Efficacy and safety of a food supplement for iron deficiency anaemia: A monocentric prospective study.

Iron deficiency anaemia (IDA) is the most prevalent worldwide nutrient deficiency-related disease. The 30% of IDA female patients is represented by non-pregnant women and the 42% are pregnant women. Oral iron supplementation represents the first-line treatment for IDA. Iron sulphate is the main source of iron, but despite its effectiveness, its use correlates with a high incidence of side effects. Consequently, finding new iron sources became challenging. An innovative microencapsulated and micronized iron saccharate, empowered with vitamins (B6, B12, B9 and C), has been evaluated for the efficacy and safety in a monocentric prospective observational study. 80 female subjects diagnosed for IDA received one dose/daily of the food supplement for an observation period of 60 days (T60) and 120 days (T120). To measure IDA-related biochemical parameters, full blood tests have been collected at each time. To evaluate Quality-of-Life (QoL) the Short-form 12 Physical Component Summary and Mental Component Summary (SF-12 PCS and MCS) together with sign and symptoms collection have been used to follow improvements in IDA-related indicators. Finally, side effects have been registered along the observation period. Obtained data revealed that the food supplement was effective and well tolerated. Changes in haemoglobin levels and other iron metabolism values have been observed, confirming the effectiveness of the tested product, from the biochemical point of view. In parallel, QoL improvement and signs and symptoms reduction confirm the high bioavailability and tolerability of this innovative iron source.

Effects of an Educational Book on Paediatric Oral Health knowledge in a sample of Italian women.

AIM: Parents and caregivers, particularly in Italy, often have limited knowledge about their children's oral health. The primary objective of the study is to evaluate the educational effectiveness of a book on nutrition and prevention of oral diseases entitled "Oral health of mother and child in the first 1000 days of life". MATERIALS: The sample for this study was composed of 103 adult Italian women who were potential caregivers of one or more children (e.g., mothers, grandmothers, babysitters, and educators). The enrolled women completed a preliminary online survey which included questions about their socio-demographic characteristics and their knowledge on oral health in the first 1000 days of life of newborns (30 questions). Following the survey, they received the educational book. After reading it, the participants completed a second online survey with the same 30 questions, to measure any improvement in their knowledge. CONCLUSION: It appears that our educational book about nutrition and prevention of oral diseases was effective in enhancing knowledge among the participants in our study. These findings suggest that this educational resource has the potential to be a valuable tool in preventing oral diseases in paediatric populations. However, further confirmation of these results should be obtained through randomised controlled trials.

Innovative and conventional "conservative" technologies for the treatment of uterine fibroids in Italy: a multidimensional assessment.

BACKGROUND: To evaluate the potential benefits of the Magnetic Resonance-guided high intensity Focused Ultrasound (MRgFUS) introduction in the clinical practice, for the treatment of uterine fibroids, in comparison with the standard "conservative" procedures, devoted to women who wish to preserve their uterus or enhance fertility: myomectomy and uterine artery embolization (UAE). METHODS: A Health Technology Assessment was conducted, assuming the payer's perspective (Italian National Healthcare Service). The nine EUnetHTA Core Model dimensions were deeply investigated, by means of i) a literature review; ii) the implementation of health economics tools (useful for uterine fibroids patients' clinical pathway economic evaluation, and budget impact analysis), to define MRgFUS economic and organizational sustainability, and iii) administration of specific questionnaires filled by uterine fibroids' experts, to gather their perceptions on the three possible conservative approaches (MRgFUS, UAE and myomectomy). RESULTS: Literature revealed that MRgFUS would generate several benefits, from a safety and an efficacy profile, with significant improvement in symptoms relief. Advantages emerged concerning the patients' perspective, thus leading to a decrease both in the length of hospital stay (p-value< 0.001), and in patients' productivity loss (p-value = 0.024). From an economic point of view, the Italian NHS would present an economic saving of - 6.42%. A positive organizational and equity impact emerged regarding the capability to treat a larger number of women, thus performing, on average, 131.852 additional DRGs. CONCLUSIONS: Results suggest that MRgFUS could be considered an advantageous technological alternative to adopt within the target population affected by uterine fibroids, demonstrating its economic and organisational feasibility and sustainability, with consequent social benefits.

Brain stem death induces pro-inflammatory cytokine production and cardiac dysfunction in sheep model.

INTRODUCTION: Organs procured following brain stem death (BSD) are the main source of organ grafts for transplantation. However, BSD is associated with inflammatory responses that may damage the organ and affect both the quantity and quality of organs available for transplant. Therefore, we aimed to investigate plasma and bronchoalveolar lavage (BAL) pro-inflammatory cytokine profiles and cardiovascular physiology in a clinically relevant 6-h ovine model of BSD. METHODS: Twelve healthy female sheep (37-42 Kg) were anaesthetized and mechanically ventilated prior to undergoing BSD induction and then monitored for 6 h. Plasma and BAL endothelin-1 and cytokines (IL-1ß, 6, 8 and tumour necrosis factor alpha (TNF-α)) were assessed by ELISA. Differential white blood cell counts were performed. Cardiac function during BSD was also examined using echocardiography, and cardiac biomarkers (A-type natriuretic peptide and troponin I were measured in plasma. RESULTS: Plasma concentrations big ET-1, IL-6, IL-8, TNF-α and BAL IL-8 were significantly (p < 0.01) increased over baseline at 6 h post-BSD. Increased numbers of neutrophils were observed in the whole blood (3.1 × 109 cells/L [95% confidence interval (CI) 2.06-4.14] vs. 6 × 109 cells/L [95%CI 3.92-7.97]; p < 0.01) and BAL (4.5 × 109 cells/L [95%CI 0.41-9.41] vs. 26 [95%CI 12.29-39.80]; p = 0.03) after 6 h of BSD induction vs baseline. A significant increase in ANP production (20.28 pM [95%CI 16.18-24.37] vs. 78.68 pM [95%CI 53.16-104.21]; p < 0.0001) and cTnI release (0.039 ng/mL vs. 4.26 [95%CI 2.69-5.83] ng/mL; p < 0.0001), associated with a significant reduction in heart contractile function, were observed between baseline and 6 h. CONCLUSIONS: BSD induced systemic pro-inflammatory responses, characterized by increased neutrophil infiltration and cytokine production in the circulation and BAL fluid, and associated with reduced heart contractile function in ovine model of BSD.

Impacted post-traumatic maxillary central incisor: A multidisciplinary approach.

AIM: The aim of this paper is to provide clinicians useful information for the management of impacted central incisor due to early childhood trauma. CASE REPORT: It is reported the case of an impacted right maxillary central incisor in an 8-year-old male patient who had an intrusive luxation trauma of primary tooth at the age of 4. After clinical and radiographic evaluation, a multidisciplinary treatment plan was planned. Therapy involved a surgical and orthodontic approach in order to expose the tooth and move the incisor in the normal position with a self-ligating appliance system. RESULTS: Through a multidisciplinary approach it was possible to move the impacted incisor in the occlusal plane, preserving periodontal tissues and tooth vitality. CONCLUSION: When a permanent tooth is impacted, the multidisciplinary approach of surgery and orthodontic treatment is the best way to obtain a suitable outcome in terms of gingival contour, occlusal plane and aesthetics, when compared with other treatment options.

Prevalence and determinants of early childhood caries in Italy.

AIM: Still limited data from representative surveys are available on the prevalence of Early Childhood Caries (ECC; i.e., the presence of one or more decayed, missing, or filled tooth surfaces in any primary tooth in a child aged 71 months or younger), particularly for infant. We conducted a survey in Italian children aged 0 to 71 months. MATERIALS AND METHODS: A cross-sectional study on ECC was conducted in Italy in 2018 on a sample of parents who were members of an online panel. Using an online questionnaire, 2,522 parents provided information on a total sample of 3,000 children, representative of the Italian population aged 0-71 months. RESULTS: ECC prevalence was 8.2% overall, 2.9% in children aged 0-23 months, 6.2% in children aged 24-47 and 14.7% in children aged 48-71 months (p for trend<0.001). ECC was more frequently observed among children using baby bottle with milk to fall asleep (multivariate odds ratio, OR, 1.36, 95% confidence interval, CI: 1.03-1.78), baby bottle with sugary beverages (OR 2.87, 95% CI: 2.05-4.03) and pacifier with sugary substances (OR 2.49, 95% CI: 1.79-3.47), consuming beverages other than water (OR for ?1/day vs never 2.29, 95% CI: 1.35-3.90), a higher number of snacks between meals (OR for ?3 vs <2 meals 2.05, 95% CI: 1-38-3.06), a lower frequency of tooth brushing (OR for <1 vs ?2 times/day 2.26, 95% CI: 1.42-3.58) and a high number of siblings (compared to 0, OR for ?2 siblings 2.28, 95% CI: 1.56-3.34). ECC increased with parents' mean age (p for trend=0.048), parents' smoking habit (OR for at least one smoker 1.54, 95% CI: 1.17-2.03), parents' poor oral hygiene (OR for ?1 vs >1 time/day of tooth brushing 1.42, 95% CI: 1.03-1.96) and high number of caries (OR for ?7 vs 0 caries was 2.38, 95% CI: 1.35-4.20). CONCLUSION: The present large and representative survey for the first time shows that ECC might be frequent also among infants. We confirm that ECC might be prevented if parents follow simple good practices. Information campaign and intervention programmes are needed to inform parents about unfavourable habits that favour the onset of ECC.

Characterization of airborne viromes in cheese production plants.

AIMS: To characterize airborne virus-like particles isolated from two cheese production plants in order to reveal their complexity in terms of viral communities and microbial genes potentially mobilized by viruses. METHODS AND RESULTS: Airborne virus-like particles have been isolated from Grana Padano and Gorgonzola PDO cheese production plants and ripening cellars. A shotgun metagenomics analysis of the isolated viromes highlighted a high complexity of the viral communities both in terms of viral taxonomy and phage-host associations. Bacterial reads in each of the viromes were confirmed to be abundant and their taxonomy appeared to be associated with the environmental parameters and the technological processes that characterize the sampling area. Antibiotic resistance genes have been identified in each virome thus confirming that phages could be involved in the mobilization of antimicrobial resistances among bacterial populations. Interestingly human viruses were also identified even if the contamination source was not revealed. CONCLUSIONS: The environmental conditions, which are imposed by the technology of the dairy process, seam to shape the viral populations as a consequence of the adaptation of microbial taxa to those environments. The identification of sequences belonging to Legionella pneumophila and to the human papillomavirus, raised some considerations about the safety of cheese-ripening cellars. SIGNIFICANCE AND IMPACT OF THE STUDY: In conclusion, the analysis of the dairy airborne viromes, has revealed a high complexity of the viral communities even if the environments where the samples were collected were confined environments. Metagenomics of airborne viral population could be a promising monitoring tool for the biological characterization of dairy environments.

Muerte fetal: caracterización epidemiológica / Stillbirth: epidemiological characterization

La muerte fetal es la defunción del feto antes de su expulsión o separación completa del cuerpo de la madre, independientemente de la duración del embarazo. En un alto porcentaje se desconocen sus causas, aunque la literatura ha establecido como factores de riesgo la hipoxia intrauterina y las malformaciones congénitas. Se realizó un estudio retrospectivo, descriptivo, con el objetivo de determinar, a través de revisión de las historias clínicas, las características epidemiológicas de las muertes fetales en la Maternidad Dr. José Luis Facchin de Boni, en el período enero 2007 marzo 2013. La población fue 1236 gestantes con diagnóstico de muerte fetal, determinando una tasa de 56,28 muertes fetales por cada 1000 nacimientos y abortos. La mayoría de dichas muertes fetales (85,03%) ocurrieron por debajo de las 37 semanas, con predominio del sexo masculino. Además los factores médicos como el síndrome anémico, los obstétricos como las malformaciones fetales y las complicaciones hemorrágicas fueron los más frecuentemente encontrados en los casos de muerte fetal. Otro hallazgo importante de la investigación, fue que el peso de los fetos muertos fue menor que el peso de los nacidos vivos de la misma edad gestacional.

Stillbirth is the death of the fetus before their expulsion or complete separation of the body of the mother, regardless of the length of pregnancy. A high percentage of its causes are unknown, although the literature has established as risk factors intrauterine hypoxia and birth defects. A retrospective, descriptive study was conducted in order to determine, through review of medical records, the epidemiological characteristics of stillbirths in the Maternidad Dr. José Luis Facchin Boni, between January 2007 and March 2013. The population was 1236 pregnant women diagnosed with stillbirth, determining a rate of 56.28 stillbirths per 1000 births and abortions. Most of these stillbirths (85.03%) were below 37 weeks, with predominance of males. Medical factors such as anemic syndrome, the obstetric factors such as fetal malformations and hemorrhagic complications were most frequently found in cases of stillbirth. Another important finding of the research was that the weight of dead fetuses was less than the weight of live births of the same gestational age.

Human skin-derived fibroblasts used as a 'Trojan horse' for drug delivery.

BACKGROUND: Drug toxicity currently represents the main challenge of tumour chemotherapy. Our group recently developed a new method for drug delivery inspired by the 'Trojan Horse' concept. Human mesenchymal stem cells (hMSCs) have been shown to play the role of new 'horses' in delivering anti-tumour agents, without involving any genetic manipulation. As human stromal dermal fibroblasts (hSDFs) represent an interesting alternative to hMSCs, being easy to isolate, they could be an ideal candidate for this kind of procedure. AIM: To investigate whether hSDFs can take up and deliver paclitaxel (PTX) in sufficient concentrations to inhibit a very aggressive melanoma tumour (IgR39) in vitro. METHODS: hSDFs were primed with high doses of PTX, and then the effect of drug delivery on IgR39 melanoma proliferation in vitro was evaluated using several assays (antiproliferation, transwell cocultures, rosette assays and colony growth assays). Furthermore, the cell cycle and PTX uptake/release mechanism of hSDFs were studied both under both normal and hypoxic conditions. RESULTS: hSDFs incorporated PTX and then released it with unaffected pharmacological activity, inhibiting human IgR39 melanoma growth in vitro. The hypoxic conditions did not induce changes in cell cycle pattern and the uptake-release mechanism with PTX was not affected. CONCLUSIONS: hSDFs can be used as a Trojan horse, as the released drug was functionally active. These results indicated that these cells could be used for clinical treatment as the drug was released into the cellular environment and the primed cells underwent apoptosis.

Chlamydophila pneumonia and increased TLR4 gene expression in leukocytes are associated with acute myocardial infarction.

We investigated the relationship of the positivity for Chlamydophila pneumoniae (Cpn) and Mycoplasma pneumonia (Mpn), inflammatory and metabolic markers, and mRNA expression and polymorphisms of the TLR2, TLR4, IL-6 and TNFA genes with acute myocardial infarction (AMI). Two hundred and eighteen individuals (98 AMI and 120 non-AMI) were selected at two Clinical Centers. Blood samples were drawn to extract DNA and RNA and to measure laboratory variables including anti-Cpn IgM and IgG. Cpn and Mpn genomic DNA as well as TLR2, TLR4, IL-6 and TNFA mRNA expression were evaluated by quantitative real-time PCR (qPCR). Gene polymorphisms were detected by PCR-HRM. AMI patients had higher positivity for Cpn-DNA (17.3%) than non-AMI group (6.7%, p=0.018). In addition, Cpn-DNA positivity was an independent predictor of risk for AMI (OR: 2.56, CI: 1.08 - 6.04, p=0.031). Positivity for anti-Cpn IgG and Mpn-DNA was similar between AMI and non-AMI (> 0.05). TLR4 mRNA expression was higher in AMI than non-AMI individuals (p=0.005). CD14 -260C> T, TNFA -308A> G, TLR2 c.2258G> A, TLR4 c.896A> G and TLR4 c.1196> T variants were not associated with increased risk for AMI (p> 0.05). In the AMI group, individuals carrying CD14 -260CC genotype had higher hsCRP levels than CT/TT carriers (p=0.041). These results are suggestive that Cpn-DNA positivity and increased TLR4 mRNA expression in blood leukocytes may be associated with AMI and could be useful markers to evaluate the severity and progression of the atherosclerotic disease in AMI patients.

Expresión de KI67, P53, BCL2 en el carcinoma de mama en nuestro medio / Ki67 expression, P53, Bcl-2 in breast carcinoma in our midst

Objetivo: Determinar la expresión del Ki67, p53 y Bcl2 en pacientes con diagnóstico de cáncer de mama en nuestro medio. Métodos: Se realizó un estudio descriptivo, retrospectivo de diseño no experimental de tipo transeccional de la expresión por técnica inmunohistoquímica de los marcadores moleculares Ki67, p53 y Bcl2 de casos con el diagnóstico de carcinoma de mama en un grupo de 110 mujeres que acudieron consecutivamente a una consulta de mama en la Clínica Docente los Jarales (CDLJ) durante el período comprendido 2005 - 2011. La muestra fue intencional y conformada por los casos seleccionados del archivo historias de la consulta que cumplieron los siguientes criterios de inclusión. Resultados: La edad promedio fue de 51,81 años, más del 60 % eran posmenopáusicas. El tumor en la mayoría se localizó en la mama izquierda, Más del 60 % de los tumores tenían un tamaño entre los 2 a 5 cm y más del 80 % metástasis regionales. En más de la mitad de los tumores se observó inmunoexpresión de los receptores hormonales. El 60 % de los tumores correspondieron al subtipo luminal A. El Ki67 se observó en mayor porcentaje de casos en los tumores de pacientes entre 25 a 46 años y el p53 y Bcl2 en aquellos entre 36 a 46 y 58 a 68 años respectivamente. El Ki67, p53 y Bcl2 marcaron en mayor número de casos clasificados estadio clínico II-III, como de tumores entre 2 a 5 cm y con más de 7 ganglios metastásicos. Conclusión: Es necesario generar aún más evidencia sobre las características propias de nuestra población femenina afectada por la neoplasia para comprender su comportamiento en ellas y racionalizar en consecuencia lo correspondiente a su terapéutica.

Objective: To determine the expression of Ki67, p53 and Bcl2 in patients diagnosed with breast cancer in our midst. Methods: A descriptive, retrospective design nonexperimental transeccional expression by immunohistochemistry of molecular markers Ki67, p53 and Bcl2 in cases with a diagnosis of breast cancer in a group of 110 consecutive women attending a breast query the Jarales Teaching Clinic (CDLJ) during the period from 2005 to 2011. The sample was composed of intentional and file cases selected records of the query that met the following inclusion criteria. Results: The mean age was 51.81 years, over 60 % were postmenopausal. The tumor was located in most of the left breast, over 60 % of the tumors had a size between 2-5 cm and over 80 % regional metastases. In more than half of the tumors was observed immunoexpression hormone receptors. 60 % of the tumors corresponded to the luminal subtype A. Ki67 was observed in the highest percentage of cases in tumors from patients aged 25 to 46 years and the p53 and Bcl2 in those between 36 to 46 and 58 to 68 respectively. The Ki67, p53 and Bcl2 marked in more cases classified clinical stage II-III, as tumors between 2-5 cm and more than 7 metastatic nodes. Conclusion: It is necessary to generate further evidence on the characteristics of our female population affected by neoplasia to understand their behavior accordingly rationalize them and what matches your therapy.

Diagnóstico definitivo de la imagen probablemente benigna y sospechosa de malignidad del estudio mamográfico

Objetivo: Identificar el diagnóstico definitivo de la imagen probablemente benigna y sospechosa de malignidad del estudio mamográfico en un grupo de mujeres de nuestro medio. Métodos: Se realizó un estudio de las imágenes probablemente benignas y sospechosas de malignidad en las mamografías del grupo de mujeres que acudieron con el estudio a una consulta de mama en la Clínica Docente los Jarales durante junio 2009 a diciembre 2011. Se revisó el archivo de historias de la consulta, seleccionando aquellas de acuerdo a los criterios de inclusión: informe anexo de la mamografía descriptivo de imágenes probablemente benignas y sospechosas de malignidad, sin distinción por el centro que realizó el estudio, nota de lectura de la imagen visualizada durante la valoración, digitalización y archivo de las anteriores, resultado de la biopsia consecutiva, además se evaluó edad, menarquía, paridad, estatus hormonal, tratamiento hormonal, antecedentes de cáncer de mama (familiar y personal), volumen mamario, hallazgo en la evaluación, tiempo de realizado el estudio. Resultados: De los 150 casos estudiados, la edad promedio fue de 42,12 años, 70 % posmenopáusicas, menos del 10 % tenía antecedentes de cáncer de mama. En más de 70 % de las pacientes se palpó un nódulo. En mamografía la densidad nodular definida fue el hallazgo más común. La categoría BIRADS 3 se informó en más del 60 %. El VPP de la mamografía con categoría BIRADS 3 para lesión benigna fue de 99,03 % y en aquellas BIRADS 4 para lesión maligna fue de 90,38 %. Conclusión: Es necesario insistir en el uso del sistema BIRADS para la descripción e informe de las imágenes en la mamografía.

Objective: Identifity the definitive diagnosis of probably benign image and suspicious for malignancy of mammography in a group of women in our country. Methods: We performed a study of images probably benign or suspicious for malignancy on mammograms of women attending group to study a breast query the Jarales Teaching Clinic during June 2009 to December 2011. Revised stories file query, selecting those according to the inclusion criteria: Annex report descriptive mammography images probably benign or suspicious for malignancy, without distinction by the center that conducted the study, note reading image displayed during titration, scanning and archiving of previous consecutive biopsy results also assessed age at menarche, parity, hormonal status, hormone treatment, breast cancer history (family and personal), breast volume, finding in evaluation, the study was conducted time. Results: Of the 150 cases studied, the average age was 42.12 years, 70 % postmenopausal, less than 10 % had a history of breast cancer. In over 70 % of the patients felt a nodule. In defined nodular density mammogram was the most common finding. 3 BIRADS category reported in more than 60 %. The PPV of mammography with BIRADS category 3 for benign lesion was 99.03 % and those BIRADS 4 for malignancy was 90.38 %. Conclusion: It is necessary to insist on using BIRADS system to describe and report on mammography images.

Autonomous reparative unit (ARU): a new concept of repairing free flap donor site with local full-thickness skin graft.

Usually, harvesting free flap in the limbs creates an inevitable sequence of aesthetic damage not only in the donor site but also in the area of the graft used to repair the free flap donor site. Aim of the study was to standardize a simple method, defined Autonomous Reparative Unit, that allows closing of the donor site defects with a skin graft from the adjacent cutaneous area, avoiding further aesthetic damage in a third area. We define the "Autonomous Reparative Unit" as the rectangular shaped skin area of the flap and the dermoepidermic skin graft designed as an isoscele triangle with the base adjacent to the smaller side of the flap defect. From 2003 to 2008, at the Fondazione IRCCS Istituto Nationale Tumori of Milan, 143 free radial forearm flaps and 42 free osteofasciocutaneous fibula flaps have been performed for head and neck cancer. The autonomous reparative unit has been applicable in 177 cases (92.1%). The autonomous reparative unit method allows a "standard"primary reconstructive unit to be created which can be used in a single or in multiple ways thus avoiding an additional surgical scar and a subsequent additional aesthetic impairment.

The mysterious case of spontaneous disappearance of hepatocellular carcinoma.

We describe the case of a 77-year-old woman with chronic hepatitis C and well compensated cirrhosis in whom a single encapsulated 5.5 cm hepatocellular carcinoma was found in the right liver lobe. The patient was symptomatic with left upper quadrant pain and had elevated alfa-fetoprotein levels (3133 ng/ml). While she was waiting for liver resection and 2 months after the initial diagnosis the pain improved and alfa-fetoprotein levels normalized. A computerized tomography scan showed reduction in size of the lesion to 2.5 cm, with no central arterial enhancement, but with the demonstration of a peripheral rim enhancing in all dynamic phases. Follow up computerized tomography and magnetic resonance imaging examinations showed further reduction in size of the lesion to 1.3 cm with persistence of the enhancing rim 20 months after the initial diagnosis. The spontaneous and durable regression of the HCC and the persistent peripheral enhancing rim could be explained by a strong and persistent activation of the immune system directed against the neoplastic cells.

Iron and insulin resistance.

BACKGROUND: Preliminary clinical and experimental results suggest that iron can modify hepatocytes' insulin sensitivity by interfering with insulin receptor and intracellular insulin signalling. AIM: To evaluate in vivo the influence of iron on insulin resistance and insulin release in patients with non-alcoholic fatty liver disease and in vitro the interaction between iron and insulin sensitivity by analysing the effect of iron manipulation on insulin receptor expression in hepatoblastoma HepG2 cell line. RESULTS: Insulin resistance evaluated by homeostatis model assessment (HOMA)-insulin resistance significantly decreased after diet, and a further reduction was observed after phlebotomies. Iron depletion by desferrioxamine increased by twofold the 125I-insulin-specific binding, whereas iron addition reduced insulin binding, similarly to cells exposed to high glucose concentration. CONCLUSION: Iron status affects insulin sensitivity by modulating the transcription and membrane expression/affinity of insulin receptor expression in hepatocytes and influencing insulin-dependent gene expression suggesting that increased insulin clearance and decreased insulin resistance may contribute to the positive effect of iron depletion in patients with non-alcoholic fatty liver disease.

Posterior fossa vestibular neurotomy as primary surgical treatment of Menière's disease: a re-evaluation.

Fifty-eight patients underwent vestibular neurotomy via the posterior fossa approach between September 1992 and December 1998 at the ENT department of Legnano. All patients presented a history of disabling unilateral Menière's disease and underwent complete neuro-otologic evaluation following the 1985 American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guidelines. All patients underwent MRI imaging, ABR and electronystagmographic testing before surgery. Objective analysis of results is reported using the criteria published by the Committee on Hearing and Equilibrium of the AAO-HNS in 1985. According to the AAO formula, 52 patients obtained a score of 0, indicating complete control of major vertigo spells, while four were classified within the 'substantial control' group. Immediate hearing results indicated that 93 per cent of the patients maintained a level within 10 dB from the pre-operative level. Only one patient experienced a subtotal hearing loss yet retained measurable hearing. No major complications were reported. We conclude that a retrosigmoid approach to vestibular neurotomy can be considered a safe and effective procedure in relieving medically refractory vertigo in Menière's disease while preserving the hearing. Tinnitus and long-term hearing deterioration are not influenced by the procedure.

[Trans-labyrinthine approach for the resection large and giant acoustic nerve neuromas]. / Abordaje translaberíntico para resección de neurinomas de gran tamaño y gigantes del nervio acústico.

The standard translabyrinthine approach for acoustic neuromas removal was introduced by W. House in 1964. After several years of experience the original translabyrinthine approach has been progressively modified into the current "enlarged" approach by extending the area of bone removal. This increased surgical field has made the translabyrinthine approach suitable for the removal of tumours of all sizes. We present our serie of 71 large (52) and giant (19) neuromas of the VIIIth nerve removed through a translabyrinthine approach between 1993 and 1998 at the ENT Department of Legnano.

Hypersomnolence in fibromyalgia syndrome.

OBJECTIVE: To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. METHODS: Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) completed a sleep questionnaire and underwent the following evaluations: lung function tests; polysomnography; the Epworth sleepiness scale (ESS), which measures sleep complaints and daytime hypersomnolence; and the visual analogical scale (VAS) to detect subjective pain, fatigue, anxiety and depression. RESULTS: The FMS patients were divided into two groups based on their ESS score. Patients complaining of daytime hypersomnolence had a higher number of tender points (15 +/- 2 vs. 12 +/- 1, p < 0.01), a higher subjective pain score (72 +/- 15 vs. 52 +/- 13, p < 0.05), and more fatigue (p < 0.05). The diffusing capacity of the lung (Tlco) was more impaired and the occurrence of periodic breathing was higher. FMS patients complaining of daytime somnolence had significantly less efficient sleep than the FMS patients with no daytime somnolence (p < 0.05), i.e. a lower proportion of stage 3 sleep (5 +/- 2% vs. 12 +/- 3%; p < 0.001), stage 4 sleep (1 +/- 0.5% vs. 4 +/- 1%; p < 0.001), and twice as many arousals per hour of sleep (p < 0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p < 0.05). The short length of apneas and hypopnoeas did not affect the apnea/hypopnea index (5.1 +/- 3 vs. 7 +/- 4; ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 +/- 6 vs. 6 +/- 5; p < 0.05). Pulmonary volumes did not differ between the two groups. The EES score was significantly correlated in FMS patients, and even more markedly in the FMS patients with hypersomnolence, TLco, A/I, and disease duration. The ESS score was correlated significantly with the number of tender points only in FMS patients with daytime hypersomnolence. CONCLUSION: The occurrence of daytime hypersomnolence in FMS patients is linked to a greater severity of fibromyalgia symptoms and to more severe polysomnographic alterations.

Targeting of a tail-anchored protein to endoplasmic reticulum and mitochondrial outer membrane by independent but competing pathways.

Many mitochondrial outer membrane (MOM) proteins have a transmembrane domain near the C terminus and an N-terminal cytosolic moiety. It is not clear how these tail-anchored (TA) proteins posttranslationally select their target, but C-terminal charged residues play an important role. To investigate how discrimination between MOM and endoplasmic reticulum (ER) occurs, we used mammalian cytochrome b(5), a TA protein existing in two, MOM or ER localized, versions. Substitution of the seven C-terminal residues of the ER isoform or of green fluorescent protein reporter constructs with one or two arginines resulted in MOM-targeted proteins, whereas a single C-terminal threonine caused promiscuous localization. To investigate whether targeting to MOM occurs from the cytosol or after transit through the ER, we tagged a MOM-directed construct with a C-terminal N-glycosylation sequence. Although in vitro this construct was efficiently glycosylated by microsomes, the protein expressed in vivo localized almost exclusively to MOM, and was nearly completely unglycosylated. The small fraction of glycosylated protein was in the ER and was not a precursor to the unglycosylated form. Thus, targeting occurs directly from the cytosol. Moreover, ER and MOM compete for the same polypeptide, explaining the dual localization of some TA proteins.