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Atypical chronic lymphocytic leukemia (CLL) is still defined according to morphological criteria. However, deviance from the typical surface immunological profile suggests an atypical immunological-based CLL. A large cohort of patients with CLL was retrospectively evaluated aiming at assessing morphological (FAB criteria), immunophenotypical (two or more discordances from the typical profile), and clinical-biological features of atypical CLL. Compared to typical cases, morphologically atypical CLL showed a greater percentage of unmutated IgVH and CD38 positivity, and a higher expression of CD20. Immunophenotypically atypical CLL was characterized by more advanced clinical stages, higher expression of CD20, higher rate of FMC7, CD79b and CD49d positivity, and by an intermediate-high expression of membrane surface immunoglobulin, compared to typical cases. When patients were categorized based on immunophenotypic and morphologic concordance or discordance, no difference emerged. Finally, morphological features better discriminated patients' prognosis in terms of time-to-first treatment, while concordant atypical cases showed overall a worse prognosis. Discordant cases by immunophenotype and/or morphology did not identify specific prognostic groups. Whether-in the era of molecular markers used as prognostic indicators-it does make sense to focus on morphology and immunophenotype features in CLL is still matter of debate needing further research.

Tau tubulin kinase-1 (TTBK1), a neuron-specific tau kinase, is highly expressed in the entorhinal cortex and hippocampal regions, where early tau pathology evolves in Alzheimer's disease (AD). The protein expression level of TTBK1 is elevated in the cortex brain tissues with AD patients compared to the control subjects. We therefore hypothesized that antisense oligonucleotide (ASO) based targeting Ttbk1 could prevent the accumulation of phosphorylated tau, thereby delaying the development of tau pathology in AD. Here we show that in vivo administration of ASO targeting mouse Ttbk1 (ASO-Ttbk1) specifically suppressed the expression of Ttbk1 without affecting Ttbk2 expression in the temporal cortex of PS19 tau transgenic mice. Central administration of ASO-Ttbk1 in PS19 mice significantly reduced the expression level of representative phosphor-tau epitopes relevant to AD at 8 weeks post-dose, including pT231, pT181, and pS396 in the sarkosyl soluble and insoluble fractions isolated from hippocampal tissues as determined by ELISA and pS422 in soluble fractions as determined by western blotting. Immunofluorescence demonstrated that ASO-Ttbk1 significantly reduced pS422 phosphorylated tau intensity in mossy fibers region of the dentate gyrus in PS19 mice. RNA-sequence analysis of the temporal cortex tissue revealed significant enrichment of interferon-gamma and complement pathways and increased expression of antigen presenting molecules (Cd86, Cd74, and H2-Aa) in PS19 mice treated with ASO-Ttbk1, suggesting its potential effect on microglial phenotype although neurotoxic effect was absent. These data suggest that TTBK1 is an attractive therapeutic target to suppress TTBK1 without compromising TTBK2 expression and pathological tau phosphorylation in the early stages of AD., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The need for treating subclinical hypothyroidism (SCH) in women undergoing assisted reproduction technology (ART) is under debate. Moreover, it is known that controlled ovarian hyperstimulation (COH) protocols may impair the thyroidal axis. Therefore, we evaluated if levothyroxine (L-T4) supplementation in SCH women before undergoing ART positively affects the main reproductive outcomes. We retrospectively analyzed in vitro fertilization (IVF) data of 4147 women submitted to 6545 cycles in a tertiary care IVF Center (January 2009-December 2014). L-T4 (1.4-2.0 mcg/kg) treatment was offered to all women with a pre-cycle TSH >2.5 mIU/L before starting COH and main ART outcomes were compared in euthyroid and L-T4-treated women undergoing ART. Among 4147 women, 1074 (26%) were affected by SCH and were treated with L-T4 before COH was started. No statistically significant differences among L-T4-treated and euthyroid women group were observed regarding pregnancy rate, respectively, per cycle (27.67% vs 26.37%; p = .314) and per embryo transfer (30.13% vs 29.17%; p = .489), live birth rate, respectively, per cycle (21.58% vs 20.38%; p = .304) and per embryo transfer (23.49 vs 22.54%; p = .449) and the rest of primary and secondary efficacy endpoints. Early L-T4 treatment for infertile women with a subtle thyroid dysfunction may mitigate and protect from the negative effects of SCH in the setting of ART, and may preventively overcome also the negative impact of COH on thyroidal axis.

Purpose: To analyse the impact of female characteristics on assisted reproductive technology outcome among male haematological cancer survivors., Methods: A retrospective analysis of 93 haematological cancer survivors attending our tertiary referral fertility centre between June 1998 and June 2017 for achieving fatherhood with assisted reproductive technology treatments., Results: A progressive increase in the median female age was observed during the study period (32.2 years until the year 2007 and 36.9 years from the year 2012). Fifty-five out of 93 patients were treated with intracytoplasmic sperm injection (ICSI) (113 ovarian stimulations, 108 ICSI procedures). Cryopreserved ejaculated sperm was used in 28 couples, fresh sperm in 19, and thawed testicular sperm in 8 couples. Mean female age at ovarian stimulation was 37.0 ± 4.7 years. Twenty-six pregnancies resulted in a full-term birth (23% per started ovarian stimulation; 43.6% per couple) and 33 children were born. No significant differences were observed according to source of sperm (fresh, frozen, testicular) and multivariate analysis confirmed that maternal age was the only variable inversely related to the cumulative delivery rate, being five times lower (15.7%) when the female partner was ≥ 40 years (OR = 0.22, 95% CI 0.06-0.77) vs. 58.3% with younger women (p = 0.0037)., Conclusions: Delayed childbearing and female ageing affect ICSI outcome in couples where the male is a survivor of haematological cancer. This topic should be discussed when counselling male cancer patients about fertility preservation.

Introduction: In-vitro and in-vivo models suggest the influence of low-molecular weight heparin on conception in infertile women undergoing in vitro fertilization procedures (IVF). In this randomized controlled trial we assessed whether a low-molecular weight heparin (parnaparin) could affect IVF outcomes., Materials and Methods: 271cycles were analyzed in 247 women having a first or subsequent IVF cycle at Fertility Center of Humanitas Research Hospital. Patients, without severe thrombophilia and hormonal or active untreated autoimmune disorders, were randomly allocated (1:1) to receive for the whole cycle parnaparin, or routine hormonal therapy only. The primary endpoint was the clinical pregnancy rate and the secondary endpoints included implantation rate and live birth rate., Results: The clinical pregnancy and the live birth rate were similar in treated and controls (21.5% vs. 26.7%, p=0.389; 18.5% vs. 20.6%, p=0.757). The abortion rate was 10.3% vs 22.9%, p=0.319, respectively. The subgroups analysis, ≤35, 36-38, 39-40years, showed the following: comparable clinical pregnancy rate (22.5% vs 38.8%, p=0.124; 21.8% vs 17.3%, p=0.631; 19.4% vs 23.3%, p=0.762 respectively) and live birth rate (16.3% vs 32.7%, p=0.099; 20.0% vs 13.5%, p=0.443; 19.4% vs 13.3%, p=0.731 respectively) in treated vs controls. Sensitivity analyses on women with ≥3 previous attempts and first enrolment only, and subgroup analyses according to trial conclusion conditioning a small sample size with low statistical power., Conclusions: Our study excludes positive effect of parnaparin, once a day for the whole cycle, on clinical pregnancy rate in infertile women undergoing in vitro fertilization techniques., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The objective of this study was to define the sociodemographic and behavioral characteristics of people unaware of being HIV-positive at AIDS diagnosis. A multi-center cross-sectional study was conducted in 11 Italian centers of infectious diseases, recruited on a voluntary basis. Each center enrolled individuals diagnosed with AIDS aged ≥ 18 years from May 2003 to December 2005. The patients were classified into two groups on the basis of the amount of time that elapsed from diagnosis of HIV infection to AIDS diagnosis. "Late testers" were defined as those with a time period of ≤ 6 months between first HIV positive test and AIDS diagnosis. In order to evaluate the factors independently associated with being a late tester, a multivariate logistic regression model was performed. The McNemar χ(2) test was used to analyze behavioral changes before and after HIV diagnosis. During the study period, 245 patients were enrolled; of these, 51.8% were late testers. The variables independently associated with being a late testers were as follows: being employed; having acquired the infection through sexual contacts; having taken the HIV test because they didn't feel well; having at least one symptom or illness among those indicating infection; and not having had paid sex within the 12 months prior to HIV diagnosis. Before and after HIV diagnosis a significant increase in safe-sex behaviors was observed among individuals with no delay in diagnosis. However, the proportion of people who continue not to use condoms is still high. This study seems to indicate that sexual transmission is often associated with late testing. Individuals enrolled seem to have a low perception of risk, they do not undergo HIV testing, and consequently miss the opportunity of early diagnosis.

ALS is a devastating neurodegenerative disorder with no effective treatment. In the present study, we found that daily doses of lithium, leading to plasma levels ranging from 0.4 to 0.8 mEq/liter, delay disease progression in human patients affected by ALS. None of the patients treated with lithium died during the 15 months of the follow-up, and disease progression was markedly attenuated when compared with age-, disease duration-, and sex-matched control patients treated with riluzole for the same amount of time. In a parallel study on a genetic ALS animal model, the G93A mouse, we found a marked neuroprotection by lithium, which delayed disease onset and duration and augmented the life span. These effects were concomitant with activation of autophagy and an increase in the number of the mitochondria in motor neurons and suppressed reactive astrogliosis. Again, lithium reduced the slow necrosis characterized by mitochondrial vacuolization and increased the number of neurons counted in lamina VII that were severely affected in saline-treated G93A mice. After lithium administration in G93A mice, the number of these neurons was higher even when compared with saline-treated WT. All these mechanisms may contribute to the effects of lithium, and these results offer a promising perspective for the treatment of human patients affected by ALS.

The production of an effective vaccine for HIV infection is one of the major challenges for the third millennium public health. Here we review published studies addressing the issue of incentives and barriers influencing the choice to participate in a vaccine trial. Currently available literature clearly indicates the need to include psychosocial dimensions in the preparation and implementation of vaccine trials. The underestimation of participants' satisfaction about information communication may lead to non-adherence and to drop-out from the trials. Proper attention to communication skills of professionals involved in participants' enrollment and follow-up is essential to ensure trial success.

Objectives: During a survey regarding infant health in 7 regions, diffusion and length of time of breast-feeding nowadays in Italy were studied., Materials and Methods: By OMS Epi methodology, 210 children sampled from each area of study and specialized health workers carried out the interviews at home using a specific questionnaire. The mothers were questioned about the length of time they breast fed their child., Results: 76% of mothers said they breastfed, 32% said they did it for less than 3 months and 44% for more. In each area, the percentage of breastfeeding was 70% or more. This percentage changed only if the birth weight was very low or the mothers' instruction was high, but this is probably because the most cultured mothers answered easier they breast fed longer., Discussion: It seems that mothers are pro-breastfeeding and, in each region, just a quarter of them don't practise it. Besides, about half women breastfed for more than 3 months. This study doesn't permit us to know why some women don't breastfeed or why they wean their children too early. For this reason, we need to curry out further studies.