Systematic evaluation of a holmium:yttrium-aluminum-garnet laser lithotripsy device with variable pulse peak power and pulse duration

AbstractObjectiveThe Holmium:yttrium-aluminum-garnet (Ho:YAG) laser is the standard lithotrite for ureteroscopy. This paper is to evaluate a Ho:YAG laser with a novel effect function in vitro, which allows a real-time variation of pulse duration and pulse peak power.MethodsTwo types of phantom calculi with four degrees of hardness were made for fragmentation and retropulsion experiments. Fragmentation was analysed at 5 (0.5 J/10 Hz), 10 (1 J/10 Hz), and 20 (2 J/10 Hz) W in non-floating phantom calculi, retropulsion in an ureteral model at 10 (1 J/10 Hz) and 20 (2 J/10 Hz) W using floating phantom calculi. The effect function was set to 25%, 50%, 75%, and 100% of the maximum possible effect function at each power setting. Primary outcomes: fragmentation (mm3), the distance of retropulsion (cm); ≥5 measurements for each trial.ResultsAn increase of the effect feature (25% vs. 100%), i.e., an increase of pulse peak power and decrease of pulse duration, improved Ho:YAG laser fragmentation. This effect was remarkable in soft stone composition, while there was a trend for improved fragmentation with an increase of the effect feature in hard stone composition. Retropulsion increased with increasing effect function, independently of stone composition. The major limitations of the study are the use of artificial stones and the in vitro setup.ConclusionChanges in pulse duration and pulse peak power may lead to improved stone fragmentation, most prominently in soft stones, but also lead to increased retropulsion. This new effect function may enhance Ho:YAG laser fragmentation when maximum power output is limited or retropulsion is excluded

OSBPL2 encodes a protein of inner and outer hair cell stereocilia and is mutated in autosomal dominant hearing loss (DFNA67)

Background: Early-onset hearing loss is mostly of genetic origin. The complexity of the hearing process is reflected by its extensive genetic heterogeneity, with probably many causative genes remaining to be identified. Here, we aimed at identifying the genetic basis for autosomal dominant non-syndromic hearing loss (ADNSHL) in a large German family. Methods: A panel of 66 known deafness genes was analyzed for mutations by next-generation sequencing (NGS) in the index patient. We then conducted genome-wide linkage analysis, and whole-exome sequencing was carried out with samples of two patients. Expression of Osbpl2 in the mouse cochlea was determined by immunohistochemistry. Because Osbpl2 has been proposed as a target of miR-96, we investigated homozygous Mir96 mutant mice for its upregulation. Results: Onset of hearing loss in the investigated ADNSHL family is in childhood, initially affecting the high frequencies and progressing to profound deafness in adulthood. However, there is considerable intrafamilial variability. We mapped a novel ADNSHL locus, DFNA67, to chromosome 20q13.2-q13.33, and subsequently identified a co-segregating heterozygous frameshift mutation, c.141-142delTG (p.Arg50Alafs∗103), in OSBPL2, encoding a protein known to interact with the DFNA1 protein, DIAPH1. In mice, Osbpl2 was prominently expressed in stereocilia of cochlear outer and inner hair cells. We found no significant Osbpl2 upregulation at the mRNA level in homozygous Mir96 mutant mice. Conclusion: The function of OSBPL2 in the hearing process remains to be determined. Our study and the recent description of another frameshift mutation in a Chinese ADNSHL family identify OSBPL2 as a novel gene for progressive deafness.</p

A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential

Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adherently and can be expanded to 1015 cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel protein, and various neurotransmitter phenotypes. Stereotactic implantation of USSCs into intact adult rat brain revealed that human Tau-positive cells persisted for up to 3 mo and showed migratory activity and a typical neuron-like morphology. In vivo differentiation of USSCs along mesodermal and endodermal pathways was demonstrated in animal models. Bony reconstitution was observed after transplantation of USSC-loaded calcium phosphate cylinders in nude rat femurs. Chondrogenesis occurred after transplanting cell-loaded gelfoam sponges into nude mice. Transplantation of USSCs in a noninjury model, the preimmune fetal sheep, resulted in up to 5% human hematopoietic engraftment. More than 20% albumin-producing human parenchymal hepatic cells with absence of cell fusion and substantial numbers of human cardiomyocytes in both atria and ventricles of the sheep heart were detected many months after USSC transplantation. No tumor formation was observed in any of these animals

The neural bases of tinnitus : Lessons from deafness and cochlear implants

Subjective tinnitus is the conscious perception of sound in the absence of any acoustic source. The literature suggests various tinnitus mechanisms, most of which invoke changes in spontaneous firing rates of central auditory neurons resulting from modification of neural gain. Here, we present an alternative model based on evidence that tinnitus is: (i) rare in people who are congenitally deaf, (ii) common in people with acquired deafness, and (iii) potentially suppressed by active cochlear implants used for hearing restoration. We propose that tinnitus can only develop after fast auditory fiber activity has stimulated the synapse formation between fast-spiking parvalbumin positive (PV+) interneurons and projecting neurons in the ascending auditory path and co-activated fronto-striatal networks after hearing onset. Thereafter, fast auditory fiber activity promotes feedforward and feedback inhibition mediated by PV+ interneuron activity in auditory-specific circuits. This inhibitory network enables enhanced stimulus resolution, attention-driven contrast improvement, and augmentation of auditory responses in central auditory pathways (neural gain) after damage of slow auditory fibers. When fast auditory fiber activity is lost, tonic PV+ interneuron activity is diminished, resulting in the prolonged response latencies, sudden hyperexcitability, enhanced cortical synchrony, elevated spontaneous gamma oscillations, and impaired attention/stress-control that have been described in previous tinnitus models. Moreover, because fast processing is gained through sensory experience, tinnitus would not exist in congenital deafness. Electrical cochlear stimulation may have the potential to re-establish tonic inhibitory networks and thus suppress tinnitus. The proposed framework unites many ideas of tinnitus pathophysiology and may catalyze cooperative efforts to develop tinnitus therapies

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Innovationen im Retail Banking - Status quo und Innovationsmatrix

Die zunehmende Digitalisierung des Bankgeschäfts führt auch im Retail Banking zu einem stetigen Wandel. Innovationen an der Kundenschnittstelle führen zu Veränderungen in der Wertschöpfungskette von Banken und Sparkassen und bringen sowohl Chancen als auch Risiken mit sich. Von den Verantwortlichen zu entscheiden ist daher möglichst frühzeitig, welche Innovation im eigenen Unternehmen zu adaptieren ist, um Wettbewerbsvorteile zu generieren und sich gegen alte und neue Konkurrenten zu behaupten

Managing caliceal stones

The natural course of untreated asymptomatic caliceal calculi has not been clearly defined, especially in terms of disease progression, and the indications for and outcomes of surgical intervention are not precise. Caliceal stones may remain asymptomatic but, in case of migration, ureteral calculi can cause acute ureteric colic with severe complications. The decision for an active treatment of caliceal calculi is based on stone composition, stone size and symptoms. Extracorporal shock-wave lithotripsy (ESWL) has a low complication rate and is recommended by the current guidelines of the European Association of Urology as a first-line therapy for the treatment of caliceal stones <2 cm in diameter. However, immediate stone removal is not achieved with ESWL. The primary stone-free rates (SFR) after ESWL depend on stone site and composition and, especially for lower pole calculi, the SFR differ widely from other caliceal stones. Minimally-invasive procedures including percutaneous nephrolithotomy and ureteroscopy are alternatives for the treatment of caliceal stones, associated with low morbidity and high primary SFR when performed in centers of excellence

A Cohort Study on Neuropathic Pain of the Sural Nerve-Can Neurectomy Be Considered a Valid Treatment Option?

BACKGROUND Sural nerve neuroma is often caused by an injury during prior surgery, for example, osteosynthesis or ligament refixations at ankle level. Different surgical techniques to treat neuroma have been described. Neurectomy of an injured symptomatic sural nerve has been described as a treatment option for neuropathic pain. The aim of this study was to evaluate the outcomes of this technique to operatively treat sural nerve neuroma in our department. METHODS From 2010 to 2020, a total of 30 consecutive patients with neuropathic pain and suspected neuroma of the sural nerve underwent sural nerve neurectomy. A medical chart review was performed to collect patient-, pain-, and treatment-specific factors. Outcomes were registered. RESULTS After neurectomy, 22 patients (73.3%) had persisting pain. In logistic regression models evaluating the risk of persisting pain after sural nerve neurectomy, no independent predictor of higher risk of persisting pain could be identified. CONCLUSION For sural nerve neuromas, neurectomy remains an option as the surgical morbidity is minor, but patients need to be counseled that only a fourth of those undergoing surgery will be pain-free afterward