The End Is the Beginning: Parkinson's Disease in the Light of Brain Imaging

Parkinson's disease (PD), the most common neurodegenerative disorder, is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healin

Distal corporal anchoring stitch: a technique to address distal corporal crossovers and impending lateral extrusions of a penile prosthesis

Background: Unidentified distal crossovers, delayed distal crossovers, and impending lateral extrusion are complications of penile prosthesis implant insertion but are not as common as prosthesis infection or mechanical failure. Aim: To evaluate results of a surgical technique, the distal corporal anchoring stitch, that addresses fixation of the penile prosthesis in patients with these complications. Methods: A lateral sub-coronal incision is used on the side where the crossover or laterally extruding cylinder should be positioned. Dissection is carried through the Buck fascia, followed by a transverse incision of the tunica albuginea, where the distal aspect of the affected cylinder is delivered. A 4-0 PDS suture is threaded through the distal cylinder ring of the implant. A new, properly positioned intracorporal channel is created and the suture is passed through the distal end of the channel. Once the suture is through the glans and the cylinder is in the correct position, a small cruciate incision is made on the glans at the location of the anchor stitch. The suture is tied with the knot buried in the glans tissue. Outcomes: Fifty-three patients underwent treatment of their distal penile implant crossover with a distal corporoplasty using this method and their anatomic and functional outcomes and overall satisfaction were evaluated. Results: This technique ensured that the cylinder remained in the newly created, appropriately positioned channel. No patients developed infections, wound-healing defect, glandular hypoesthesia, anesthesia, or altered sensation or pain in the glans related to the suture and only two reported recurrence of a lateral herniation that did not require further treatment. Clinical Implications: Distal fixation of the penile prosthesis is a useful surgical adjunct to treating patients with prosthetic lateral extrusions or crossovers that can be applied in almost all cases. Strengths and Limitations: Considering these rare complications, our experience is based on a relatively large number of patients and showed a low incidence of complications and a high satisfaction rate. The main limitation of this study is the retrospective nature of the data and the series included patients from two high-volume surgeons that might not be generalizable to all practices. Conclusion: The distal corporal anchoring stitch is safe and effective in securing distal fixation of the extruding inflatable penile prosthesis

Persistent and transient olfactory deficits in COVID-19 are associated to inflammation and zinc homeostasis

IntroductionThe Coronavirus Disease 2019 (COVID-19) is mainly a respiratory syndrome that can affect multiple organ systems, causing a variety of symptoms. Among the most common and characteristic symptoms are deficits in smell and taste perception, which may last for weeks/months after COVID-19 diagnosis owing to mechanisms that are not fully elucidated. MethodsIn order to identify the determinants of olfactory symptom persistence, we obtained olfactory mucosa (OM) from 21 subjects, grouped according to clinical criteria: i) with persistent olfactory symptoms; ii) with transient olfactory symptoms; iii) without olfactory symptoms; and iv) non-COVID-19 controls. Cells from the olfactory mucosa were harvested for transcriptome analyses. Results and discussionRNA-Seq assays showed that gene expression levels are altered for a long time after infection. The expression profile of micro RNAs appeared significantly altered after infection, but no relationship with olfactory symptoms was found. On the other hand, patients with persistent olfactory deficits displayed increased levels of expression of genes involved in the inflammatory response and zinc homeostasis, suggesting an association with persistent or transient olfactory deficits in individuals who experienced SARS-CoV-2 infection

Electromechanical and robotic devices for gait and balance rehabilitation of children with neurological disability: a systematic review

In the last two decades, a growing interest has been focused on gait and balance robot-assisted rehabilitation in children with neurological disabilities. Robotic devices allow the implementation of intensive, task-specific training fostering functional recovery and neuroplasticity phenomena. However, limited attention has been paid to the protocols used in this research framework. This systematic review aims to provide an overview of the existing literature on robotic systems for the rehabilitation of gait and balance in children with neurological disabilities and their rehabilitation applications. The literature search was carried out independently and synchronously by three authors on the following databases: MEDLINE, Cochrane Library, PeDro, Institute of Electrical and Electronics Engineers, ScienceDirect, and Google Scholar. The data collected included three subsections referring to clinical, technical, and regulatory aspects. Thirty-one articles out of 81 found on the primary literature search were included in the systematic review. Most studies involved children with cerebral palsy. Only one-third of the studies were randomized controlled trials. Overall, 17 devices (nine end-effector systems and eight exoskeletons) were investigated, among which only 4 (24%) were bore the CE mark. Studies differ on rehabilitation protocols duration, intensity, and outcome measures. Future research should improve both rehabilitation protocols\u2019 and devices\u2019 descriptions

The End Is the Beginning: Parkinson’s Disease in the Light of Brain Imaging

Parkinson’s disease (PD), the most common neurodegenerative disorder, is characterized by abnormal accumulation of α-synuclein aggregates known as Lewy bodies (LB) and loss of nigrostriatal dopaminergic neurons. Recent neuroimaging studies suggest that in the early phases of PD, synaptic and axonal damage anticipate the onset of a frank neuronal death. Paralleling, even post mortem studies on the brain of affected patients and on animal models support that synapses might represent the primary sites of functional and pathological changes. Indeed, α-synuclein microaggregation and spreading at terminals, by dysregulating the synaptic junction, would block neurotransmitter release, thus triggering a retrograde neurodegenerative process ending with neuronal cell loss by proceeding through the axons. Rather than neurodegeneration, loss of dopaminergic neuronal endings and axons could thus underlie the onset of connectome dysfunction and symptoms in PD and parkinsonisms. However, the manifold biases deriving from the interpretation of human brain imaging data hinder the validation of this hypothesis. Here, we present pivotal evidence supporting that novel comparative brain imaging studies, in patients and experimental models of PD in preliminary stages of disease, could be instrumental for proving whether synaptic endings are the sites where degeneration begins and initiating the factual achievement of disease modifying approaches. The need for such investigations is timely to define an early therapeutic window of intervention to attempt disease halting by terminal and/or axonal healing

Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome

Polycystic ovarian syndrome (PCOS) induces anovulation in women of reproductive age, and is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Indeed, PCOS women are characterized by poor quality oocytes. Therefore, a treatment for enhancing oocyte quality becomes crucial for these patients. Myo-Inositol and melatonin proved to be efficient predictors for positive IVF outcomes, correlating with high oocyte quality. We tested the synergistic effect of myo-inositol and melatonin in IVF protocols with PCOS patients in a randomized, controlled, double-blind trial. Five-hundred twenty-six PCOS women were divided into three groups: Controls (only folic acid: 400 mcg), Group A (Inofolic® plus, a daily dose of myo-inositol: 4000 mg, folic acid: 400 mcg, and melatonin: 3 mg), and Group B (Inofolic®, a daily dose of myo-inositol: 4000 mg, and folic acid: 400 mcg). The main outcome measures were oocyte and embryo quality, clinical pregnancy and implantation rates. The treatment lasted from the first day of the cycle until 14 days after embryo transfer. Myo-inositol and melatonin have shown to enhance, synergistically, oocyte and embryo quality. In consideration of the beneficial effect observed in our trial and on the bases of previous studies, we decided to integrate routinely MI and M supplementation in the IVF protocols. The same treatment should be taken carefully in consideration in all procedures of this kin

Three-component hydraulic penile prosthesis malfunction due to penile fibrolipoma secondary to augmentative phalloplasty: A case report

Fibrolipomas are an infrequent type of lipomas. We describe a case of a man suffering from subcutaneous penile fibrolipoma, who twelve months earlier has been submitted to augmentative phalloplasty due to aesthetic dysmorphophobia. The same patient three years earlier has been submitted to three-component hydraulic penile prostheses implantation due to erectile dysfunction. After six months from removing of the mass, the penile elongation and penile enlargement were stable, the prostheses were correctly functioning and the patient was satisfied with his sexual intercourse and life. The diagnostics and surgical characteristics of this case are reported

Interferon-beta injection site reactions in patients with multiple sclerosis.

Interferon-beta (IFNβ) is effective treatments for relapsing multiple sclerosis (MS). IFNβ treatment includes subcutaneous (SC) IFNβ-1b, intramuscular (IM) and SC IFNβ-1a, and SC pegylated IFNβ-1a (PEG-IFNβ-1a). PEG-IFNβ-1a offers the advantage of a prolonged duration of action with a less frequent administration (every 2 weeks) and a higher patient adherence. However, the use of SC interferons could be characterized by potential skin toxicity. Injection site reactions (ISRs), featured by erythema, edema, pain, and pruritus, are the most common adverse reactions. ISRs are mild or moderate in the vast majority of cases, but they can be severe enough to induce drug discontinuation. Therefore, it is very important to adopt strategies to minimize ISRs by proper patient education and counseling. These include rotation of injection sites, use of autoinjectors, use of medication at room temperature, cold compress, or local anesthetic cream before injection, early application of medium to high potency topical corticosteroids with gauze medication, and nonsteroidal anti-inflammatory drugs taken before and for 24 h after the injection

Ovarian Stimulation Protocol in IVF: An Up-to-Date Review of the Literature

The Assisted Reproductive Technology (ART) was born in order to help couples with infertility issues in having a baby. The first treatments of IVF used the spontaneous cycle of the women, with the retrieval of only one oocyte. Further studies have shown that it is possible to induce ovulation by administrating gonadotropins during the menstrual cycle, in order to obtain a higher number of oocytes. Many stimulation protocols have been introduced for controlled ovarian hyperstimulation of patients undergoing in vitro fertilization treatment. This review describe the different stimulation protocols using follicle-stimulating hormone (FSH) in combination with Gonadotropin releasing hormone (GnRH) either agonist or antagonist, oral supplementations and ovarian triggering. Using GnRH antagonist protocols have been demonstrated to improve significantly the clinical pregnancy rates for expected poor and high-responders, and in those women at high risk of developing ovarian hyperstimulation syndrome (OHSS). Two meta-analyses showed a better outcome in terms of the live birth rate when highly purified human menopausal gonadotropin (HMG) was used for ovarian stimulation compared with recombinant follicle stimulating hormone (rFSH) in the GnRH agonist long protocol. One of the most efficient stimulation protocol is the use of a combined protocol of human derived urinary FSH (uFSH) and rFSH. Combined protocol has resulted in a significant increase in the proportion of mature metaphase II oocytes and grade 1 embryos when compared to either rFSH or uFSH alone. A significantly higher delivery rate was achieved in rFSH+uFSH compared to the other protocols in poor and normal responders. Studying the combination of melatonin with myo-inositol and folic acid has also showed a higher percentage of mature oocytes in the melatonin group and a higher percentage of G1 embryos as well. However, It remains a crucial step to confirm the efficacy of such protocols for clinical application and it is still needs to comparison studies on larger scale with more focused on the differences in patients' response criteria and additional confounding variables, in order to draw more defined conclusions