Distinct TORC1 signalling branches regulate Adc17 proteasome assembly chaperone expression.

When stressed, cells need to adapt their proteome to maintain protein homeostasis. This requires increased proteasome assembly. Increased proteasome assembly is dependent on increased production of proteasome assembly chaperones. In Saccharomyces cerevisiae, inhibition of the growth-promoting kinase complex TORC1 causes increased proteasome assembly chaperone translation, including that of Adc17. This is dependent upon activation of the mitogen-activated protein kinase (MAPK) Mpk1 and relocalisation of assembly chaperone mRNA to patches of dense actin. We show here that TORC1 inhibition alters cell wall properties to induce these changes by activating the cell wall integrity pathway through the Wsc1, Wsc3 and Wsc4 sensor proteins. We demonstrate that, in isolation, these signals are insufficient to drive protein expression. We identify that the TORC1-activated S6 kinase Sch9 must be inhibited as well. This work expands our knowledge on the signalling pathways that regulate proteasome assembly chaperone production.

MPK1/SLT2 Links Multiple Stress Responses with Gene Expression in Budding Yeast by Phosphorylating Tyr1 of the RNAP II CTD.

The RNA polymerase II largest subunit C-terminal domain consists of repeated YSPTSPS heptapeptides. The role of tyrosine-1 (Tyr1) remains incompletely understood, as, for example, mutating all Tyr1 residues to Phe (Y1F) is lethal in vertebrates but a related mutant has only a mild phenotype in S. pombe. Here we show that Y1F substitution in budding yeast resulted in a strong slow-growth phenotype. The Y1F strain was also hypersensitive to several different cellular stresses that involve MAP kinase signaling. These phenotypes were all linked to transcriptional changes, and we also identified genetic and biochemical interactions between Tyr1 and both transcription initiation and termination factors. Further studies uncovered defects related to MAP kinase I (Slt2) pathways, and we provide evidence that Slt2 phosphorylates Tyr1 in vitro and in vivo. Our study has thus identified Slt2 as a Tyr1 kinase, and in doing so provided links between stress response activation and Tyr1 phosphorylation.

A switch from noncanonical to canonical Wnt signaling stops neuroblast migration through a Slt-Robo and RGA-9b/ARHGAP-dependent mechanism.

Members of the Wnt family of secreted glycoproteins regulate cell migration through distinct canonical and noncanonical signaling pathways. Studies of vertebrate development and disease have shown that these pathways can have opposing effects on cell migration, but the mechanism of this functional interplay is not known. In the nematode Caenorhabditis elegans, a switch from noncanonical to canonical Wnt signaling terminates the long-range migration of the QR neuroblast descendants, providing a tractable system to study this mechanism in vivo. Here, we show that noncanonical Wnt signaling acts through PIX-1/RhoGEF, while canonical signaling directly activates the Slt-Robo pathway component EVA-1/EVA1C and the Rho GTPase-activating protein RGA-9b/ARHGAP, which are required for migration inhibition. Our results support a model in which cross-talk between noncanonical and canonical Wnt signaling occurs through antagonistic regulation of the Rho GTPases that drive cell migration.

Comparing the efficiency of speech and language therapy and transcranial magnetic stimulation for treating Broca's aphasia.

OBJECTIVES: Aphasia is an acquired language-cognitive disorder that highly affects an individual's speech, language, and communication skills. Recovery from aphasia requires attentive treatment since it is a long and dynamic process. This study aimed to show interactive benefits of combining classical intervention strategies with new technological approaches and demonstrating their effectiveness. MATERIALS AND METHODS: A total of 40 individuals with Broca's aphasia were included in the study. The participants were divided into Application-1 Speech and Language Therapy, Application-2 Transcranial Magnetic Stimulation, Application-3 (consecutive Transcranial Magnetic Stimulation and Speech and Language Therapy), and Application-4 (Control Group) experimental groups, with 10 participants in each group. RESULTS: Analysis indicated that individuals in the group in which Transcranial Magnetic Stimulation and Speech and Language Therapy were applied consecutively had further increases in speech fluency, repetition, and naming scores from pre-test to post-test (p<0.01). Picture naming and quality-of-life communication scores of individuals in the group in which Speech and Language Therapy was performed increased further from pre-test to post-test (p<0.01). CONCLUSIONS: The results of the study showed a positive effect on language skills, naming scores, and participation in social life of Turkish-speaking aphasic individuals with the Speech and Language Therapy and Transcranial Magnetic Stimulation methods. The use of Transcranial Magnetic Stimulation alone is insufficient in this context. Although Speech and Language Therapy alone is effective in naming ability, Transcranial Magnetic Stimulation in addition to Speech and Language Therapy significantly increases the gain obtained with therapies.

An Exploratory Retrospective Data Analysis Comparing the Outcomes of Selective Laser Trabeculoplasty and Argon Laser Trabeculoplasty in Patients with Open-Angle Glaucoma or Ocular Hypertension in Vienna, Austria, from the Year 2012 to 2022.

Background and Objectives: The aim of the present study was to compare the short-term outcomes of selective laser trabeculoplasty (SLT) with argon laser trabeculoplasty (ALT) in patients with glaucoma in a real-world setting. Materials and Methods: The present study was conducted as a retrospective case-control study. The main outcome was the change in intraocular pressure (IOP) three months after laser surgery. In addition, the number of substances used for lowering of IOP and adverse events (AEs) were assessed. Results: Charts from 25 patients were included in the present study, of which 12 had received ALT and 13 SLT. In both groups, IOP significantly decreased from baseline values 6 weeks and 3 months after laser treatment (p < 0.01 vs. baseline at each timepoint for both groups). While after 6 weeks, no difference between groups was found, after 3 months, the decrease in IOP was significantly more pronounced in the SLT group (-26 ± 21% in the ALT group vs. -41 ± 14% in the SLT group, p = 0.018 between groups, ANOVA). Three months after laser treatment, the number of IOP-lowering substances used by each patient had decreased with no difference between groups (ALT: from 2.7 ± 0.8 to 2.3 ± 0.9 substances; SLT: from 1.8 ± 1.2 to 1.3 ± 1.1 substances, p = 0.386). Only a few AEs were observed. Two patients in the ALT and one patient in the SLT group required trabeculectomy within 1 year after laser treatment due to IOP decompensation. Conclusions: In the present study, SLT was at least as effective as ALT with fewer AEs and a similar reduction in concomitant IOP-lowering medication.

Effectiveness and safety of VISULAS® green selective laser trabeculoplasty: a prospective, interventional multicenter clinical investigation.

PURPOSE: To evaluate the effectiveness and safety of Selective Laser Trabeculoplasty (SLT) with the SLT mode of the VISULAS® green laser in patients with primary open-angle glaucoma (POAG). METHODS: This prospective, interventional multicenter clinical investigation included patients with POAG who either needed a treatment escalation because the individual intraocular pressure (IOP) target was not met or treatment initiation and had an IOP ≥ 17 mmHg at baseline in the study eye. The study was conducted in five research centers across Germany. Approximately 100 laser applications were delivered to 360° of the trabecular meshwork. Glaucoma medications were not modified during the 3-month follow-up to allow evaluation of the sole effect of VISULAS® green with SLT. Efficacy outcomes were postoperatively absolute and relative IOP changes at 1 and 3 months. Safety outcomes analyzed the rate of intra- and postoperative adverse events. RESULTS: Thirty-four eyes of 34 POAG patients were included. The overall mean number of preoperative glaucoma medications was 2.2 ± 1.4 in 29 treated eyes, 5 eyes were treatment naïve. Mean baseline IOP (mmHg) was 21.0 ± 2.69 and was reduced by - 3.53 ± 3.34 [95% CI - 4.61; - 2.45] and - 3.59 ± 3.41 [95% CI - 4.64; - 2.53] at the 1- and 3-month follow-up, respectively (p < 0.0001), with 48.5% of cases achieving a ≥ 20% IOP reduction at 3 months [95% CI = 30.8%; 66.5%]. The mean relative IOP reduction was - 16.4% and - 16.3% at 1 and 3 months, respectively (p < 0.0001). Potentially device- or procedure-related adverse events were mild to moderate and included 3 postoperative IOP-spikes and 6 reports regarding eye pain and discomfort. All were resolved without sequelae. CONCLUSIONS: SLT performed with the VISULAS® green laser achieved clinically significant additional IOP reductions in medically treated as well as in treatment naïve eyes with POAG and there were no relevant safety issues. The results are comparable to other reported SLT studies.

Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial.

BACKGROUND: Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes. METHODS: A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18-75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7-10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization. RESULTS: Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526). CONCLUSIONS: Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients. TRIAL REGISTRATION: This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.

Peripheral anterior synechiae after selective laser trabeculoplasty among Chinese patients.

PURPOSE: Peripheral anterior synechiae (PAS) have been reported as a complication after argon laser trabeculoplasty, but rarely reported after selective laser trabeculoplasty (SLT). This study aims to determine the incidence and predictors of this potential complication in phakic eyes of Chinese patients. METHODS: A retrospective review of consecutive Chinese phakic patients who underwent SLT for primary open-angle glaucoma or ocular hypertension from 2011 to 2015 was analyzed for post-operative outcomes, including the development of PAS. RESULTS: There was a total of 292 patients (509 eyes) that were of Chinese ethnicity and eligible in our analysis. The 4-year incidence of PAS was 13.57% for the 221 eyes with documented gonioscopy after SLT, and the time, since first SLT, to PAS diagnosis was 5.62 years (2052 ± 75.2 days). After accounting for the inter-eye correlation by the mixed effect Cox regression model (AUC = 0.885), the predictors of earlier PAS diagnosis were baseline intraocular pressure (≥ 18 versus < 18) (HR = 4.6, p = 0.031), baseline use of bimatoprost (HR = 14.97, p = 0.006), and pre-existing hypertension (HR = 11.78, p = 0.016). There was no significant association of earlier PAS diagnosis with age (p = 0.434), baseline number of medications used (p = 0.693), and baseline use of brinzolamide (p = 0.326). CONCLUSION: PAS development after SLT appears to be more common in Chinese patients, with a presumed 4-year incidence of 13.6%, based on retrospective review of eyes with subsequent documented gonioscopy findings. TRIAL REGISTRATION: Hong Kong University Clinical Trials Registry (HKUCTR-2350).

Use of selective laser trabeculoplasty as an alternative in patients who developed ocular hypertension after intravitreal dexamethasone implants: a series of 35 eyes.

PURPOSE: Steroid-induced ocular hypertension (OHT) occurs in about a third of cases after dexamethasone implant (DEXi) intravitreal injection (IVI), for which treatment discontinuation may be required. The aim of this study was to assess the benefit of selective laser trabeculoplasty (SLT) in patients who developed transient OHT after DEXi injection to prevent subsequent steroid-induced OHT peaks during reinjections. METHODS: A real-life, retrospective, and observational study was conducted to assess the intraocular pressure (IOP) after SLT in steroid responders after DEXi injection (IOP > 21 mmHg). Were analyzed: IOP 1 and 2 months after SLT, maximum IOP (IOPmax) after each new DEXi IVI, and the number of prophylactic hypotensive treatments needed at the time of DEXi reinjections. RESULTS: Thirty-five eyes of 29 patients were included. The mean macular edema follow-up duration was 38.4 ± 28.4 months. SLT was performed after a mean number of 6.3 ± 4.7 DEXi IVIs. After SLT, the IOPmax measured after the first reinjection was lowered by 36.6 ± 14.7% (p < 0.0001). The mean number of hypotensive treatments was 2.1 ± 0.9 before versus 1.5 ± 0.8 after SLT. The post-reinjection lowering in OHT peak was maintained during the subsequent 3 DEXi IVIs: - 29.1 ± 25.5% (p = 0.0009), - 35.8 ± 13.1% (p = 0.0078), and - 45.4 ± 8.6% (p = 0.0312) after the second, third, and fourth DEXi reinjections. SLT allowed continuing injections in 88.6% of patients. CONCLUSION: The use of 180° SLT in this indication could be an effective therapeutic alternative to control steroid-induced OHT and safely continue DEXi injections.

Neomycin Interferes with Phosphatidylinositol-4,5-Bisphosphate at the Yeast Plasma Membrane and Activates the Cell Wall Integrity Pathway.

The cell wall integrity pathway (CWI) is a MAPK-mediated signaling route essential for yeast cell response to cell wall damage, regulating distinct aspects of fungal physiology. We have recently proven that the incorporation of a genetic circuit that operates as a signal amplifier into this pathway allows for the identification of novel elements involved in CWI signaling. Here, we show that the strong growth inhibition triggered by pathway hyperactivation in cells carrying the "Integrity Pathway Activation Circuit" (IPAC) also allows the easy identification of new stimuli. By using the IPAC, we have found various chemical agents that activate the CWI pathway, including the aminoglycoside neomycin. Cells lacking key components of this pathway are sensitive to this antibiotic, due to the disruption of signaling upon neomycin stimulation. Neomycin reduces both phosphatidylinositol-4,5-bisphosphate (PIP2) availability at the plasma membrane and myriocin-induced TORC2-dependent Ypk1 phosphorylation, suggesting a strong interference with plasma membrane homeostasis, specifically with PIP2. The neomycin-induced transcriptional profile involves not only genes related to stress and cell wall biogenesis, but also to amino acid metabolism, reflecting the action of this antibiotic on the yeast ribosome.

Students' views and experiences of the training and use of phonetic transcription in speech and language therapy - the Irish perspective.

Phonetic transcription is an essential skill for a practising speech and language therapist (SLT) required during the assessment, diagnosis and management of clients with speech difficulties. It is vital that appropriate training is received by student SLTs to ensure that they carry out phonetic transcription accurately and reliably once out in the workplace. This study investigates the views and experiences of final year SLT students regarding the training in phonetic transcription they received in university, with the aim to identify what poses difficulties for them and what could be done to enhance their learning. Responses from 40 participants representing one cohort of SLT students, graduates of a particular year, were collected using an online questionnaire. The majority of the respondents consider phonetic transcription an important professional skill and plan on maintaining it after graduating. Learning phonetic transcription was easy/quite easy for 57% of the respondents; however, the confidence in transcription skills was rather low: 70% of them reported not being confident and fully equipped to enter the workforce with their transcription skills. The main difficulties were associated with narrow (impressionistic) transcription and transcription of disordered speech. 58% of the respondents found the teaching environment suitable; however, a recurring theme is the need for small-group tutorials during which the lecturers could provide feedback to individual students more efficiently. Participants' responses suggest that more clinically relevant transcription practice of disordered speech, the opportunity to refresh and apply phonetic transcription skills throughout the four-year curriculum and smaller group teaching would benefit their learning and enhance their confidence using transcription on placements and in the workforce.

A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2.

Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved signaling proteins involved in the regulation of most eukaryotic cellular processes. They are downstream components of essential signal transduction pathways activated by the external stimuli, in which the signal is conveyed through phosphorylation cascades. The excellent genetic and biochemical tractability of simple eukaryotes such as Saccharomyces cerevisiae has significantly contributed to gain fundamental information into the physiology of these key proteins. The budding yeast MAPK Slt2 was identified 30 years ago and was later revealed as a fundamental element of the cell wall integrity (CWI) pathway, one of the five MAPK routes of S. cerevisiae. As occurs with other MAPKs, whereas Slt2 displays the core typical structural traits of eukaryotic protein kinases, it also features conserved domains among MAPKs that allow an exquisite spatio-temporal regulation of their activity and binding to activating kinases, downregulatory phosphatases, or nuclear transcription factors. Additionally, Slt2 bears a regulatory extra C-terminal tail unique among S. cerevisiae MAPKs. Here, we review the structural and functional basis for the signaling role of Slt2 in the context of the molecular architecture of this important family of protein kinases.

10-year outcomes of first-line selective laser trabeculoplasty (SLT) for primary open-angle glaucoma (POAG).

BACKGROUND: To evaluate long-term efficacy of selective laser trabeculoplasty (SLT) in treatment-naive early primary open-angle glaucoma (POAG) eyes. METHODS: Retrospective study, 108 treatment-naïve eyes of 54 early POAG patients followed up for a mean (± standard deviation (SD)) of 83(27) months. Eyes treated with 360° SLT. Energy levels ranged from 0.6 to 1.4 mJ per pulse. Success of treatment defined as achieving at least 20% reduction of intraocular pressure (IOP) and IOP <19 mmHg. MAIN OUTCOME MEASURE: proportion of eyes achieving success. SECONDARY OUTCOME MEASURES: average time to re-treatment and change in visual field mean deviation (MD) over the follow-up period. RESULTS: Baseline IOP (±SD) was 22.2 (± 4.9). Baseline MD (±SD) of standard automated perimetry was - 1.28 (± 2.36). Decrease in IOP was 6.5 (±3.6) mmHg at 1 year (n=108), 5.2 (±4.6) mmHg at 5 years (n=84) and 3.8 (±2.7) mmHg at 10 years (n=18). Treatment success rate 98% at year 1, 89% at year 5 and 72% at year 10. Failure most common after the third year. Median time to re-treatment 81 months (CI 60-100 months), with 60% needing re-treatment by 10 years. Higher baseline IOP associated with an increased risk of re-treatment. Treatment changed to drops in 4 eyes, but no cases needed glaucoma surgery. Change in visual field MD for the whole group averaged - 0.2 dB per annum. CONCLUSIONS: Treatment of early POAG with first-line SLT, with re-treatments as required, is an effective strategy lasting a period of several years. 60% required re-treatments in the long-term with effective control of IOP and visual field loss remaining at an early stage. The potential for economic benefits in avoiding medications, and simultaneously improving quality of life in these cases is substantial.

Differential Role of Threonine and Tyrosine Phosphorylation in the Activation and Activity of the Yeast MAPK Slt2.

The Mitogen-Activated Protein Kinase (MAPK) Slt2 is central to signaling through the yeast Cell Wall Integrity (CWI) pathway. MAPKs are regulated by phosphorylation at both the threonine and tyrosine of the conserved TXY motif within the activation loop (T190/Y192 in Slt2). Since phosphorylation at both sites results in the full activation of MAPKs, signaling through MAPK pathways is monitored with antibodies that detect dually phosphorylated forms. However, most of these antibodies also recognize monophosphorylated species, whose relative abundance and functionality are diverse. By using different phosphospecific antibodies and phosphate-affinity (Phos-tag) analysis on distinct Slt2 mutants, we determined that Y192- and T190-monophosphorylated species coexist with biphosphorylated Slt2, although most of the Slt2 pool remains unphosphorylated following stress. Among the monophosphorylated forms, only T190 exhibited biological activity. Upon stimulation, Slt2 is first phosphorylated at Y192, mainly by the MAPKK Mkk1, and this phosphorylation is important for the subsequent T190 phosphorylation. Similarly, dephosphorylation of Slt2 by the Dual Specificity Phosphatase (DSP) Msg5 is ordered, with dephosphorylation of T190 depending on previous Y192 dephosphorylation. Whereas Y192 phosphorylation enhances the Slt2 catalytic activity, T190 is essential for this activity. The conserved T195 residue is also critical for Slt2 functionality. Mutations that abolish the activity of Slt2 result in a high increase in inactive Y192-monophosphorylated Slt2. The coexistence of different Slt2 phosphoforms with diverse biological significance highlights the importance of the precise detection of the Slt2 phosphorylation status.

Roles of High Osmolarity Glycerol and Cell Wall Integrity Pathways in Cadmium Toxicity in Saccharomyces cerevisiae.

Cadmium is a carcinogen that can induce ER stress, DNA damage, oxidative stress and cell death. The yeast mitogen-activated protein kinase (MAPK) signalling pathways paly crucial roles in response to various stresses. Here, we demonstrate that the unfolded protein response (UPR) pathway, the high osmolarity glycerol (HOG) pathway and the cell wall integrity (CWI) pathway are all essential for yeast cells to defend against the cadmium-induced toxicity, including the elevated ROS and cell death levels induced by cadmium. We show that the UPR pathway is required for the cadmium-induced phosphorylation of HOG_MAPK Hog1 but not for CWI_MAPK Slt2, while Slt2 but not Hog1 is required for the activation of the UPR pathway through the transcription factors of Swi6 and Rlm1. Moreover, deletion of HAC1 and IRE1 could promote the nuclear accumulation of Hog1, and increase the cytosolic and bud neck localisation of Slt2, indicating crucial roles of Hog1 and Slt2 in regulating the cellular process in the absence of UPR pathway. Altogether, our findings highlight the significance of these two MAPK pathways of HOG and CWI and their interrelationship with the UPR pathway in responding to cadmium-induced toxicity in budding yeast.

Not just the wall: the other ways to turn the yeast CWI pathway on.

The Saccharomyces cerevisiae cell wall integrity (CWI) pathway took this name when its role in the cell response to cell wall aggressions was clearly established. The receptors involved in sensing the damage, the relevant components operating in signaling to the MAPK Slt2, the transcription factors activated by this MAPK, as well as some key regulatory mechanisms have been identified and characterized along almost 30 years. However, other stimuli that do not alter specifically the yeast cell wall, including protein unfolding, low or high pH, or plasma membrane, oxidative and genotoxic stresses, have been also found to trigger the activation of this pathway. In this review, we compile almost forty non-cell wall-specific compounds or conditions, such as tunicamycin, hypo-osmotic shock, diamide, hydroxyurea, arsenate, and rapamycin, which induce these stresses. Relevant aspects of the CWI-mediated signaling in the response to these non-conventional pathway activators are discussed. The data presented here highlight the central and key position of the CWI pathway in the safeguard of yeast cells to a wide variety of external aggressions.

Rational 3D Coiled Morphology for Efficient Solar-Driven Desalination.

Aiming at the global water scarcity, solar-driven desalination based on photothermal materials is identified as a promising strategy for freshwater production because of sustainability, spontaneity, and flexibility. Water transfer in photothermal materials, especially ones with 3D morphologies, can adjust the evaporation efficiency as a critical factor. In this work, a rationally designed roll morphology has been introduced into photothermal to advance the water transfer evaporation via controllable capillary action. The vertical intervals of the roll, similar to slit pore, can pump the water up to the entire materials to not only keep a stable vapor generation rate but reject salt precipitation. Additionally, the roll morphology also improves the light-harvesting via both the high roughness surface and confinement absorption inside the intervals. With excellent water transfer and energy management, photothermal roll showed an evaporation rate up to 1.93 ± 0.05 kg m-2 h-1, which was over 44% higher than the flat sample in the same constituents. Under actual conditions, the freshwater generation rate was achieved up to 1.09 kg m-2 h-1 on average of the whole daylight hours. The work provides novel insights into the design of efficient morphology in photothermal materials and advances their practical applications in sustainable water generation.

Influence of Selective Laser Trabeculoplasty (SLT) on the iStent inject® outcomes.

BACKGROUND: To evaluate the influence of Selective Laser Trabeculoplasty (SLT) on iStent inject® outcomes in open-angle glaucoma (OAG). METHODS: In this retrospective comparative cohort outcome study, 66 patients who were treated with two iStent inject® devices were included. Patients were divided into two subgroups consisting of patients without SLT treatment prior to surgery and patients who had been treated previously with 360° SLT but without sufficient response. Outcome measures included intraocular pressure (IOP) and number of antiglaucoma medications after 6 weeks with three, six, 12, and 24 month follow-ups. RESULTS: Mean preoperative IOP decreased from 20.4 ± 5.3 mmHg to 14.8 ± 3.0 mmHg for patients without SLT treatment prior to surgery (p = 0.001) and from 19.2 ± 4.5 mmHg to 14.0 ± 1.6 mmHg for patients with insufficient response to 360° SLT treatment (p = 0.027) at 12 months after iStent inject® implantation. No significant difference was found between the two groups (p >  0.05). The number of antiglaucoma medications did not change in both groups (p >  0.05) and showed no significant difference between the two groups (p >  0.05). CONCLUSION: Prior SLT treatment seems to have no negative influence on the IOP lowering-effect of iStent inject® implantation in patients with OAG. It is therefore an appropriate incremental procedure with no exclusion criterion for an iStent inject® implantation.

Outcomes of hemi- versus whole liver transplantation in patients from mainland china with high model for end-stage liver disease scores: a matched analysis.

BACKGROUND: Adult hemiliver transplantation (AHLT) is an important approach given the current shortage of donor livers. However, the suitability of AHLT versus adult whole liver transplantation (AWLT) for recipients with high Model for End-Stage Liver Disease (MELD) scores remains controversial. METHODS: We divided patients undergoing AHLT and AWLT into subgroups according to their MELD scores (≥ 30: AHLT, n = 35; AWLT, n = 88; and < 30: AHLT, n = 323; AWLT, n = 323). Patients were matched by demographic data and perioperative conditions according to propensity scores. A cut-off value of 30 for MELD scores was determined by comparing the overall survival data of 735 cases of nontumor liver transplantation. RESULTS: Among patients with an MELD score ≥ 30 and < 30, AHLT was found to be associated with increased warm ischemia time, operative time, hospitalization time, and intraoperative blood loss compared with AWLT (P < 0.05). In the MELD ≥ 30 group, although the 5-year survival rate was significantly higher for AWLT than for AHLT (P = 0.037), there was no significant difference between AWLT and AHLT in the MELD < 30 group (P = 0.832); however, we did not observe a significant increase in specific complications following AHLT among patients with a high MELD score (≥ 30). Among these patients, the incidence of complications classified as Clavien-Dindo grade III or above was significantly higher in patients undergoing AHLT than in those undergoing AWLT (25.7% vs. 11.4%, P = 0.047). For the MELD < 30 group, there was no significant difference in the incidence of complications classified as Clavien-Dindo grade III or above for patients undergoing AHLT or AWLT. CONCLUSION: In patients with an MELD score < 30, AHLT can achieve rates of mortality and overall survival comparable to AWLT. In those with an MELD score ≥ 30, the prognosis and incidence of complications classified as Clavien-Dindo III or above are significantly worse for AHLT than for AWLT; therefore, we may need to be more cautious regarding the conclusion that patients with a high MELD score can safely undergo AHLT.

COVID-19 and ENT SLT services, workforce and research in the UK: A discussion paper.

BACKGROUND: The COVID-19 pandemic and the UK government's subsequent coronavirus action plan have fundamentally impacted on every aspect of healthcare. One area that is severely affected is ear, nose and throat (ENT)/laryngology where speech and language therapists (SLTs) engage in a diverse range of practice with patients with a range of conditions, including voice disorders, airway problems, and head and neck cancers (HNCs). A large majority of these patients are in high-risk categories, and many specialized clinical practices are vulnerable. In addition, workforce and research issues are challenged in both the immediate context and the future. AIMS: To discuss the threats and opportunities from the COVID-19 pandemic for SLTs in ENT/laryngology with specific reference to clinical practice, workforce and research leadership. METHODS & PROCEDURES: The relevant sections of the World Health Organisation's (WHO) health systems building blocks framework (2007) were used to structure the study. Expert agreement was determined by an iterative process of multiple-group discussions, the use of all recent relevant policy documentation, and other literature and shared documentation/writing. The final paper was verified and agreed by all authors. MAIN CONTRIBUTION: The main threats to ENT/laryngology SLT clinical services include increased patient complexity related to COVID-19 voice and airway problems, delayed HNC diagnosis, reduced access to instrumental procedures and inequitable care provision. The main clinical opportunities include the potential for new modes of service delivery and collaborations, and harnessing SLT expertise in non-instrumental assessment. There are several workforce issues, including redeployment (and impact on current services), training implications and psychological impact on staff. Workforce opportunities exist for service innovation and potential extended ENT/SLT practice roles. Research is threatened by a reduction in immediate funding calls and high competition. Current research is affected by very limited access to participants and the ability to conduct face-to-face and instrumental assessments. However, research opportunities may result in greater collaboration, and changes in service delivery necessitate robust investigation and evaluation. A new national set of research priorities is likely to emerge. CONCLUSIONS & IMPLICATIONS: The immediate impact of the pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. It is unclear when any of these areas will resume operations and whether permanent changes to clinical practice, professional remits and research priorities will follow. However, significant opportunity exists in the post-COVID era to re-evaluate current practice, embrace opportunities and evaluate new ways of working. What this paper adds What is already known on the subject ENT/laryngology SLTs manage patients with a range of conditions, including voice disorders, airway problems and HNCs. The diverse scope of clinical practice involves highly specialized assessment and treatment practices in patients in high-risk categories. A large majority of active research projects in this field are patient focused and involve instrumental assessment. The COVID-19 pandemic has created both opportunities and threats for ENT SLT clinical services, workforce and research. What this paper adds to existing knowledge This study provides a discussion of the threats and opportunities from the COVID-19 pandemic for ENT/laryngology SLT with specific reference to clinical practice, workforce and research leadership. What are the potential or actual clinical implications of this work? The COVID-19 pandemic has resulted in major disruption to all aspects of clinical delivery, workforce and research for ENT/laryngology SLT. Changes to clinical practice, professional remits and research priorities are of indeterminant duration at this time, and some components could be permanent. Significant clinical practice, workforce and research opportunities may exist in the post-COVID era.