Fabrication and design of transdermal fluconazole spray

The objective of the present study was to formulate fluconazole transdermal spray for obtaining modified drug transport using eutectic mixture, ethyl cellulose, polyethylene oxide and alcohol. The formulated products were characterized. The selection of the optimized batch was done considering the results of drug transport in the first hour, the time required for 90% drug transport, viscosity and spray angle of the formulations. The inclusion of eutectic mixture, consisting of equal parts of camphor and menthol, showed improved drug transport through rat skin. The optimized batch exhibited larger mean zone of inhibition (antifungal activity), efficient in vivo activity and short term stability.     

Comparison of morphological and molecular genetic sex-typing on mediaeval human skeletal remains

Archaeological excavations conducted at an early mediaeval cemetery in Volders (Tyrol, Austria) produced 141 complete skeletal remains dated between the 5th/6th and 12th/13th centuries. These skeletons represent one of the largest historical series of human remains ever discovered in the East Alpine region. Little historical information is available for this region and time period. The good state of preservation of these bioarchaeological finds offered the opportunity of performing molecular genetic investigations. Adequate DNA extraction methods were tested in the attempt to obtain as high DNA yields as possible for further analyses. Molecular genetic sex-typing using a dedicated PCR multiplex (“Genderplex”) gave interpretable results in 88 remains, 78 of which had previously been sexed based on morphological features. We observed a discrepancy in sex determination between the two methods in 21 cases. An unbiased follow-up morphological examination of these finds showed congruence with the DNA results in all but five samples.     

Tracing Staphylococcus aureus in small and medium-sized food-processing factories on the basis of molecular sub-species typing

Contamination by Staphylococcus aureus of the production environment of three small or medium-sized food-processing factories in Slovakia was investigated on the basis of sub-species molecular identification by multiple locus variable number of tandem repeats analysis (MLVA). On the basis of MLVA profiling, bacterial isolates were assigned to 31 groups. Data from repeated samplings over a period of 3 years facilitated to draw spatial and temporal maps of the contamination routes for individual factories, as well as identification of potential persistent strains. Information obtained by MLVA typing allowed to identify sources and routes of contamination and, subsequently, will allow to optimize the technical and sanitation measures to ensure hygiene.     

Elucidation of demographic,clinical and trichoscopic features for early diagnosis of self-healing acute diffuse and total alopecia

The term “acute diffuse and total alopecia” (ADTA) has been often used as a synonym for self-regressing severe alopecia areata (AA). However, ADTA is originally defined as a rapidly-progressive subtype of AA (RP-AA) with short recovery time and favorable prognosis irrespective of interventions. Indeed, a subpopulation of ADTA recovers spontaneously. We focused on this unique subset of AA, which we coined as “self-healing ADTA” (sADTA). Prompt and accurate differentiation of sADTA from other RP-AA is important to avoid unnecessary treatments, which is still challenging due to the lack of predictive diagnostic hallmarks. In this study, 18 sADTA patients were retrospectively analyzed to delineate their demographics and clinical features, including gentle hair pull test and trichoscopic findings, followed by statistical comparison with those of RP-AA. All sADTA cases were female and the average age was 38.1 ± 15.9 years. The progression of hair loss areas peaked at 3.6 ± 1.5 months, and complete hair regrowth was achieved in 7.9 ± 1.7 months. The identified factors supporting the diagnosis of sADTA included being female; the absence of scalp pain and itch; the absence of extra-scalp hair loss; club hair predominance in hair pull test; predominant short vellus hairs; and increase in vacant follicular ostia on trichoscopy. Subsequently, a scoring system for early diagnosis of sADTA was developed by counting the number of six identified factors present in a tested case. When analyzed by the developed system, all sADTA cases, including an additional four cases, had scores of 4 or above, while all RP-AA cases had scores below 3 except one case. Therefore, the system successfully differentiated sADTA from RP-AA (P < 0.01). Despite some technical limitations, the current study suggested that sADTA is a distinctive entity with unique pathophysiology and that early diagnosis before intervention is feasible based on the characteristics.     

Genicular Artery Embolization for the Treatment of Knee Pain Secondary to Osteoarthritis

PurposeTo evaluate the efficacy and safety of embolization of hyperemic synovial tissue for the treatment of knee pain secondary to osteoarthritis (OA).Materials and MethodsTwenty patients with radiographic knee OA and moderate-to-severe pain refractory to conservative therapy were enrolled in a prospective, 2-site pilot study. Genicular artery embolization (GAE) was performed with 75- or 100-μm spherical particles. Patients were assessed with magnetic resonance imaging at baseline and at 1 month and with the Visual Analogue Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and at 1, 3, and 6 months. Adverse events were recorded at all timepoints.ResultsEmbolization of at least 1 genicular artery was achieved in 20/20 (100%) patients. Mean VAS improved from 76 mm ± 14 at baseline to 29 mm ± 27 at 6-month follow-up (P < .01). Mean WOMAC score improved from 61 ± 12 at baseline to 29 ± 27 at 6-month follow-up (P < .01). Self-limiting skin discoloration occurred in 13/20 (65%) patients. Two of 20 (10%) patients developed plantar sensory paresthesia that resolved within 14 days.ConclusionsGAE to treat knee pain secondary to OA can be performed safely and demonstrates potential efficacy. Further randomized comparative studies are needed to determine true treatment effect versus placebo effect.     

Short photoperiod restores ventral subicular lesion-induced deficits in affective and socio-cognitive behavior in male Wistar rats

Photoperiod (day-length) has enduring effects on an organism's physiological functions like metabolism and behavioral phenotypes including cognition and affect. Circadian rhythm manipulations are potentially effective non-pharmacological strategies in the management of central nervous system insults. In our previous study, we demonstrated the efficacy of short photoperiod regime (SPR; 06/18 hr light-dark cycle) in establishing functional recovery in ventral subicular lesion (VSL) rats. The present study further demonstrates the efficacy of SPR in mitigating anxiety and depression as well as facilitating socio-cognitive behavior in VSL rats. VSL elevated the basal plasma corticosterone levels, increased anxiety, anhedonia, and behavioral despair with decreased self-care. The VSL rats also exhibited a considerable degree of impaired social cognition, in terms of altered social preference and social novelty. Exposure to SPR for 21 days mitigated the anxiety- and depressive-like phenotypes as well as improved social cognition significantly. Thus, the study demonstrated the effectiveness of SPR strategy in reversing most of the behavioral deficits caused by VSL. SPR, perhaps, would have regulated the hypothalamo-pituitary-adrenal axis responsiveness as we observed a decrease in plasma corticosterone levels following SPR in VSL rats. The study implies the need for developing a task-dependent SPR strategy to achieve complete behavioral recovery as the functional demands of each behavior is distinct. In summary, the study highlights the efficacy of photoperiod manipulation as a novel, non-pharmacological approach in mitigating the affective and cognitive deficits associated with neuropsychiatric disorders such as bipolar disorder and Alzheimer's disease wherein circadian rhythm alterations are implicated.     

Tracking Spinal Cord Injury Functional Outcomes Across the Lifespan: Validation of Linking Coefficients

ObjectiveValidation of linking coefficients to transform Pediatric Spinal Cord Injury Activity Measure (PEDI-SCI/AM) scores to adult Spinal Cord Injury-Functional Index (SCI-FI) scores.DesignThis cross-sectional study administered PEDI-SCI/AM and SCI-FI computerized adaptive tests (CATs) and short forms (SFs) to children with SCI and parents or caregivers.SettingHospitals, university, and rehabilitation institute.ParticipantsAbout 107 children with SCI and 96 parent or caregivers.InterventionsNot applicable.Main Outcome MeasuresLinking coefficients estimated SCI-FI (est-SCI-FI) scores from PEDI-SCI/AM scores for matched domains. Correlations between est-SCI-FI and actual SCI-FI scores were calculated. If correlations exceeded the criterion linking (0.866), the following analyses to compare est-SCI-FI and actual SCI-FI scores were conducted: paired t tests, intraclass correlation coefficients (ICCs 3, 1), percent of cases with absolute score differences at different thresholds.ResultsTwo matched domains, PEDI-SCI/AM Daily Routine/SCI-FI Self-Care and PEDI-SCI/AM General Mobility/SCI-FI Basic Mobility, met the linking criterion for both respondent-types (parent and child) and administration modes (CAT and SF). PEDI-SCI/AM Daily Routine and SCI-FI Fine Motor Function did not meet linking criterion for respondent type or mode. The linking criterion was met for wheelchair domains (child SF and CAT) and ambulation domains (child SF only). Significant differences between est-SCI-FI and actual SCI-FI scores were noted for all matched domains except Daily Routine/Self-Care (child SF only; parent SF and CAT). ICC values showed excellent agreement (range=0.75-0.89). Absolute differences between est-SCI-FI and actual SCI-FI scores were less than 1 standard deviation (except wheelchair CAT child).ConclusionsLinking coefficients applied to PEDI-SCI/AM scores can provide valid SCI-FI estimates that vary by domain, mode, and respondent type.     

The melatonin metabolite N1‐acetyl‐5‐methoxykynuramine facilitates long‐term object memory in young and aging mice

Melatonin (MEL) has been reported to enhance cognitive processes, making it a potential treatment for cognitive decline. However, the role of MEL’s metabolites, N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine (AFMK) and N1‐acetyl‐5‐methoxykynuramine (AMK), in these effects are unknown. The current study directly investigated the acute effects of systemic MEL, AFMK, and AMK on novel object recognition. We also analyzed MEL, AFMK, and AMK levels in hippocampus and temporal lobe containing the perirhinal cortex following systemic MEL and AMK treatment. AMK administered post‐training had a more potent effect on object memory than MEL and AFMK. AMK was also able to rescue age‐associated declines in memory impairments when object memory was tested up to 4 days following training. Results from administering AMK at varying times around the training trial and the metabolism time course in brain tissue suggest that AMK’s memory‐enhancing effects reflect memory consolidation. Furthermore, inhibiting the MEL‐to‐AMK metabolic pathway disrupted object memory at 24 hours post‐training, suggesting that endogenous AMK might play an important role in long‐term memory formation. This is the first study to report that AMK facilitates long‐term object memory performance in mice, and that MEL crosses the blood‐brain barrier and is immediately converted to AMK in brain tissue. Overall, these results support AMK as a potential therapeutic agent to improve or prevent memory decline.