Covid-19 pandemic and clinical activity stop: oral health study in a group of children.

AIM: Public and private health services, which provide both preventive and health promotion interventions, were forced to suddenly stop their activities to limit the risk of infections during the pandemic emergency. Oral health administration, including that of children, was affected by these planned medical service closures, from both therapeutic and preventive perspectives. This study aims to analyse the consequences, at the oral cavity level, of failures to treat patients of childhood age, considering the impact of carious pathology on quality of life and incorrect eating and oral hygiene habits, which may occur in this age group. METHODS: This is a cross-sectional, single-center, observational study. One hundred patients from the Odontostomatological University Center (C.O.U.) of Perugia were randomly enrolled. CONCLUSION: Oral health status of the examined sample is satisfactory overall, considering the clinic's interruption of treatments with the resulting long period of no follow-up and the emotional and economic stress generated by the pandemic condition for both the young patients and their caregivers.

Delayed recovery from severe acute respiratory syndrome coronavirus-2 related anosmia predicts incomplete olfactory restoration.

OBJECTIVE: This study aimed to assess the olfactory recovery rates and patterns in a cohort of coronavirus disease 2019 positive patients, and to investigate the clinical predictors of poor long-term olfactory restoration. METHODS: An observational retrospective study was conducted on 146 patients between September 2020 and January 2021 at a tertiary referral hospital. Coronavirus disease 2019 positive patients with olfactory dysfunction were sent a modified version of the COVID-19 Anosmia Reporting Tool for Clinicians via e-mail. RESULTS: The difference in median recovery time between complete recovery and incomplete or no recovery was statistically significant. On multivariate analysis, the only significant factor associated with incomplete or no recovery was anosmia duration. CONCLUSION: After a mean time of 5.6 months from severe acute respiratory syndrome coronavirus-2 infection, persistent olfactory disorders were self-reported in 36.7 per cent of patients. Complete recovery was more likely to occur within 15 days. Given the high prevalence of coronavirus disease 2019, a large number of patients are expected to suffer from long-term olfactory morbidity.

Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares / Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: our preliminary results

INTRODUCCIÓN: Nuestro objetivo fue evaluar los cambios metabólicos corticales y el resultado clínico en los pacientes afectados por la hidrocefalia idiopática de presión normal (iNPH) después de la colocación de una derivación ventriculoperitoneal (VP). MATERIALES Y MÉTODOS: Diez pacientes afectados por la sospecha de iNPH se sometieron a una evaluación de la hidrodinámica del LCR basada en una prueba de infusión lumbar. El principal criterio de selección para la cirugía se basó en la elasticidad intracraneal (EI)>0,30. Todos los sujetos con una EI> 0,30 se sometieron a una exploración PET con 18 fluorodesoxiglucosa (18F-FDG) en la línea de base (PET1) y un mes después de la cirugía (PET2). Además, los mismos pacientes fueron sometidos a una evaluación clínica antes y un mes después de la cirugía mediante pruebas neuropsicológicas y análisis de la marcha. RESULTADOS: Se realizó un número total de 20 exploraciones de PET 18F-FDG en todos los pacientes reclutados. En comparación con la PET1, la PET2 mostró un aumento en el consumo de glucosa en el lóbulo frontal izquierdo y el lóbulo parietal izquierdo en la PET2 en comparación con la PET1 (p < 0,001). Todos los pacientes reclutados presentaron un aumento significativo en las puntuaciones neuropsicológicas (i.e. Batería de evaluación frontal y Evaluación cognitiva de Montreal) y han mejorado clínicamente en el análisis de la marcha. Se encontró una correlación significativa entre el aumento del consumo de glucosa cortical en el área parietal izquierda y la mejoría cognitiva detectable por la evaluación neuropsicológica. CONCLUSIONES: La mejora en 18F-FDG PET del metabolismo de la glucosa podría considerarse un marcador de imagen útil para la evaluación de la respuesta de la iNPH a la derivación ventriculoperitoneal

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting

Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: Our preliminary results. / Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares.

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting.

C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition.

Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.

Long-term usability and bio-integration of polyimide-based intra-neural stimulating electrodes.

Stimulation of peripheral nerves has transiently restored lost sensation and has the potential to alleviate motor deficits. However, incomplete characterization of the long-term usability and bio-integration of intra-neural implants has restricted their use for clinical applications. Here, we conducted a longitudinal assessment of the selectivity, stability, functionality, and biocompatibility of polyimide-based intra-neural implants that were inserted in the sciatic nerve of twenty-three healthy adult rats for up to six months. We found that the stimulation threshold and impedance of the electrodes increased moderately during the first four weeks after implantation, and then remained stable over the following five months. The time course of these adaptations correlated with the progressive development of a fibrotic capsule around the implants. The selectivity of the electrodes enabled the preferential recruitment of extensor and flexor muscles of the ankle. Despite the foreign body reaction, this selectivity remained stable over time. These functional properties supported the development of control algorithms that modulated the forces produced by ankle extensor and flexor muscles with high precision. The comprehensive characterization of the implant encapsulation revealed hyper-cellularity, increased microvascular density, Wallerian degeneration, and infiltration of macrophages within the endoneurial space early after implantation. Over time, the amount of macrophages markedly decreased, and a layer of multinucleated giant cells surrounded by a capsule of fibrotic tissue developed around the implant, causing an enlargement of the diameter of the nerve. However, the density of nerve fibers above and below the inserted implant remained unaffected. Upon removal of the implant, we did not detect alteration of skilled leg movements and only observed mild tissue reaction. Our study characterized the interplay between the development of foreign body responses and changes in the electrical properties of actively used intra-neural electrodes, highlighting functional stability of polyimide-based implants over more than six months. These results are essential for refining and validating these implants and open a realistic pathway for long-term clinical applications in humans.

TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells.

Metastatic growth in breast cancer (BC) has been proposed as an exclusive property of cancer stem cells (CSCs). However, formal proof of their identity as cells of origin of recurrences at distant sites and the molecular events that may contribute to tumor cell dissemination and metastasis development are yet to be elucidated. In this study, we analyzed a set of patient-derived breast cancer stem cell (BCSC) lines. We found that in vitro BCSCs exhibit a higher chemoresistance and migratory potential when compared with differentiated, nontumorigenic, breast cancer cells (dBCCs). By developing an in vivo metastatic model simulating the disease of patients with early BC, we observed that BCSCs is the only cell population endowed with metastatic potential. Gene-expression profile studies comparing metastagenic and non-metastagenic cells identified TAZ, a transducer of the Hippo pathway and biomechanical cues, as a central mediator of BCSCs metastatic ability involved in their chemoresistance and tumorigenic potential. Overexpression of TAZ in low-expressing dBCCs induced cell transformation and conferred tumorigenicity and migratory activity. Conversely, loss of TAZ in BCSCs severely impaired metastatic colonization and chemoresistance. In clinical data from 99 BC patients, high expression levels of TAZ were associated with shorter disease-free survival in multivariate analysis, thus indicating that TAZ may represent a novel independent negative prognostic factor. Overall, this study designates TAZ as a novel biomarker and a possible therapeutic target for BC.

[Scrotal ultrasound: anatomy and pathological findings]. / Ecografia del testicolo: anatomia e quadri patologici.

Ultrasonography (US) is the imaging modality of choice for the evaluation of scrotal disease. It provides high anatomical detail and in most cases, it is essential to enable a correct diagnosis and to obtain the right management of the patient. Color Doppler ultrasonography is a non invasive technique that aids important information about testicular perfusion, necessary in reaching a specific diagnosis in many pathologic conditions; moreover contrast-enhanced ultrasonography (CEUS), recently introduced in the clinical practice, may be considered an additional tool in the classification and differentiation of testicular pathology. The purpose of this review, is to provide the state of the art on the role of ultrasonography in the evaluation of different scrotal pathologies including vaginal process' disorders, acute scrotum, varicocele, hydrocele, chronic inflammatory diseases and testicular tumours.

Erythrocyte glutathione transferase: a new biomarker for hemodialysis adequacy, overcoming the Kt/V(urea) dogma?

Kt/V(urea) ratio is commonly used to assess the delivered dose of dialysis in maintenance hemodialysis (MHD) patients. This parameter only reflects the efficacy of dialytic treatments in removing small toxins, but not middle and protein-bound toxins. Erythrocyte glutathione transferase (e-GST), an enzyme devoted to cell depuration against a lot of large and small toxins, is overexpressed in uremic patients. Aim of the present study is to verify whether e-GST may represent a novel biomarker to assess the adequacy of different dialytic techniques complementary to Kt/V(urea) parameter. Furthermore, it will be investigated whether e-GST could reflect the 'average' adequacy of multiple dialytic sessions and not of a single one treatment as it occurs for Kt/V(urea). One hundred and three MHD patients and 82 healthy subjects were tested. Fourty four patients were treated with standard bicarbonate hemodialysis (HD) and 59 patients were on online hemodiafiltration (HDF). In all MHD patients e-GST activity was 60% higher than in healthy controls. In HDF, e-GST activity was lower than in HD subgroup (8.2±0.4 versus 10.0±0.4 U/g(Hb), respectively). Single-pool Kt/V(urea) and total weekly Kt/V(urea) were higher in HDF than in HD, but no correlation was found between e-GST activity and Kt/V(urea) data. e-GST, whose level is stable during the erythrocyte life-span, provides information on the long-term depurative efficacy of dialysis treatments.

Epigenetically silenced miR-34b/c as a novel faecal-based screening marker for colorectal cancer.

BACKGROUND: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker. METHODS: The 5-aza-2'-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. RESULTS: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P=0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P=0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P=0.561. CONCLUSIONS: These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker.

Primary hyperlipidemias in children: effect of plant sterol supplementation on plasma lipids and markers of cholesterol synthesis and absorption.

Plant sterols lower serum cholesterol concentration. Available data have confirmed the lipid-lowering efficacy in adults, while there is a relative dearth of data in children and almost exclusively restricted to subjects with familial hypercholesterolemia (FH). Aim of the present study was to evaluate the efficacy, tolerability and safety of plant sterol supplementation in children with different forms of primary hyperlipidemias. The effect of plant sterol consumption on plasma lipids was evaluated in 32 children with heterozygous FH, 13 children with Familial Combined Hyperlipidemia (FCH) and 13 children with Undefined Hypercholesterolemia (UH) in a 12-week open-label intervention study using plant sterol-enriched yoghurt. Plasma lipids and apolipoproteins were measured by routine methods. Markers of cholesterol synthesis (lathosterol) and absorption (campesterol and sitosterol) were measured by GC-MS. Tolerability and adherence to recommended regimen was very high. A significant reduction was observed in LDL-cholesterol in the three groups (10.7, 14.2 and 16.0% in FH, FCH and UH, respectively). Lathosterol concentrations were unchanged, reflecting a lack of increased synthesis of cholesterol. Of the two absorption markers, only sitosterol showed a slight but significant increase. Daily consumption of plant sterol dairy products favorably changes lipid profile by reducing LDL-cholesterol. To our knowledge, this is the first report of the use of plant sterols-enriched foods in treating children with primary hyperlipidemia such as FCH and UH, likely to be the most frequent form also in the young age in the western populations.

The usefulness of the prognostic inflammatory and nutritional index (PINI) in a haemodialysis population.

BACKGROUND AND AIM: Protein-Energy Wasting and inflammation are the principal risk factors of haemodialysis complications. We evaluated the reliability of a simple and non expensive test, the Prognostic Inflammatory and Nutritional Index (PINI), for regular screening of maintenance haemodialysis (MHD) patients in order to detect early onset of inflammation and malnutrition. METHODS AND RESULTS: 121 adult patients on maintenance dialysis were followed up for 32 months and screened every 6 months for PINI, calculated as alpha1-Acid Glycoprotein (alpha1-AG)xC-Reactive Protein (CRP)/AlbuminxTransthyretin. PINI score < or =1 was considered normal. Patients were stratified according to their PINI score: 86 patients (71.66%) had a normal score, whereas 35 (28.33%) had PINI > or = 1. The latter also had higher CRP levels, despite no clinical evidence of inflammation at the time of enrolment. Survival in patients with normal PINI was similar to patients with normal CRP, while in patients with abnormal PINI it was significantly lower than in patients with low serum albumin (p<0.05) or elevated CRP (p<0.05). After follow-up, all surviving MHD patients with PINI > or = 1 had at least one cardiovascular event vs 2.5% of patients with PINI > or = 1. CONCLUSION: The assessment of PINI can reliably identify MHD patients at higher risk of mortality and morbidity even in the absence of overt Malnutrition-Inflammation Complex Syndrome (MICS). This simple test appears to be more sensitive and specific of the single components, and not expensive, so that it could be routinely used to identify patients with sub-clinical inflammation and/or malnutrition.

Melanoma-associated markers expression in blood: MUC-18 is associated with advanced stages in melanoma patients.

BACKGROUND: Multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) was originally reported to reveal melanoma-associated mRNAs (MAMs) in melanoma cells but not in the peripheral blood of healthy individuals. OBJECTIVES: To evaluate the expression of MAMs in the peripheral blood of melanoma patients at different American Joint Committee on Cancer (AJCC) stages, and to correlate their presence with early and/or advanced stages of the disease. MATERIALS AND METHODS: One hundred blood samples of melanoma patients (AJCC I-IV) were analysed using multimarker RT-PCR to assess the co-expression of Tyr-OH, MART-1, MAGE-3, MUC-18/MCAM and p97. Patients were stratified into two disease categories: early and advanced stages. The former includes in situ and melanoma stages AJCC I-II, the latter AJCC III-IV. chi(2) and Fisher's exact tests were used to statistically evaluate the association between each MAM and disease categories. The recognized significant associations were subsequently resubmitted to univariate logistic regression. Furthermore, sensitivity and specificity were established. RESULTS: At least one MAM could be detected in 24% of our series. Tyr-OH was the most common marker (14%), followed by MUC-18 (12%), MART-1 (5%), MAGE-3 (4%) and p97 (3%). No significant association among Tyr-OH, MART-1, MAGE-3, p97 and disease stages were evidenced. Only MUC-18 was statistically associated (P < 0.009) with advanced stages alone or co-expressed with other MAMs. According to logistic regression univariate analysis, MUC-18 increases the probability (odds ratio: 33) being in advanced stages and the incidence of recurrences (95% CI 2.9-374). CONCLUSIONS: MUC-18 RT-PCR assay could be proposed as an adjunctive molecular method in the management of melanoma patients and is useful in the monitoring of study protocols.

Stromelysin gene promoter polymorphism and common carotid geometry in diabetic subjects.

AIM: Stromelysin (MMP3), through its action on collagen and other matrix metalloproteinases, influences arterial wall remodeling. In healthy subjects, the 5A/6A polymorphism located in the promoter of the MMP3 gene is associated with common carotid remodeling, 6A/6A subjects having increased arterial diameter, wall thickness (intima-media thickness, IMT) and decreased wall shear stress (WSS). In the present study, we have investigated the influence of the 5A/6A polymorphism on common carotid remodeling in subjects with diabetes mellitus. METHODS: Diabetic subjects (N.=136) and age-matched healthy male controls (N.=101) have been studied. Common carotid diameter, IMT and flow velocity have been measured by echo-Doppler. Blood viscosity has been measured by a cone/plate viscometer. WSS has been calculated. RESULTS: Diabetic patients had increased common carotid diameter, IMT, and decreased flow velocity and WSS (all P<0.05), compared with controls. In controls, subjects homozygous for the 6A allele had increased diameter, IMT and decreased WSS. In diabetics, no difference was observed in vascular parameters among the three genotypes. CONCLUSION: The 5A/6A polymorphism of the MMP3 gene influences arterial remodeling of the common carotid artery in healthy subjects, but not in patients with diabetes mellitus. Therefore, the significance of the 5A/6A polymorphism as a marker of risk in this high cardiovascular risk population seems to be somehow blunted.

Beta-sitosterolaemia: a new nonsense mutation in the ABCG5 gene.

BACKGROUND: Sitosterolaemia is a rare autosomal recessive disorder characterised by elevated plasma levels of plant sterols and cholesterol. Sitosterolaemia is caused by gene mutations in either of two ATP-binding cassette (ABC) half transporters, ABCG5 and ABCG8. The plasma sterol profile and genetic analysis of a 10-year-old girl who had tuberous xanthomas is the subject of this report. MATERIALS AND METHODS: Genomic DNA was isolated from white blood cells from the proband, her family and a control group of healthy people. All exons of ABCG5 and ABCG8 were sequenced. Plasma cholesterol and triglycerides were measured by routine methods. All other plasma sterols were measured by Gas Chromatography coupled to Mass Spectrometry. RESULTS: The proband was found to be homozygous for a single nucleotide mutation in exon 10 of the ABCG5 gene, consisting of a C to T transition at nucleotide 1336 of the coding sequence, which results in the premature termination of the ABCG5 protein at amino acid 446 (Arg446X). Her mother and brother were also homozygous for the same mutation and all had elevated plasma beta-sitosterol levels. The father was heterozygous and showed normal beta-sitosterol levels. This mutation was not found in healthy normolipidaemic subjects. CONCLUSIONS: We describe a novel nonsense mutation in exon 10 of the ABCG5 gene in a 10-year-old girl showing clinical and biochemical features of sitosterolaemia. This family study broadens the spectrum of the ABCG5/ABCG8 mutations causing sitosterolaemia and helps highlight the correlations between such gene mutations, biochemical phenotype and the development of cardiovascular disease.

Missense mutations in the TGM2 gene encoding transglutaminase 2 are found in patients with early-onset type 2 diabetes. Mutation in brief no. 982. Online.

Transglutaminase 2 (TG2 or TGM2) is a multi-functional enzyme which catalyzes transamidation reactions or acts as a G-protein in intracellular signalling. Tgm2-/- Mice lacking TG2 activity are glucose intolerant and show impairment of insulin secretion, suggesting an important physiological role for TG2 in the pancreatic beta cell. We have previously described a TGM2 heterozygous missense mutation ((c.998A>G, p.N333S) in a 14 year-old patient with insulin-treated diabetes and in his diabetic father. The aim of this study was to further investigate the role of TG2 in early-onset type 2 diabetes. We analysed the TGM2 gene in 205 patients with clinically defined Maturity Onset Diabetes of the Young (MODY) or early-onset type 2 diabetes. We found two novel heterozygous mutations (c.989T>G, p.M330R; c.992T>A, p.I331N), which were not detected in 300 normoglycemic controls. All mutations were in residues which are located close to the catalytic site and impaired transamidating activity in vitro. Gene expression of TGM family genes and localization of TG2 in normal human pancreas indicated that TG2 is the only transglutaminase significantly expressed in human pancreatic islet cells. We conclude that reduced TG2 activity can contribute to disorders of glucose metabolism possibly via an impairment of insulin secretion.

[Feasibility study of biological monitoring of chemical agents by means of evaluation of the effects on their in vitro effects on the complement system]. / Studio di fattibilità del monitoraggio biologico di agenti chimici mediante valutazione degli effetti su sistemi multienzimatici del plasma coinvolti nella risposta immune.

Immunological methods for the study of the plasma complement system have been standardized in order to be good and reproducible indicators of some biological effects of the substances under study in in vitro experiments. The substances tested were not capable of interfering within 10 times the possible hypothetical plasma concentration reached in vivo with the function of the different reagents used in the study of complement. Five substances (Skin-ACGIH) have been studied for their effects on the complement system in vitro; four of them could be fully studied (allylic alcohol, cyclohexanone, phenol, dimethylacetamide). After this deep insight we can conclude that: 1. These substances are capable of interfering with the immune response through their complement activating capacity 2. These substances, throughout complement activation, can induce inflammation and reduction of important defensive functions that are complement mediated. 3. The results obtained encourage to study the complement system and especially CH50 in workers exposed to the selected substances in order to verify the possibility to enclose this test in the medical surveillance program.

Divergent phenotype of two siblings human leukocyte antigen identical, affected by nonclassical and classical congenital adrenal hyperplasia caused by 21-hydroxylase deficiency.

CONTEXT: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders most often caused by enzyme 21-hydroxylase deficiency. Most mutations causing enzymatic deficiency are generated by recombinations between the active gene CYP21 and the pseudogene CYP21P. Only 1-2% of affected alleles result from spontaneous mutations. The phenotype of CAH varies greatly, usually classified as classical or nonclassical, depending on variable degree in 21-hydroxylase activity. Here we report a divergent phenotype of two human leukocyte antigen identical siblings, affected by nonclassical and classical CAH caused by 21-hydroxylase deficiency due to different genotype. PATIENTS AND METHODS: Using direct sequencing method and Southern blot, we studied two children (one male and one female), affected, respectively, by nonclassical and classical CAH and their parents. RESULTS: The mother was heterozygous for the Q318X mutation, and the father was heterozygous for the V281L mutation. The brother was a compound heterozygote for the mutations V281L and Q318X, whereas the proband was compound heterozygote for the Q318X mutation and a large conversion. The two children are human leukocyte antigen identical (A*02;B*14;DRB1*01/A*33;B*14;DRB1*03). CONCLUSIONS: Different phenotype of the proband is the result of compound heterozygosity for the maternal mutation Q318X and a de novo large conversion.

Delusion symptoms are associated with ApoE epsilon4 allelic variant at the early stage of Alzheimer's disease with late onset.

Alzheimer's disease (AD) is a neurodegenerative disorder with mixed cognitive and behavioural clinical manifestations. The possession of apolipoprotein-E (ApoE) epsilon4 allelic variant is one of the most important risk factors for developing late-onset AD (LOAD). In this study we analysed the relationship between the entire range of behavioural symptoms, cognitive deficit, and sociodemographic characteristics and ApoE epsilon4 allele possession with multivariate logistic regression models in LOAD patients. Patients included (n = 171) were consecutively admitted in a memory clinic for the first diagnostic visit. Levels of behaviour and cognition within the last month were assessed by the Neuropsychiatric Inventory and Mini Mental State Examination. Presence of clinically significant psychosis, delusions and hallucinations at the early stage of the illness, from the onset to the first visit, was measured with diagnostic criteria. ApoE epsilon4 allele possession was associated with increased levels of delusions within the last month from the first visit (OR 1.23; 95% CI 1.01-1.50; P < 0.05) and with the presence of categorical delusions at the early stage until the first visit (OR 3.11; 95% CI 1.21-8.01; P < 0.02). In this study, which considers the entire range of behavioural expressions in LOAD patients at the early stage of the illness, the relationship between behaviour and ApoE epsilon4 allele is confirmed for delusions only.