Ketogenic nutritional therapy (KeNuT)-a multi-step dietary model with meal replacements for the management of obesity and its related metabolic disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-diet therapies in endocrinology and metabolism.

PURPOSE: The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. METHODS: This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. CONCLUSION: This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)-Diet Therapies in Endocrinology and Metabolism.

Role of Mediterranean diet in endocrine diseases: a joint overview by the endocrinologist and the nutritionist.

PURPOSE: The purpose of this review is to examine the current evidence on the potential role of Mediterranean diet (MD) in the prevention and management of endocrine disorders and to highlight the importance of interdisciplinary collaboration between endocrinologists and nutritionists. METHODS: A literature search was conducted using PubMed and Google Scholar databases to identify relevant studies published in English. Studies were selected based on their relevance to the role of MD in the prevention and management of endocrine disorders. The search terms included "Mediterranean diet," "endocrine disorders," "thyroid disorders," "gonadal disorders," and "neuroendocrine tumors". RESULTS: The studies reviewed suggest that MD may have a beneficial effect in the prevention and management of various endocrine disorders, including thyroid disorders, gonadal disorders, and neuroendocrine tumors. MD has been associated with decreased risk of nodular thyroid disease and thyroid cancer, improved male and female reproductive health, and a potential role in the management of neuroendocrine tumors. MD's anti-inflammatory and antioxidant properties, as well as its high levels of phytochemicals, may play a role in its beneficial effects. CONCLUSION: Interdisciplinary collaboration between endocrinologists and nutritionists is essential for the optimal management of endocrine disorders, including the potential role of MD in their prevention and management. While further research is needed, the current evidence suggests that MD may have a protective effect against endocrine disorders, and its incorporation into dietary recommendations may be beneficial.

Obesity: a gender-view.

PURPOSE: There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on anthropometric characteristics and nutritional and pharmacological aspects of obesity from a gender perspective. METHODS: A literature search within PubMed was performed. Selected publications related to obesity and gender differences were reviewed. RESULTS: The prevalence of obesity among men is higher than in women, but women have a higher percentage of body fat content compared to men, and gender appears to be an important factor in the manifestation of central (android) or peripheral (gynoid) obesity. In addition, while in most clinical trials, women are still underrepresented, in clinical registration trials of anti-obesity drugs, women are commonly up-represented and gender-specific analysis is uncommon. Considering that adipose tissue is one of the factors affecting the volume of distribution of many drugs, mainly lipophilic drugs, gender differences might be expected in the pharmacokinetics and pharmacodynamics of anti-obesity drugs. Indeed, although Liraglutide 3 mg, a long-acting glucagon-like peptide-1 receptor agonist, and naltrexone/bupropion display lipophilic properties, currently, a gender-dose adjustment for both these drugs administration is not recommended. In addition, despite that predicted responders to treatment offer substantial opportunities for efficient use, especially of expensive new therapies, such as anti-obesity drugs, data on gender differences to identify early responders to both these have not yet been investigated. Finally, bariatric surgery gender disparity reflects healthcare practices. Weight loss similar, but differing effects: women need more correction and face psychology challenges; men have worse physiology and fewer comorbidity improvements. CONCLUSION: Gender differences exist in obesity prevalence and phenotype, body fat distribution, drug efficacy, clinical trial representation, and different secondary effects of bariatric surgery. Gender is an important variable in obesity analysis.

Effects of very low-calorie ketogenic diet on hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in controlling stress responses in humans under physiological and pathological conditions; cortisol is the main hormone produced by the HPA axis. It is known that calorie restriction acts as a stressor and can lead to an increase in cortisol production. Renin-angiotensin-aldosterone system (RAAS) is a complex endocrine network regulating blood pressure and hydrosaline metabolism, whose final hormonal effector is aldosterone. RAAS activation is linked to cardiometabolic diseases, such as heart failure and obesity. Obesity has become a leading worldwide pandemic, associated with serious health outcomes. Calorie restriction represents a pivotal strategy to tackle obesity. On the other hand, it is well known that an increased activity of the HPA may favour visceral adipose tissue expansion, which may jeopardize a successful diet-induced weight loss. Very low-calorie ketogenic diet (VLCKD) is a normoprotein diet with a drastic reduction of the carbohydrate content and total calorie intake. Thanks to its sustained protein content, VLCKD is extremely effective to reduce adipose tissue while preserving lean body mass and resting metabolic rate. PURPOSE: The purpose of this narrative review is to gain more insights on the effects of VLCKD on the HPA axis and RAAS, in different phases of weight loss and in different clinical settings.

Liraglutide and polycystic ovary syndrome: is it only a matter of body weight?

Despite Polycystic Ovary Syndrome (PCOS) is a very prevalent disorder among women of reproductive age, there is widespread agreement that until now, no pharmacological options are available to tackle the entire spectrum of clinical manifestations encountered in the clinical practice. Obesity and insulin resistance, which commonly characterized this syndrome, prompted the design of studies investigating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) in PCOS. Indeed, a very impressive number of randomized controlled clinical trials (RCTs) and systematic reviews provided robust evidence on the effectiveness of GLP-1RA in PCOS as a new, appealing approach, producing both satisfactory and permanent weight loss, and improvement of insulin resistance at the same time. However, most of the subjects included in the RCTs are PCOS patients with obesity/overweight, whereas a portion of PCOS women, which can even reach 50%, might present a lean phenotype. Moreover, some benefits on clinical and metabolic features of PCOS may not have fully emerged due to the low or medium doses employed in the vast majority of the current studies. Thus, pitfalls in the methodology of these studies have led sometimes to misleading results. In addition, some aspects of GLP-1 beyond weight loss, such as preclinical evidence on GLP-1 effects in directly modulating the hypothalamus-pituitary-gonadal axis, or the effects of GLP-1RA on clinical and biochemical expression of hyperandrogenism, still deserve a greater insight, especially in light of a possible therapeutic use in PCOS women independently of obesity. Aim of this review is to further unravel the possible role of GLP-1 in PCOS pathogenesis, tempting to provide additional supports to the rationale of treatment with GLP-1RA in the management of PCOS also independent of weight loss. For this purpose, the outcomes of RCTs investigating in PCOS the anthropometric and metabolic changes have been treated separately to better underpin the effects of GLP-1 RA, in particular liraglutide, beyond weight loss.

Vitamin D and chronotype: is there any relationship in individuals with obesity?

PURPOSE: Chronotype is the attitude to perform most of the daily activities in the morning ("morning chronotype", MC) or in the evening ("evening chronotype", EC). The latter, as well as vitamin D deficiency, has been associated with an increased risk of obesity-related complications, likely through the promotion of insulin resistance. Therefore, we aimed to investigate whether there is any relationship between vitamin D (25-OH-D) and chronotype in individuals with obesity. METHODS: In this cross-sectional study, we enrolled 59 individuals (43.1 ± 13 years; 17M/42F) with obesity. Anthropometric parameters, lifestyle habits, personal medical history, chronotype, insulin resistance, and 25-OH-D were assessed. RESULTS: Individuals with EC presented significantly higher BMI than MC (p < 0.001), greater waist (p = 0.012), and hip circumferences (p = 0.001). Individuals with EC showed significantly lower insulin sensitivity (p = 0.017) and 25-OH-D than MC. In addition, the prevalence of vitamin D deficiency and impaired fasting glucose was significantly higher in EC than in MC. 25-OH-D directly correlated with chronotype score (r = 0.351; p = 0.019) whereas inversely with BMI (r = - 0.363; p = 0.016). The regression analysis showed that BMI was most tightly associated with 25-OH-D concentrations (ß = - 0.323, p = 0.032), followed by chronotype score (ß = 0.340, p = 0.042). Using chronotype score as the dependent variable, BMI significantly predicted a lower chronotype score (ß = - 0.586, p < 0.001). CONCLUSION: The present study showed that 25-OH-D, as well as chronotype, correlate independently with obesity.

Weight stigma speaks Italian, too.

PURPOSE: Weight stigma is the negative weight related attitudes and beliefs towards individuals because of their overweight or obesity. Subjects with obesity are often victim of weight-related stigma resulting in a significant negative social consequence. As obesity epidemic is growing so fast, there is urgency to act on weight-stigma related social consequences being potentially serious and pervasive. This study investigated experiences, interpersonal sources, and context of weight stigma in Italy in a sample of adult subjects with obesity. METHODS: An online questionnaire was distributed to respondents via a snowball sampling method among subjects with obesity belonging to Italian Associations for people living with obesity aged 18 years and above. RESULTS: Four hundred and three respondents (47.18 ± 9.44 years; body mass index (BMI) 33.2 ± 8.48 kg/m2) participated to the study. Most respondents were females (94.8%). The age first dieted was 15.82 ± 7.12 years. The mean period of obesity was 27.49 ± 11.41 years. Frequency analyses reported that stigmatizing situations were experienced by 98% of participants: 94.82% during adulthood, 89.88% during adolescence and 75.39% during childhood. Verbal mistreatments (92.43%) was the most reported stigmatizing situation, strangers (92.43%) were the most common interpersonal sources of stigma and public settings (88.08%) were the most common location of stigma. CONCLUSIONS: Identifying strategies acting on the identified weight stigma targets could contribute to reduce weight stigma and thus to result in important implications for obesity treatment in Italy.

From the inside out: a new species of armoured catfish Corydoras with the description of poorly-explored character sources (Teleostei, Siluriformes, Callichthyidae).

A new species of the armoured catfish genus Corydoras is described from the Xingu-Tapajos ecoregion, Brazilian Amazon. The new species can be distinguished from its congeners by having the following combination of features: short mesethmoid, with anterior tip poorly developed, smaller than 50% of bone length; posterior margin of pectoral spine with serrations directed towards spine tip or perpendicularly oriented; infraorbital 2 only in contact with sphenotic; ventral laminar expansion of infraorbital 1 poorly or moderately developed; flank midline covered by small dark brown or black saddles with similar size to remaining markings on body; relatively larger, scarcer and more sparsely distributed dark brown or black spots on body; absence of stripe on flank midline; caudal fin with conspicuous dark brown or black spots along its entire surface; slender body; and strongly narrow frontals. A more comprehensive description of poorly-explored internal character sources, such as the gross morphology of the brain, Weberian apparatus and swimbladder capsule elements is presented.

Pancratium triflorum Roxb. (Amaryllidaceae) and Molineria trichocarpa (Wight) N.P. Balakr (Hypoxidaceae): Cytotoxic and antioxidant activities.

The present investigation was carried out to evaluate the antioxidant and cytotoxic activities of Pancratium triflorum Roxb and Molineria trichocarpa were collected from South Vagaikulam, Tirunelveli district, Tamil Nadu, India. The antioxidant activities of P. triflorum extracts were as follows with the IC50 values methanol (228.13 µg/mL) > chloroform (311.33 µg/mL) > acetone (398.08 µg/mL) > petroleum ether (410.16 µg/mL). The antioxidant activities of P. triflorum and M. trichocarpa extracts were as follows with the IC50 values methanol (80.93 µg/mL) > acetone (98.02 µg/mL) > chloroform (186.84 µg/mL) > petroleum ether (209.64 µg/mL). Among the various extracts of P. triflorum, methanolic extracts showed the strongest phosphomolybdenum reduction (140.56 g AA/100 g). Among the tested extracts, acetone extracts of M. trichocarpa showed maximum inhibition with 71.36 ±â€¯5.86%. In P. triflorum, chloroform extracts showed maximum inhibition (69.51%). The petroleum ether extract of M. trichocarpa was found to be most effective at which 50% mortality (LC50) and 90% mortality (LC90) of brine shrimp nauplii were found to be 29.22 and 184.82 mg/mL. This study results revealed the antioxidant and cytotoxic properties of P. triflorum and M. trichocarpa. Further investigations are needed to isolate and validate the active principles of the extract responsible various pharmacological properties.

Bone marrow concentrated cells and stromal vascular fraction cells injections for osteoarthritis treatment: a systematic review.

The aim of this systematic review is to examine current clinical evidences supporting the intraarticular injection of bone marrow concentrate cells (BMC) and adipose-derived stromal vascular fraction cells (SVF) for the treatment of osteoarthritis (OA). The research was performed on PubMed (Medline), EMBASE and Cochrane Library considering the English literature. Only clinical trials have been included. The systematic research identified twelve clinical trials. Articles included in the study, were one of level II, four of level III, six of level IV and one level V. Among clinical trials, none were randomized, four were comparative, seven were case series, and one was a case report. Seven studies were focused on the use of SVF (1332 patients) and five on the use of BMC (963 patients), with preliminary interesting findings in the OA treatment. Despite the growing interest in this biological approach for OA, knowledge on this topic is still preliminary. Randomized controlled trials are needed to support the potential of BMC and SVF injections and to evaluate advantages and disadvantages with respect to the available treatments.

E2F4 plays a key role in Burkitt lymphoma tumorigenesis.

Sporadic Burkitt lymphoma (sBL) is a rapidly growing B-cell non-Hodgkin's lymphoma whose treatment requires highly aggressive therapies that often result severely toxic. Identification of proteins whose expression or function is deregulated in sBL and play a role in its formation could facilitate development of less toxic therapies. We have previously shown that E2F1 expression is deregulated in sBL. We have now investigated the mechanisms underlying E2F1 deregulation and found that the E2F sites in its promoter fail to repress its transcriptional activity in BL cells and that the transcriptional repressor E2F4 barely interacts with these sites. We also have found that E2F4 protein levels, but not those of its mRNA, are reduced in sBL cell lines relative to immortal B-cell lines. E2F4 protein expression is also decreased in 24 of 26 sBL tumor samples from patients compared with control tissues. Our data demonstrate that enforced E2F4 expression in BL cells not only diminishes E2F1 levels, but also reduces selectively the tumorigenic properties and proliferation of BL cells, while increasing their accumulation in G(2)/M. Our results therefore point to E2F4 as a target for developing novel and less toxic treatments for sBL.

Identification of MNDA as a new marker for nodal marginal zone lymphoma.

Clinical and biological studies on nodal marginal zone lymphoma (NMZL) are hampered by the lack of specific diagnostic markers and the low reproducibility of this diagnosis. A comparative expression-profiling study has shown a set of markers to be differentially expressed in NMZL compared with follicular lymphoma (FL), including myeloid cell nuclear differentiation antigen (MNDA), a nuclear protein expressed by myeloid cells and a subset of B-cells. The aim of this study was to characterize the expression of MNDA in normal and reactive human tissue, and in a large series of non-Hodgkin's B-cell lymphomas, with particular emphasis on NMZL and FL. Our results showed that MNDA is expressed in normal tissue by a subset of the marginal zone B cells. They also showed MNDA expression in subgroups of chronic lymphocytic leukemia, mantle-cell lymphoma, and diffuse large B-cell lymphoma, but MNDA was especially expressed by lymphomas derived from the marginal zone, such as mucosa-associated lymphoid-tissue lymphoma, splenic marginal-zone lymphoma and NMZL. MNDA expression was rarely observed in FL, a characteristic that is of potential value in distinguishing between NMZL and FL. MNDA expression is thus a useful tool for the recognition of NMZL.

beta-Catenin, Nf-kappaB and FAS protein expression are independent events in head and neck cancer: study of their association with clinical parameters.

In spite of much effort, no good markers have yet been found for predicting prognosis or response to therapy in advanced head and neck squamous cell carcinoma (HNSCCs) patients. beta-catenin, a protein involved in the cytoskeleton, cell-cell adhesion and gene transcription, is a factor associated with tumour progression. Recently, an interaction has been reported between beta-catenin, and NF-kappaB coupled with an inverse association of beta-catenin, and FAS (CD95/APO-1) protein expression in breast and colorectal tumours. To confirm these observations and to test their clinical impact in HNSCCs we have evaluated the expression of beta-catenin, NF-kappaB and FAS proteins. We used tissue microarrays to simultaneously analyse the levels of these proteins immunohistochemically in 118 HNSCCs. Among the 113 tumours evaluable for beta-catenin, increased and decreased levels were detected in 41 (36%) and 62 (55%) of the tumours, respectively. beta-catenin, protein staining was mainly membranous but 10 tumours (9%) showed the clear presence of protein in the cytoplasm, and none in the nucleus. Moreover, 81% of the tumours had decreased FAS protein expression, indicating that loss of FAS protein is a common feature of HNSCCs. Abnormal or nuclear NF-kappaB staining was observed in 24% of the tumours. No association was detected between the expression levels of the proteins evaluated. Regarding clinical associations, tumours from the hypopharynx had significantly lower levels of beta-catenin expression than those from other locations (P<0.05). Moreover, our data revealed that patients whose tumours had low levels of beta-catenin protein expression had decreased survival probability (24.8 months vs. NR, P=0.03) and reduced response to therapy (15.4 vs. 43 months; P=0.01) compared with patients whose tumours had high levels of beta-catenin. Taken together, our observations indicate that beta-catenin, NF-kappaB and FAS expression are independent events during HNSCC development and that levels of beta-catenin protein may identify subsets of advanced HNSCCs patients with different prognosis and response to therapy capabilities.

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma.

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.

Occurrence and biogeographic aspects of Melipona quinquefasciata in NE Brazil (Hymenoptera, Apidae)

The stingless bee Melipona quinquefasciata is not included among the nine bee species of Melipona described in literature of NE Brazil. However, reports of some farmers raised suspicion on the occurrence of M. quinquefasciata in the state of Ceará, in NE Brazil. Investigations were carried out from July 1997 to September 2000, by means of trips to the areas of probable occurrence of this bee species. Results confirmed the presence of M. quinquefasciata in Ceará and determined its habitat along the chapada do Araripe (Araripe plateau) and all extension of planalto da Ibiapaba (Ibiapaba plateau), in altitudes between 600 and 900 m. Melipona quinquefasciata lives in the phytocoenosis of cerrado (Brazilian savanna), cerradão (savanna forest) and carrasco (montane deciduous shrub vegetation) on the top of Araripe plateau, and only carrasco in the Ibiapaba plateau. Due to pressures caused by reduction of the area covered with native vegetation, large use of agrochemicals in anthropic areas and generalised predatory hunting of honey and beeswax, M. quinquefasciata is in risk of disappearing from the ecosystems of Araripe and Ibiapaba plateaus within a few years.

A abelha sem ferrão Melipona quinquefasciata não consta entre as nove espécies de Melipona relatadas na literatura para o Nordeste do Brasil. Porém, relatos de agricultores levaram à suspeita de sua ocorrência no Ceará. Investigações foram conduzidas de julho de 1997 a setembro de 2000, por meio de viagens sistemáticas às áreas de provável ocorrência. Os resultados confirmaram a presença de M. quinquefasciata no Ceará e determinaram seu habitat ao longo da chapada do Araripe e toda a extensão do planalto da Ibiapaba/Serra Grande, em altitudes variando entre 600 e 900 m. Melipona quinquefasciata ocupa as fitocenoses de cerrado, cerradão e carrasco sobre a chapada do Araripe, e apenas o carrasco no planalto da Ibiapaba/Serra Grande. Devido a pressões causadas à espécie pela redução da área coberta com vegetação nativa, ao uso indiscriminado de agrotóxicos nas áreas antropizadas e ao extrativismo de mel e cera feito de forma predatória e em larga escala, M. quinquefasciata corre o risco de desaparecer dos ecossistemas da chapada do Araripe e planalto da Ibiapaba/Serra Grande em alguns anos.

Occurrence and biogeographic aspects of Melipona quinquefasciata in NE Brazil (Hymenoptera, Apidae)

The stingless bee Melipona quinquefasciata is not included among the nine bee species of Melipona described in literature of NE Brazil. However, reports of some farmers raised suspicion on the occurrence of M. quinquefasciata in the state of Cearß, in NE Brazil. Investigations were carried out from July 1997 to September 2000, by means of trips to the areas of probable occurrence of this bee species. Results confirmed the presence of M. quinquefasciata in Cearß and determined its habitat along the chapada do Araripe (Araripe plateau) and all extension of planalto da Ibiapaba (Ibiapaba plateau), in altitudes between 600 and 900 m. Melipona quinquefasciata lives in the phytocoenosis of cerrado (Brazilian savanna), cerradõo (savanna forest) and carrasco (montane deciduous shrub vegetation) on the top of Araripe plateau, and only carrasco in the Ibiapaba plateau. Due to pressures caused by reduction of the area covered with native vegetation, large use of agrochemicals in anthropic areas and generalised predatory hunting of honey and beeswax, M. quinquefasciata is in risk of disappearing from the ecosystems of Araripe and Ibiapaba plateaus within a few years

Occurrence and biogeographic aspects of Melipona quinquefasciata in NE Brazil (Hymenoptera, Apidae).

The stingless bee Melipona quinquefasciata is not included among the nine bee species of Melipona described in literature of NE Brazil. However, reports of some farmers raised suspicion on the occurrence of M. quinquefasciata in the state of Ceará, in NE Brazil. Investigations were carried out from July 1997 to September 2000, by means of trips to the areas of probable occurrence of this bee species. Results confirmed the presence of M. quinquefasciata in Ceará and determined its habitat along the chapada do Araripe (Araripe plateau) and all extension of planalto da Ibiapaba (Ibiapaba plateau), in altitudes between 600 and 900 m. Melipona quinquefasciata lives in the phytocoenosis of cerrado (Brazilian savanna), cerradão (savanna forest) and carrasco (montane deciduous shrub vegetation) on the top of Araripe plateau, and only carrasco in the Ibiapaba plateau. Due to pressures caused by reduction of the area covered with native vegetation, large use of agrochemicals in anthropic areas and generalised predatory hunting of honey and beeswax, M. quinquefasciata is in risk of disappearing from the ecosystems of Araripe and Ibiapaba plateaus within a few years.

Non-gaussianity versus nonlinearity of cosmological perturbations.

Following the discovery of the cosmic microwave background, the hot big-bang model has become the standard cosmological model. In this theory, small primordial fluctuations are subsequently amplified by gravity to form the large-scale structure seen today. Different theories for unified models of particle physics, lead to different predictions for the statistical properties of the primordial fluctuations, that can be divided in two classes: gaussian and non-gaussian. Convincing evidence against or for gaussian initial conditions would rule out many scenarios and point us toward a physical theory for the origin of structures. The statistical distribution of cosmological perturbations, as we observe them, can deviate from the gaussian distribution in several different ways. Even if perturbations start off gaussian, nonlinear gravitational evolution can introduce non-gaussian features. Additionally, our knowledge of the Universe comes principally from the study of luminous material such as galaxies, but galaxies might not be faithful tracers of the underlying mass distribution. The relationship between fluctuations in the mass and in the galaxies distribution (bias), is often assumed to be local, but could well be nonlinear. Moreover, galaxy catalogues use the redshift as third spatial coordinate: the resulting redshift-space map of the galaxy distribution is nonlinearly distorted by peculiar velocities. Nonlinear gravitational evolution, biasing, and redshift-space distortion introduce non-gaussianity, even in an initially gaussian fluctuation field. I investigate the statistical tools that allow us, in principle, to disentangle the above different effects, and the observational datasets we require to do so in practice.

Unique phenotypic profile of monocytoid B cells: differences in comparison with the phenotypic profile observed in marginal zone B cells and so-called monocytoid B cell lymphoma.

Monocytoid B cells (MBCs) are a subset of B cells that may be recognized in several reactive and tumoral lymph node conditions, including toxoplasmic lymphadenitis, infectious mononucleosis, and Hodgkin's lymphoma. Although this is a commonly observed cell population, which has even given its name to a type of lymphoma, MBC lymphoma, scarcely any information is available about the function and characteristics of this cell type. A relationship with marginal zone (MZ) B lymphocytes has been claimed for MBCs, but this has not yet been fully proven. Indeed, specific markers for MBCs are still lacking, which has made it difficult to analyze their relationship with other B cell subpopulations and confirm the existence of tumors deriving from this B cell subset. We used a panel of cell cycle markers to explore the characteristics of MBCs and their relationship with MZ B cells, nodal MZ lymphoma, and splenic MZ lymphoma. We therefore compared the phenotypic profile of MBCs in different conditions with normal MZ B cells within the spleen and mesenteric lymph nodes, with a group of seven cases of nodal MZ/MBC lymphoma and another group of five cases of splenic MZ lymphoma. MBCs were mainly in the G(0) to G(1) phases, as deduced from the presence of a proportion of between 10 and 35% Ki67-positive cells, whereas very low expression was observed with cyclin A and cyclin B staining. Nests of MBCs were clearly labeled by the expression of p21(WAF1), a cyclin-dependent kinase inhibitor (CKI), rarely detectable in benign lymphocytes, and by cyclin E. Basically all MBCs were bcl-2-negative, and high cyclin D2 and cyclin D3 were also detected in these cells, at proportions and intensities above expected levels, when the percentage of proliferating cells was taken into account. p27(KIP1) expression was characterized by homogeneous reactivity, higher than that observed in other B cell populations with a relatively high-growth fraction. Immunoglobulin staining showed undetectable light and heavy chains. However, splenic MZ cells, nodal MZ lymphoma, and splenic MZ lymphoma showed a distinct expression of IgM and bcl-2, with high p27 (KIP1) nuclear expression and undetectable or low levels of cyclin A, B, E, or D, or p21(WAF1) expression. The data from this study show an unexpected immunophenotype in MBCs, different from the one observed in splenic and lymph node MZ B cells. This suggests that either MBCs are a unique B cell population from a distinct cell lineage, or if related to MZ cells, they would represent a definite differentiation stage characterized by a distinctive immunophenotype. They also show so-called MZ/MBC lymphoma to be more closely related to lymph node and splenic MZ B cells, as they do not share the most distinctive features of MBCs.