Low-dose curcuminoid-loaded in dextran nanobubbles can prevent metastatic spreading in prostate cancer cells.

Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.

[Translated article] Study of femoral component malrotation as a cause of pain after total knee arthroplasty.

INTRODUCTION: The total knee arthroplasty (TKA) has been shown to be a successful and cost-benefit procedure in terms of pain improvement in patient with symptomatic knee osteoarthritis. However, almost a 20% of the patients are not satisfied with the result of the surgery. MATERIAL AND METHOD: We have carried out a transversal unicentric cases controls study with clinical cases of the own hospital, obtained by a clinical records revision. A total of 160 patients with a TKA with at least 1 year of follow-up were selected. Demographic variables, functional scales (WOMAC and VAS) and rotation of the femoral component through the analysis of the images obtained by CT scan were collected. RESULTS: The total was 133 patients that was divided in two groups. A control group and pain group. The Control group was made up of 70 patients with a mean age of 69.59 years (23 men and 47 women) and the pain group was made up of 63 patients with a mean age of 69.48 years (13 men and 50 women). We didn't find difference regarding the analysis of the rotation of the femoral component. In addition, we were not found significant differences when applying a stratification by sex. And, the analysis of the malrotation of the femoral component, previously defining limits of value rotation considered as extreme, in any of the case did not show significant differences. CONCLUSION: The results of the study confirm that malrotation of the femoral component had no influence on the presence of pain at a minimum of one year of follow-up after TKA implantation.

Sharp rates of decay of solutions to the nonlinear fast diffusion equation via functional inequalities.

The goal of this paper is to state the optimal decay rate for solutions of the nonlinear fast diffusion equation and, in self-similar variables, the optimal convergence rates to Barenblatt self-similar profiles and their generalizations. It relies on the identification of the optimal constants in some related Hardy-Poincaré inequalities and concludes a long series of papers devoted to generalized entropies, functional inequalities, and rates for nonlinear diffusion equations.

Study of femoral component malrotation as a cause of pain after total knee arthroplasty. / Estudio de la malrotación del componente femoral como causa de dolor tras la implantación de una artroplastia total de rodilla.

INTRODUCTION: The total knee arthroplasty (TKA) has been shown to be a successful and cost-benefit procedure in terms of pain improvement in patient with symptomatic knee osteoarthritis. However, almost a 20% of the patients are not satisfied with the result of the surgery. MATERIAL AND METHOD: We have carried out a transversal unicentric cases controls study with clinical cases of the own hospital, obtained by a clinical records revision. A total of 160 patients with a TKA with at least 1year of follow-up were selected. Demographic variables, functional scales (WOMAC and VAS) and rotation of the femoral component through the analysis of the images obtained by CT scan were collected. RESULTS: The total was 133 patients that was divided in two groups. A control group and pain group. The control group was made up of 70 patients with a mean age of 69.59years (23 men and 47 women) and the pain group was made up of 63 patients with a mean age of 69.48years (13 men and 50 women). We did not found difference regarding the analysis of the rotation of the femoral component. In addition, we were not found significant differences when applying a stratification by sex. The analysis of the malrotation of the femoral component, previously defining limits of value rotation considered as extreme, in any of the case did not show significant differences. CONCLUSION: The results of the study confirm that malrotation of the femoral component had no influence on the presence of pain at a minimum of one year of follow-up after TKA implantation.

Nilotinib in steroid-refractory cGVHD: prospective parallel evaluation of response, according to NIH criteria and exploratory response criteria (GITMO criteria).

We conducted a phase I-II study to evaluate Nilotinib (NIL) safety and pharmacokinetics in 22 SR-cGVHD patients; we also evaluated ORR by using in parallel NIH criteria and an exploratory approach, combining objective improvement (OI) without failure criteria (GITMO criteria). Results: 22 patients were enrolled. After dose escalation up to 600 mg/day, MTD was not reached. Main toxicities were asthenia, headache, nausea, pruritus, cramps, and mild anemia. Mean and median plasma concentrations of NIL (C-NIL) were 817 (SD ± 450) and 773 ng/ml. ORR at 6 months, according to 2005 and 2014 NIH and GITMO criteria were 27.8%, 22.2%, and 55.6% respectively; close correspondence has been observed for ORR, according to 2014 NIH criteria, both assessed in a conventional way and assisted by dedicated software (CROSY). At 48 months OS was 75% while FFS, according to NIH and GITMO criteria, was 30 and 25%. In conclusion the safety profile of NIL and long-term outcome makes NIL an attractive option in SR-cGVHD. Exploratory GITMO criteria could represent an alternative tool for easy response evaluation in patients with prevalent skin and lung involvement, but require validation in a larger population; CROSY software showed excellent reliability in capturing ORR according to the 2014 NIH criteria.

Surgical resection of persistent pulmonary fungus nodules and secondary prophylaxis are effective in preventing fungal relapse in patients receiving chemotherapy or bone marrow transplantation for leukemia.

Antifungal therapy may be unable to eradicate invasive mycosis in leukemia patients. The presence of persisting pulmonary nodules owing to mycosis seems to increase the risk of fungal relapse after chemotherapy and transplant procedures. Between 1997 and 2004, 10 acute leukemia patients underwent pulmonary surgery for invasive mycosis. The median time from diagnosis of mycosis to surgery was 135 days (range 21-147). Three patients underwent emergency surgery, owing to hemoptysis. In the other seven patients with nodule/cavitation remaining after antifungal treatment, surgery (three wedge resections, four lobectomies) was scheduled before transplant. Pathologic examination confirmed two aspergillosis and three zygomycosis. The only side effect was pneumothorax in one case. Nine patients were considered cured. Six patients underwent bone marrow transplantation (three allogeneic, three autologous) with antifungal prophylaxis without relapse during the transplant procedure. In selected patients scheduled for bone marrow transplantation, surgical resection of localized pulmonary fungus nodules combined with antifungal prophylaxis seem to be an effective treatment for preventing mycotic relapse.

Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged ⩽55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

Laparoscopic splenectomy: A retrospective review of 75 cases.

Laparoscopic splenectomy (LS) is considered a safe procedure for spleens of normal size as well as for larger spleens. Seventy-five consecutive patients underwent LS. Splenomegaly was defined by diameter >15 cm and by weight >400 g. Thirty patients had splenomegaly. The outcomes with spleens <15 cm and spleens >15 cm were compared. LS was successfully completed in 73 cases (97.4%). Spleens >15 cm required longer operating time and were associated with greater blood loss (P < 0.001), longer hospital stay, and more complications. Two patients needed blood transfusion. No overwhelming postsplenectomy infection was registered, and operative mortality was zero.

Association between Neospora caninum seropositivity and reproductive disorders in girolando cows / [Associação entre a soropositividade para Neospora caninum e distúrbios reprodutivos em vacas girolando]

The aim of this study was to investigate the presence of anti-Neospora caninum antibodies in Girolando cows, in order to evaluate the association between seropositivity and reproductive disorders. Blood samples were collected from 40 dairy cows in their reproductive phase from the cranial superficial epigastric vein. The blood samples were tested using the Indirect Fluorescence Antibody Test (IFAT) to detect anti-N.caninum antibodies. The serological results were used to verify whether there was any association with the manifestation of reproductive disorders based on data from the records of reproductive history from 2017 to 2018 as well as the clinical observations of the herd throughout this study. The Fisher exact test was used to verify the existence of an association between the serology and reproductive disorders, adopting a 95% confidence level. The serological results showed a 27.5% seroprevalence in the herd for N. caninum, however, after statistical analysis, no association between seropositivity and reproductive disorders was found in the evaluated herd. Although the studied population is infected with Neospora caninum, we can infer that anti-Neospora caninum antibodies present in Girolando dairy cows at the UFRRJ Dairy Cattle Facility are not associated with the occurrence of reproductive disorders.(AU)

O objetivo deste estudo foi investigar a presença de anticorpos anti-Neospora caninum em vacas Girolando, avaliando-se a associação entre a soropositividade e os distúrbios reprodutivos. Foram coletadas amostras de sangue da veia epigástrica superficial cranial de 40 vacas leiteiras em fase reprodutiva, sendo as amostras testadas pela reação de imunofluorescência indireta (RIFI) para detecção de anticorpos anti-N. caninum. A partir dos resultados sorológicos, foi realizada a verificação de associação, ou não, com a manifestação de distúrbios reprodutivos, coletados nos registros de histórico reprodutivo entre 2017 e 2018 e observações do rebanho no transcorrer do estudo. O teste exato de Fisher foi utilizado para verificar a existência de associação entre a sorologia e os distúrbios reprodutivos, adotando-se nível de confiança de 95%. O resultado do estudo demonstrou uma soroprevalência no rebanho de 27,5% para N. caninum, contudo, após análise estatística, não foi confirmada a associação entre soropositividade e distúrbios reprodutivos no rebanho avaliado. Apesar de a população estudada estar infectada com o Neospora caninum, pode-se inferir que anticorpos anti-Neospora caninum presentes em vacas leiteiras Girolando do Setor de Bovinocultura de Leite da UFRRJ não estão associados à ocorrência de distúrbios reprodutivos.(AU)

Prevalence and clinical correlates of microalbuminuria in essential hypertension: the MAGIC Study. Microalbuminuria: A Genoa Investigation on Complications.

The prevalence of microalbuminuria and its relationship with several cardiovascular risk factors and target organ damage were evaluated in a cohort of 787 untreated patients with essential hypertension. Albuminuria was measured as the albumin-to-creatinine ratio in three nonconsecutive, first morning urine samples. The prevalence of microalbuminuria was 6.7%. Albuminuric patients were more likely to be men and to be characterized by higher blood pressure, body mass index, and uric acid levels and lower HDL cholesterol and HDL cholesterol-to-LDL cholesterol ratio. Piecewise linear regression analysis demonstrated that uric acid and diastolic blood pressure significantly influence albuminuria and together account for a large part of its variations. K-means cluster analysis performed on the entire cohort of patients confirmed that microalbuminuria is associated with a worse cardiovascular risk profile. Furthermore, microalbuminuria was associated with the presence of target organ damage (eg, electrocardiographic [ECG] abnormalities and retinal vascular changes). Age and the presence of microalbuminuria act as independent risk factors for the development of ECG abnormalities and retinal vascular changes. Cluster analysis allowed us to identify three subgroups of patients who differed in the presence or absence of microalbuminuria, retinopathy, and ECG abnormalities. We conclude that the prevalence of microalbuminuria in essential hypertension is lower than previously reported. Increased urinary albumin excretion is associated with a worse cardiovascular risk profile and is a concomitant indicator of early target organ damage.

Structural and compositional features of untranslated regions of eukaryotic mRNAs.

The important role of 5' and 3' untranslated regions of eukaryotic mRNAs in gene regulation and expression is now widely accepted. In order to study the general structural and compositional features of these sequences we developed UTRdb, a specialized database of 5' and 3'-UTR sequences from seven different taxonomic groups of eukaryotic mRNAs cleaned of redundancy. The analysis of the UTR sequences contained in this database showed that 5'-UTR sequences, on average 200 nucleotides long, are 1.5-3 times shorter than the corresponding 3'-UTR sequences in the various taxonomic groups considered here. As to their compositional properties on average 5'-UTR sequences resulted in all cases GC richer than 3'-UTR sequences, and significant correlations were found between the GC content of 5' and 3'-UTR sequences and the GC content of the third silent codon positions of the corresponding protein coding genes. The dinucleotide analysis showed a differential depletion of CpG in vertebrate 5' and 3'-UTR, with 5'-UTR sequences being more CpG-rich, and a generalized depletion of TpA in both 5' and 3'-UTR was observed in all eukaryotic sequence collections.

Analysis of oligonucleotide AUG start codon context in eukariotic mRNAs.

The AUG start codon context features have been investigated by analyzing eukaryotic mRNAs belonging to various taxonomic groups. The functional relevance of each specific position surrounding the AUG start codon has been established as a function of the measured shift between base composition observed at that particular position, and base composition averaged over all the 5'untranslated regions. A more detailed analysis carried out on human genes belonging to different isochores showed significant isochore-specific fea-tures that cannot be explained only by a mutational bias effect. The most represented heptamers spanning from position -3 to +4 with respect to the initiator AUG have been determined for mRNAs belonging to different taxonomic groups and a web page utility has been set up (http://bigarea.area.ba.cnr.it:8000/BioWWW/ATG.html) to determine the relative abundance of a user submitted oligonucleotide context in a given species or taxon.

Structural and functional features of eukaryotic mRNA untranslated regions.

The crucial role of the non-coding portion of genomes is now widely acknowledged. In particular, mRNA untranslated regions are involved in many post-transcriptional regulatory pathways that control mRNA localization, stability and translation efficiency. We review in this paper the major structural and compositional features of eukaryotic mRNA untranslated regions and provide some examples of bioinformatic analyses for their functional characterization.

GeneUp: a program to select short PCR primer pairs that occur in multiple members of sequence lists.

A computer program is presented that selects a small set of short primer pairs for PCR to sample all the sequences in a user-specified list of mRNAs. Such primer pairs could be used to increase the probability of sampling mRNAs of particular interest in differential display and to generate simplified hybridization probes for DNA chips or arrays. The program uses simulated PCR to find pairs of primers that sample more than one sequence in the list. A small set of such primer pairs is selected that give maximal coverage of the sequences in the list. Primer pairs are excluded that: (i) generate simulated PCR products of the same size from a number of sequences in the list, (ii) can easily form primer dimers, (iii) are outside a specified range of G + C content or (iv) occur in another list of undesirable sequences, such as rRNAs and Alu repeats. Five lists consisting of from 48-285 cDNA sequences were used to test the program. A small number of pairs of primers, 8-10 bases in length, were selected that fit the above criteria and that generate one or more simulated PCR products in all or most of the cDNAs in each list.

Efficacy of an early intensification treatment integrating chemotherapy, autologous stem cell transplantation and radiotherapy for poor risk primary mediastinal large B cell lymphoma with sclerosis.

The aim of our study was to evaluate the impact of an early intensification programme including chemotherapy (CHT), autologous stem cell transplantation (ASCT) and radiation therapy (RT) in patients with primary mediastinal large B cell lymphoma (MLCL) with sclerosis presenting with adverse prognostic factors. Between 1993 and 1999, 19 patients with MLCL were referred to our institution. Four patients were classified as low risk according to the age-adjusted International Prognostic Index (AA-IPI). Fifteen (79%) were categorised in the high-intermediate or high risk group and were considered eligible for ASCT. Induction therapy consisted of VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin) for 12 weeks. After induction therapy the four low risk patients achieved a complete remission (CR) and did not undergo ASCT. Of the 15 poor risk patients, five achieved CR, seven partial remission (PR), and three showed refractory disease (RD). All these patients received mobilising therapy consisting of high-dose cyclophosphamide. After peripheral stem cell (PSC) collection, to obtain a greater tumor mass reduction before transplantation, the seven patients in PR underwent further treatment with high-dose etoposide and those with RD received two cycles of DHAP (dexamethasone, cytarabine and cisplatin). At the time of ASCT, seven patients were in CR, six in PR and two had RD. After transplantation using BEAM as preparative regimen, all patients but one achieved a CR. Seven patients with minimal (<25%) residual mass at computed tomography scan received further mediastinal RT even if they had a negative Ga(67) scan. At a median follow-up of 35 months from transplantation the disease free survival is 93%. The outcome following this programme of early intensification in poor prognosis MLCL results in a high incidence of durable remissions even in patients with refractory disease.

[Cutaneous tuberculosis with multifocal visceral involvement]. / Tubercolosi cutanea con coinvolgimento viscerale multifocale.

The case of a young Senegalese man who developed a form of cutaneous tuberculosis associated with a disseminated disease, successfully treated with appropriate antitubercular chemotherapy is reported. We found Mycobacterium Microti in the cutaneous ulcers, the only organism isolated after many cultural and microscopical examinations of different exudates and tissues. This mycobacterium was considered up to now to be pathogenic to rodents, but not man. Its possible pathogenicity to man (under certain situations) is also suggested, and it is expected that this possibility will be supported by other reports in the near future. In addition, stress is laid on the problems of diagnosis and classification of the cutaneous tuberculosis, so uncommon in the Western Hemisphere, and its possible association with leprosy.

[The natural history of Still's disease. Description of a clinical case with repeated recurrences and long remission periods]. / La storia naturale della malattia di Still. Descrizione di un caso clinico a decorso policiclico e con lunga remissione.

A case of Still's disease is presented that demonstrates the uncertain prognosis and the duration of the treatment required to prevent recurrences. The importance of frequent check-ups is also emphasised.

[Night eating in severely obese patients]. / "Night eating" in pazienti obesi.

BACKGROUND: To investigate the frequency of night eating among obese patients, its biological correlates and its relationships with binge eating. METHODS: The eating behavior of a group of patients enrolled in a weight-loss program was evaluated by Eating Inventory (EI) and by semistructured interviews designed to detect binge and night eating; in all cases body weight (BW) and energy expenditure (REE) were measured. RESULTS: Night eating was more frequent among binge eating patients, than in among non-binge ones. However, two-way ANOVA demonstrated that in binge eating patients the EI disinhibition and hunger score was higher than in their no-bingeing counterparts and in night eating individuals. Furthermore, between night eating and non-night eating patients, no differences in BW and REE were found. CONCLUSIONS: Binge eating and night eating appear to be related to different psychological constructs, the overlapping between the two behaviors, however, being quite frequent.

[Nonketotic hyperosmolar coma. Clinical aspects and treatment in 12 cases]. / Il coma iperosmolare non chetosico. Aspetti clinici e trattamento in 12 casi.

Non-ketotic hyperosmolar diabetic coma is a complication of diabetes characterised by extreme dehydration, plasmatic hyperosmolarity and the absence of ketosis. The mortality rate is very high, especially in elderly subjects with type II diabetes. A personal series of 12 cases is reported with an assessment of general features, triggering factors, biochemical parameters at onset and treatment given. The data confirm reports in the literature and the results show the therapeutic superiority of continuous endovenous infusions of insulin at 3-10 mu/hour over other treatment protocols.

Disodium clodronate in painful nonresponsive periarthropathy of the hip.

This article identifies and describes a small group of patients with trochanteric tendinitis and bursitis in whom all modes of traditional therapy failed. We hypothesized that obstinate pain could be due to an increase in bone turnover associated with the formation of marginal bony outgrowths or enthesophytes. Injectable disodium clodronate is known to be highly efficacious in inhibiting bone reabsorption and is able to reduce several types of bone pain. The aim of the study was to evaluate the effectiveness of disodium clodronate in periarticular pathology of the hip in a group of patients resistant to traditional treatments and who were hypothesized to have a component of bone pain in their pain syndrome. Periarticular ultrasound examination is a useful method for detecting soft tissue alterations and is of interest in the study of these patients. In this study ultrasound examination showed periarticular alterations even when results of radiography were negative. Reduction in the hyperechoic ultrasound image, which confirms periarticular calcification, was observed in 75% of the patients treated with disodium clodronate vs. 33% of those treated with paracetamol. At the end of the study, all patients treated with disodium clodronate had a reduction in spontaneous and provoked pain > or = 1/3 vs. the basal visual analogue scale, unlike those treated with paracetamol.