New Applications of Photodynamic Therapy in the Management of Candidiasis.

The most important aetiological agent of opportunistic mycoses worldwide is Candida spp. These yeasts can cause severe infections in the host, which may be fatal. Isolates of Candida albicans occur with greater frequency and variable resistance patterns. Photodynamic therapy (PDT) has been recognised as an alternative treatment to kill pathogenic microorganisms. PDT utilises a photosensitizer, which is activated at a specific wavelength and oxygen concentration. Their reaction yields reactive oxygen species that kill the infectious microorganism. A systematic review of new applications of PDT in the management of candidiasis was performed. Of the 222 studies selected for in-depth screening, 84 were included in this study. All the studies reported the antifungal effectiveness, toxicity and dosimetry of treatment with antimicrobial PDT (aPDT) with different photosensitizers against Candida spp. The manuscripts that are discussed reveal the breadth of the new applications of aPDT against Candida spp., which are resistant to common antifungals. aPDT has superior performance compared to conventional antifungal therapies. With further studies, aPDT should prove valuable in daily clinical practice.

Biomarkers in Glycogen Storage Diseases: An Update.

Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. In this study we reviewed the literature from 1977 to 2020 concerning GSDs, biomarkers, and metabolic imbalances in the symptoms of some GSDs. Most of the reported studies were performed with very few patients. Classification of emerging biomarkers between different types of diseases (hepatics GSDs, McArdle and PDs and other possible biomarkers) was done for better understanding. Calprotectin for hepatics GSDs and urinary glucose tetrasaccharide for Pompe disease have been approved for clinical use, and most of the markers mentioned in this review only need clinical validation, as a final step for their routine use. Most of the possible biomarkers are implied in hepatocellular adenomas, cardiomyopathies, in malfunction of skeletal muscle, in growth retardation, neutropenia, osteopenia and bowel inflammation. However, a few markers have lost interest due to a great variability of results, which is the case of biotinidase, actin alpha 2, smooth muscle, aorta and fibroblast growth factor receptor 4. This is the first review published on emerging biomarkers with a potential application to GSDs.

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis.

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript.

Biomarkers of Inflammation in Obesity-Psoriatic Patients.

Psoriasis is a common chronic inflammatory multisystemic disease with a complex pathogenesis consisting of genetic, immunological, and environmental components. It is associated with a number of comorbidities, including diabetes, metabolic syndrome, obesity, and myocardial infarction. In addition, the severity of psoriasis seems to be related to the severity of obesity. Patients with higher levels of obesity show poorer response to systemic treatments of psoriasis. Several studies have demonstrated that white adipose tissue is a crucial site of the formation of proinflammatory adipokines such as leptin, adiponectin, and resistin and classical cytokines such as interleukin- (IL-) 6 and tumour necrosis factor-α. In psoriasis, due to the proliferation of Th1, Th17, and Th22 cells, IL-22, among others, is produced in addition to the abovementioned cytokines. With respect to leptin and resistin, both of these adipokines are present in high levels in obese persons with psoriasis. Further, the plasma levels of leptin and resistin are related to the severity of psoriasis. These results strongly suggest that obesity, through proinflammatory pathways, is a predisposing factor to the development of psoriasis and that obesity aggravates existing psoriasis. Different inflammatory biomarkers link psoriasis and obesity. In this paper, the most important ones are described.

Two different scenarios of advanced basal cell carcinomas during the use of vismodegib: Cases of oral administration and administration directly to the stomach.

No effective therapy exists for locally advanced or metastatic basal cell carcinoma (BCC). Vismodegib is a small molecule that is an inhibitor of the hedgehog pathway. An oral treatment to inactivate Smoothened would be a new therapeutic approach to treat advanced BCC. We studied two patients with advanced BCC and analysed variables, including age and sex of the patient, tumour location and size, time of evolution and nature of the tumour (primary or recurrent), type of treatment, route of administration, treatment duration, and treatment response. The most important side effects were determined. The patients received oral vismodegib (150 mg) daily. The male patient experienced difficulty in swallowing, which necessitated administration of the drug using a percutaneous endoscopic gastrostomy tube. In the first few months of treatment, both patients displayed significant improvement with almost complete disappearance of the skin lesions in one case and more than 50% in the other case. The median duration of response was 7.6 months. The side effects observed were of slight relevance; alopecia, dysgeusia, asthenia, and fatigue were easily resolved with the appropriate treatments. Vismodegib appears to be well tolerated and effective in treating advanced and metastatic BCC. No serious adverse events were reported.

Protein biomarkers of mood disorders.

Psychiatric evaluation presents a significant challenge because it conceptually integrates the input from multiple psychopathological approaches. Recent technological advances in the study of protein structure, function, and interactions have provided a breakthrough in the diagnosis and treatment of mood disorders (MD), and have identified novel biomarkers to be used as indicators of normal and disease states or response to drug treatment. The investigation of biomarkers for psychiatric disorders, such as enzymes (catechol-O-methyl transferase and monoamine oxidases) or neurotransmitters (dopamine, serotonin, norepinephrine) and their receptors, particularly their involvement in neuroendocrine activity, brain structure, and function, and response to psychotropic drugs, should facilitate the diagnosis of MD. In clinical settings, prognostic biomarkers may be revealed by analyzing serum, saliva, and/or the cerebrospinal fluid, which should promote timely diagnosis and personalized treatment. The mechanisms underlying the activity of most currently used drugs are based on the functional regulation of proteins, including receptors, enzymes, and metabolic factors. In this study, we analyzed recent advances in the identification of biomarkers for MD, which could be used for the timely diagnosis, treatment stratification, and prediction of clinical outcomes.