Reduced probability of improving viro-immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

Introduction: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients. Methods: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm3 , and CD4+/CD8+ ratio ≥ 1. Results: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). Conclusions: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years

Mental Insanity Assessment of Pedophilia: The Importance of the Trans-Disciplinary Approach. Reflections on Two Cases

A 60 plus-year-old male was charged with pedophilia for forcing a child to touch him inappropriately near a primary school fence. In another case, a 70 plus-year-old male was charged with pedophilia for intimately touching a boy in a cinema. What led them to manifest this socially-inappropriate and legally-relevant behavior? Is there an explanation for the sexually-related behavioral changes emerging late in life of these two men? Indeed, a common point exists between the two men: both were found to suffer from highly-disabling neurological conditions, known to have a potential effect on social behavior. Specifically, a large right frontoparietal meningioma was found to have important influence on the first man's cognition and control inhibition, whereas frontotemporal dementia prevented the second man from understanding the moral disvalue of his sexually-inappropriate behavior and controlling his sexual impulses. In the current presentation, particular emphasis is placed on the logical reasoning supporting the conclusions that both the pedophiles should be considered not guilty by reason of insanity. Furthermore, experimental methods have been used to explore both cases, which rely on the existence of cognitive models for the phenomena under study, the integration of insights offered by different disciplines and the application of a variety of tools and approaches that follow the “convergence of evidence” principle, which could be safely used in court to support a mental insanity claim. Here, we describe how the use of the experimental method could become useful to reduce the uncertainty in mental insanity assessments. The use of a transdisciplinary, scientifically-grounded approach can help to change the way legal phenomena are interpreted. For instance, when assessing mental insanity, consultants should not only investigate the eventual existence of a diagnosis, but should assess the cognitive/affective abilities that are necessary to understand our own behavior and emotions as well as those of others. The criteria for responsibility should be symptoms-based and not diagnosis-based. Since pedophilia is among the most hideous behaviors condemned by society, a more comprehensive and transdisciplinary approach is recommended in court

Breast Implants Failure: Correlation of Explanted Implants Properties and Patient’s Clinical Data

Silicone gel breast implants are today widely used for breast reconstruction after mastectomy. Unfortunately, they can cause painful complications, such as capsular contracture, leading to the explantation. This work was aimed at evaluating the effects of the in vivo environment on breast implants, after their explantation, and the assessment of a possible correlation between the status of explanted prostheses and patients’ clinical data (age, implantation time, prosthesis model). Particularly, breast implants in patients treated with radiation therapy were compared to not irradiated ones. The explanted breast implants were investigated by macroscopic analysis and by SEM observation; uniaxial tensile tests were performed on the shells. The obtained results indicate that the radiotherapy and the time of implantation affect the mechanical properties of the implant, causing an increase in stiffness of the shell. In addition, different implants exhibited some cracks onto the surface of the shell

DESIGN OF MICROFLUIDIC DEVICES FOR DRUG SCREENING ON IN-VITRO CELLS TO OPTIMIZE OSTEOPOROSIS THERAPIES

The processes of bone resorption and formation are tightly gover regulatory agents. In addition, minerals and trace elements affect bone formation and resorption through direct or indirect effects on bone cells or bone mineral. Some trace elements closely chemically related to calcium, such as strontium, have pharmacological effects on bone when present at levels higher than those required for normal cell physiology. Indeed, strontium was found to exert several effects on bone cells. In addition to its antiresorptive activity, stron have significant beneficial effects on bone balance in normal and osteopenic animals. Accordingly, strontium ranelate has been thought to have potential interest in the treatment of osteoporosi aimed at designing a microfluidic device for pharmacological in individuating the concentration range in which the drug effectiveness is guaranteed. In particular, the device will be optimized for anti therapies with strontium ranelate. The device consists of a microchannel network for the delivery and mixing of chemical species, designed to provide a controlled drug concentration to the cell culture

Water-soluble isoindolo[2,1-a]quinoxalin-6-imines: In vitro antiproliferative activity and molecular mechanism(s) of action

Water-soluble isoindoloquinoxalin (IIQ) imines and the corresponding acetates were conveniently prepared from the key intermediates 2-(2\u2032-aminophenyl)-2H-isoindole-1-carbonitriles obtained by a Strecker reaction between substituted 1,2-dicarbaldehydes and 1,2-phenylenediamines. Both series were screened by the National Cancer Institute (Bethesda, MD) and showed potent antiproliferative activity against a panel of 60 human tumor cell lines. Several of the novel compounds showed GI50 values at a nanomolar level on the majority of the tested cell lines. Among IIQ derivatives, methoxy substituents at positions 3 and 8 or/and 9 were especially effective in impairing cell cycle progression and inducing apoptosis in cancer cells. These effects were associated to IIQ-mediated impairment of tubulin polymerization at pharmacologically significant concentrations of tested compounds. In addition, impaired DNA topoisomerase I functions and perturbation in telomere architecture were observed in cells exposed to micromolar concentrations of IIQ derivatives. The above results suggest that IIQ derivatives exhibit multi-target cytotoxic activities