Detrusor ultrastructural studies in human lower urinary tract dysfunction: correlation of structural features and function.

Introduction: Lower urinary tract symptoms (LUTS), voiding dysfunction (VD) and urinary retention are common in the aging population, associated with significant morbidity.(1) LUTS can be due to overactive bladder (OAB), underactive bladder (UAB), bladder outflow obstruction (BOO), or a combination. Diagnosis is key to management, whilst avoiding harm of inappropriate therapy. Due to challenges in evaluation, there may be a role for detrusor ultrastructural analyses in diagnosis and prognosis of VD.(2,3,4) Objectives: To investigate detrusor ultrastructural changes in VD in the older population and potential clinical applications. Specifically: 1. females with bladder outflow obstruction (fBOO). 2. males with detrusor underactivity (mDU), with long term functional-structural correlation. 3. older males with coexistent overactive underactive bladders (mCOUB). Methodology and patient cohort: Patients were recruited from the Urodynamic Clinic at Concord Hospital. Patients with fBOO, mDU and mCOUB on urodynamic study who were undergoing cystoscopy as part of their clinical management were recruited. Detrusor biopsies were obtained and examined by electron microscopy. Ultrastructural analyses were performed using a standardised protocol and correlated with functional outcomes. Results Detrusor ultrastructural features of ‘myohypertrophy’ were similar in fBOO and male BOO; severity correlated with BOO duration and severity. In mDU, severe features of myohyertrophy and degeneration predicted poor long term voiding outcomes. Older mCOUB had concomitant features of myohypertrophy and dysjunctional patterns. Our standardised protocol allowed analyses of all 3 VD. Conclusions Detrusor ultrastructural features in patients with fBOO, mDU and mCOUB were described with correlations found between detrusor ultrastructure and lower urinary tract function. Detrusor ultrastructure studies not only improve understanding of VD, but may also assist in diagnosis, prognosis, and management

Cellular Network Speech Enhancement: Removing Background and Transmission Noise

The primary objective of speech enhancement is to reduce background noise while preserving the target's speech. A common dilemma occurs when a speaker is confined to a noisy environment and receives a call with high background and transmission noise. To address this problem, the Deep Noise Suppression (DNS) Challenge focuses on removing the background noise with the next-generation deep learning models to enhance the target's speech; however, researchers fail to consider Voice Over IP (VoIP) applications their transmission noise. Focusing on Google Meet and its cellular application, our work achieves state-of-the-art performance on the Google Meet To Phone Track of the VoIP DNS Challenge. This paper demonstrates how to beat industrial performance and achieve 1.92 PESQ and 0.88 STOI, as well as superior acoustic fidelity, perceptual quality, and intelligibility in various metrics

Transcriptomic Response to Feeding and Starvation in a Herbivorous Dinoflagellate

Grazing by heterotrophic protists influences plankton population dynamics, community composition, and the flux of carbon through marine planktonic food webs. To gain insight into the molecular underpinnings of grazing in dinoflagellates, a group of important heterotrophic protists, we used a RNA-Seq approach to investigate the transcriptomic response of Oxyrrhis marina under fed and starved conditions with three different phytoplankton prey (Isochrysis galbana and two strains of Heterosigma akashiwo). In response to fed and starved conditions, 1,576 transcripts were significantly differentially expressed in O. marina. Fed O. marina cells upregulated transcripts involved in the synthesis of essential fatty acids and storage carbohydrates suggesting that the predator was food satiated and excess glucose was being stored as an energy reserve. Transcripts encoding voltage-gated ion channels were also upregulated during grazing, and they are known to be involved in the detection of mechanical stimuli and the regulation of swimming behavior in several eukaryotic protists. Fed O. marina cells upregulated kinases, which can dictate cell shape changes and may be associated with phagocytosis. During starvation, upregulated O. marina transcripts included those involved in the degradation of energy-storage molecules like glucan 1,4-alpha-glycosidase and those involved in antioxidant activities and autophagy, like acid ceramidase that are associated with the digestion of polar lipids present in cell membranes. Starved O. marina also upregulated transcripts with high similarity to proton pumping proteorhodopsins suggesting that this heterotrophic protist may supplement its energy requirement during starvation with a light harvesting mechanism. Although herbivorous grazing is a pivotal transformation in the C cycle, logistical constraints limit our investigations of environmental and biological drivers. The molecular signals identified here provide new insights into the metabolic regulation of feeding and starvation in marine heterotrophic protists and can fuel hypothesis-driven research into predators’ metabolic response to prey availability

Fast phasic release properties of dopamine studied with a channel biosensor

Few other neurotransmitters are of as intense interest to neuropsychiatry and neurology as dopamine, yet existing techniques to monitor dopamine release leave an important spatiotemporal gap in our understanding. Electrochemistry and fluorescence imaging tools have been developed to fill the gap, but these methods have important limitations. We circumvent these limitations by introducing a dopamine-gated chloride channel into rat dorsal striatal medium spiny neurons, targets of strong dopamine innervation, thereby transforming dopamine from a slow transmitter into a fast transmitter and revealing new opportunities for studying moment-to-moment regulation of dopamine release. We demonstrate pharmacological and biophysical properties of the channel that make it suitable for fast, local dopamine measurements, and we demonstrate for the first time spontaneous and evoked responses to vesicular dopamine release in the dorsal striatum. Evoked dopamine currents were separated into a fast, monosynaptic component and a slower-rising and decaying disynaptic component mediated by nicotinic receptor activation. In summary, LGC-53 represents a dopamine biosensor with properties suitable for temporal separation of distinct dopamine signals in targets of dopamine innervation

Diverse voltage-sensitive dyes modulate GABAA receptor function

Voltage-sensitive dyes (VSDs) are important tools for assessing network and single-cell excitability, but an untested premise in most cases is that the dyes do not interfere with the parameters (membrane potential, excitability) that they are designed to measure. We found that popular members of several different families of voltage-sensitive dyes modulate GABA(A) receptor with maximum efficacy and potency similar to clinically used GABA(A) receptor modulators. Di-4-ANEPPS and DiBAC4(3) potentiated GABA function with micromolar and high nanomolar potency respectively and yielded strong maximum effects similar to barbiturates and neurosteroids. Newer blue oxonols had biphasic effects on GABA(A) receptor function at nanomolar and micromolar concentrations, with maximum potentiation comparable to that of saturating benzodiazepine effects. ANNINE 6 and ANNINE 6plus had no detectable effect on GABA(A) receptor function. Even dyes with no activity on GABA(A) receptors at baseline induced photodynamic enhancement of GABA(A) receptors. The basal effects of dyes were sufficient to prolong IPSCs and to dampen network activity in multielectrode array recordings. Therefore, the dual effects of voltage-sensitive dyes on GABAergic inhibition require caution in dye use for studies of excitability and network activity

The Local Food Environment and Body Mass Index among the Urban Poor in Accra, Ghana

Obesity in the sub-Saharan Africa region has been portrayed as a problem of affluence, partly because obesity has been found to be more common in urban areas and among the rich. Recent findings, however, reveal rising prevalence among the poor particularly the urban poor. A growing body of literature mostly in Western countries shows that obesity among the poor is partly the result of an obesogenic-built environment. Such studies are lacking in the African context. This study examines the characteristics of the local food environment in an urban poor setting in Accra, Ghana and further investigates the associated risk of obesity for residents. Data on the local food environment was collected using geographic positioning system (GPS) technology. The body mass indices (BMI) of females (15-49 years) and males (15-59 years) were calculated from measured weight and height. Data on the socio-demographic characteristics and lifestyle behaviors of respondents was also collected through a household survey. Spatial analysis tools were used to examine the characteristics of the local food environment while the influence of the food environment on BMI was examined using a two-level multilevel model. The measures of the food environment constituted the level 2 factors while individual socio-demographic characteristics and lifestyle behaviors constituted the level 1 factors. The local food environment in the study communities is suggestive of an obesogenic food environment characterized by an abundance of out-of-home cooked foods, convenience stores, and limited fruits and vegetables options. The results of the multilevel analysis reveal a 0.2 kg/m(2) increase in BMI for every additional convenience store and a 0.1 kg/m(2) reduction in BMI for every out-of-home cooked food place available in the study area after controlling for individual socio-demographic characteristics, lifestyle behaviors, and community characteristics. The findings of this study indicate that the local food environment in urban poor Accra is associated with increased risk of obesity through providing access to convenience stores. In order to reduce the risk of obesity in these urban poor communities, there is the need to regulate the availability of and access to convenience stores while also encouraging healthier offerings in convenience stores

Dietary Depletion of Milk Exosomes and Their MicroRNA Cargos Elicits a Depletion of miR-200a-3p and Elevated Intestinal Inflammation and Chemokine (C-X-C Motif) Ligand 9 Expression in Mdr1a−/− Mice

Background: Exosomes transfer regulatory microRNAs (miRs) from donor cells to recipient cells. Exosomes and miRs originate from both endogenous synthesis and dietary sources such as milk. miR-200a-3p is a negative regulator of the proinflammatory chemokine (C-X-C motif) ligand 9 (CXCL9). Male Mdr1a−/− mice spontaneously develop clinical signs of inflammatory bowel disease (IBD). Objectives: We assessed whether dietary depletion of exosomes and miRs alters the severity of IBD in Mdr1a−/− mice owing to aberrant regulation of proinflammatory cytokines. Methods: Starting at 5 wk of age, 16 male Mdr1a−/− mice were fed either milk exosome– and RNA-sufficient (ERS) or milk exosome– and RNA-depleted (ERD) diets. The ERD diet is characterized by a near-complete depletion of miRs and a 60% loss of exosome bioavailability compared with ERS. Mice were killed when their weight loss exceeded 15% of peak body weight. Severity of IBD was assessed by histopathological evaluation of cecum. Serum cytokine and chemokine concentrations and mRNA and miR tissue expression were analyzed by multiplex ELISAs, RNA-sequencing analysis, and qRT-PCR, respectively. Results: Stromal collapse, gland hyperplasia, and additive microscopic disease scores were (mean ± SD) 56.7% ± 23.3%, 23.5% ± 11.8%, and 29.6% ± 8.2% lower, respectively, in ceca of ERS mice than of ERD mice (P \u3c 0.05). The serum concentration of CXCL9 was 35.0% ± 31.0% lower in ERS mice than in ERD mice (P \u3c 0.05). Eighty-seven mRNAs were differentially expressed in the ceca from ERS and ERD mice; 16 of these mRNAs are implicated in immune function. The concentrations of 4 and 1 out of 5 miRs assessed (including miR-200a-3p) were ≤63% lower in livers and ceca, respectively, from ERD mice than from ERS mice. Conclusions: Milk exosome and miR depletion exacerbates cecal inflammation in Mdr1a−/− mice

Reallocation of foliicolous species of the genus Strigula into six genera (lichenized Ascomycota, Dothideomycetes, Strigulaceae)

Strigula sensu lato has been previously defined based on phenotype characters as a rather broad genus including tropical to temperate species growing on a wide array of substrata. In this study, based on a multilocus phylogenetic approach, we show that foliicolous species form six well-delimited clades that correlate with diagnostic phenotype features, including thallus morphology, carbonization of the involucrellum and excipulum, ascospore dimensions, and type of macroconidia. Given the topology, with five of the six clades emerging on long stem branches, and the strong phenotypical differentiation between the clades, we recognize these at the genus level, making mostly use of previously established genus names. Four genera, namely Phylloporis, Puiggariella, Raciborskiella, and Racoplaca, are resurrected for the S. phyllogena, S. nemathora, S. janeirensis, and S. subtilissima groups, respectively, whereas one new genus, Serusiauxiella gen. nov., is introduced for a novel lineage with peculiar macroconidia. The only sequenced non-foliicolous species, S. jamesii, is not closely related to these six foliicolous lineages but clusters with Flavobathelium and Phyllobathelium, revealing it as an additional undescribed genus-level lineage being treated elsewhere. Within the new genus Serusiauxiella, three new species are described: Serusiauxiella filifera sp. nov., S. flagellata sp. nov., and S. sinensis sp. nov. In addition, ten new combinations are proposed: Phylloporis austropunctata comb. nov., P. radiata comb. nov., P. vulgaris comb. nov., Puiggariella confluens comb. et stat. nov., P. nemathora comb. nov., P. nigrocincta comb. nov., Racoplaca maculata comb. nov., R. melanobapha comb. nov., R. transversoundulata, and R. tremens comb. nov. We also report on a peculiar, previously unrecognized growth behaviour of the macroconidial appendages in Strigula s.lat

Human Case of Swine Influenza A (H1N1) Triple Reassortant Virus Infection, Wisconsin

Zoonotic infections with swine influenza A viruses are reported sporadically. Triple reassortant swine influenza viruses have been isolated from pigs in the United States since 1998. We report a human case of upper respiratory illness associated with swine influenza A (H1N1) triple reassortant virus infection that occurred during 2005 following exposure to freshly killed pigs