Mediterranean food consumption patterns: low environmental impacts and significant health-nutrition benefits.

The Mediterranean dietary patterns comply better with recommended nutrient and micronutrient intakes. The Mediterranean diet (MD) was associated with reduced mortality and lower risk for metabolic chronic diseases. It has also low ecological, carbon and water footprints due to its high share of plant-based foods. In fact, the share of plant-based dietary energy is higher in the Mediterranean than in Northern Europe. The Mediterranean hotspot is a major centre of plant and crop diversity. Mediterranean people gather and consume about 2300 plant species. This review paper aims at highlighting the nutrition-health benefits of the MD and analysing the main environmental impacts of the Mediterranean food consumption patterns. There is a growing body of scientific evidence that the MD has significant health-nutrition benefits and low environmental footprints, so there is urgent need to reverse the ongoing erosion of the MD heritage and to promote it as a sustainable diets model.

Med Diet 4.0: the Mediterranean diet with four sustainable benefits.

OBJECTIVE: To characterize the multiple dimensions and benefits of the Mediterranean diet as a sustainable diet, in order to revitalize this intangible food heritage at the country level; and to develop a multidimensional framework - the Med Diet 4.0 - in which four sustainability benefits of the Mediterranean diet are presented in parallel: major health and nutrition benefits, low environmental impacts and richness in biodiversity, high sociocultural food values, and positive local economic returns. DESIGN: A narrative review was applied at the country level to highlight the multiple sustainable benefits of the Mediterranean diet into a single multidimensional framework: the Med Diet 4.0. Setting/subjects We included studies published in English in peer-reviewed journals that contained data on the characterization of sustainable diets and of the Mediterranean diet. The methodological framework approach was finalized through a series of meetings, workshops and conferences where the framework was presented, discussed and ultimately refined. RESULTS: The Med Diet 4.0 provides a conceptual multidimensional framework to characterize the Mediterranean diet as a sustainable diet model, by applying principles of sustainability to the Mediterranean diet. CONCLUSIONS: By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.

Human serum antibodies recognize Treponema denticola Msp and PrtP protease complex proteins.

BACKGROUND/AIMS: Treponema denticola outer membrane proteins are postulated to have key roles in microbe-host interactions in periodontitis. Because there are no reports of in vivo expression of these putative virulence factors, we examined several T. denticola strains to determine whether sera from human subjects recognized specific T. denticola outer membrane proteins. METHODS: Soluble extracts were prepared from exponential phase cultures of T. denticola strains representing three serotypes, from defined T. denticola mutants defective in Msp (major surface protein) or PrtP lipoprotein protease complex (CTLP; dentilisin), and Escherichia coli strains expressing distinctly different T. denticola Msp. Extracts were subjected to Western immunoassays using archived human serum samples. RESULTS: Human serum antibodies (immunoglobulin G class) recognized multiple protein bands in T. denticola strains. In the parent strain ATCC 35405, these included bands at 72-, 53-, 40-, and 30-kDa. Bands corresponding to Msp and the PrtP protease complex proteins were absent in isogenic msp and protease complex mutants, respectively. Individual human sera showed specificity for one or more Msp types. CONCLUSIONS: This is the first definitive report of human serum antibody responses to specific T. denticola antigens. T. denticola Msp and the proteins comprising the PrtP lipoprotein protease complex are expressed in vivo and are immunogenic in humans. Human antibody recognition of Msp exhibits strain specificity and is consistent with strain serotyping. These results demonstrate the utility of T. denticola isogenic mutants in characterizing host immune responses to periodontal pathogens.

Myeloid sarcoma occurring in the maxillary gingiva: a case without leukemic manifestations.

Myeloid sarcoma (MS) is a localized extramedullary mass of immature granulocytic cells that usually occurs in patients with acute myeloid leukemia (AML) or myeloproliferative disorders. It may rarely precede peripheral blood or bone marrow involvement, presenting a diagnostic challenge. Although MS may be found in any location, an intraoral occurrence is rare. In this report we describe a rare case of a patient with nonleukemic MS of the maxillary gingiva. The histologic specimen was first interpreted as non-Hodgkin's lymphoma. The correct diagnosis was reached after extensive immunohistologic studies. The malignant cells were myeloperoxidase positive, lysozyme positive, CD45+, CD68+, CD3-, CD10-, CD19-, CD20-, CD30-, CD34-, CD56-, CD79a-, S100-, and chloroacetate esterase negative. Induction therapy with FLAND (fludarabine, Ara-C, mitoxantrone, and dexamethasone) was started, but the patient did not achieve a remission. Some weeks later, the patient presented pleural effusion and paralysis of the seventh cranial nerve on the left side. She died a few days later. The present case indicates the importance of a correct initial diagnosis for adequate therapy, which is often delayed because of a high misdiagnosis rate. If the MS is treated without intensive chemotherapy for AML as soon as possible, the prognosis will be poor.

[Oral cancer. Retrospective analysis of 118 cases]. / Carcinoma del cavo orale. Analisi retrospettiva su 118 casi clinici.

AIM: Oral carcinoma is a form of neoplasia with well-known clinical and morphologic features. This study presents the difference of incidence and behaviour in relation to the time of onset of oral carcinoma, and describes the experience made at the Department of Oral and Maxillofacial Surgery of the Second University of Naples. METHODS: In this study 118 patients are analysed. They are divided into 3 groups according to age: group A up to 40 years; group B, from 41 to 75 years; group C from 75 years onwards. RESULTS: No patient of group A showed a carcinoma of verrucous type. This histologic type was found in group B, (14 patients: 14,1%) and in group C (6 patients: 46,1%). CONCLUSIONS: The results of this study underline the importance of the time of onset in the behaviour of oral carcinoma and the age of patients.

Merkel cell carcinoma of the head and neck region: report of two cases.

Two cases of Merkel cell carcinoma (MCC) of the head and neck region are reported in order to stress their diversity in morphological, immunohistochemical and clinical findings. The remarkable variability of MCC has been analyzed, particularly in relation to the differential diagnosis and prognostic implications.

Botulinum toxin A for mentalis muscle dysfunction.

OBJECTIVE: To describe the use of botulinum toxin A for treatment of mentalis muscle dysfunction secondary to failed augmentation mentoplasty. DESIGN: Clinical observations were made in the treatment of mentalis muscle dysfunction. Patients with the postmentoplasty signs of mental skin dimpling and soft tissue ptosis were injected with 20 U of botulinum toxin A and observed for visual and functional improvement. Photographs were taken for documentation. SETTING: Private facial plastic surgery practice. PATIENTS: Three patients with a history of failed augmentation mentoplasty were identified and signs/symptoms recorded. Each patient was treated with 20 U of botulinum toxin A and observed for clinical improvement. MAIN OUTCOME MEASURES: Pretreatment and posttreatment photographs of active and passive mentalis function together with patient satisfaction surveys. RESULTS: Of the 3 patients treated, all reported alleviation of the mentalis dysfunction and improved appearance. The symptoms began to return as the botulinum toxin A effects subsided. CONCLUSIONS: Botulinum toxin A is a safe and effective treatment of mentalis dysfunction secondary to failed augmentation mentoplasty. The effects are predictable, although temporary.

Isolation of hyperactive mutants of the MAPK p38/Hog1 that are independent of MAPK kinase activation.

Mitogen-activated protein kinases (MAPKs) play pivotal roles in growth, development, differentiation, and apoptosis. The exact role of a given MAPK in these processes is not fully understood. This question could be addressed using active forms of these enzymes that are independent of external stimulation and upstream regulation. Yet, such molecules are not available. MAPK activation requires dual phosphorylation, on neighboring Tyr and Thr residues, catalyzed by MAPK kinases (MAPKKs). It is not known how to force MAPK activation independent of MAPKK phosphorylation. Here we describe a series of nine hyperactive (catalytically and biologically), MAPKK-independent variants of the MAPK Hog1. Each of the active molecules contains just a single point mutation. Six mutations are in the conserved L16 domain of the protein. The active Hog1 mutants were obtained through a novel genetic screen that could be applied for isolation of active MAPKs of other families. Equivalent mutations, introduced to the human p38alpha, rendered the enzyme active even when produced in Escherichia coli, showing that the mutations increased the intrinsic catalytic activity of p38. It implies that the activating mutations could be directly used for production of active forms of MAPKs from yeasts to humans and could open the way to revealing their biological functions.

Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV-associated head and neck squamous cell carcinoma.

The human papillomavirus (HPV) has been implicated as an etiological factor in a subset of head and neck squamous cell carcinoma (HNSCC). Because circulating tumor DNA has previously been detected in the sera of patients with advanced HNSCC (stage III or IV), we hypothesized that HPV DNA might be present in the sera of HPV-positive HNSCC patients. Serum DNA extracts from 70 patients with HNSCC were screened for HPV using conventional PCR and a real-time quantitative assay. All samples subjected to conventional PCR were further tested by dot blot hybridization, and positives were confirmed by Southern blotting. Paired tumor DNA from archived tissues was then similarly screened for HPV genomic material (n = 51) or tested by in situ hybridization (n = 19). HPV-16 DNA was detected with L1 primers in 0 of 65 sera and in 15 of 70 (21%) tumors. Conventional PCR with E7 primers and Southern blot hybridization detected HPV-16 DNA in four (6%) sera. Using real-time quantitative PCR, six samples were found to contain various levels of circulating HPV DNA (mean, 12 copies/ml; range, <1-35.) All six serum-positive patients had corresponding tumors positive for E7. Four of these patients with HPV-positive tumors later developed distant metastases, suggesting that HPV DNA in serum may represent occult hematogenous spread of cancer cells in this subset of patients. Although a much larger prospective trial is required, the presence of HPV genomic material in serum DNA of HPV-positive HNSCC patients may serve as a useful marker of early metastatic disease.

Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.

BACKGROUND: High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. METHODS: Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5-9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis. RESULTS: HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%-30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2- 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1-12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05-0.61) and smokers (OR = 0.16; 95% CI = 0.02-1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1-167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01-0. 36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07-0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4- 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4-4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8-2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20-0.88). CONCLUSIONS: These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.

Genetics of mutations affecting the development of a barley floral bract.

Two groups of mutants that affect the morphology of the lemma, a floral bract of barley, are described. The first comprises phenotypes associated with mutant alleles of calcaroides loci. On the lemma of these mutants, a well-organized neomorphic structure is formed, termed the sac. We provide a morphological description of wild-type (WT) and mutant lemmas, based on scanning electron microscopy (SEM), showing that both consist of similar tissues, but that the mutant is characterized by reversed growth polarity. The sac is a unique structure among grasses, and it is remarkable that recessive mutations at five different genetic loci lead to the same organ. The second group of mutants carry recessive alleles of two leafy lemma genes, both of which are necessary to cause the transformation of the lemma into a structure having all characteristics of a vegetative leaf, as shown by SEM analysis. The presence of sheath, blade, and ligule in the mutant lemma suggests that wild-type lemma development is interrupted at a leaf-like stage. The genes cal a, b, C, d, 23, lel1, and lel2 have now been mapped at precise positions on linkage groups 2, 7, 7, 3, 7, 5, and 7, respectively. The mutants considered in this article are unaffected in other floral organs. A model for lemma development is suggested.

Spontaneous multivessel coronary artery dissection: repeated presentation in a healthy postmenopausal woman.

Spontaneous coronary artery dissection is a rare cause of acute myocardial infarction which is infrequently diagnosed antemortem. Most previously reported cases were found in women of whom a significant proportion presented during pregnancy or the postpartum period. We describe the first antemortem case of spontaneous coronary artery dissection, unrelated to pregnancy or the postpartum state, which ultimately resulted in diffuse involvement of both the left and right coronary arteries over a period of 4 months. Pathophysiology and case management of this disorder are discussed.

Determining the vertical and horizontal positioning of multifocal and progressive lenses.

The key to success with any ophthalmic spectacle prescription is not only the accurate determination of the refractive prescription, but the proper selection and fitting of the ophthalmic frame and lenses. Proper selection and fitting are especially important with bifocals, trifocals, or progressive lenses, which present many variables other than inaccurate interpupillary distance measurement that can lead to patient dissatisfaction. This article discusses fitting procedures for patients with new or existing multifocals. It reviews how to determine proper multifocal segment heights; and calculate distant decentration, inset, and total inset measurements; and it addresses issues involving variations in frame size and patient temperament.

Inhibition of Cdk2 activation by selected tyrphostins causes cell cycle arrest at late G1 and S phase.

We have previously reported that certain tyrphostins which block EGF-R phosphorylation in cell-free systems fail to do so in intact cells. Nevertheless, we found that this family of tyrphostins inhibits both EGF- and calf serum-induced cell growth and DNA synthesis [Osherov, N.A., Gazit, C., Gilon, and Levitzki, A. (1993). Selective inhibition of the EGF and HER2/Neu receptors by Tyrphostins. J. Biol. Chem. 268, 11134-11142.] Now we show that these tyrphostins exert their inhibitory activity even when added at a time when the cells have already passed their restriction point and receptor activation is no longer necessary. AG555 and AG556 arrest 85% of the cells at late G1, whereas AG490 and AG494 cause cells to arrest at late G1 and during S phase. No arrest occurs during G2 or M phase. Further analysis revealed that these tyrphostins act by inhibiting the activation of the enzyme Cdk2 without affecting its levels or its intrinsic kinase activity. Furthermore, they do not alter the association of Cdk2 to cyclin E or cyclin A or to the inhibitory proteins p21 and p27. These compounds also have no effect on the activating phosphorylation of Cdk2 by Cdk2 activating kinase (CAK) and no effect on the catalytic domain of cdc25 phosphatase. These compounds lead to the accumulation of phosphorylated Cdk2 on tyrosine 15 which is most probably the cause for its inhibition leading to cell cycle arrest at G1/S. A structure-activity relationship study defines a very precise pharmacophore, suggesting a unique molecular target not yet identified and which is most probably involved in the regulation of the tyrosine-phosphorylated state of Cdk2. These compounds represent a new class of cell proliferation blockers whose target is Cdk2 activation.

A meiosis-specific protein kinase, Ime2, is required for the correct timing of DNA replication and for spore formation in yeast meiosis.

In this report we study the regulation of premeiotic DNA synthesis in Saccharomyces cerevisiae. DNA replication was monitored by fluorescence-activated cell sorting analysis and by analyzing the pattern of expression of the DNA polymerase alpha-primase complex. Wild-type cells and cells lacking one of the two principal regulators of meiosis, Ime1 and Ime2, were compared. We show that premeiotic DNA synthesis does not occur in ime1 delta diploids, but does occur in ime2 delta diploids with an 8-9 h delay. At late meiotic times, ime2 delta diploids exhibit an additional round of DNA synthesis. Furthermore, we show that in wild-type cells the B-subunit of DNA polymerase alpha is phosphorylated during premeiotic DNA synthesis, a phenomenon that has previously been reported for the mitotic cell cycle. Moreover, the catalytic subunit and the B-subunit of DNA polymerase alpha are specifically degraded during spore formation. Phosphorylation of the B-subunit does not occur in ime1 delta diploids, but does occur in ime2 delta diploids with an 8-9 h delay. In addition, we show that Ime2 is not absolutely required for commitment to meiotic recombination, spindle formation and nuclear division, although it is required for spore formation.

The titanium grommet in flexible implant arthroplasty of the radiocarpal joint: a long-term review of 44 cases.

Flexible implant arthroplasty of the radiocarpal joint has come under increasing criticism since its introduction in 1967. Recent long-term reviews report high failure and revision rates. In 1984, titanium grommets became available. By providing a protective interface between sharp bone edges and the flexible hinge device, this refinement raised hope for improved performance. This report provides the first long-term review of the grommet's efficacy. The overall success rate was 95 percent. No implant fractures were observed in the setting of nondisplaced grommets; however, one implant did fracture in association with grommet displacement. Radiographic review of cortical bone density showed an increase in the region of the grommet in virtually all cases. These results offer significant improvement over those reported for flexible implant radiocarpal wrist arthroplasties done without protective grommets. The results suggest a wider indication for implant arthroplasty of the radiocarpal joint and hold promise for longer-term durability.

Lack of long-term ventricular arrhythmia reduction by enalapril in heart failure. SOLVD Investigators.

Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mostly small and of short duration. We prospectively studied 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction < or = 35%). Five hundred fifty-three patients from the prevention trial and 181 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months of double-blind therapy with either placebo or enalapril (2.5 to 10 mg twice daily). The prospectively defined primary analysis was by intent-to-treat and revealed no significant differences in ventricular premature complexes between the placebo and enalapril groups at baseline (87 +/- 13 vs 84 +/- 13/hour), 4 months (100 +/- 15 vs 85 +/- 12/hour), or 12 months (80 +/- 12 vs 90 +/- 14/hour). Likewise, there was no difference between the placebo and enalapril groups in runs of nonsustained ventricular tachycardia: baseline (8.3 +/- 4.1 vs 1.9 +/- 0.4 runs/day), 4 months (16 +/- 12 vs 7.2 +/- 4.1 runs/day), or after 12 months of blinded therapy (11 +/- 7.0 vs 6.1 +/- 4.4 runs/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arrhythmic events in the postinfarction period. The Cardiac Arrhythmia Suppression Trial/Signal-Averaged Electrocardiogram (CAST/SAECG) Substudy Investigators.

OBJECTIVES: The goal of this study was to establish guidelines for the prognostic use of the time domain signal-averaged electrocardiogram (ECG) after myocardial infarction. BACKGROUND: Previous studies of the prognostic use of the signal-averaged ECG in postinfarction patients had one or more of the following limitations: a small study group, empiric definition of an abnormal recording and possible bias in the selection of high risk groups or classification of arrhythmic events, or both. To correct for these limitations, a substudy was conducted in conjunction with the Cardiac Arrhythmia Suppression Trial (CAST). METHODS: Ten centers recruited 1,211 patients with acute myocardial infarction without application of the ejection fraction or Holter criteria restrictions of the main CAST protocol. Several clinical variables, ventricular arrhythmias on the Holter recording, ejection fraction and six signal-averaged ECG variables were analyzed. Patients with bundle branch block were excluded from the analysis, and the remaining 1,158 were followed for up to 1 year after infarction. The classification of arrhythmic events was reviewed independently by the CAST Events Committee. RESULTS: During an average (+/- SD) follow-up of 10.3 +/- 3.2 months, 45 patients had a serious arrhythmic event (nonfatal ventricular tachycardia or sudden cardiac arrhythmic death). A Cox regression analysis with only the six signal-averaged ECG variables indicated that the filtered QRS duration at 40 Hz > or = 120 ms (QRSD-40 Hz) at a cutpoint > or = 120 ms was the most predictive criterion of arrhythmic events. In a regression analysis that included all clinical, Holter and ejection fraction variables, a QRSD-40 Hz > or = 120 ms was the most significant predictor (p < 0.0001). The positive, negative and total predictive accuracy and odds ratio for QRSD-40 Hz > or = 120 ms were 17%, 98%, 88% and 8.4, respectively, and improved to 32%, 97%, 94% and 16.7, respectively, after combination with ejection fraction < or = 40% and complex ventricular arrhythmias on the Holter recording. CONCLUSIONS: The signal-averaged ECG predicts serious arrhythmic events in the first year after infarction better than do clinical, ejection fraction and ventricular arrhythmia variables, and QRSD-40 Hz > or = 120 ms provides the best predictive criterion in this clinical setting.

The cardiac mutant gene c in axolotls: cellular, developmental, and molecular studies.

The cardiac mutant axolotl is an interesting model for studying heart development. The mutant gene results in a failure of heart cells to form organized myofibrils and as a consequence the heart fails to beat. Experiments have shown that mutant hearts can be "rescued" (i.e., turned into normally contracting organs) by the addition of RNA purified from conditioned media produced by normal embryonic anterior endoderm-mesoderm cultures. These corrected hearts form myofibrils of normal morphology. New advances in recombinant DNA technology applied to this system should provide significant insights into the regulatory mechanisms of myofibrillogenesis as well as the inductive processes related to the control of gene expression during embryonic heart development. In a broader biological sense, the use of gene c in axolotls is potentially capable of helping to solve major unanswered questions in modern biology related to the genetic regulation of differentiation in vertebrates.