A case of severe allergic eosinophilic asthma with nasal polyposis in a patient affected by Birt-Hogg-Dubé syndrome successfully treated with benralizumab.

SUMMARY: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic pathology characterized by cutaneous fibrofolliculomas, pulmonary cysts and kidney tumours. Severe asthma is the most serious form of asthma that does not respond to standard treatments. We present the case of a 68 years-old male patient who had frequent respiratory tract infections, shortness of breath and decline in lung function, nasal polyposis and hypertrophy of the nasal turbinates, for this reason was treated as a severe asthmatic patient for several years with ICS + LABA and high doses of OCS. When we tried to reduce OCS the patient had worsening of the symptoms, we requested a HRTC scan that showed presence of several cysts spread ubiquitously. The patient had a family history of pneumothorax, for this reason we requested a genetic test that resulted in a heterozygous point mutation on exon 12 (c.1429 C > T) of FLCN gene. Despite the diagnosis of BHD syndrome, the patient's clinical condition kept on suggesting an underlying severe asthma and the blood tests we requested pointed out a high percentage of eosinophils, for this reason we opted for the administration of benralizumab that resulted in an excellent asthma control and increased quality of life.

Production of Hydronium Ion (H3O)+ and Protonated Water Clusters (H2O)nH+ after Energetic Ion Bombardment of Water Ice in Astrophysical Environments.

Water ice exists on many objects in space. The most abundant icy species, among them water, are present in the icy satellites of the outer Solar System giant planets. The nuclei of comets, which are mainly composed of water ice, give another example of its abundance. In the interstellar medium (ISM), ice mantles, formed by molecular species sticking on dust grains, consist mainly of water ice. All these objects are exposed to ionizing radiation like ions, UV photons, and electrons. Sputtering of atoms, molecules, ions, and radicals from icy surfaces may populate and maintain exospheres of icy objects in the Solar System. In other respects, ionized hydrides such as OH+, H2O+, and H3O+ have been detected in the gas phase in star-forming regions. Interactions with cosmic rays could be an additional explanation to the current models for the formation of those species. In fact, laboratory simulations showed that the main components of the sputtered ionic species from water ice are oxygen hydrides. In this work, water ice targets were irradiated at several temperatures (10-200 K) by 90 keV O6+ ions, yielding an electronic stopping power of about 12 eV/Å, when the nuclear stopping power is comparable to the electronic stopping power. Sputtering of secondary ions after bombardment of the ice target was analyzed by time-of-flight mass spectrometry (TOF-SIMS). Besides hydrogen ions (H+, H2+, H3+), also O+, O2+, OH+, (H2O)+, and clusters of (H2O)nH+ with n = 1-8 are emitted. Our results show a progressive yield decrease with increasing temperature of all of the detected species. This is related to the structure of the ice: the ionic sputtering yield for crystalline ice is much lower than for an amorphous ice. For instance, amorphous ice at 10 K exhibits a yield of the order of 2 × 10-6 secondary (H2O)nH+ hydride ions/projectile (with n = 1-8). As the temperature is increasing toward the phase transition to crystalline ice, the yields decrease by about one order of magnitude.

Alpha-lipoic acid, but not di-hydrolipoic acid, activates Nrf2 response in primary human umbilical-vein endothelial cells and protects against TNF-α induced endothelium dysfunction.

The antioxidants role in cell response regulation attracted great interest in the last decades and it is undergoing to a profound reconsideration. The mere concept of "biological antioxidant" has been frequently misconceived or misused, possibly leading to the misinterpretation of some experimental observation. Organosulfur compounds in general and α-lipoic acid, a dithiol molecule, can be considered a typical example of the kind. Reduced α-lipoic acid, dehydrolipoic acid has been in fact originally considered a bona fide, reducing, electron donor molecule. A more recent approach, according to stoichiometric and thermodynamic evidences, lead to a reinterpretation of the biochemical role of "antioxidants". The electrophilic nature of oxidized nucleophilic molecules, including α-lipoic acid, renders more plausible a mechanism based on the ability to activate Nrf2/EpRE mediated hormetic response. In this study, we demonstrate that nmolar concentrations of oxidized α-lipoic acid, but not dehydrolipoic acid, protect human umbilical primary endothelial cells (HUVEC) from TNF-α induced dysfunction, inhibit NF-κB activation and block apoptosis following the activation of Nrf2 transcription factor. Our observations corroborate the concept that the major, if not the unique, mechanism by which α-lipoic acid can non-enzymatically exert its reducing activity is related to the electrophilic nature of the oxidized form.

Relationship between serum anti-Mullerian hormone and intrafollicular AMH levels in PCOS women.

Polycystic ovary syndrome is a complex disease characterized by various endocrine disorders that are the potential cause of anovulation and hyperandrogenism. Anti-Müllerian hormone expression is suspected to be overexpressed in PCOS granulosa cells. AMH acts as a regulator of folliculogenesis: it is produced by the granulosa cells of follicles from the stage of the primary follicle to the initial formation of the antrum. Serum and intrafollicular AMH levels are elevated in patients with PCOS due to increased number of small follicles and an increased secretion within each of these small follicles. This excess of AMH is strongly suspected to play a role in the characteristic follicular arrest of PCOS, through a negative action on aromatase expression and on FSH action. Value above 5 ng/ml or 35 pmol/l might be considered as a diagnostic criterion for PCOS. The aim of our study is to demonstrate the presence of higher AMH serum levels and higher AMH intrafollicular fluid level of PCOS patients, undergone to IVF cycles, compared to normovulatory patients. The results clearly indicate that blood and intrafollicular AMH levels are significantly higher in PCOS women comparing to the normovulatory population. Serum AMH level appears to be a good predictive marker for the risk ovarian hyperstimulation syndrome: thus, its evaluation should be recommended before starting a controlled ovarian stimulation for IVF.

Effects of myo-inositol, gymnemic acid, and L-methylfolate in polycystic ovary syndrome patients.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine and metabolic disorder, characterized by chronic anovulation/oligomenorrhea, hyperandrogenism, and insulin-resistance. Moreover, some studies propose a possible association between insulin resistance and hyperhomocysteinemia, which is a significant long-term risk for factor for atherogenesis and chronic vascular damage, especially in situations where insulin levels are increased. Insulin-sensitizing agents are used in the treatment of PCOS: in fact, inositols were shown to have insulin-mimetic properties. Synergic action to myo-inositol is that of gymnemic acids that have antidiabetic, anti-sweetener, and anti-inflammatory activities. Gymnemic acid formulations have also been found useful against obesity due to their ability to delay the glucose absorption in the blood. L-methyl-folate increases peripheral sensitivity to insulin, maintaining folatemia stable, and thus restoring normal homocysteine levels. Unlike folic acid, L-methyl folate has a higher bioavailability, no drug/food interferences, high absorption, and it is stable to UV-A exposure. The aim of our study is to compare the clinical, endocrine, and metabolic parameters in 100 PCOS women treated with myo-inositol, gymnemic acid, and l-methylfolate (Group A) or myo inositol and folic acid only (Group B), continuously for 6 months. From a clinical point of view, it was noticed a more significant improvement of the menstrual cycle regularity and a more significant reduction of BMI in Group A. Moreover, a more significant decrease of total testosterone and increase of SHBG serum levels were noticed in Group A. The metabolic assessment found a more significant decrease of total cholesterol and homocysteine levels; OGTT glycemia and insulinemia values were significantly more improved after treatment with myo-inositol + gymnemic acid. In conclusion, we can state that a good option for the treatment of PCOS is the combined administration of myo-inositol + gymnemic acid + l-methyl-folate, especially for overweight/obese patients with marked insulin resistance and with associated hyperhomocysteinemia.

CHI3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes. MATERIALS AND METHODS: We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times. We also divided the sALS patients into smokers and non-smokers. In order to extend our analysis, we explored two additional microarray datasets, GSE833 and GSE26927, of post-mortem spinal cord biopsies from sALS patients. RESULTS: The analysis showed that CHI3L1 and CHI3L2 expression levels were significantly upregulated in the motor cortex of sALS patients, compared to the healthy controls. Moreover, their expression levels were negatively correlated with survival time. Interesting results were obtained when we compared the expression levels of Chitinases among smokers. We showed that CHI3L1 and CHI3L2 were significantly upregulated in sALS smokers compared to non-smokers. Furthermore, we found that four genes belonging to the Chitinases network (SERPINA3, C1s, RRAD, HLA-DQA1) were significantly upregulated in the motor cortex of sALS patients and positively correlated with Chitinases expression levels. Similar results were obtained during the exploration of the two-microarray dataset. CONCLUSIONS: This study suggests that CHI3L1 and CHI3L2 are associated with the progression of neurodegeneration in motor cortex and spinal cord of sALS patients.

Placenta accreta and balloon catheterization: the experience of a single center and an update of latest evidence of literature.

PURPOSE: We studied the efficacy of using pre-cesarean delivery (CD) temporary occlusion of internal iliac arteries with balloon catheters in case of placenta previa-accreta in terms of maternal and neonatal outcomes and to test accuracy of ultrasound (US) and magnetic resonance imaging (MRI) for prenatal diagnosis. METHODS: From March 2014 to January 2018, women with an US and/or MRI diagnosis of placenta previa-accreta and a planned delivery were enrolled and divided into two groups: balloon catheterization group (women treated with preoperative catheters and CD) and control group (women candidates to elective CD). RESULTS: 37 patients were enrolled: 16 in balloon catheterization group and 21 in control group. Significant differences were detected in estimated blood loss. Prophylactic balloon catheterization could reduce intraoperative red blood cell transfusion. The incidence of hysterectomy was lower in balloon group. No statistical difference was found for neonatal outcomes. Both US and MRI have showed to be useful and complementary to diagnose placenta previa-accreta. CONCLUSIONS: Temporal, perioperative, and prophylactic positioning of balloon vascular catheters is an effective method for managing severe hemorrhage caused by placenta previa-accreta as it reduced intraoperative blood loss, lessened perioperative hemostatic measures and intraoperative red cell transfusions, and reduced hysterectomies.

SERPING1 mRNA overexpression in monocytes from HIV+ patients.

OBJECTIVE: The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway. METHODS: In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs. RESULTS: Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1-an antiviral molecule belonging to the genes network-correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels. CONCLUSIONS: From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.

Vitamin D3 inhibits TNFα-induced latent HIV reactivation in J-LAT cells.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to suppress NF-kB activity by interfering with its pathways. The aim of this study was to investigate the ability of 1,25(OH)2D3 in reducing the reactivation of the HIV virus J-LAT cells, an established model of latently infected cells, which were treated with TNFalpha (100 ng/ml) for 2 h with or without 24 h 1,25(OH)2D3 (100 nM) pretreatment. Reactivation of HIV RNA in J-LAT was evaluated in terms of green fluorescent protein (GFP) expression. The same experimental setting was repeated on T cells from HIV-infected patients. Treatment with TNFalpha was associated with a 16 % increase in GFP+ cells and a five-fold increase in unspliced HIV RNA expression (p < 0.04). Pretreatment of J-LAT cells with 1,25(OH)2D3 for 24 h followed by TNFalpha (100 ng/ml) for 2 h reduced the percentage of GFP+ cells by 8 %; moreover, a 2.4-fold decrease in unspliced HIV RNA expression was observed (p < 0.002). In T cells from patients, treatment with TNFalpha significantly increased unspliced HIV RNA expression (sixfold increase, p < 0.02), whereas prestimulation with 1,25(OH)2D3 reduced its expression (2.5-fold decrease, p < 0.02) compared to controls.1,25(OH)2D3 is able to reduce the ability of TNFalpha to upregulate the transcription of HIV RNA from latently infected cells. These data provide further understanding of the pathogenic mechanisms regulating viral reactivation from latent reservoirs, along with new insight in viral internalization.

Quantitative determination by screening ELISA and HPLC-MS/MS of microcystins LR, LY, LA, YR, RR, LF, LW, and nodularin in the water of Occhito lake and crops.

The occurrence of harmful cyanobacterial blooms in surface waters is often accompanied by the production of a variety of cyanotoxins, and these toxins are designed to target in humans specific organs on which they act. When introduced into the soil ecosystem by spray irrigation of crops, they may affect the same molecular pathways in plants having identical or similar target organs, tissues, cells, or biomolecules. There are also several indications that terrestrial plants, including crops, can bioaccumulate cyanotoxins and present, therefore, potential health hazards for humans. During this project, for monitoring purposes, water samples were collected from lake Occhito, in which there was an algal bloom (Planktothrix rubescens) in 2009, and from three tanks which acted as hydraulic junctions. In addition, crop samples irrigated with water from the three tanks mentioned above were also picked. Finally, the characterization of principal cyanobacteria was performed, to determine the presence of cyanotoxins such as microcystins and validate a method of screening ELISA for the determination of microcystins in vegetable samples and a confirmatory method by HPLC-ESI-MS/MS. Graphical abstract Occhito lake (left), microcystin LR (center), Tomato field in Foggia (right); figures below: ELISA (left), HPLC-MS/MS (right).

Quality of supervision: postgraduate dental research trainees' perspectives.

INTRODUCTION: Supervision is a pillar in enhancing the student's learning environment throughout her/his higher education. Multiple studies qualify graduate supervision among the most important contributors to the successful completion of a higher education degree and to graduate students' positive academic experience. The aim of this study was to assess the views of graduate students enrolled in the Dental Sciences and Craniofacial Research Graduate Programs at McGill University (n = 64) regarding the quality of supervision they are receiving. METHODS AND MATERIALS: An online questionnaire composed of 22 open and closed-ended format items was used and covered five domains: student profile, supervisory relationship, conflict resolution, student progress/thesis writing and career development. Descriptive statistics, chi-square tests and interpretative qualitative analysis were used to evaluate students' perspectives. RESULTS: Fifty-nine students completed the survey (92.2%). The distribution of sample in regard to the graduate student level was almost identical (M.Sc. level n = 28, Ph.D. n = 31). Overall, most graduate students appeared satisfied with the supervision they received and had similar perspectives about the surveyed domains. There was one statistically significant difference (P < 0.05) between MSc and PhD students when asked if their supervisors aided them in career development outside the supervisory relationship, where 77.4% (n = 24) of doctoral students agreed as opposed to 21.4% (n = 12) of Masters' students. CONCLUSIONS: Our results showed that McGill graduate students appeared to be overall satisfied with the supervision they received. The main elements contributing to a positive supervision experience were support, guidance, availability and good communication between supervisees and supervisors.

Transcriptome analysis of human primary endothelial cells (HUVEC) from umbilical cords of gestational diabetic mothers reveals candidate sites for an epigenetic modulation of specific gene expression.

Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG.

Thermal and energetic processing of ammonia and carbon dioxide bearing solid mixtures.

We present new experimental results on thermal and ion irradiation processing of frozen ammonia-carbon dioxide mixtures. Some mixtures were deposited at low temperatures (T ≈ 16 K). Upon warming up to 160 K, complex chemical reactions occur leading to the formation of new molecules and, in particular, of ammonium carbamate. We also show that the same species are produced when water is the dominant species in the ternary mixture with ammonia and carbon dioxide. The samples have been irradiated with 144 keV S(9+) ions at 16 K and 50 K. Also in this case, new chemical species are formed as e.g. ammonium formate, CO and OCN(-). The results are discussed in the light of their relevance to the chemical evolution of ices in the interstellar medium and in the solar system. In particular, we suggest searching for them among the gas phase species sublimating from grains around young stellar objects and from the cometary nuclei approaching the Sun.

Improving rates of cotrimoxazole prophylaxis in resource-limited settings: implementation of a quality improvement approach.

OBJECTIVE: To demonstrate the effectiveness of quality improvement methods to monitor and improve administration of cotrimoxazole (CTX) prophylaxis to improve health outcomes among adults living with HIV/AIDS in low resource countries. DESIGN: Program evaluation. SETTING: HIV/AIDS health care facilities in Uganda, Mozambique, Namibia and Haiti. INTERVENTION: Performance measures based on national guidelines are developed in each country. These may include CD4 monitoring, ART adherence and uptake of CTX prophylaxis. CTX prophylaxis is routinely selected, because it has been shown to reduce HIV-related morbidity and mortality. Patient records are sampled using a standard statistical table to achieve a minimum confidence interval of 90% with a spread of ±8% in participating clinics. If an electronic medical record is available, all patients are reviewed. Routine review of performance measures, usually every 6 months, is conducted to identify gaps in care. Improvement interventions are developed and implemented at health facilities, informed by performance results, and local/national public health priorities. MAIN OUTCOME MEASURE: Median clinic rates of CTX prophylaxis. RESULTS: Median performance rates of CTX prophylaxis generally improved for adult HIV+ patients between 2006 and 2013 across countries, with median clinic rates higher than baseline at follow-up in 16 of 18 groups of clinics implementing CTX -focused improvement projects. CONCLUSIONS: Quality management offers a data-driven method to improve the quality of HIV care in low resource countries. Application of improvement principles has been shown to be effective to increase the rates of CTX prophylaxis in national HIV programs in multiple countries.

Effects of a similar amount of regular non-structured or competitive physical activity across late adulthood: a cross-sectional study.

Introduction: Master athletes are examples of successful aging. It is not clear whether it is the competitive-oriented training or just the amount of total regular exercise that reduces the age-related decline in physiological functions. We aimed to compare health-related parameters in competitive (C) and physically active older adults (A) that performed the same weekly physical activity (PA) amount. Methods: Seventeen C and 17 A were matched for age (8 and 9 male participants under and over 70 years old respectively, for both groups) and weekly PA amount (GPAQ). Body composition, leg and arm maximal strength, balance and reaction time were measured; moreover, leg and arm exercise efficiency, estimated VO2max, and VO2/HR relationships were evaluated. Perception of life and sleep quality was also assessed through specific questionnaires (SF-36 and PSQI). The effect of group (C vs. A), age (U70 vs. O70) and their interaction was examined through a Two-Way ANOVA test. Results: C dedicated more time to vigorous PA compared to A (p = 0.03), while less to moderate daily work (p < 0.01) and active commuting (p = 0.06). C exhibited better body composition (all p < 0.05), higher leg maximal strength (p < 0.05) and a trend for elevated arm strength (p = 0.06). Reaction time, leg and arm cycling efficiency were similar in the two groups (all p > 0.05), while balance reduced in A O70. Estimated VO2max was higher for C in leg cycling (p = 0.05) and remained constant across ages (all p > 0.05). VO2/HR relationship, life and sleep quality did not differ for groups and ages. Conclusions: Regular physical exercise of about 6,000 METs/week seems to have a beneficial effect on health-related parameters, both in non-structured and competitive PA, when compared to sedentary behaviour. However, the older adults engaged in competitive training exhibit further advantages: better body composition, higher arm and leg muscle strength, and higher leg VO2max. This study highlights the importance of encouraging active lifestyles for maintaining long-term health, high levels of life quality perception and reducing age-related decline. However, vigorous training suitability needs to be verified by a team of PA specialists.

Multicentric data analysis of the learning curve for laparoscopic Shull's repair of pelvic floor defects.

Introduction: Pelvic organs prolapse remains a significant health concern affecting millions of women worldwide. The use of native tissues to suspend the apex has acquired relevance in urogynecologic surgery. One of the most commonly used procedures performed without mesh is the technique described by Shull, consisting of suturing the vaginal apex to the uterosacral ligaments. The objective of the study is to evaluate the learning curve of laparoscopic Shull's repair for the correction of pelvic floor defects, including the surgery time and surgical outcomes. Materials and methods: This is a retrospective study conducted at the Policlinico G. Martino, University of Messina, Messina, Italy, and Policlinico Vanvitelli, Vanvitelli University, Naples, Italy. All patients affected by grade I-IV POP, consisting of apical prolapse with or without cystocele, and who underwent laparoscopic Shull's technique for prolapse correction were enrolled. The endpoints to estimate the learning curve for the procedure were the percentage of laparoscopic procedures completed, operative time, and the early complication rate. Results: A total of 31 laparoscopic Shull repairs were collected for the study. To evaluate the learning curve of the technique, we divided the 31 cases into three different groups: Procedures 0-10; 11-20; 21-31. The parameter for evaluating technique learning was the operative time. Group 21-31 demonstrated an operative time of 97 min (SD 20), compared with 121 min (SD 23) in group 0-10 and 120 min (SD 13) in group 11-20. A comparison of these means through ANOVA showed a p-value of 0.01 for the entire system, and 0.95 for the comparison between 0 and 10 and 11-20, 0.04 for 0-10 vs. 21-31, and 0.02 between 11 and 20 and 21-31. Conclusions: The rate of surgical improvement in terms of time became effective after an average of 20 procedures. However, the improvement seems to be effective case by case for surgeons skilled in basic endoscopy.

Human-mouse genome comparisons to locate regulatory sites.

Elucidating the human transcriptional regulatory network is a challenge of the post-genomic era. Technical progress so far is impressive, including detailed understanding of regulatory mechanisms for at least a few genes in multicellular organisms, rapid and precise localization of regulatory regions within extensive regions of DNA by means of cross-species comparison, and de novo determination of transcription-factor binding specificities from large-scale yeast expression data. Here we address two problems involved in extending these results to the human genome: first, it has been unclear how many model organism genomes will be needed to delineate most regulatory regions; and second, the discovery of transcription-factor binding sites (response elements) from expression data has not yet been generalized from single-celled organisms to multicellular organisms. We found that 98% (74/75) of experimentally defined sequence-specific binding sites of skeletal-muscle-specific transcription factors are confined to the 19% of human sequences that are most conserved in the orthologous rodent sequences. Also we found that in using this restriction, the binding specificities of all three major muscle-specific transcription factors (MYF, SRF and MEF2) can be computationally identified.

Beta-Thalassemia major and pregnancy.

OBJECTIVE: It was studied the clinical management and the medical outcomes of 6 pregnancies in 5 women affected by Beta Thalassemia major, based on last guidelines and pharmacological treatments. BACKGROUND: Paediatric Department and Department of Obstetrics and Gynaecology of the University of Catania. METHODS: These patients were taken among a group of 116 women affected by beta-thalassemia major divided into three subgroups, according to the characteristics of their menstrual cycle: 1) women with primitive amenorrhoea, 2) women with secondary amenorrhoea and 3) women with normal menstruation. Only one woman, affected by primitive amenorrhoea, needed the induction of ovulation. An accurate and detailed pre-pregnancy assessment was effected before each conception. This was constituted by a series of essays, including checks for diabetes and hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover were evaluated: cardiac function, rubella immunity and transaminases. Other pregnancy monitoring, and cares during labour and delivery were effected according to usual obstetrics practice. RESULTS: All the women were in labour when they were 38 week pregnant, and the outcome were six healthy babies born at term. There were no complications related to the pregnancy and to the immediate outcome after delivery. CONCLUSIONS: The improvements of current treatments, especially in the management of iron deposits, the prolongation of survival rate, will result in a continuous increase of pregnancies in thalassemic women. Pregnancy is now a real possibility for women affected by such disease. Although numerous complications can occur, vigilant monitoring by both experienced obstetricians and hematologists can lead to successful pregnancy outcomes (Tab. 1, Fig. 1, Ref. 16).

A real-life experience using panitumumab in chemo-refractory metastatic colorectal cancer patients: a retrospective analysis at the Jewish General Hospital, 2009-2012.

BACKGROUND: Panitumumab is a fully human monoclonal antibody, directed against the epidermal growth factor receptor, that was shown to be effective in third-line metastatic colorectal cancer. We performed a retrospective analysis of patients with chemo-refractory non-KRAS-mutated metastatic colorectal cancer, who received panitumumab at the Jewish General Hospital in Montreal, Canada, between 2009 and 2012. METHODS: This chart review included 44 patients (median age: 60 years; performance status: 0-3), of whom 50% had already received three lines of treatment. The primary endpoint was progression-free survival (pfs). Secondary endpoints were overall survival and safety. Tumour progression was determined by radiologic assessments performed once every 3 months per clinical guidelines or by clinical deterioration as determined by the clinician-investigator. RESULTS: In our sample, median pfs was 21.86 ± 5.23 weeks (95% confidence interval: 12.9 to 36.9 weeks) and overall survival was 35.14 ± 7.75 weeks (95% confidence interval: 25.6 to 73.4 weeks) with a median of 5 cycles of panitumumab treatment. The most frequently reported toxicities with panitumumab were skin toxicity (16.2% grade 3) and hypomagnesemia (10.8% grade 3). No infusion reactions were reported. CONCLUSIONS: Despite a small sample size from a single institution, our survival and efficacy data are encouraging and comparable to results obtained from the registration panitumumab trial. Our findings suggest that panitumumab can be effective and tolerable in a real-world setting.

Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages.

Vitamin D3 [1α,25-(OH)(2)D(3)], involved in the regulation of body calcium homeostasis, promotes immature myeloid precursor cells differentiation into monocytes/macrophages. In this study we compared the regulatory interaction between 1α,25-(OH)(2)D(3) and tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS) in the mRNA expression of interleukin (IL)-1ß, (IL)-6, TNF-α, toll like receptors (TLR)-2 and (TLR)-4 in freshly isolated human monocyte (MonoT0) and in macrophages cultured for seven days (MØT7). Additionally, we detected the effect of 1α,25-(OH)(2)D(3) on macrophages chemotaxis. The expression of IL-1ß, IL-6 and TNF-α, as well as TLR-2 and TLR-4 in MonoT0 and in MØT7 was examined by real time RT-PCR. Macrophages chemotaxis was analyzed by using horizontal chemotaxis agarose spot assay. We found that 1α,25-(OH)(2)D(3) influences macrophages chemotaxis and differently modulates the expression of IL-1ß, IL-6, TNF-α and TLRs in the two different stages of monocytes/macrophage maturation. In conclusion our data add new information about the role of 1α,25-(OH)(2)D(3) on the expression of inflammatory mediators in human monocyte/macrophages, underlying the complex function of these cells. Investigating the differences in the pattern of expression of immune-mediators produced by MonoT0 and MØT7 may provide a new way to examine their biochemical and molecular function and may constitute a model system with well-defined behavior with respect to early or tardive events in the innate immune response.