Immunosuppression, as seen in solid organ transplant recipients, is highly associated with the development of keratinocyte carcinomas (KCs). Reducing the level of immunosuppression lowers the ...incidence of KCs but at the cost of increased potential morbidity and mortality. Recent studies have revealed a greater prevalence of HPV DNA, especially that of β-HPV, in KCs of immunocompromised patients compared to KCs of immunocompetent individuals. A prior report demonstrated that the HPV vaccine was associated with reducing KC incidence in immunocompetent patients. The nonavalent HPV vaccine was administered to two immunosuppressed individuals with histories of multiple prior KCs. Both patients are male, with Patient 1 being a liver transplant recipient who was on tacrolimus for an extended period and Patient 2 having Crohn's disease and currently being treated with mercaptopurine. The treatment was well tolerated without adverse events and was associated with dramatic reductions in average incidence of KCs/year in both patients. Patient 1 demonstrated an 88% reduction in new KCs/year (87% squamous cell carcinomas (SCCs); 100% basal cell carcinomas (BCCs) post-injection of the intramuscular vaccine and Patient 2 demonstrated a 63% reduction in incidence of KCs/year (30% SCCs; 100% BCCs). Evidence links the β-HPV genera to the development of SCCs and actinic keratoses. The nonavalent HPV vaccine, containing antigens of the α-HPV genera, may also induce humoral immunity to β-HPV due to shared expression of L1 and L2 capsid proteins. The HPV vaccine may be an effective tool in the prevention of KCs in immunosuppressed patients. J Drugs Dermatol. 2022;21(5):526-528. doi:10.36849/JDD.6536.
To evaluate the effectiveness of a novel oral supplement, Forti5
, containing green tea extract, omega 3 and 6 fatty acids, cholecalciferol, melatonin, beta-sitosterol, and soy isoflavones, and in ...the management of subjects with androgenetic alopecia.
A prospective case series of 10 subjects.
Open-label, evaluator-blinded, proof-of-concept study.
Ten adult subjects with androgenetic alopecia completed the study. Subjects were not allowed to use oral or topical hair growth products in the 24 weeks preceding the study or during the study. The nutritional supplement was administered at a dosage of two tablets daily for 24 weeks.
Clinical evaluations were performed at baseline and at 24 weeks. Efficacy was evaluated using hair mass index measured by cross section trichometer, terminal hair count measured with dermoscopy and Investigator Global Photography Assessment.
Overall 80 percent of subjects (8/10) were rated as improved after 24 weeks of supplementation (mean change of +1.4 equivalent to slightly-to-moderately increased). Forty percent of subjects (4/10) were rated as moderately improved (2+), and 10 percent (1/10) were rated as greatly improved (3+). There was a significant improvement in terminal hair count (mean increase of 5.9% or 4.2 more terminal hairs in the area examined,
=0.014) and in Hair Mass Index (mean increase of 9.5% or 4.5 higher Hair Mass Index,
=0.003).
These preliminary results indicate that Forti5
a novel nutritional supplement that contains cholecalciferol, omega 3 and 6 fatty acids, melatonin, antioxidants, and botanical 5-alpha reductase inhibitors, may be a useful adjunct in the treatment of androgenetic alopecia.
Mutations, toxic insults and radiation exposure are known to slow or arrest the migration of cortical neurons, in most cases by unknown mechanisms. The movement of migrating neurons is saltatory, ...reflecting the intermittent movement of the nucleus (nucleokinesis) within the confines of the plasma membrane. Each nucleokinetic movement is analogous to a step. Thus, average migration speed could be reduced by lowering step frequency and/or step distance.
To assess the kinetic features of cortical neuron migration we developed a cell culture system that supports fiber-guided migration. In this system, the majority of fiber-apposed cells were neurons, expressed age-appropriate cortical-layer specific markers and migrated during a 30 min imaging period. Comparison of the slowest and fastest quartiles of cells revealed a 5-fold difference in average speed. The major determinant of average speed in slower cells (6-26 microm/hr) was step frequency, while step distance was the critical determinant of average speed in faster cells (>26 microm/hr). Surprisingly, step distance was largely determined by the average duration of the step, rather than the speed of nucleokinesis during the step, which differed by only 1.3-fold between the slowest and fastest quartiles.
Saltatory event frequency and duration, not nucleokinetic speed, are the major determinants of average migration speed in healthy neurons. Alteration of either saltatory event frequency or duration should be considered along with nucleokinetic abnormalities as possible contributors to pathological conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the ...incidence of KCs.
We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention.
Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: 0.02, 0.15). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: 0.14, 0.42). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P<0.001).
A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334.
Cortical development involves complex interactions between neurons and non-neuronal elements including precursor cells, blood vessels, meninges and associated extracellular matrix. Because they ...provide a suitable organotypic environment, cortical slice explants are often used to investigate those interactions that control neuronal differentiation and development. Although beneficial, the slice explant model can suffer from drawbacks including aberrant cellular lamination and migration. Here we report a whole cerebral hemisphere explant system for studies of early cortical development that is easier to prepare than cortical slices and shows consistent organotypic migration and lamination. In this model system, early lamination and migration patterns proceed normally for a period of two days in vitro, including the period of preplate splitting, during which prospective cortical layer six forms. We then developed an ex utero electroporation (EUEP) approach that achieves -80% success in targeting GFP expression to neurons developing in the dorsal medial cortex. The whole hemisphere explant model makes early cortical development accessible for electroporation, pharmacological intervention and live imaging approaches. This method avoids the survival surgery required of in utero electroporation (IUEP) approaches while improving both transfection and areal targeting consistency. This method will facilitate experimental studies of neuronal proliferation, migration and differentiation.
Abstract
Background
Mutations, toxic insults and radiation exposure are known to slow or arrest the migration of cortical neurons, in most cases by unknown mechanisms. The movement of migrating ...neurons is saltatory, reflecting the intermittent movement of the nucleus (nucleokinesis) within the confines of the plasma membrane. Each nucleokinetic movement is analogous to a step. Thus, average migration speed could be reduced by lowering step frequency and/or step distance.
Results
To assess the kinetic features of cortical neuron migration we developed a cell culture system that supports fiber-guided migration. In this system, the majority of fiber-apposed cells were neurons, expressed age-appropriate cortical-layer specific markers and migrated during a 30 min imaging period. Comparison of the slowest and fastest quartiles of cells revealed a 5-fold difference in average speed. The major determinant of average speed in slower cells (6–26 μm/hr) was step frequency, while step distance was the critical determinant of average speed in faster cells (>26 μm/hr). Surprisingly, step distance was largely determined by the average duration of the step, rather than the speed of nucleokinesis during the step, which differed by only 1.3-fold between the slowest and fastest quartiles.
Conclusion
Saltatory event frequency and duration, not nucleokinetic speed, are the major determinants of average migration speed in healthy neurons. Alteration of either saltatory event frequency or duration should be considered along with nucleokinetic abnormalities as possible contributors to pathological conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Disseminated histoplasmosis is often seen in immunocompromised individuals, such those with acquired immunodeficiency syndrome (AIDS). The initial infection mainly involves the lungs ...but it may develop into a disseminated form especially in immunocompromised patients. Since it can be a systemic disease with cutaneous manifestations, dermatologists must be able to recognize its clinical presentation to ensure prompt management.Case: We present a man in his 50s with past medical history of AIDS who developed disseminated histoplasmosis with skin and gastrointestinal involvement over a one-month period of time. Despite receiving induction therapy with intravenous amphotericin B followed by oral itraconazole, the patient expired. His death was attributed to his persistently low CD4 T-cell count and secondary bacteremia.Discussion: This condition should be recognized early and treated aggressively. However, patients with multiple comorbidities are at increased risk of mortality even despite adequate treatment. This case highlights the significant mortality risk of disseminated histoplasmosis in patients with AIDS.
Background: Psoriasis is a chronic remitting and relapsing skin disease. For many patients, improved quality of life (QoL) is as important as clinical improvement of lesions.Objective: To review ...reporting of Dermatology Life Quality Index (DLQI) in randomized controlled trials (RCTs) of biologics for adult patients with plaque psoriasis.Methods: A systematic review was conducted in 4 databases for RCTs that measured DLQI at baseline and endpoint. A data collection form was created for collecting study variables. Risk of bias was assessed using the Cochrane risk of bias tool.Results: Thirty-four RCTs enrolling 16,784 patients were included. Complete baseline and final mean DLQI data was retrieved for 24 studies (70.6%). The mean DLQI at baseline was reported in 79.4% of RCTs. The median at baseline was reported in 14.7% of RCTs. The mean DLQI at endpoint was reported in 23.5% of RCTs and the median DLQI at endpoint was reported in 5.9% of RCTs. The mean change in DLQI was reported in 64.7% of RCTs.Conclusions: DLQI was measured in most clinical trials assessing the efficacy of biologics for psoriasis. Studies did not adhere to uniform standards in publishing results, making analysis of the impact on DLQI challenging.Key Words: plaque psoriasis, quality of life, Dermatology Life Quality Index, Systematic Review, biologic therapy
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