Tinea capitis caused by Trichophyton tonsurans among adults: Clinical characteristics and treatment response.

BACKGROUND: Trichophyton tonsurans tinea capitis has become a growing epidemiological concern. Yet, its clinical manifestations and treatment response, specifically among adults, have only been described among small sample size studies. OBJECTIVE: To assess clinical manifestations and treatment outcome of T. tonsurans tinea capitis among adults. PATIENTS AND METHODS: A retrospective cohort study was carried out among 111 adults with T. tonsurans tinea capitis. Diagnosis was confirmed by fungal culture or polymerase chain reaction. Examinees' demographics, disease characteristics and treatment response were measured. The risk factors for the treatment failure were evaluated. RESULTS: The mean age was 20.1 years (±3.1), with men (98.2%) outnumbering women. The follow-up lasted 12.2 months (±5.6). The majority of T. tonsurans tinea capitis was seen in the occipital area (87.6%). In 78.9% of the cases, the scalp manifestation was non-inflammatory (scaly plaques and papules:76.1% and seborrhoea-like: 2.8%). 21.1% of cases presented with inflammatory tinea capitis (21.1%; Kerion: 10.1% and pustular: 11%). Concomitant involvement of other than scalp areas was common: tinea corporis was seen in 38.7% of the cases; tinea faciei and barbae in 24.3%; nape and anterior neck in 76.6% and 2.7% of the cases, respectively. An adequate treatment course with oral terbinafine resulted in 83.2% clinical cure rate. Treatment failure was significantly associated with concomitant tinea corporis (odds ratio 3.9; 95% confidence interval 1.3-12.1, p-Value< .02). CONCLUSION: The most common clinical presentation of T. tonsurans tinea capitis included occipital scaly plaques and papules with concomitant non-scalp lesions. Oral terbinafine was found to be highly effective. Concomitant tinea corporis increased the risk for treatment failure.

Comorbidities in patients with palmoplantar plaque psoriasis.

BACKGROUND: Psoriasis has been shown to be associated with several comorbidities. Whether the palmoplantar subtype of plaque psoriasis carries similar risks for comorbidities as generalized plaque psoriasis remains to be defined. OBJECTIVE: To examine the association between palmoplantar plaque psoriasis and comorbidities known to be associated with generalized plaque psoriasis. METHODS: We retrospectively compared the prevalence of comorbidities previously found to be associated with generalized plaque psoriasis among 163 patients with palmoplantar plaque psoriasis who had been treated with topical psoralen and ultraviolet A from 2009 to 2017 and a cohort of 781 control individuals. Each patient with psoriasis was matched according to sex and age (±1 year) with up to 5 control individuals. Conditional logistic regression was used to evaluate the associations after matching. RESULTS: Diabetes mellitus (odds ratio [OR], 2.296), cardiovascular disease (OR, 1.797), and most remarkably, mood disorders (OR, 6.232) were significantly associated with palmoplantar plaque psoriasis. Dyslipidemia, hypertension, and psoriatic arthritis were more frequent among patients with palmoplantar plaque psoriasis, but those associations did not reach statistical significance. LIMITATIONS: The retrospective nature of this study, the fact that some data were collected through a survey questionnaire, and the relatively small sample size suggest the need to validate the present data in a prospective manner. Additionally, within the psoriasis group, patients were assessed for the presence of comorbidities during the whole follow-up period, whereas the comorbidities of individuals in the control group were assessed during a baseline visit. CONCLUSIONS: Several comorbidities known to be associated with psoriasis vulgaris were also found to be prevalent in a series of patients with plaque palmoplantar psoriasis. Individuals affected with plaque palmoplantar psoriasis showed a particularly high risk for mood disorders.

SVEP1 plays a crucial role in epidermal differentiation.

SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell-cell adhesion in an integrin-dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT-PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three-dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1-specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell-cell adhesion with disadhesion between cells in Svep1-deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation.

Cole Disease Results from Mutations in ENPP1.

The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases.

The sound of silence: autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12.

Autosomal recessive congenital ichthyosis refers to a heterogeneous group of cornification disorders of major impact on patients' life. The disease has been linked so far to mutations in 8 distinct genes. We report a consanguineous family of Arab Muslim origin with several members displaying a severe form of congenital ichthyosiform erythroderma. Using a panel of polymorphic microsatellite markers, we identified a region of homozygosity shared by all patients on 2q34, in a region harbouring the ABCA12 gene. Direct sequencing of genomic DNA derived from a patient failed to reveal any obviously pathogenic change in the coding sequence of this gene. In contrast, cDNA sequence analysis revealed the existence of a 163-bp-long deletion in exon 24, thus pointing to a splicing defect. Careful reanalysis of the genomic DNA sequence revealed apart from several known single-nucleotide polymorphisms, a hitherto unreported homozygous synonymous mutation in exon 24 (c.3456G>A; p.S1152S), which was found to lead to the formation of a novel splicing acceptor site. Synonymous mutations have been shown to uncommonly cause inherited disorders in humans. Here, we present the first example of a congenital form of ichthyosis resulting from such a genetic defect.

Cell-free DNA--a marker to predict ischemic brain damage in a rat stroke experimental model.

BACKGROUND: The animal model of stroke that is most frequently used is a rat model of focal brain ischemia caused by middle cerebral artery occlusion (MCAO). Several studies have reported a link between levels of cell-free DNA (CFD) and neurologic outcome in human stroke. The purpose of this study was to assess brain injury and measure CFD levels in 2 models of MCAO in rats, and to determine whether brain injury correlates with CFD. METHODS: A total of 60 rats were used for this study. Twenty rats underwent a sham procedure, 20 rats had MCAO using a monofilament, and 20 rats had MCAO with a silicon-coated filament. Groups were further divided into 2 subgroups. In 1 subgroup of 10 rats, neurologic performance [measured as a neurologic severity score, (NSS)] was measured at 1 and 24 hours after the procedure, and brain edema and infarct volume were determined at 24 hours. In the second subgroup of 10 rats, CFD was measured at 0, 1, 2, 4, 8, 12, and 24 hours and at 2, 3, 4, and 5 days. Neurologic performance (measured as a NSS) was measured at 1 and 24 hours after the procedure. RESULTS: The main finding was a significant increase in CFD levels observed 24 hours after the onset of MCAO. The correlation between the total infarct volume and CFD levels of the 3 groups was R=0.78, P<0.0001. Brain edema and NSS also were strongly correlated with CFD levels at 24 hours after MCAO (R=0.91, P<0.0001 and R=0.73, P<0.0001, respectively). CONCLUSIONS: We found that CFD levels correlate well with the extent of ischemic injury, brain edema, and neurologic outcome in rats 24 hours post-MCAO. We have also shown that CFD correlates well with the expected temporal progression of ischemic injury. These findings place CFD in a unique place as a biomarker for stroke, both experimentally and possibly clinically.

Morphological and neuro-behavioral parallels in the rat model of stroke.

Middle cerebral artery occlusion (MCAO) is widely used as a rat model of focal brain ischemia. Evaluation of brain damage often includes the morphological analysis of the injury area, MRI, and various scales which depend on functional tests, commonly known as neurological severity score (NSS). We determined the optimal number of NSS tests and assessed their capacity for non-invasive evaluation of brain ischemic injury in the rat MCAO model. 275 male Sprague-Dawley rats were randomly divided into five groups, given either permanent (p) MCAO or transient (t) MCAO using an uncoated 4-0 monofilament catheter or a silicone-coated monofilament. The rats' neurological status was examined before and at 1 and 24h following MCAO. The size of brain injury was then measured histologically and the extent of right cerebral hemisphere edema was calculated. We established a correlation between these tests and morphological data for brain injury. Adjusted R(2) of the prediction of total histology score was 0.7. The Hosmer-Lemeshow p-value of this model was 0.812 for total brain histology. For the brain edema the adjusted R(2) of the prediction model was 0.48. The Hosmer-Lemeshow p-value of this model was 0.558 for brain edema. Our methods of estimating infarct size produces reliable and well correlated results at 24h and demonstrates to be an easy and quick way to assess infarct size soon after ischemic injury has occurred. The described method for neurological assessment could ultimately aid in assessing various treatment modalities in the early hours following stroke.

An experimental model of focal ischemia using an internal carotid artery approach.

Animal models of cerebral ischemia represent an important contribution to both our understanding of stroke mechanism and the development of new therapies. The technique of MCAO (middle cerebral artery occlusion) via ECA (external carotid artery) occlusion is widely utilized. Disruption of the ECA and its branches leads to impaired mastication and oral intake, post-surgical body weight loss, and poor neurological recovery which can possibly confound one's interpretation of rats' neurological outcome. Here, we developed a novel modified technique for MCAO without ligation or coagulation of the ECA and its branches using an approach via the internal carotid artery (ICA). In our modified technique, we perform an additional fixation of the filament in the ICA which improves the stability of the model and increases the homogeneity in stroke size. Compared with the original MCAO technique via the ECA, our modified technique via the ICA demonstrated decreased variability in the percent infarcted volume and brain edema, as well as a decreased mortality. Additionally, we observed that with our modified technique, rats gained more weight after surgery and there was less initial weight loss after the surgical preparation. Our new approach may serve as an effective model for stroke, and may lead to a better understanding of stoke pathophysiology and to the future development of new drugs and other neuroprotective agents.

Vaginismus as an independent risk factor for cesarean delivery.

OBJECTIVE: The present study was aimed to investigate pregnancy outcome of patients with vaginismus, and specifically the relationship between vaginismus and cesarean delivery. METHODS: A population based study comparing all pregnancies in patients with and without vaginismus was conducted. Patients lacking prenatal care were excluded from the analysis. Deliveries occurred during the years 1988-2007. A multivariate logistic regression model, with backward elimination, was constructed to find independent risk factors associated with vaginismus. RESULTS: During the study period there were 192,954 deliveries, of which 118 occurred in patients with vaginismus. Patients with vaginismus tended to be younger (26.04+/-4.89 vs. 28.61+/-5.83; p < 0.001) and delivered smaller children (3024.2+/-517 g vs. 3160.9+/-576 g; p = 0.01) when compared with patients without vaginismus. Patients with vaginismus had higher rates of infertility treatments (5.9%vs. 2.7%, odds ratio [OR] 2.3; 95% confidence interval [CI] 1.1-4.9; p = 0.04) and labor induction (37.3%vs. 27.4%, OR 1.6; 95% CI 1.1-2.3; p = 0.02), vacuum extraction (9.3%vs. 2.8%, OR 3.6, 95% CI 1.9-6.7; p < 0.001), and cesarean delivery (39.0%vs. 14.5%, OR 3.8; 95% CI 2.6-5.5; p < 0.001) when compared with the comparison group. Even after controlling for possible confounders associated with cesarean delivery such as previous cesarean delivery, pathological presentations, and fetal distress, vaginismus remained as an independent risk factor for cesarean delivery (OR 7.1; 95% CI 4.5-11.1; p < 0.001). CONCLUSION: Vaginismus is an independent risk factor for cesarean delivery.