Topical sirolimus in dermatology: a systematic review.

CONTEXT: Topical sirolimus is increasingly utilised off-license to manage various dermatological conditions whilst avoiding typical adverse effects associated with systemic sirolimus. However, widespread use is limited by a highly heterogeneous evidence base of mixed quality. OBJECTIVE: to evaluate the current evidence base for the indications, efficacy and safety profile for topical sirolimus in dermatology. DATA SOURCES: A literature search was conducted from 2005 to July 4th, 2023, of English language studies, with the following databases consulted: MEDLINE, PubMed, Embase, CENTRAL and EBSCO. Key words included 'topical', 'rapamycin', 'sirolimus' and 'dermatology'. DATA EXTRACTION: Data on drug efficacy, concentration, side effects, co-interventions and follow up were extracted. RESULTS: The search identified 202 studies; 71 studies met the inclusion criteria. Efficacy of topical sirolimus was demonstrated in facial angiofibromas (799 patients) compared to placebo across multiple randomised controlled trials with a predominant concentration of 0.1%. Evidence was mixed for sirolimus use in port-wine stains (61 patients), with evidence of effectiveness in combined sirolimus and pulsed-dye laser. Multiple case reports demonstrated clinical improvement with topical sirolimus use in cutaneous vascular abnormalities (33 patients) at a higher concentration of 1%. Other applications of topical sirolimus were predominantly case reports demonstrating generally favourable outcomes. Topical sirolimus was generally well tolerated - most reported adverse effects were localised irritation and pruritus. Ointment-based preparations and once-daily dosing appeared to confer a better side effect profile. CONCLUSION: Most high-quality data pertain to the efficacy of topical sirolimus in treating facial angiofibromas in tuberous sclerosis. Outcomes are generally promising in other indications and good tolerability, but data quality is mixed.

Intraoperative somatosensory evoked potential (SEP) monitoring: an updated position statement by the American Society of Neurophysiological Monitoring.

Somatosensory evoked potentials (SEPs) are used to assess the functional status of somatosensory pathways during surgical procedures and can help protect patients' neurological integrity intraoperatively. This is a position statement on intraoperative SEP monitoring from the American Society of Neurophysiological Monitoring (ASNM) and updates prior ASNM position statements on SEPs from the years 2005 and 2010. This position statement is endorsed by ASNM and serves as an educational service to the neurophysiological community on the recommended use of SEPs as a neurophysiological monitoring tool. It presents the rationale for SEP utilization and its clinical applications. It also covers the relevant anatomy, technical methodology for setup and signal acquisition, signal interpretation, anesthesia and physiological considerations, and documentation and credentialing requirements to optimize SEP monitoring to aid in protecting the nervous system during surgery.

Revision Rates After Single-Level Cervical Disc Arthroplasty Versus Anterior Cervical Discectomy and Fusion: An Observational Study With 5-Year Minimum Follow-Up.

STUDY DESIGN: Retrospective Case-Control study. OBJECTIVES: This study aimed to compare rates and risk factors for all-cause 5-year revisions for patients undergoing primary single-level cervical disc arthroplasty (CDA) versus Anterior Cervical Discectomy and Fusion (ACDF). SUMMARY OF BACKGROUND DATA: Prospective studies have compared patient reported outcomes, adjacent segment degeneration, and long-term revisions between CDA and ACDF. Despite these high-level evidence studies, well-powered, large investigations have not been adequately reported. PATIENTS AND METHODS: A nationwide database was queried for patients undergoing primary single level CDA or ACDF for degenerative cervical spine pathology. Further inclusion criteria consisted of patients having a minimum of 5-year follow-up. Patients undergoing CDA were 1:5 ratio matched to patients undergoing ACDF by age, sex, comorbidities, and overall Elixhauser comorbidity index (ECI). Objectives were to compare the rates and risk factors of all-cause 5-year revisions for those undergoing single level CDA versus ACDF. Multivariate logistic regression models computed odds ratios (OR) of revisions within 5 years. P values less than 0.001 were significant. RESULTS: A total of 32,953 patients underwent single level CDA (N=5,640) or ACDF (N=27,313) with 5-Year minimum follow-up. The incidence of all cause revisions within 5 years were 1.24% for CDA and 9.23% for ACDF (P<0.001). After adjustment, patients undergoing single level ACDF had significantly higher odds of all-cause revisions within 5 years (OR: 8.09; P<0.0001). Additional patient specific factors associated with revisions were a history of reported drug abuse (OR: 1.51; P<0.0001), depression (OR: 1.23; P<0.0001), cardiac arrythmias (OR: 1.21; P=0.0008), hypertension (OR: 1.20; P=0.0006), and tobacco use (OR: 1.18; P=0.0003). CONCLUSIONS: In this study of nearly 33,000 single level cervical spine surgeries with minimum 5-year follow-up, all-cause revision rates were significantly lower for patients undergoing CDA. Surgeons may use this data to counsel patients regarding 5-year revisions following single level CDA or ACDF. LEVEL OF EVIDENCE: III.

Towards net zero: A technological review on the potential of space-based solar power and wireless power transmission.

The global need for energy is increasing at a high rate and is expected to double or increase by 50%, according to some studies, in 30 years. As a result, it is essential to look into alternative methods of producing power. Solar photovoltaic (PV) power plants utilize the sun's clean energy, but they're not always dependable since they depend on weather patterns and requires vast amount of land. Space-based solar power (SBSP) has emerged as the potential solution to this issue. SBSP can provide 24/7 baseload carbon-free electricity with power density over 10 times greater than terrestrial alternatives while requiring far less land. Solar power is collected and converted in space to be sent back to Earth via Microwave or laser wirelessly and used as electricity. However, harnessing its full potential necessitates tackling substantial technological obstacles in wireless power transmission across extensive distances in order to efficiently send power to receivers on the ground. When it comes to achieving a net-zero goal, the SBSP is becoming more viable option. This paper presents a review of wireless power transmission systems and an overview of SBSP as a comprehensive system. To introduce the state-of-the-art information, the properties of the system and modern SBSP models along with application and spillover effects with regard to different sectors was examined. The challenges and risks are discussed to address the key barriers for successful project implementation. The technological obstacles stem from the fact that although most of the technology is already available none are actually efficient enough for deployment so with, private enterprises entering space race and more efficient system, the cost of the entire system that prevented this notion from happening is also decreasing. With incremental advances in key areas and sustained investment, SBSP integrated with other renewable could contribute significantly to cross-sector decarbonization.

Gaining exposure on perceptions of sunscreen: a national survey of melanoma patients.

Melanoma incidence is increasing. We ascertained perceptions regarding sunscreen and factors influencing choice in patients with melanoma. A survey was distributed to all the supporters of a melanoma patient support group. 571 responses were received across six weeks. Most (79.2%; n=452) indicated they knew how much sunscreen to apply; the most popular frequency of application was once daily (32%, n=180). The most popular cosmetic benefit respondents indicated was reduced redness on sun-exposed areas of skin (73.2%; n=418). Most (96.7%; n=552) agreed more education is needed regarding importance of wearing sunscreen. The three most popular factors in influencing sunscreen choice were SPF more than 50 (n=299; 52.4%), recommendation by a dermatologist (n=267; 46.8%) and price (n=262; 45.9%). Sustainable package design (n=45; 7.9%) and ethical sourcing of ingredients (n=65; 11.4%) were not ranked highly. Given 42% (n=240) only applied sunscreen during sunshine, an education campaign is required. Industry should consider public education regarding sustainability. A further study ascertaining views and perceptions of sunscreen in the non-melanoma cohort is strongly encouraged.

Left ventricular diastolic function and cardiotoxic chemotherapy.

BACKGROUND: Left ventricular ejection fraction falls when the myocardium has already lost a significant portion of its functional capacity. There are conflicting data on whether diastolic dysfunction precedes systolic dysfunction after cardiotoxic chemotherapy. We aimed to study systolic and diastolic dysfunction after cardiotoxic chemotherapy and whether diastolic dysfunction can predict subsequent risk of systolic dysfunction. It was an observational prospective cohort study, and patients receiving cardiotoxic chemotherapy were included. Baseline, demographic, and clinical details were recorded. Echocardiographic measurements of left ventricular systolic function, global longitudinal strain, and diastolic function were noted at baseline, three months, and 6 months. RESULTS: We included eighty patients. The mean age of the patients was 54.92 ± 7.6 years, predominantly females (80%). The mean left ventricular ejection fraction fell from 64.92 ± 1.96 to 60.97 ± 4.94 at 6 months. Low ejection fraction was seen in 8 (10%) patients at 6 months. The mean global longitudinal strain (GLS) at baseline was - 18.81 ± 0.797 and fell to - 17.65 ± 2.057 at 6 months, with 12 (15%) patients having low GLS (< - 18). Grade 1 diastolic dysfunction was seen in 22 (27.5%) patients, and grade 2 diastolic dysfunction was seen in 3 (3.8%) patients at 6 months. There was a significant decrease in E/A ratio (inflow early diastolic velocity/Inflow late diastolic velocity), mitral tissue Doppler velocity, and an increase in isovolumic relaxation time, mitral valve deceleration time, and E/e' (inflow early diastolic velocity/tissue Doppler mitral annular velocity), at three months and 6 months. Ejection fraction at 6 months was significantly and negatively correlated with diastolic dysfunction at three months (r = - 0.595, p = 0.02). CONCLUSIONS: Cardiotoxic chemotherapy is associated with early diastolic dysfunction. Early diastolic dysfunction predicts subsequent left ventricular systolic dysfunction.

Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Digital twin: Data exploration, architecture, implementation and future.

A Digital Twin (DT) is a digital copy or virtual representation of an object, process, service, or system in the real world. It was first introduced to the world by the National Aeronautics and Space Administration (NASA) through its Apollo Mission in the '60s. It can successfully design a virtual object from its physical counterpart. However, the main function of a digital twin system is to provide a bidirectional data flow between the physical and the virtual entity so that it can continuously upgrade the physical counterpart. It is a state-of-the-art iterative method for creating an autonomous system. Data is the brain or building block of any digital twin system. The articles that are found online cover an individual field or two at a time regarding data analysis technology. There are no overall studies found regarding this manner online. The purpose of this study is to provide an overview of the data level in the digital twin system, and it involves the data at various phases. This paper will provide a comparative study among all the fields in which digital twins have been applied in recent years. Digital twin works with a vast amount of data, which needs to be organized, stored, linked, and put together, which is also a motive of our study. Data is essential for building virtual models, making cyber-physical connections, and running intelligent operations. The current development status and the challenges present in the different phases of digital twin data analysis have been discussed. This paper also outlines how DT is used in different fields, like manufacturing, urban planning, agriculture, medicine, robotics, and the military/aviation industry, and shows a data structure based on every sector using recent review papers. Finally, we attempted to give a horizontal comparison based on the features of the data across various fields, to extract the commonalities and uniqueness of the data in different sectors, and to shed light on the challenges at the current level as well as the limitations and future of DT from a data standpoint.

A review on self-healing featured soft robotics.

Soft robots are becoming more popular because they can solve issues stiff robots cannot. Soft component and system design have seen several innovations recently. Next-generation robot-human interactions will depend on soft robotics. Soft material technologies integrate safety at the material level, speeding its integration with biological systems. Soft robotic systems must be as resilient as biological systems in unexpected, uncontrolled situations. Self-healing materials, especially polymeric and elastomeric ones, are widely studied. Since most currently under-development soft robotic systems are composed of polymeric or elastomeric materials, this finding may provide immediate assistance to the community developing soft robots. Self-healing and damage-resilient systems are making their way into actuators, structures, and sensors, even if soft robotics remains in its infancy. In the future, self-repairing soft robotic systems composed of polymers might save both money and the environment. Over the last decade, academics and businesses have grown interested in soft robotics. Despite several literature evaluations of the soft robotics subject, there seems to be a lack of systematic research on its intellectual structure and development despite the rising number of articles. This article gives an in-depth overview of the existing knowledge base on damage resistance and self-healing materials' fundamental structure and classifications. Current uses, problems with future implementation, and solutions to those problems are all included in this overview. Also discussed are potential applications and future directions for self-repairing soft robots.

Inhibition of Marek's Disease Virus Replication and Spread by 25-hydroxycholesterol and 27-hydroxycholesterol In Vitro.

Marek's disease virus (MDV) causes a deadly lymphoproliferative disease in chickens, resulting in huge economic losses in the poultry industry. It has been suggested that MDV suppresses the induction of type I interferons and thus escapes immune control. Cholesterol 25-hydroxylase (CH25H), a gene that encodes an enzyme that catalyses cholesterol to 25-hydroxycholesterol (25-HC), is an interferon-stimulating gene (ISG) known to exert antiviral activities. Other oxysterols, such as 27-hydroxycholesterols (27-HC), have also been shown to exert antiviral activities, and 27-HC is synthesised by the catalysis of cholesterol via the cytochrome P450 enzyme oxidase sterol 27-hydroxylase A1 (CYP27A1). At 24 h post infection (hpi), MDV stimulated a type I interferon (IFN-α) response, which was significantly reduced at 48 and 72 hpi, as detected using the luciferase assay for chicken type I IFNs. Then, using RT-PCR, we demonstrated that chicken type I IFN (IFN-α) upregulates chicken CH25H and CYP27A1 genes in chicken embryo fibroblast (CEF) cells. In parallel, our results demonstrate a moderate and transient upregulation of CH25H at 48 hpi and CYP27A1 at 72hpi in MDV-infected CEF cells. A significant reduction in MDV titer and plaque sizes was observed in CEFs treated with 25-HC or 27-HC in vitro, as demonstrated using a standard plaque assay for MDV. Taken together, our results suggest that 25-HC and 27-HC may be useful antiviral agents to control MDV replication and spread.

Evaluation of chromosome 1p/19q deletion by Fluorescence in Situ Hybridization (FISH) as prognostic factors in malignant glioma patients on treatment with alkylating chemotherapy.

BACKGROUND: Either deletion or co-deletion of chromosomal arms 1p or 19q is a characteristic and early genetic event in oligodendroglial tumors that is associated with a better prognosis and enhanced response to therapy. Information of 1p/19q status is now regarded as the standard of care when managing oligodendroglial tumors for therapeutic options in anticipation of the increased survival and progression-free survival times associated with it. Keeping this in view, we first time attempted to establish the FISH based detection of 1p/19q deletion in glioma tissue samples to evaluate its role and involvement in the disease. METHOD: Overall 39 glioma cases of different histologies were evaluated by fluorescence in situ hybridization (FISH) technique using specific FISH probes with Olympus BX43 fluorescent microscope to detect chromosomes 1p and 19q or co-deletions therein. RESULTS: Of the 39 glioma samples, overall 27 (69.2%) were found to have deletion either in 1p, 19q or both. Deletions were observed in 23.0%, 7.6% and 38.4% in 1p, 19q and 1p/19q co-deletions respectively. Overall oligidendrioglioma presented with 53.8% (21 of 39) deletions, astrocytoma group showed 12.8% and GBM accounted for 2.5% deletions. Overall survival and disease free survival was seen significantly better in oligidendrioglioma and astrocytoma with deleted tumors as compared to non-deleted ones (p<0.05). CONCLUSION: Allelic losses on 1p and 19q, either discretely or shared, were more frequent in classic oligodendrogliomas than in either astrocytoma or Glioblastoma with better survival and response to therapy.