 uptake (<10–15%), raised conjugated dienes (CD; 1.75 ± 0.15 A233 mn), one early death, multiple seizures, high NDS (243 ± 16) and extensive cerebral infarcts (2,3,5-triphenyl tetrazolium chloride stain) and oedema (84.1 ± 0.6%). Conversely, pulsatile-controlled reperfusion pigs exhibited normal O2 uptake, low CD levels (1.31 ± 0.07 A233 mn; P < 0.01 versus uncontrolled reperfusion), no seizures and a low NDS (32 ± 14; P < 0.001 versus uncontrolled reperfusion); three showed complete recovery (NDS = 0) and all could sit and eat. Post-mortem brain oedema was minimal (81.1 ± 0.5; P < 0.001 versus uncontrolled reperfusion) and no infarctions occurred. CONCLUSIONS Pulsatile perfusion lowers cerebral vascular resistance and improves global O2 uptake to potentially offset post-ischaemic oedema following high-pressure reperfusion. The irreversible functional and anatomic damage that followed uncontrolled reperfusion after a 30-min warm global brain ischaemia interval was reversed by pulsatile-controlled reperfusion, as its delivery resulted in consistent near complete neurological recovery and absent brain infarction. [ABSTRACT FROM AUTHOR]

Copyright of Medicina y Seguridad del Trabajo is the property of Escuela Nacional de Medicina del Trabajo - Instituto de Salud Carlos III and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Pneumologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PURPOSE: The mayor symptoms of chronic anal fissure are permanent pain, intense pain during defecation that lasts for hours, blood in the stools, and sphincter cramps. It is subsequent to formation of fibrosis infiltrate that leads to an increased anal tone with poor healing tendency. This vicious circle leads to fissure recurrence and chronicity. This study was designed to show the efficacy of gonyautoxin infiltration in healing patients with anal fissures. METHODS: Gonyautoxin is a paralyzing phytotoxin produced by dinoflagellates. Fifty recruited patients received clinical examination, including proctoscopy and questionnaire to evaluate the symptoms. Anorectal manometries were performed before and after toxin injection. Doses of 100 units of gonyautoxin in a volume of 1 ml were infiltrated into both sides of the anal fissure in the internal anal sphincter. RESULTS: Total remission of acute and chronic anal fissures were achieved within 15 and 28 days respectively. Ninety-eight percent of the patients healed before 28 days with a mean time healing of 17.6 ± 9 days. Only one relapsed during 14 months of follow-up. Neither fecal incontinence nor other side effects were observed. All patients showed immediate sphincter relaxation. The maximum anal resting pressures recorded after two minutes decreased to 56.2 ± 12.5 percent of baseline. CONCLUSIONS: Gonyautoxin breaks the vicious circle of pain and spasm that leads to anal fissure. This study proposes gonyautoxin anal sphincter infiltration as safe and effective alternative therapeutic approach to conservative, surgical, and botulinum toxin therapies for anal fissures. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) has a high prevalence worldwide. Li et al performed a well-designed study on the efficacy of modified Xiaochaihu decoction (MXD) for GERD, which showed that MXD is an optional therapy for GERD beyond proton pump inhibitors (PPIs). The herbal granule administration mode minimized the bias from traditional herbal formula in clinical trials. One limitation of that study was that it lacked records of side effects and rescue medication. As a chronic disease with recurrent symptoms, GERD rehabilitation requires prolonged observation of the clinical course with MXD therapy., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)