Reflectance Confocal Microscopy and Dermoscopy of Facial Pigmented and Non-Pigmented Actinic Keratosis Features before and after Photodynamic Therapy Treatment.

Actinic keratosis (AK), due to its widespread prevalence, as well as the possibility of progression to an invasive form of squamous cell carcinoma, requires treatment regardless of the clinical stage. New imaging techniques, such as in vivo reflectance confocal microscopy (RCM), significantly increase the accuracy of diagnosis and allow noninvasive evaluation of the therapeutic efficacy of the ongoing treatment. Our objective was to evaluate the prevalence of specific (video)dermoscopy and RCM features of pigmented and classical subtypes of AK before and after photodynamic therapy (PDT) treatment. We included patients with facial grade II AKs (25 pigmented, 275 non-pigmented) were included in the study. Skin lesions were evaluated by (video)dermoscopy and RCM at the baseline and three months after PDT. In classic AK, the most frequent dermoscopic findings were fine wavy vessels (96%), scale (92%), microerosions (48%), and "strawberry" pattern (36%), while pigmented AK was characterized mostly by "rhomboidal pattern" (80%), scale (60%), white globules (48%), "jelly sign", and superficial pigmentation (40%). RCM's most characteristic classic AK findings were abnormal honeycomb pattern in the spinous layer, epidermal inflammatory infiltrate, and solar elastosis that were present in 96% of lesions. Pigmented AKs presented mostly with dark central areas of parakeratosis (72%), mottled pigmentation (72%), dermal inflammatory infiltrate (64%), solar elastosis (60%), and abnormal honeycomb pattern in the spinous layer (56%). Dermoscopically, PDT resulted in complete disappearance of the "rhomboidal pattern" in both classical and pigmented AKs, "starburst pattern" and "jelly sign" in classical AKs, and inner gray halo, "rosette sign" and central crust in pigmented AKs. Three months after one PDT session, RCM evaluation showed mostly solar elastosis in both classical and pigmented AK subtypes, epidermal inflammatory infiltrate in classical AKs, and dermal inflammatory infiltrate in pigmented AKs. New noninvasive imaging techniques such as RCM and (video)dermoscopy can help practitioners better visualize the efficacy of the ongoing PDT treatment in either classical or pigmented AK subtypes.

Photodynamic Therapy in Pigmented Basal Cell Carcinoma-A Review.

This review summarizes the effectiveness of photodynamic therapy (PDT) in the treatment of the pigmented subtype of basal cell carcinoma (BCC) based on the current literature. PDT is a light-activated treatment, non-invasive, that selectively destroys tumor cells and tissues via the interaction of a photosensitizer, light, and molecular oxygen. It can induce cancer cell death through direct tumor vascular damage or via the induction of immune response. However, human skin is also an absorption and scattering medium since it contains hemoglobin and melanin that act as chromophores. Eumelanin can be considered a light-absorber and an intracellular antioxidant that can neutralize PDT-induced ROS and, therefore, decrease PDT success. Various factors, including tumor depth, the degree of pigmentation in malignant cells, and the individual's skin phototype, can impact the outcome of this intricate biochemical process. It has been widely recognized that PDT exhibits limited efficacy in the treatment of pigmented lesions. However, new combination techniques such as curettage or debulking before PDT show promising results in the treatment of pigmented BCC.

Photodynamic Therapy is an Effective Treatment of Facial Pigmented Actinic Keratosis.

BACKGROUND: Actinic keratosis (AK), or solar keratosis, is a precancerous condition of the skin, mainly caused by excessive and chronic exposure to ultraviolet radiation. Pigmented AK (pAK) is a rare variant of AK. Photodynamic therapy (PDT) is widely used to treat the classical variant of AK, but very limited data are available on the use of PDT in patients with pAK. The objective of this study was to assess the usefulness of PDT in the treatment of pAK. METHODS: The study included 16 patients with 20 pAK lesions treated with PDT. All skin lesions were clinically and dermatoscopically assessed for typical features characteristic of pAK. Reflectance confocal microscopy (RCM) was also used to assess keratinocyte atypia, confirm pAK diagnosis, and rule out other disease entities. RESULTS: After three PDT sessions, the complete resolution of all clinical features of pAK was observed in 80% of the studied lesions. Dermatoscopically, 65% of the lesions achieved 100% response and no cellular atypia was seen in the follow-up RCM images of 85% of lesions. CONCLUSIONS: Photodynamic therapy is an effective treatment modality for pAK in fair-skinned individuals.

Resveratrol as a factor preventing skin aging and affecting its regeneration.

Resveratrol, a compound belonging to polyphenols, besides its action on the cardiovascular system, affects also wound healing, regeneration, and photoaging of the skin. By interactions with numerous substances and pathways, e.g. MAPK, MAPKK, FOXO3, TGF or metalloproteinase 1, it protects the skin against the harmful effects of type B ultraviolet radiation, which is the main factor in the skin aging processes. It also enhances collagen synthesis by activating the oestrogen receptor and reduces wrinkles. In damaged tissues, it accelerates skin regeneration and healing by activating, among others, VEGF. Based on the review of the literature, there is no doubt that resveratrol has the potential to be used in cosmetology, dermatology and plastic surgery. It can be used as a compound of anti-aging products or as a topical treatment of scars and wounds. In the future this polyphenol might be applied in pharmacotherapy of many dermatoses.

YY1 Is a Key Player in Melanoma Immunotherapy/Targeted Treatment Resistance.

Malignant melanoma, with its increasing incidence and high potential to form metastases, is one of the most aggressive types of skin malignancies responsible for a significant number of deaths worldwide. However, melanoma also demonstrates a high potential for induction of a specific adaptive anti-tumor immune response being one of the most immunogenic malignancies. Yin Yang 1 (YY1) transcription factor is essential to numerous cellular processes and the regulation of transcriptional and posttranslational modifications of various genes. It regulates programmed cell death 1 (PD1) and lymphocyte-activation gene 3 (LAG3) by binding to its promoters, as well as suppresses both Fas and TRAIL by negatively regulating DR5 transcription and expression and interaction with the silencer region of the Fas promoter, rendering cells resistant to apoptosis. Moreover, YY1 is considered a master regulator in various stages of embryogenesis, especially in neural crest stem cells (NCSCs) survival and proliferation as it acts as transcriptional repressor on cancer stem cells-related transcription factors. In addition, YY1 increases the metastatic potential of melanoma through negative regulation of microRNA-9 (miR-9) expression, acts as a cofactor of transcription factor EB (TFEB) and contributes to autophagy regulation, mainly due to increased transcription of genes related to autophagy and lysosome biogenesis. Therefore, focusing on the detailed biology and administration of therapies that directly target YY1 or crosstalk pathways in malignant melanoma could facilitate the development of new and more effective treatment strategies and improve patients' outcomes.

COVID-19 and Postural Control-A Stabilographic Study Using Rambling-Trembling Decomposition Method.

Background and Objectives: Some respiratory viruses demonstrate neurotropic capacities. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently taken over the globe, causing coronavirus disease 2019 (COVID-19). The aim of the study was to evaluate the impact of COVID-19 on postural control in subjects who have recently recovered from the infection. Materials and Methods: Thirty-three convalescents who underwent COVID-19 within the preceding 2-4 weeks, and 35 healthy controls were enrolled. The ground reaction forces were registered with the use of a force platform during quiet standing. The analysis of the resultant center of foot pressure (COP) decomposed into rambling (RAMB) and trembling (TREMB) and sample entropy was conducted. Results: Range of TREMB was significantly increased in subjects who experienced anosmia/hyposmia during COVID-19 when the measurement was performed with closed eyes (p = 0.03). In addition, subjects who reported dyspnea during COVID-19 demonstrated significant increase of length and velocity of COP (p < 0.001), RAMB (p < 0.001), and TREMB (p < 0.001), indicating substantial changes in postural control. Conclusions: Subjects who had experienced olfactory dysfunction or respiratory distress during COVID-19 demonstrate symptoms of balance deficits after COVID-19 recovery, and the analysis using rambling-trembling decomposition method might point at less efficient peripheral control. Monitoring for neurological sequelae of COVID-19 should be considered.

Resveratrol in the treatment of neuroblastoma: a review.

Resveratrol, polyphenol naturally occurring in grapes or nuts, has anti-cancer properties in the treatment of neuroblastoma - the most common childhood solid tumor. It affects cancer cells by increasing apoptosis, inducing cell necrosis and reducing tumor mass. Mechanism of action - (1) converting procaspases, mainly procaspases three and nine into active forms - caspases, (2) blocking kinases, and also (3) leading the cell to the S-cell cycle, where it is most effective while increasing the concentration of cyclin E and lowering the concentration of p21 protein. In vitro, as well as, rodent animal models studies are available and show promising results. Therapeutic doses, currently within 10-100 µmol/L, are also being tested, as well as other forms of resveratrol, such as its trans-4,4'-dihydroxystilbene analog and polyphenol lipoconjugates. In our review, we presented the known molecular mechanisms of polyphenol anti-tumor activity against neuroblastoma and discussed the studies confirming its effectiveness.

Effect of Mirabegron on the Body's Exercise Capacity: A Review.

Mirabegron is a ß3-agonist drug approved by the FDA for use in 2012 and administered in overactive bladder. Activating of adrenergic receptors leads to the relaxation of the detrusor muscle. According to the latest research and reports, it also has lipolytic activity, affecting the reduction of mainly brown adipose tissue (BAT) but also of white adipose tissue (WAT). This results in a decrease in body weight and triglyceride concentration and an increase in lipoprotein lipase activity, as well as in the level of free fatty acids or adipokines in the plasma. The drug indirectly participates in the regulation of carbohydrate metabolism, influencing the increase in insulin sensitivity, supporting cellular uptake of glucose. However, due to the elevation of blood pressure and pulse, as a supplement, the drug should be taken with care to avoid cardiovascular complications. In our review, below, we present a description and discussion of available studies in terms of mirabegron action on the exercise capacity of the body in the context of its potential use as a doping agent.

Pridopidine in the treatment of Huntington's disease.

Huntington's disease (HD) is a highly common inherited monogenic neurodegenerative disease, and the gene responsible for its development is located in the 4p16.3 chromosome. The product of that gene mutation is an abnormal huntingtin (Htt) protein that disrupts the neural conduction, thus leading to motor and cognitive disorders. The disease progresses to irreversible changes in the central nervous system (CNS). Although only a few drugs are available to symptomatic treatment, 'dopamine stabilizers' (as represented by the pridopidine) may be the new treatment options. The underlying causes of HD are dopaminergic conduction disorders. Initially, the disease is hyperkinetic (chorea) until it eventually reaches the hypokinetic phase. Studies confirmed a correlation between the amount of dopamine in the CNS and the stage of the disease. Pridopidine has the capacity to be a dopamine buffer, which could increase or decrease the dopamine content depending on the disease phase. A research carried out on animal models demonstrated the protective effect of pridopidine on nerve cells thanks to its ability to alter the cortical glutamatergic signaling through the N-methyl-D-aspartate (NMDA) receptors. Studies on dopamine stabilizers also reported that pridopidine has a 100-fold greater affinity for the sigma-1 receptor than for the D2 receptor. Disturbances in the activity of sigma-1 receptors occur in neurodegenerative diseases, including HD. Their interaction with pridopidine results in the neuroprotective effect, which is manifested as an increase in the plasticity of synaptic neurons and prevention of their atrophy within the striatum. To determine the effectiveness of pridopidine in the treatment of HD, large multicenter randomized studies such as HART, MermaiHD, and PRIDE-HD were carried out.

Endocrine systems of the skin.

Apart from its protective function, the skin is also both hormonally and metabolically active. Many hormones are produced in the skin and the regulation of these changes is controlled, as are other organs, by the pituitary gland and hypothalamus. Under the influence of stress factors such as ultraviolet radiation, many reactions are stimulated. After exposure to light in keratinocytes apart from eumelanin, also proopiomelanocortin, dopamine, and opioid substances - ß-endorphins are produced. The skin also has a hypothalamic-pituitary-adrenal axis homolog. A corticotropin-releasing hormone is produced and reacts with its skin receptors that lead to, among others, increasing vascular permeability or induce keratinocytes differentiation. A similar homologous system found in skin structures is the hypothalamic-pituitary-thyroid axis, which is expressed by the presence of e.g. thyroid-stimulating hormone (TSH) receptors or thyroglobulin genes. Our review presents selected hormonal skin systems, reactions within them and their products.

Predicted difficulties, educational needs, and interest in working in end of life care among nursing and medical students.

BACKGROUND: The need to provide care for the dying patient and his/her family may occur in every medical setting. Newly graduated nurses and physicians should therefore be prepared to deliver it at a high-quality level. OBJECTIVES: To explore (a) the primary difficulties participants anticipate they will encounter whilst working with dying patients, (b) their interest in developing competencies in caring for dying patients, and (c) their interest in working in palliative/hospice settings or with dying patients in the future. DESIGN: A cross-sectional study. SETTINGS: A medical university in Poland. PARTICIPANTS: Convenience sample of nursing (=112) and medical students (=101) at the end of their undergraduate education. METHODS: Questionnaire distributed online and in hard-copy format. RESULTS: Half of the participants anticipated experiencing various emotional and professional difficulties in caring for dying individuals, especially medical students. These difficulties pertained mostly the reaction of family members to the patient's death, addressing the psychological needs of the dying person, and coping with his/her own emotions when dealing with the patient's death. Students reported that working with dying patients could cause occupational stress - more so among medical students. The majority of them showed an interest in improving knowledge regarding palliative care and also in this case this was mostly true of medical rather than nursing students. However, more than half of the participants preferred avoiding work in palliative/hospice settings, with no differences between the two groups. Participants attributed this attitude to two factors: (a) the desire to avoid negative emotions and stress that could be triggered by dealing with death and dying; and (b) because they felt they lacked the required skills and personal abilities to handle such situations. CONCLUSIONS: Undergraduate curricula that include strategies for coping with negative emotions associated with facing the process of death and dying should be developed. Interprofessional education should be encouraged, especially regarding the psychosocial aspects of end-of-life care.

Comparison of the effectiveness of the Montreal Cognitive Assessment 7.2 and the Mini-Mental State Examination in the detection of mild neurocognitive disorder in people over 60 years of age. Preliminary study. / Porównanie skutecznosci Montreal Cognitive Assessment 7.2 z Mini-Mental State Examination w wykrywaniu lagodnych zaburzen neuropoznawczych u osób po 60. roku zycia. Doniesienie wstepne.

OBJECTIVES: Analysis of reliability of the Polish version of the MoCA 7.2 vs. the MMSE in mild NCD detecting, while taking into consideration the sensitivity and specificity of cut-off points for each type of education. METHODS: Cross-sectional study was conducted at the Department of Geriatrics, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun. The study was conducted between September 2014 and December 2015. The study involved 131 participants, including 54 people assigned to the group without NCD and 77 to the group with mild NCD. Recruitment for both groups was performed on the basis of specific inclusion and exclusion criteria. RESULTS: Mean scores of the MoCA 7.2 and the MMSE showed a statistically significant difference between the groups with and without mild NCD. The optimal cut-off point on the MoCA scale for mild NCD was 24/25. The optimal cut-off point on the MMSE scale for mild NCD was 28/29. In the ROC curve analysis, area under the curve (AUC) for the MoCA was significantly greater than the AUC for the MMSE. CONCLUSIONS: The MoCA 7.2 detect mild NCD with greater sensitivity than the MMSE. In the case of this tool, we propose the use of 24/25 cut-off point which has a higher sensitivity than the recommended 25/26 cut-off point. The MoCA 7.2 therefore can be used by primary healthcare and in the geriatric practice as a screening tool in detecting early cognitive impairment.

Systemic lupus erythematosus of the urinary tract: focus on lupus cystitis.

Systemic lupus erythematosus (SLE) frequently manifests as urinary tract disease, most commonly in the form of lupus nephritis. Bladder involvement in the disease course takes a subclinical form and may affect both children and adults. Lupus cystitis can precede SLE diagnosis and may present with very unspecific urinary and digestive tract symptoms or no symptoms at all. The exact mechanism of bladder inflammation in lupus is not fully understood; however, histopathological studies suggest a possible role of immune complex-mediated small vessel vasculitis. Lupus cystitis is a rare SLE manifestation, but poses a challenge for physicians, due to its complex diagnostics and treatment.

Is the Montreal Cognitive Assessment (MoCA) test better suited than the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) detection among people aged over 60? Meta-analysis. / Czy test Montreal Cognitive Assessment (MoCA) moze byc skuteczniejszy od powszechnie stosowanego Mini-Mental State Examination (MMSE) w wykrywaniu lagodnych zaburzen funkcji poznawczych u osób po 60. roku zycia? Metaanaliza.

OBJECTIVES: Screening tests play a crucial role in dementia diagnostics, thus they should be very sensitive for mild cognitive impairment (MCI) assessment. Nowadays, the MiniMental State Examination (MMSE) is the most commonly used scale in cognitive function evaluation, albeit it is claimed to be imprecise for MCI detection. The Montreal Cognitive Assessment (MoCA), was created as an alternative method for MMSE. Aim. MoCA vs. MMSE credibility assessment in detecting MCI, while taking into consideration the sensitivity and specificity by cut-off points. METHODS: A systematic literature search was carried out by the authors using EBSCO host Web, Wiley Online Library, Springer Link, Science Direct and Medline databases. The following medical subject headings were used in the search: mild cognitive impairment, mini-mental state examination, Montreal cognitive assessment, diagnostics value. Papers which met inclusion and exclusion criteria were chosen to be included in this review. At the end, for the evaluation of MoCA 20, and MMSE 13 studies were qualified. Research credibility was established by computing weighted arithmetic mean, where weight is defined as population for which the result of sensitivity and specificity for the cut-off point was achieved. The cut-offs are shown as ROC curve and accuracy of diagnosis for MoCA and MMSE was calculated as the area under the curve (AUC). RESULTS: ROC curve analysis for MoCA demonstrated that MCI best detection can be achieved with a cut-off point of 24/25 (n = 9350, the sensitivity of 80.48% and specificity of 81.19%). AUC was 0.846 (95% CI 0.823-0.868). For MMSE, it turned out that more important cut-off was of 27/28 (n = 882, 66.34% sensitivity and specificity of 72.94%). AUC was 0.736 (95% CI 0.718-0.767). CONCLUSIONS: MoCA test better meets the criteria for screening tests for the detection of MCI among patients over 60 years of age than MMSE.