TLR2 activation in corneal stromal cells by Staphylococcus aureus‐induced keratitis

The Toll‐Like Receptor 2 (TLR2) plays an active and important role in Staphylococcus aureus‐induced chronic ocular inflammation. The aim of this study was to investigate the expression and function of TLR2 of corneal stromal cells in ex vivo rabbit model of S. aureus keratitis. Corneal buttons with sclera rims placed in an ex vivo air‐interface organ culture were assigned to two groups: corneas with epithelial and stromal abrasions. Each group was then divided into two sub‐groups exposed to UV‐killed S. aureus ATCC 6538P and S. aureus ATCC 29213, respectively. TLR2 and IL‐8 mRNA expressions were analyzed by quantitative real‐time RT‐PCR. TLR2 localization was visualized by immunofluorescence analysis. The results demonstrated that TLR2 and IL‐8 mRNA were significantly expressed in the stromal cells of the groups exposed to S. aureus strains. Moreover, it has been demonstrated that, after corneal injury, keratocytes differentiated into myofibroblasts became able to express TLR2 only when exposed to S. aureus. Identification of mechanisms regulation of corneal TLRs may lead to development of therapeutic interventions aimed at controlling corneal inflammation. This ex vivo model can be used to clarify the molecular events of bacterial‐corneal tissue interactions and their inflammatory consequences.     

Functional and Patient Reported Outcomes Following Total Glans Resurfacing

BackgroundWhilst there is a trend away from aggressive nonorgan sparing surgical treatments for malignant penile disease, a variety of penile preservation options exist but functional outcomes and patient reported outcomes (PROs) in this area are poorly reported to date.AimThe aim of this study is to report functional outcomes and PROs of total glans resurfacing (TGR) in a consecutive series of patients with lichen sclerosis (LS) or localized penile cancer (PC).MethodsFrom 2004 to 2018 a consecutive series of patients underwent TGR for the management of LS or localized PC in a tertiary referral network. Patient clinical records and operative notes were retrospectively reviewed. Statistical analysis was conducted with Stata 12.OutcomesUrinary and sexual outcomes were recorded utilizing both the International Index of Erectile Function (IIEF) and International Prostate Symptom Score (IPSS) validated questionnaires while PROs were extrapolated from a 5-item “ad hoc” telephone questionnaire administered at 1 year post procedure.Results37 consecutive patients were enrolled. Histology results demonstrated LS in 16 patients, with the remaining 21 having a diagnosis of PC. The most common reasons for patient presentation were local pain (32.4%), pruritus (37.8%) and bleeding (29.7%). Median follow-up was 22 (IQR 13–77) months. Median age was 62 (IQR 55–68).Neither of the questionnaires assessing urinary and sexual function showed any significant deterioration after surgery. Glans sensitivity was fully maintained in 89.2% of cases. 94.5% of patients reported to be fully satisfied with the aesthetic appearance of the penis and would consider undergoing the same procedure again if necessary. 91.9% of patients would recommend the same procedure to someone else. An overall improvement of the quality of life was reported by 86.4% of patients.Clinical ImplicationsTGR should be considered a treatment of choice for selected cases of benign or malignant penile lesionsStrengths and LimitationsOur study has some limitations, the first being its retrospective nature. Furthermore, despite being one of the largest series to date, follow-up duration is somewhat limited and a control group is lacking.ConclusionTGR represents an excellent surgical option ensuring satisfactory voiding and sexual function, as well as cosmesis for selected cases of penile lesions.M. Preto, M. Falcone, G. Blecher, et al. Functional and Patient Reported Outcomes Following Total Glans Resurfacing. J Sex Med 2021;18:1099–1103.     

Dopaminergic Regulation of Innate Immunity: a Review

Dopamine (DA) is a neurotransmitter in the central nervous system as well as in peripheral tissues. Emerging evidence however points to DA also as a key transmitter between the nervous system and the immune system as well as a mediator produced and released by immune cells themselves. Dopaminergic pathways have received so far extensive attention in the adaptive branch of the immune system, where they play a role in health and disease such as multiple sclerosis, rheumatoid arthritis, cancer, and Parkinson’s disease. Comparatively little is known about DA and the innate immune response, although DA may affect innate immune system cells such as dendritic cells, macrophages, microglia, and neutrophils. The present review aims at providing a complete and exhaustive summary of currently available evidence about DA and innate immunity, and to become a reference for anyone potentially interested in the fields of immunology, neurosciences and pharmacology. A wide array of dopaminergic drugs is used in therapeutics for non-immune indications, such as Parkinson’s disease, hyperprolactinemia, shock, hypertension, with a usually favorable therapeutic index, and they might be relatively easily repurposed for immune-mediated disease, thus leading to innovative treatments at low price, with benefit for patients as well as for the healthcare systems.     

COVID-19-induced liver injury in adult patients: A brief overview

Coronavirus disease has spread worldwide since 2019, causing important pandemic issues and various social health problems to date. Little is known about the origin of this virus and the effects it has on extra-pulmonary organs. The different mechanisms of the virus and the influence it has on humans are still being studied, with hopes of finding a cure for the disease and the pathologies associated with the infection. Liver damage caused by coronavirus disease 2019 (COVID-19) is sometimes underestimated and has been of important clinical interest in the past few years. Hepatic dysfunctions can manifest in different forms which can sometimes be mild and without specific signs and symptoms or be severe with important clinical implications. There are several studies that have tried to explain the mechanism of entry (hepatotropism) of the virus into hepatocytes and the effects the virus has on this important organ. What clearly emerges from the current literature is that hepatic injury represents an important clinical aspect in the management of patients infected with COVID-19, especially in frail patients and those with comorbidities. The aim of our brief overview is to summarize the current literature regarding the forms of hepatic damage, complications, mechanisms of pathology, clinical features of liver injury, influence of comorbidities and clinical management in patients with COVID-19 infection.     

Validity,potential clinical utility and comparison of a consumer activity tracker and a research‐grade activity tracker in insomnia disorder II: Outside the laboratory

Accurate assessment of sleep can be fundamental for monitoring, managing and evaluating treatment outcomes within diseases. A proliferation of consumer activity trackers gives easy access to objective sleep. We evaluated the performance of a commercial device (Fitbit Alta HR) relative to a research‐grade actigraph (Actiwatch Spectrum Pro) in measuring sleep before and after a cognitive behavioural intervention in insomnia disorder. Twenty‐five individuals with DSM‐5 insomnia disorder (M = 50.6 ± 15.9 years) wore Fitbit and Actiwatch and completed a sleep diary during an in‐laboratory polysomnogram, and for 1 week preceding and following seven weekly sessions of cognitive‐behavioural intervention for insomnia. Device performance was compared for sleep outcomes (total sleep time, sleep latency, sleep efficiency and wake after sleep onset). The analyses assessed (a) agreement between devices across days and pre‐ to post‐treatment, and (b) whether pre‐ to post‐treatment changes in sleep assessed by devices correlated with clinical measures of change. Devices generally did not significantly differ from each other on sleep variable estimates, either night to night, in response to sleep manipulation (pre‐ to post‐treatment) or in response to changes in environment (in the laboratory versus at home). Change in sleep measures across time from each device showed some correlation with common clinical measures of change in insomnia, but not insomnia diagnosis as a categorical variable. Overall, the Fitbit provides similar estimates of sleep outside the laboratory to a research grade actigraph. Despite the similarity between Fitbit and Actiwatch performance, the use of consumer technology is still in its infancy and caution should be taken in its interpretation.