Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.     

Biochemical and Metabolical Pathways Associated with Microbiota-Derived Butyrate in Colorectal Cancer and Omega-3 Fatty Acids Implications: A Narrative Review

Knowledge regarding the influence of the microbial community in cancer promotion or protection has expanded even more through the study of bacterial metabolic products and how they can modulate cancer risk, which represents an extremely challenging approach for the relationship between intestinal microbiota and colorectal cancer (CRC). This review discusses research progress on the effect of bacterial dysbiosis from a metabolic point of view, particularly on the biochemical mechanisms of butyrate, one of the main short chain fatty acids (SCFAs) with anti-inflammatory and anti-tumor properties in CRC. Increased daily intake of omega-3 polyunsaturated fatty acids (PUFAs) significantly increases the density of bacteria that are known to produce butyrate. Omega-3 PUFAs have been proposed as a treatment to prevent gut microbiota dysregulation and lower the risk or progression of CRC.     

The Level of Anxiety and Pain Perception of Endodontic Patients

Objectives

to compare the level of anxiety reported by patients and assessed by dentists. Also, the expected and actual pain during the treatment perceived by the patient and dentist were assessed.

Methods

sixty six endodontic patients filled in two questionnaires, prior to and after the treatment, so did their therapists. The first set of questions for patients was regarding demographics, the frequency of dental visits, the level of anxiety and expectations about the level of pain. Before the treatment, dentists estimated the level of patients'' anxiety and the expected intensity of pain. After the treatment, the patients evaluated the level of experienced pain and dentists'' empathy during the treatment, while dentists reassessed the intensity of patients'' pain.The data were statistically analysed by t-test for paired samples and by Spearmans''s Rho correlation coefficient at level of significance set at 0.05.

Results

Patients'' expectation of pain intensity was higher than the actual pain during the treatment (t-test=3.540, p=0.001). There was no difference in the level of pain which dentists expected and their perception of pain during the procedure. There was a statistically significant correlation between the patients'' level of anxiety and recognition of it by dentists (Spearman Rho=0.460, p<0.001). A higher level of anxiety increased the expected intensity of pain (Spearman Rho=0.401, p=0.001). Actual intensity of pain was not significantly associated with dental anxiety (Spearman Rho=0.080, p=0.524).

Conclusion

Since the level of dental anxiety was associated with the increased intensity of expected pain, a vicious cycle of pain and anxiety may be terminated by giving positive information to the patient before and during endodontic procedures.     

Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage

Objective The aim of this study was to evaluate the correlation between sympathetic nervous activation and the immune response in patients following subarachnoid haemorrhage (SAH).Design and setting Clinical study in a neurosurgical intensive care unit.Patients and participants Fourteen patients with acute non-traumatic SAH were included. Fifteen healthy, age-matched volunteers served as controls for measurement of catecholamine spillover.Intervention Blood sampling for C3a, C5b-9, IL-6, IL-8 and norepinephrine kinetic determination was made within 48 h, at 72 h and on the 7th–10th day after the SAH.Measurements and results SAH patients exhibited a profound increase in the rate of norepinephrine spillover to plasma at 48 h, 72 h and 7–10 days after the insult, 3–4 times that in healthy individuals. The plasma levels of C3a, IL-6 and C5b-9 were significantly elevated at 48 h, at 72 h and 7–10 days after the SAH, but the plasma level of IL-6 decreased significantly 7–10 days after the SAH. There was no relationship between the magnitude of sympathetic activation and the levels of inflammatory markers.Conclusions Following SAH a pronounced activation of the sympathetic nervous system and the inflammatory system occurs. The lack of significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and the immune response, following SAH are not quantitatively linked. In spite of a persistent high level of sympathetic activation the plasma level of IL-6 decreased significantly one week after SAH.     

Folliculotropism in pigmented facial macules: Differential diagnosis with reflectance confocal microscopy

Pigmented facial macules are common on sun damage skin. The diagnosis of early stage lentigo maligna (LM) and lentigo maligna melanoma (LMM) is challenging. Reflectance confocal microscopy (RCM) has been proven to increase diagnostic accuracy of facial lesions. A total of 154 pigmented facial macules, retrospectively collected, were evaluated for the presence of already‐described RCM features and new parameters depicting aspects of the follicle. Melanocytic nests, roundish pagetoid cells, follicular infiltration, bulgings from the follicles and many bright dendrites and infiltration of the hair follicle (ie, folliculotropism) were found to be indicative of LM/LMM compared to non‐melanocytic skin neoplasms (NMSNs), with an overall sensitivity of 96% and specificity of 83%. Concerning NMSNs, solar lentigo and lichen planus‐like keratosis resulted better distinguishable from LM/LMM because usually lacking malignant features and presenting characteristic diagnostic parameters, such as epidermal cobblestone pattern and polycyclic papillary contours. On the other hand, distinction of pigmented actinic keratosis (PAK) resulted more difficult, and needing evaluation of hair follicle infiltration and bulging structures, due to the frequent observation of few bright dendrites in the epidermis, but predominantly not infiltrating the hair follicle (estimated specificity for PAK 53%). A detailed evaluation of the components of the folliculotropism may help to improve the diagnostic accuracy. The classification of the type, distribution and amount of cells, and the presence of bulging around the follicles seem to represent important tools for the differentiation between PAK and LM/LMM at RCM analysis.     

Effect of gender on suicide attempters versus nonattempters in an adolescent inpatient unit

BACKGROUND: Although gender differences have been noted in the risk factors for suicide and attempted suicide, comparative studies to date have used only 2 groups and a limited number of measures. The present study compared the effect of gender on suicide among 4 groups of psychiatrically hospitalized adolescents using a cross-sectional design. METHODS: The study sample consisted of 404 patients, aged between 12 and 21, who were divided into 4 groups: 76 male suicide attempters, 103 male nonattempters, 143 female suicide attempters, and 82 female nonattempters. Patients were tested for life events, affective disorders, aggression, impulsivity, ego defense mechanisms, and death perception with the Child Suicide Potential Scale, Beck Depression Inventory, State-Trait Anxiety Inventory, Overt Aggression Scale, Multidimensional Anger Inventory, Impulsivity Control Scale, and Life Style Index. Findings were analyzed by multivariate regression with stepwise logistic models. RESULTS: Depression and anxiety were more prevalent in female nonattempters than in male nonattempters; there were no such gender differences among the attempters. Antisocial behavior was more prevalent in male attempters than in female attempters; there were no gender differences on this aspect among the nonattempters. There were gender differences for defense mechanisms in the attempters. Logistic regression models for men and women separately revealed that antisocial behavior and anxiety were common predictors of suicide attempt, that destructiveness was a predictor in women only, and that depression was associated with suicide attempt in men only. CONCLUSIONS: Suicide-prone female and male adolescent inpatients show distinct differences in psychopathology, ego defense mechanisms, and life events compared to psychiatrically hospitalized adolescents without any history of suicide attempt. Any deviation from a gender-specific behavior must raise suspicion of a risk of attempted suicide.     

High frequency of the TCRBV20S1 null allele in the Sardinian population

Single nucleotide polymorphisms (SNPs) in the T-cell receptor (TCR) gene segments might play a role in shaping the TCR repertoire. Three polymorphisms have been described for the TCRBV20S1 gene segment, one of which is responsible for a nucleotide substitution at position 524, resulting in the introduction of a stop codon. Individuals homozygous for this inactivating polymorphism ("null allele") are unable to express TCRBV20 gene products. Using DNA restriction digestion analysis, we investigated the frequency of this polymorphism in 111 healthy Sardinian subjects. Inhabitants of the Mediterranean island of Sardinia are considered to represent a genetically isolated population. Our analyses revealed an incidence of 19.8% of homozygosity for the null allele, corresponding to an allele frequency of 0.45. Such an incidence, significantly higher than the one detected in 83 non-Sardinian Caucasians (6%), is the most elevated so far reported in the literature. BV20 is a single member subfamily and the null allele produces a gap in the potential TCR repertoire. Therefore, it is possible that an undetermined selective pressure could have played a role in determining the high frequency of this inactivating polymorphism in Sardinians. Alternatively, this finding could be related to a founder effect in this ancient island population.