MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and Translocation in Insulin Resistance

The solute carrier family 2 facilitated glucose transporter member 4 (GLUT4) plays a key role in the insulin-induced glucose uptake by muscle and adipose tissues. In prediabetes and diabetes, GLUT4 expression/translocation has been detected as reduced, participating in mechanisms that impair glycemic control. Recently, a class of short endogenous noncoding RNAs named microRNAs (miRNAs) has been increasingly described as involved in the posttranscriptional epigenetic regulation of gene expression. The present review focuses on miRNAs potentially involved in the expression of GLUT4 expression, and proteins related to GLUT4 and translocation in skeletal muscle, seeking to correlate them with insulin resistance and diabetes. So far, miR-21a-5p, miR-29a-3p, miR-29c-3p, miR-93-5p, miR-106b-5p, miR-133a-3p, miR-133b-3p, miR-222-3p, and miR-223-3p have been reported to directly and/or indirectly regulate the GLUT4 expression; and their expression is altered under diabetes-related conditions. Besides, some miRNAs that have been linked to the expression of proteins involved in GLUT4 translocation machinery in muscle could also impact glucose uptake. That makes these miRNAs promising targets for preventive and/or therapeutic approaches, which could improve glycemic control, thus deserving future new investigations

ATOMS (Adjustable Transobturator Male System) Is an Effective and Safe Second-Line Treatment Option for Recurrent Urinary Incontinence after Implantation of an AdVance/AdVance XP Fixed Male Sling? A Multicenter Cohort Analysis

(1) Background: This study examined outcomes of second-line ATOMS implantation after failure of the fixed male sling (FMS) AdVance/AdVance XP. (2) Methods: A retrospective multicenter cohort analysis was carried out in men implanted with an ATOMS between 2011 and 2020 after failure of an AdVance/AdVance XP. Success was assessed on the basis of objective (dryness, 0–1 pad/24 h or >20 g/24 h pad test) and subjective results (PGI-I). We performed the Wilcoxon rank sum test, Fisher’s exact test, logistic regression, and multivariate analysis. (3) Results: The study included 88 patients from 9 centers with a mean age of 71.3 years. No Clavien–Dindo > II complications occurred within the first 3 months after ATOMS implantation. A total of 10 cases (9%) required revision in the ensuing clinical course. After a mean follow-up of 42.5 months, 76.1% achieved social continence, and 56.8% used no pads at all. Mean urine leakage/24 h dropped from 422 g (3.9 pads) to 38 g (0.69 pads) and the mean ICIQ-SF decreased from 16.25 to 5.3 (p < 0.0001). PROMs (patient-reported outcome measures) showed improvement in 98.9% of cases, and 63.6% gave a “very much better” PGI-I rating. Multivariate analysis identified a lower probability of achieving maximum satisfaction for the following factors: the AdVance XP as first-line therapy (OR 0.35), a lower ICIQ-SF question 1 (OR 0.26), status post-irradiation (OR 0.14), and more severe pain prior to ATOMS implantation (OR 0.51). (4) Conclusions: Implantation of an ATOMS is an effective and safe second-line treatment option for recurrent urinary incontinence after implantation of an AdVance/AdVance XP sling. High patient satisfaction was demonstrated in a long-term follow-up

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). Methods: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (b-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. Results: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with b-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. Conclusion: In patients with PCa and bone metastases treated with ZA, b-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially importantThis study was supported by Novartis Oncology Spai

MicroRNAs-Mediated Regulation of Skeletal Muscle GLUT4 Expression and Translocation in Insulin Resistance

The solute carrier family 2 facilitated glucose transporter member 4 (GLUT4) plays a key role in the insulin-induced glucose uptake by muscle and adipose tissues. In prediabetes and diabetes, GLUT4 expression/translocation has been detected as reduced, participating in mechanisms that impair glycemic control. Recently, a class of short endogenous noncoding RNAs named microRNAs (miRNAs) has been increasingly described as involved in the posttranscriptional epigenetic regulation of gene expression. The present review focuses on miRNAs potentially involved in the expression of GLUT4 expression, and proteins related to GLUT4 and translocation in skeletal muscle, seeking to correlate them with insulin resistance and diabetes. So far, miR-21a-5p, miR-29a-3p, miR-29c-3p, miR-93-5p, miR-106b-5p, miR-133a-3p, miR-133b-3p, miR-222-3p, and miR-223-3p have been reported to directly and/or indirectly regulate the GLUT4 expression; and their expression is altered under diabetes-related conditions. Besides, some miRNAs that have been linked to the expression of proteins involved in GLUT4 translocation machinery in muscle could also impact glucose uptake. That makes these miRNAs promising targets for preventive and/or therapeutic approaches, which could improve glycemic control, thus deserving future new investigations

Adjustable Transobturator Male System (ATOMS) Infection: Causative Organisms and Clinical Profile

Objective To evaluate the clinical profile and the organisms producing adjustable transobturator male system (ATOMS) infection in a contemporary series. Methods Multicenter retrospective study evaluating patients undergoing ATOMS explant for clinical signs of infection from a series of 902 patients treated in 9 academic institutions. Clinical and microbiological data were evaluated. Results Infection presented in 24 patients (2.7%). The median age was 73 ± 7yrs and the median interval from ATOMS implantation to explant 11 ± 26.5mo. Infection was diagnosed within 3-months after surgery in 7(29.2%). Scrotal port erosion was present in 6 cases (25%) and systemic symptoms of parenchymatous testicular infection in 2(8.3%). The culture of the periprosthetic fluid was positive in 20(83.3%): 12(50%) Gram-negative bacteria, 9(37.5%) Gram-positive cocci and 1(4.2%) yeast. The most frequent isolates were Enterococcus and Proteus sp. (16.7% each), followed by Pseudomona sp. and S. epidermidis (12.5% each). Methicillin resistant S. aureus was detected only in 1 case (4.2%). Despite the infection 17 patients (70.8%) were satisfied with the implant and 18(75%) received a second device (11 repeated ATOMS and 7 AUS) at a median 9.7 ± 12.6mo after explant. Limitations include retrospective design and lack of microbiological cultures in ATOMS explanted for non-infective cause. Conclusion Infection of a prosthetic device is a disturbing complication. A proportion of patients with ATOMS infection is associated to scrotal port erosion and/or parenchymatous urinary tract infection. Enterococcus and Proteus sp. are the most common organisms producing ATOMS infection and this could have implications for the selection of the most appropriate surgical prophylaxis.Sin financiación2.649 JCR (2020) Q3, 52/89 Urology & Nephrology0.604 SJR (2021) Q2, 38/108 UrologyNo data IDR 2020UE

Artificial urinary sphincter or a second adjustable transobturator male system offer equivalent outcomes in patients whom required revision on the initial ATOMS device: An international multi-institutional experience

Aim: To evaluate treatment options after surgical revision of adjustable transobturator male system (ATOMS) and the results of further incontinence implantation. Materials and methods: A retrospective multicenter study evaluating patients with surgical revision of ATOMS in academic institutions. Causes and factors affecting revision-free interval were studied and also the frequency of device explant and placement of second ATOMS or artificial urinary sphincter (AUS) at surgeon discretion. Operative results, complications (Clavien-Dindo), and efficacy (postoperative pad-test, pad-count, patient satisfaction, and patient global impression of improvement [PGI-I scale]) of each treatment option were compared. Results: Seventy-eight out of 902 patients (8.65%) with ATOMS underwent surgical revision at 4.1 ± 2.4 years mean follow-up and 75 (8.3%) were explanted. The main causes for revision included persistence of incontinence (35.9%) and scrotal port erosion (34.6%). Independent risk factors of the shortened revision-free interval were previous anti-incontinence surgery (HR, 1.83; 95% CI, 1.06-3.16; p = 0.007) and port erosion (HR, 1.83; 95% CI, 1.06-3.16; p = 0.0027). Fifty-eight (6.4%) received a second implant: 31 repeated ATOMS and 27 AUS. Operative time was longer for AUS (p = .003). The visual analog scale of pain at hospital discharge (p = 0.837) and postoperative complications (p = 0.154) were equivalent. The predominant cuff size for AUS was 4.5 cm (59.3%). Mean follow-up after the second implant was 29.1 ± 25.8 months. Postoperative efficacy of secondary treatment results favored ATOMS based on pad-test (p = 0.016), pad-count (p = 0.029), patient satisfaction (p = 0.04), and PGI-I (p = 0.025). Conclusions: ATOMS surgical revision due to different reasons generally leads to device explant. Rescue treatment is possible with ATOMS or AUS. No difference in postoperative complications was detected between secondary devices, but efficacy favors repeating ATOMS implantation.Sin financiación2.696 JCR (2020) Q3, 50/89 Urology & Nephrology1.288 SJR (2021) Q1, 73/378 Neurology (clinical)No data IDR 2020UE

Vía degli Augustali VII 4, 28 : las evidencias cerámicas de una fosa singular de mediados del siglo II a.C.

In 2011 the excavations conducted in the taberna in Via degli Augustali 28 (promoted by the Centre Jean Bérard -Institut Français de Naples-, the Secció d'Investigació Arqueològica Municipal - Ajuntament de València - and the Institut Valencià de Conservacio i Restauració - Generalitat Valenciana) a part of a large pit, whose fill dated to de mid 2nd century BC, was discovered. The pit had been dug in the geological layer. It does not appear to be a domestic rubbish tip, owning to the conspicuous repetition of certain Italic cooking and table ware types, indicating a specific usel/consumption and selection. Besides, the reiterative presence of some peculiar faunal remains (a great amount of goat/sheep horns), would point to a kind of ritual feast

Expanding the functional role of miRNAs in the establishment of permanent atrial fibrillation

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