Mannoprotein from Cryptococcus neoformans promotes T-helper type 1 anticandidal responses in mice

We previously demonstrated that mannoprotein (MP) from Cryptococcus neoformans (CnMP) stimulates interleukin-12 production by human monocytes, thus fostering a T-helper type 1 (Th1) protective anticryptococcal response. In this paper we show that CnMP was also able to induce a Candida albicans-directed protective Th1 response. This was demonstrated for mice immunized with CnMP by induction of a delayed-type hypersensitivity (DTH) reaction to C. albicans MP (CaMP) as well as induction of gamma interferon production by CD4(+) and CD8(+) splenic T cells stimulated in vitro with CaMP. CnMP-immunized mice were also partially protected from lethal systemic challenge with C. albicans, as shown by prolonged median survival times and decreased fungal burden in the kidney. Much evidence supports the validity of these cross-reactive and functional Th1 responses: (i) a non-cross-reactive C. albicans antigen, such as enolase, did not produce a DTH response to CaMP; (ii) passive adoptive transfer of T cells primed with CnMP induced a DTH reaction; (iii) C. neoformans extract elicited a DTH response to CaMP; and (iv) a monoclonal antibody (7H6) directed against a major and immunodominant T-cell-stimulatory 65-kDa MP (MP65) of C. albicans also recognized discrete 100-kDa constituents of C. neoformans extracts, as well as secretory constituents of the fungus. These results suggest the presence of common Th1 antigenic determinants in the mannoproteic material of C. neoformans and C. albicans epitopes, which should be considered in devising common strategies for immunoprophylactic or immunotherapeutic control of the fungi.     

Thrombomodulin expression in endothelial cells after contact with bone cement

The expression of thrombomodulin after contact with CMW 1 bone cement extracts was studied in human umbilical vein endothelial cells. Cement extracts after 1 h and 7-day curing induced no significant variations in thrombomodulin antigen levels and in mRNA expression. Significant increase of thrombomodulin was observed when endothelial cells were treated with all-trans retinoic acid (ATRA). ATRA induced the increase of thrombomodulin also in cells incubated with cement extracts. These results suggest that CMW 1 bone cement does not impair the expression of thrombomodulin in endothelial cells.     

Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes

Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy.     

Confirmatory factor analysis and measurement invariance by gender,age and levels of psychological distress of the short TEMPS-A

Background

The Temperament Evaluation of Memphis, Pisa, Paris and San Diego – Autoquestionnaire (TEMPS-A) is a widely used self-reported tool aimed at measuring the affective temperaments that define the bipolar spectrum, with cyclothymic, depressive, irritable, hyperthymic, and anxious subscales. Confirmatory factor analysis (CFA) was rarely used to confirm the expected five-factor model. Measurement invariance was never tested.

Methods

Cross-sectional, survey design involving 649 Italian college students (males: 47%). The short 39-item TEMPS-A and the 12-item General Health Questionnaire (GHQ-12) were used as measures of the affective temperaments and of psychological distress, respectively. CFA was applied to the TEMPS-A. Measurement invariance by gender, age and levels of psychological distress on the GHQ-12 was calculated with the establishment of subsequent equivalence constraints in the model parameters across groups.

Results

The expected five-factor model had the best fit for all CFA indexes. Configural, metric and scalar invariance of the five-factor model of the TEMPS-A was proved across gender, age and levels of psychological distress of the participants. The hyperthymic temperament subscale has low or no links with the other affective temperament subscales, which were interrelated with medium to large effect sizes.

Limitations

College students might be not representative of the general population. No information on the clinical status of the students was available beyond self-report data.

Conclusion

The study proved the measurement invariance of the (short) TEMPS-A, which is a pre-requisite to compare groups or individuals in cross-sectional and longitudinal surveys. Generalizability cannot be assumed without replication of the findings in clinical samples.     

Neurological phenotype of Potocki–Lupski syndrome

Potocki–Lupski syndrome is a condition mainly characterized by infantile hypotonia, developmental delay/intellectual disability (DD/ID), and congenital anomalies, caused by duplications of the 17p11.2 region, encompassing RAI1 gene. Its clinical presentation is extremely variable, especially for what concerns the cognitive level and the behavioral phenotype. Such aspects, as well as the dysmorphic/malformative ones, have been covered by previous studies; otherwise neurological features have never been systematically described. In order to delineate the neurological phenotype of Potocki–Lupski Syndrome, we collect an 8‐patients cohort. Developmental milestones are delayed and a mild to moderate cognitive impairment is present in all patients, variably associated with features of autism spectrum disorder, behavioral disturb, and sleep disturb. Hypotonia appears a less frequent finding than what previously reported, while motor clumsiness/coordination impairment is frequent. EGG registration demonstrated a common pattern with excess of diffuse rhythmic activity in sleep phases or while the patient is falling asleep. Brain MRI did not reveal common anomalies, although unspecific white matter changes may be present. We discuss such findings and compare them to literature data, offering an overview on the neurological and cognitive‐behavioral presentation of the syndrome.     

Macaca mulatta, fascicularis and nemestrina in AIDS vaccine development

Over the past 20 years, many efforts have been made to develop a vaccine against AIDS. The lack of an animal model that can be productively infected with HIV-1 has been partially replaced by macaque species infected with SIV or chimeric SHIV. Natural SIV and chimeric SHIV cause an infection resembling human AIDS, and Asian monkeys of genus Macaca (species mulatta, fascicularis and nemestrina) should be considered a useful surrogate in vaccine trials. A multitude of vaccines and immunization approaches have been evaluated, including live-attenuated viruses, DNA vaccines, subunit proteins and viral and bacterial vectors. The results of all these studies are often difficult to interpret due to lack of standardizations, choice of challenging virus and differences in the macaque species used. This article aims at summarizing the main characteristics of the three macaque species used in vaccine trials.     

Cell proliferation in breast cancer is a major determinant of clinical outcome in node-positive but not in node-negative patients.

The growth rate of a tumor cell population depends on two major factors: the percentage of proliferating cells (cell growth fraction) and the rapidity of their duplication (cell proliferation rate). The authors evaluated the prognostic and predictive value of both kinetics parameters in a large series of breast cancer patients (n=504). The cell growth fraction was determined by MIB-1 immunostaining, the cell proliferation rate by AgNOR analysis. Ki-67 LI (labeling index) and AgNOR area were significantly associated with histotype, histologic grade, tumor size, estrogen/progesterone receptor status, patient age, and lymph node involvement (P<0.005). In the entire series of patients, both kinetics variables were significantly and independently associated with the clinical outcome, but their prognostic relevance was quite different when node-negative and node-positive patients were considered separately. Although in node-positive patients Ki-67 LI and AgNOR area were the unique independent predictors of disease-free and overall survival, they were excluded by the multivariate Cox model in node-negative patients, where only tumor size and estrogen receptor status retained a significant P-value. These results show that in breast carcinoma the cell growth fraction and the cell proliferation rate have a different prognostic impact with respect to the lymph node status and are major determinants of clinical outcome in node-positive patients only. Within this subgroup, the rapidity of cell proliferation as assessed by AgNOR analysis also served as a sensitive predictor of the response to adjuvant treatments.     

Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate

Purpose

To compare two different surgical techniques, stripping or cystectomy, in patients treated with the same post-operative medical therapy in terms of recurrence of endometrioma, recurrence of pain and spontaneous pregnancy rate within 2 years from surgery.

Methods

The inclusion criteria of this study were: (1) 25–40 years old; (2) ovarian endometrioma more than 3 cm of diameter detected by transvaginal ultrasonography (3) regular menstrual cycle (4) post-operative treatment with GnRH analogs, (5) tubal patency assessed by laparoscopic chromopertubation (6) normal human semen characteristics. Exclusion criteria were uterine myoma, previous medical treatment for endometriosis, presence of adenomyosis, previous surgery of ovarian endometrioma, multiple cysts, bilateral involvement, co-existence of deep endometriosis. Patients were assigned to two study groups: group A (N = 45) patients undergoing stripping technique and group B (N = 64) patients undergoing cystectomy technique for ovarian endometrioma.

Results

In group B the percentage of ultrasonographic recurrence (15.4 %, N = 15) is much lower than in group A (55.6 %, N = 25). (p value 0.001). In group B the percentage of symptomatic recurrence (21.8 %, N = 14) is much lower than in group A (53.3 %, N = 24) (p value 0.001). Spontaneous pregnancy rate in group A patients was of 4.4 % (N = 2) and in group B 22.3 % (N = 21), (p value 0.0072). However, the percentage of specimen with adjacent healthy ovarian tissue was lower in group A (26.6 %) than in group B (50 %) (p value 0.01).

Conclusions

Among the different treatment options for surgical treatment of ovarian endometrioma, in our experience cystectomy appears to be the most appropriate treatment, both in terms of recurrence and pregnancy rate.