Radiation-Induced Lumbosacral Plexopathy.

Lumbosacral plexopathy (LSP) encompasses a group of disorders affecting post-ganglionic fibers derived from the L1-S4 roots. The differential diagnosis is challenging and includes other neuropathies of medullary, radicular, or peripheral origin. Defining the etiology is equally crucial, as LSP management relies on its cause. A thorough clinical history should address potential neoplastic disease (new-onset, progression, or relapse), diabetes mellitus, lumbar or pelvic trauma, and previous exposure to radiation. This is the case of a 78-year-old male, with a history of prostatic adenocarcinoma, treated with image-guided radiation therapy and hormone therapy five years before, with no evidence of relapse on follow-up. The patient presented with bilateral weakness, numbness, and paresthesia of lower limbs, gradually progressing over a three-month period, and followed by an acute worsening with inability to stand or walk. He also referred to distal mild edema, episodic hematuria, and urinary incontinence. Physical examination revealed paraparesis affecting proximal and distal leg muscles, along with bilateral hypoesthesia, impaired deep tendon reflexes, and proprioception below knee level. Pelvic, dorsal, and lumbosacral MRI excluded neoplastic lesions but identified somatic fracture of L5 without medullary or conus medullaris compromise. These findings did not explain the clinical picture. Further neurophysiologic studies characterized sensory-motor deficits as post-ganglionic, with specific spontaneous discharges of the muscle fibers, known as myokymia. These findings were consistent with radiation-induced LSP and were supported by MRI. Radiation-induced cystitis was also documented in pelvic MRI and urethral cystoscopy. This case highlights the clinical picture and differential diagnosis of radiation-induced LSP. Despite more typical symptoms and course, a neoplastic origin should always be carefully investigated and excluded. Radiation protocol should be carefully accessed, and its complications should not be overlooked, as they might cause severe morbidity.

Urethrocystography: a guide for urological surgery?

Urethrocystography remains the gold-standard technique for urethral pathology diagnosis. Nowadays, of the various indications for performing urethrocystography, the most common is due to a clinical suspicion of urethral stricture. Due to the high prevalence of strictures and their substantial impact on a patient's quality of life, the examination must allow the location, exclusion of multifocality, and assessment of the extent of the stricture to influence surgical planning. This article intends to demonstrate that the radiologist's role, by performing and interpreting the modality of urethrocystography, influences and is crucial for the urologic therapeutic decision and that the patients who were submitted to reconstruction by urethroplasty had a better success rate. The authors aim to review the radiological anatomy of the male urethra, discuss the modalities of choice for imaging the urethra (retrograde urethrography and voiding cystourethrography), provide an overview of the different indications for performing the study, examine the different etiologies for urethral strictures, understand the relevance of the different appearances of urethral pathology, and identify the surgical options, especially in the treatment of urethral strictures. Simultaneously, the study exposes cases of urethral trauma, fistulas, diverticulum, and congenital abnormalities.

An Interpretable Digital Twin for Self-Aware Industrial Machines.

This paper presents a proposed three-step methodology designed to enhance the performance and efficiency of industrial systems by integrating Digital Twins with particle swarm optimization (PSO) algorithms while prioritizing interpretability. Digital Twins are becoming increasingly prevalent due to their capability to offer a comprehensive virtual representation of physical systems, thus facilitating detailed simulations and optimizations. Concurrently, PSO has demonstrated its effectiveness for real-time parameter estimation, especially in identifying both standard and unknown components that influence the dynamics of a system. Our methodology, as exemplified through DC Motor and Hydraulic Actuator simulations, underscores the potential of Digital Twins to augment the self-awareness of industrial machines. The results indicate that our approach can proficiently optimize system parameters in real-time and unveil previously unknown components, thereby enhancing the adaptive capacities of the Digital Twin. While the reliance on accurate data to develop Digital Twin models is a notable consideration, the proposed methodology serves as a promising framework for advancing the efficiency of industrial applications. It further extends its relevance to fault detection and system control. Central to our approach is the emphasis on interpretability, ensuring a more transparent understanding and effective usability of such systems.

The Brazilian Zika virus strain causes birth defects in experimental models.

Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barré syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

Uroguanylin inhibits H-ATPase activity and surface expression in renal distal tubules by a PKG-dependent pathway.

Cumulative evidence suggests that guanylin peptides play an important role on electrolyte homeostasis. We have previously reported that uroguanylin (UGN) inhibits bicarbonate reabsorption in a renal distal tubule. In the present study, we tested the hypothesis that the bicarbonaturic effect of UGN is at least in part attributable to inhibition of H(+)-ATPase-mediated hydrogen secretion in the distal nephron. By in vivo stationary microperfusion experiments, we were able to show that UGN inhibits H(+)-ATPase activity by a PKG-dependent pathway because KT5823 (PKG inhibitor) abolished the UGN effect on distal bicarbonate reabsorption and H89 (PKA inhibitor) was unable to prevent it. The in vivo results were confirmed by the in vitro experiments, where we used fluorescence microscopy to measure intracellular pH (pHi) recovery after an acid pulse with NH4Cl. By this technique, we observed that UGN and 8 bromoguanosine-cGMP (8Br-cGMP) inhibited H(+)-ATPase-dependent pHi recovery and that the UGN inhibitory effect was abolished in the presence of the PKG inhibitor. In addition, by using RT-PCR technique, we verified that Madin-Darby canine kidney (MDCK)-C11 cells express guanylate cyclase-C. Besides, UGN stimulated an increase of both cGMP content and PKG activity but was unable to increase the production of cellular cAMP content and PKA activity. Furthermore, we found that UGN reduced cell surface abundance of H+-ATPase B1 subunit in MDCK-C11 and that this effect was abolished by the PKG inhibitor. Taken together, our data suggest that UGN inhibits H(+)-ATPase activity and surface expression in renal distal cells by a cGMP/PKG-dependent pathway.