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An expanded role for cardiac implantable electronic devices (CIEDs) in recent decades reflects an aging population and broader indications for devices, including both primary prevention and management of dysrhythmias. CIED infection is one of the most important device-related complications and has a major impact on mortality, quality of life, healthcare utilization, and cost. Unfortunately, the investigation and management of CIED infection remain complex, often necessitating complete and timely removal of the device and leads in order to eradicate the infection. In addition, the translation of knowledge from an extensive literature to a disparate group of medical practitioners has often been inadequate. This review of CIED infection management highlights the significant advances made during the past decade, including diagnostic criteria, advanced imaging, and next-generation sequencing for culture-negative cases or those in which uncertainty remains. We also outline the role and indication for powered lead extraction, the process of antibiotic choice and treatment duration, considerations related to the timing and location for reimplantation, and preimplantation risk stratification and associated interventions to reduce the risk of CIED infection. Résumé: L’élargissement du rôle des dispositifs électroniques cardiaques implantables (DECI) au cours des dernières décennies reflète le vieillissement de la population et les indications plus vastes des dispositifs, notamment dans la prévention primaire et la prise en charge des dysrythmies. Les infections liées aux DECI sont l’une des plus importantes complications liées aux dispositifs et ont des conséquences majeures sur la mortalité, la qualité de vie, l’utilisation et les coûts des soins de santé. Malheureusement, le dépistage et la prise en charge des infections liées aux DECI demeurent complexes et nécessitent souvent le retrait complet et rapide du dispositif et des sondes en vue d’éradiquer l’infection. De plus, l’application des connaissances issues d’une vaste littérature à un groupe disparate de médecins praticiens a souvent été inadéquate. La présente revue sur la prise en charge des infections liées aux DECI illustre les avancées importantes réalisées au cours de la dernière décennie, notamment les critères diagnostiques, l’imagerie avancée et le séquençage de prochaine génération des cas à culture négative ou de ceux pour lesquels des incertitudes demeurent. Nous avons aussi décrit le rôle et les indications d’extraction des sondes fonctionnelles, le processus du choix des antibiotiques et de la durée du traitement, les considérations relatives au moment et au lieu de la réimplantation, et la stratification du risque en préimplantation et les interventions associées afin de réduire le risque d’infections liées aux DECI.

Activating leucine-rich repeat kinase 2 (LRRK2) mutations cause Parkinson's and phosphorylation of Rab10 by pathogenic LRRK2 blocks primary ciliogenesis in cultured cells. In the mouse brain, LRRK2 blockade of primary cilia is highly cell type specific: For example, cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2-pathway mutant mice. We show here that the cell type specificity of LRRK2-mediated cilia loss is also seen in human postmortem striatum from patients with LRRK2 pathway mutations and idiopathic Parkinson's. Single nucleus RNA sequencing shows that cilia loss in mouse cholinergic interneurons is accompanied by decreased glial-derived neurotrophic factor transcription, decreasing neuroprotection for dopamine neurons. Nevertheless, LRRK2 expression differences cannot explain the unique vulnerability of cholinergic neurons to LRRK2 kinase as much higher LRRK2 expression is seen in medium spiny neurons that have normal cilia. In parallel with decreased striatal dopaminergic neurite density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion protein expression; glial cells show significant loss of ferritin heavy chain. These data strongly suggest that loss of cilia in specific striatal cell types decreases neuroprotection for dopamine neurons in mice and human Parkinson's. [ABSTRACT FROM AUTHOR]

Activating LRRK2 mutations cause Parkinson’s disease, and pathogenic LRRK2 kinase interferes with ciliogenesis. Previously, we showed that cholinergic interneurons of the dorsal striatum lose their cilia in R1441C LRRK2 mutant mice (Dhekne et al., 2018). Here, we show that cilia loss is seen as early as 10 weeks of age in these mice and also in two other mouse strains carrying the most common human G2019S LRRK2 mutation. Loss of the PPM1H phosphatase that is specific for LRRK2-phosphorylated Rab GTPases yields the same cilia loss phenotype seen in mice expressing pathogenic LRRK2 kinase, strongly supporting a connection between Rab GTPase phosphorylation and cilia loss. Moreover, astrocytes throughout the striatum show a ciliation defect in all LRRK2 and PPM1H mutant models examined. Hedgehog signaling requires cilia, and loss of cilia in LRRK2 mutant rodents correlates with dysregulation of Hedgehog signaling as monitored by in situ hybridization of Gli1 and Gdnf transcripts. Dopaminergic neurons of the substantia nigra secrete a Hedgehog signal that is sensed in the striatum to trigger neuroprotection; our data support a model in which LRRK2 and PPM1H mutant mice show altered responses to critical Hedgehog signals in the nigrostriatal pathway.

Partial nephrectomy (PN) either done open, laparoscopic, or robotic is associated with the complication of renal artery pseudoaneurysm (RAP), which is rare but can have grave prognosis. Minimally invasive intervention using endovascular techniques can safely treat this problem with minimal morbidity. We present here two cases of RAP following robotic PN. The first case was a 78-year male patient who underwent robotic PN 3 months prior for a 55 mm × 53 mm clear cell carcinoma of the left lower renal pole. On his 3-month follow-up computerized tomography (CT), he was incidentally diagnosed with a 48 mm × 40 mm × 36 mm well-defined pseudoaneurysm with supply from the lower polar accessory renal artery. The second case was a 42-year male patient who had undergone a robotic PN for a 3.5 cm renal mass. On day 24 postsurgery, he developed hematuria and evaluation with renal CT angiography showed two pseudoaneurysms of approximately 8–9 mm each; associated with a hematoma extending from the mid pole of the left kidney to the tail of the pancreas. We managed to successfully embolize the RAPs endovascularly in both the patients; case one with glue and case two with coils. Both patients were discharged on the next day with no side effects, complications, or morbidity. RAP post-PN; though rare, is a dreaded complication that one should be aware of and be able to treat it timely. Knowing how to managing these situations with minimally invasive techniques should be a part of the armamentarium of all endovascular specialists.

It is imperative to design and operate sustainable solid waste management (SWM) systems in cities based on the results of waste amount and characterization study (WACS). In this work, WACS was conducted and results were used to design an SWM system for an intermediate city of Pakistan. The study revealed that about 110 tons of solid waste per day is generated with a per capita rate of 0.337 kg/day. Around 51.2% of mixed municipal solid waste (MSW) is organic in nature and its non-scientific disposal is resulting in higher greenhouse gas (GHG) emissions. It was also found that more than 80% of valuables are taken away by the informal sector during the transfer of MSW from the generation source to the dumping site. Ultimate analyses showed that the moisture content (MC) and carbon to nitrogen (C:N) ratio were 64.23% and 51.14%, respectively. Proximate analysis revealed that moisture and calorific values were 57 % and 3505 BTU/lb., respectively. Based on these results, a material sorting facility (MSF) was proposed, with an estimated investment cost of US $3.64 million. However, the efficiency of the existing collection system is limited to 32 % only. In order to improve the collection efficiency (>90 %), an additional investment of US $1.638 million was estimated with an operations and maintenance (O&M) cost of US $19.25 per ton. Existing non-scientific MSW disposal practices contribute 32,079.61 CO2e tons/year of GHG emissions. The proposed MSF followed by composting is estimated to reduce GHG emissions by 38% to 19,722.38 CO2e tons/year. [ABSTRACT FROM AUTHOR]

This study presents experimental and numerical studies of the initiation and propagation of interface debonding between the substrate and thin-bonded cement-based overlay under fatigue testing. The overlay material is mortar incorporating amorphous metallic fibres (30 kg/m 3 ) and/or rubber aggregates (30%), while the substrate is a plain mortar. Uniaxial tensile tests were carried out on overlay materials and substrate-overlay interface to obtain a residual normal stress-crack opening relationship (σ-w law) and residual normal stress and substrate-overlay interface debonding relation respectively. Three-point bending fatigue tests were carried out on the composite beam to analyse the structural behaviour of repaired beam. The propagation of debonding along the substrate-overlay interface was monitored by using the Digital 3D Image Correlation (DIC) technique. Three-point bending fatigue test was modelled by finite element method (FEM) using CAST3M, developed by French Atomic Energy Commission. Direct tension test results show reduction in tensile strength and improvement in strain capacity (1.5 times of control mortar) for rubberised mortars. For fibre-reinforced mortars, post-peak residual tensile strength is significantly enhanced. Rubberised fibre-reinforced mortars show positive synergetic effects both in the improvement of residual post-peak strength and strain capacity (3.5 times than control mortar). Results show that the rubberised fibre-reinforced thin-bonded cement-based overlay proved to be very effective in restraining crack opening, by transferring stresses through the crack, and enhancing the fatigue resistance of repair system, by limiting interface debonding propagation upto 50%. Experimental results of composite beams are in good agreement with modelling results. [ABSTRACT FROM AUTHOR]