Pediatric neurological disorders are frequently devastating and present unmet needs for effective medicine. The successful treatment of spinal muscular atrophy with splice-switching antisense oligonucleotides (SSO) indicates a feasible path to targeting neurological disorders by redirecting pre-mRNA splicing. One direct outcome is the development of SSOs to treat haploinsufficient disorders by targeting naturally occurring non-productive splice isoforms. The development of personalized SSO treatment further inspired the therapeutic exploration of rare diseases. This review will discuss the recent advances that utilize SSOs to treat pediatric neurological disorders.

In this work, the surface of polyvinyl chloride PVC sheet was modified by blending it with sunflower seed oil SSO to obtain PVC sheet/SSO films of ratios 100/0, 90/10, 80/20, 70/30, 60/40, and 50/50 (v/v)% using the solution casting method. Various techniques were used to characterize the prepared films, besides the use of hemolysis assays and blood clot formation tests. FTIR spectra revealed that there was a good interaction between the PVC sheet and the oil. The dielectric measurement indicated that SSO addition enhanced the dielectric properties of the sheet. The study of dielectric relaxation times confirmed the interaction between SSO and the sheet. DC conductivity increased to 6 × 10-6 S/m, so it could be applied in antistatic applications. Also, SSO addition increased the value of the thermal stability. According to SEM micrographs, the film was roughened at a ratio of 60/40 and smoothed out at 50/50. This behavior was confirmed with roughness and contact angle measurement results, in which the film of ratio 60/40 had the highest value equal to (72.03°) and then decreased at 50/50 to (59.62°). These results were confirmed by XRD measurement as the crystallinity increased at the film ratio of 60/40 and decreased again at 50/50. Also, the ratio of 60/40 demonstrated a large decrease in thrombus weights along with a slight increase in hemolysis, which is within the acceptable range and has a high degree of biocompatibility, so this concentration is recommended to be used in blood bags applications.

OBJECTIVE: Surgical repair of complex abdominal wall hernias remains technically demanding and is widely recognized as a risk factor for unfavorable outcomes with high recurrence and morbidity rates. The objective is to assess short- and long-term complications after open intraperitoneal onlay mesh (IPOM) repair combined with bilateral anterior component separation (ACS) for large and difficult incisional hernias, alongside evaluating hernia recurrence rates.
METHODS: This retrospective analysis utilized data sourced from Hospital electronic health records and a prospective database at an academic tertiary referral center. Data collection was carried out from patients operated between January 2006 and December 2017. Eligible patients had complex incisional hernias measuring at least 10 cm in their transverse diameter and had an open IPOM repair with bilateral ACS.
RESULTS: In our study group of 45 patients, the 30-day surgical site occurrence (SSO) rate was high (37.8%), primarily consisting of superficial postoperative complications as seroma (17.8%) and wound dehiscence (6.7%). Among six patients (13.3%), wound complications escalated to chronic infected mesh-related problems, leading to complete mesh removal in four cases (8.9%) and partial mesh removal in two cases (4.4%). Regarding long-term complications, five patients (11.1%) developed enterocutaneous fistula. The recurrence rate was modest [5 out of 41 (12.2%)] over a median follow-up period of 99 months.
CONCLUSIONS: Despite a high SSO rate, application of the open IPOM technique with ACS could serve as a valuable rescue option for managing large and complex hernias, with acceptable hernia recurrence rates at long-term follow-up.

Single Sign-On (SSO) methods are the primary solution to authenticate users across multiple web systems. These mechanisms streamline the authentication procedure by avoiding duplicate developments of authentication modules for each application. Besides, these mechanisms also provide convenience to the end-user by keeping the user authenticated when switching between different contexts. To ensure this cross-application authentication, SSO relies on an Identity Provider (IdP), which is commonly set up and managed by each institution that needs to enforce SSO internally. However, the solution is not so straightforward when several institutions need to cooperate in a unique ecosystem. This could be tackled by centralizing the authentication mechanisms in one of the involved entities, a solution raising responsibilities that may be difficult for peers to accept. Moreover, this solution is not appropriate for dynamic groups, where peers may join or leave frequently. In this paper, we propose an architecture that uses a trusted third-party service to authenticate multiple entities, ensuring the isolation of the user\'s attributes between this service and the institutional SSO systems. This architecture was validated in the EHDEN Portal, which includes web tools and services of this European health project, to establish a Federated Authentication schema.

BACKGROUND: Dry eye disease (DED) is an important health problem affecting hundreds of millions of people worldwide. In vivo confocal microscopy (IVCM) is a non-invasive imaging tool that can visualize ocular surface diseases. In this study, we aimed to evaluate corneal structures and inflammatory cells with IVCM in DED patients.
METHODS: The patients were divided into three subgroups: group 1, consisting of 22 patients with aqueous tear insufficiency; group 2, consisting of 21 patients with evaporative type DED; and group 3, consisting of 20 healthy patients. Imaging was performed with IVCM. The corneal epithelium, nerves, stroma, endothelial and inflammatory cells were compared between groups.
RESULTS: There was a significant decrease in corneal epithelial cell density in cases with DED, and there was a significant increase in corneal basal epithelial cell density in the aqueous-deficient type. Keratocyte density was significantly increased in the aqueous-deficient type. A significant decrease in the number and density of sub-basal nerves was found in aqueous-deficient cases, and an increase was found in neural pilling and folding. Dendritic cell density, size, number and area were significantly increased in the aqueous-deficient type. There was also decreased corneal endothelial cell density in DED.
CONCLUSIONS: We evaluated pathological changes in DED on the corneal surface by IVCM. This methodology is valuable in terms of objectively evaluating how the corneal surface is affected in accordance with disease severity and in predicting poor response to treatment.

Drain placement in retromuscular ventral hernia repair is controversial. Although it may reduce seroma formation, there is a concern regarding an increase in infectious complications. We aimed to perform a meta-analysis on retromuscular drain placement in retromuscular ventral hernia repair.
We performed a literature search of Cochrane, Scopus and PubMed databases to identify studies comparing drain placement and the absence of drain in patients undergoing retromuscular ventral hernia repair. Postoperative outcomes were assessed by pooled analysis and meta-analysis. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I2 statistics.
3808 studies were screened and 48 were thoroughly reviewed. Four studies comprising 1724 patients were included in the analysis. We found that drain placement was significantly associated with a decrease in seroma (OR 0.34; 95% CI 0.12-0.96; P = 0.04; I2 = 78%). Moreover, no differences were noted in surgical site infection, hematoma, surgical site occurrences or surgical site occurrences requiring procedural intervention.
Based on the analysis of short-term outcomes, retromuscular drain placement after retromuscular ventral hernia repair significantly reduces seroma and does not increase infectious complications. Further prospective randomized studies are necessary to confirm our findings, evaluate the optimal duration of drain placement, and report longer-term outcomes.

The inefficiencies and uncertainties surrounding solutions from existing inversion methods have necessitated investigation for more efficient techniques for the inversion of ill-posed magnetic problems. In this study, the Social Spider Optimization (SSO) algorithm has been modified, adopted and successfully used in modelling physical characteristics of magnetic anomalies originating from simple-shaped geologic structures. The study, aimed at testing the capacity and efficiency of the SSO algorithm to model magnetic data of varying complexity, was successfully conducted on both synthetic data with varying levels of noise and real field data obtained from mining fields in Senegal and Egypt. To assess the mathematical nature of the inverse problem considered, error energy maps were produced for each model parameter pairs in the synthetic examples. These maps enabled the pre-assessment of the resolvability model parameter for the ill-posed problem. In addition, uncertainty analysis aimed at providing insight to the reliability of the obtained solutions was carried out using the Metropolis-Hastings (M-H) sampling algorithm. Results show that the procedure converges fast and generates accurate results even when confronted with constrained multi-parameter non-linear inversion problems. Its outstanding converging speed and accuracy of the results reveal it as an excellent procedure for overcoming agelong problems of local optimal solutions associated with pre-existing algorithms. The consistency of the results with actual values affirms the efficacy of the new procedure which is pioneering in geophysical literature. It is therefore a stable and efficient tool for performing geophysical data inversion and is therefore recommended for use in inverting geophysical data with higher complexities like seismic reflection and gravity data, that require many corrections to be performed before reliable geological interpretations can be made.

Vibrio vulnificus is a naturally occurring, potentially lethal pathogen found in coastal waters, fish, and shellfish. Sewage spills in coastal waters occur when infrastructure fails due to severe storms or age, and may affect bacterial populations by altering nutrient levels. This study investigated effects of sewage on clonal and natural V. vulnificus populations in microcosms. Addition of 1% sewage to estuarine water caused the density of a pure culture of V. vulnificus CMCP6 and a natural V. vulnificus population to increase significantly, by two to three orders of magnitude, whether measured by quantitative PCR (qPCR) or culture and in batch and continuous cultures. Changes in the transcription of six virulence- and survival-associated genes in response to sewage were assessed using continuous culture. Exposure to sewage affected transcription of genes that may be associated with virulence, i.e., it modulated the oxidative stress response by altering superoxide dismutase transcription, significantly increasing sodB transcription while repressing sodA. Sewage also repressed transcription of nptA, which encodes a sodium-phosphate cotransporter. Sewage had no effect on sodC transcription or the putative virulence-associated genes hupA or wza. The effects of environmentally relevant levels of sewage on V. vulnificus populations and gene transcription suggest that sewage spills that impact warm coastal waters could lead to an increased risk of V. vulnificus infections. IMPORTANCE Vibrio vulnificus infections have profound impacts such as limb amputation and death for individuals with predisposing conditions. The warming climate is contributing to rising V. vulnificus prevalence in waters that were previously too cold to support high levels of the pathogen. Climate change is also expected to increase precipitation in many regions, which puts more pressure on wastewater infrastructure and will result in more frequent sewage spills. The finding that 1% wastewater in estuarine water leads to 100 to over 1,000-fold greater V. vulnificus concentrations suggests that human exposure to oysters and estuarine water could have greater health impacts in the future. Further, wastewater had a significant effect on gene transcription and has the potential to affect virulence during the initial environment-to-host transition.

Bariatric surgery in super-super-obese (SSO) patients remains a continuous challenge due to intraabdominal fat masses, higher liver volume and existing comorbidities. A convenient procedure in SSO patients is one anastomosis gastric bypass (OAGB). The aim of this study was to compare the outcome of SSO patients undergoing OAGB in comparison to laparoscopic sleeve gastrectomy (LSG).
We retrospectively reviewed data from SSO patients who underwent OAGB and LSG in our institution between 2008 and 2020. Primary endpoints included percentage total body weight loss and percentage BMI loss at 12, 24, and 36 months after the operation. Secondary endpoints were perioperative complications, procedure length, length of hospital stay and outcome of comorbidities.
243 patients were included in this study. 93 patients underwent LSG and 150 underwent OAGB. At any of the time points evaluated, weight loss in patients after OAGB was greater than in LSG patients, while procedure length was significantly shorter for OAGB than LSG (81.4 vs. 92.1 min, p-value < 0.001). Additionally, mean length of hospital stay was shorter in the OAGB group (3.4 vs. 4.5 days, p-value < 0.001). There were more severe complications (Clavien-Dindo ≥ 3a) in the LSG group (11.8% vs 2.7%, p-value = 0.005).
In this retrospective analysis, OAGB was superior to LSG in terms of weight loss in SSO patients. Procedure length and hospital stay were shorter after OAGB in comparison to LSG and there were fewer severe complications. OAGB can therefore be regarded a safe and effective treatment modality for SSO patients.

The androgen receptor (AR) plays a critical role in the development of prostate cancer (PCa) through the activation of androgen-induced cellular proliferation genes. Thus, blocking AR-mediated transcriptional activation is expected to inhibit the growth and spread of PCa. Using tailor-made splice-switching locked nucleic acid (LNA) oligonucleotides (SSOs), we successfully redirected splicing of the AR precursor (pre-)mRNA and destabilized the transcripts via the introduction of premature stop codons. Furthermore, the SSOs simultaneously favored production of the AR45 mRNA in lieu of the full-length AR. AR45 is an AR isoform that can attenuate the activity of both full-length and oncogenic forms of AR by binding to their common N-terminal domain (NTD), thereby blocking their transactivation potential. A large screen was subsequently used to identify individual SSOs that could best perform this dual function. The selected SSOs powerfully silence AR expression and modulate the expression of AR-responsive cellular genes. This bi-functional strategy that uses a single therapeutic molecule can be the basis for novel PCa treatments. It might also be customized to other types of therapies that require the silencing of one gene and the simultaneous expression of a different isoform.