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Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation. Mechanistically, NLRP1 mutations lead to increased self-oligomerization by disrupting the PYD and LRR domains, which are essential in maintaining NLRP1 as an inactive monomer. Primary keratinocytes from patients experience spontaneous inflammasome activation and paracrine IL-1 signaling, which is sufficient to cause skin inflammation and epidermal hyperplasia. Our findings establish a group of non-fever inflammasome disorders, uncover an unexpected auto-inhibitory function for the pyrin domain, and provide the first genetic evidence linking NLRP1 to skin inflammatory syndromes and skin cancer predisposition.
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Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Reguladoras de la Apoptosis/genética , Carcinoma/genética , Predisposición Genética a la Enfermedad , Inflamasomas/metabolismo , Queratosis/genética , Neoplasias Cutáneas/genética , Proteínas Adaptadoras Transductoras de Señales/química , Secuencia de Aminoácidos , Proteínas Reguladoras de la Apoptosis/química , Carcinoma/patología , Cromosomas Humanos Par 17/genética , Epidermis/patología , Mutación de Línea Germinal , Humanos , Hiperplasia/genética , Hiperplasia/patología , Inflamasomas/genética , Interleucina-1/metabolismo , Queratosis/patología , Proteínas NLR , Comunicación Paracrina , Linaje , Dominios Proteicos , Pirina/química , Transducción de Señal , Neoplasias Cutáneas/patología , SíndromeRESUMEN
COVID-19 pneumonia causes acute lung injury and acute respiratory distress syndrome (ALI/ARDS) characterized by early pulmonary endothelial and epithelial injuries with altered pulmonary diffusing capacity and obstructive or restrictive physiology. Growth hormone-releasing hormone receptor (GHRH-R) is expressed in the lung and heart. GHRH-R antagonist, MIA-602, has been reported to modulate immune responses to bleomycin lung injury and inflammation in granulomatous sarcoidosis. We hypothesized that MIA-602 would attenuate rVSV-SARS-CoV-2-induced pulmonary dysfunction and heart injury in a BSL-2 mouse model. Male and female K18-hACE2tg mice were inoculated with SARS-CoV-2/USA-WA1/2020, BSL-2-compliant recombinant VSV-eGFP-SARS-CoV-2-Spike (rVSV-SARS-CoV-2), or PBS, and lung viral load, weight loss, histopathology, and gene expression were compared. K18-hACE2tg mice infected with rVSV-SARS-CoV-2 were treated daily with subcutaneous MIA-602 or vehicle and conscious, unrestrained plethysmography performed on days 0, 3, and 5 (n = 7 to 8). Five days after infection mice were killed, and blood and tissues collected for histopathology and protein/gene expression. Both native SARS-CoV-2 and rVSV-SARS-CoV-2 presented similar patterns of weight loss, infectivity (~60%), and histopathologic changes. Daily treatment with MIA-602 conferred weight recovery, reduced lung perivascular inflammation/pneumonia, and decreased lung/heart ICAM-1 expression compared to vehicle. MIA-602 rescued altered respiratory rate, increased expiratory parameters (Te, PEF, EEP), and normalized airflow parameters (Penh and Rpef) compared to vehicle, consistent with decreased airway inflammation. RNASeq followed by protein analysis revealed heightened levels of inflammation and end-stage necroptosis markers, including ZBP1 and pMLKL induced by rVSV-SARS-CoV-2, that were normalized by MIA-602 treatment, consistent with an anti-inflammatory and pro-survival mechanism of action in this preclinical model of COVID-19 pneumonia.
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COVID-19 , Síndrome de Dificultad Respiratoria , Ratones , Masculino , Femenino , Animales , SARS-CoV-2 , COVID-19/patología , Pulmón/patología , Inflamación/patología , Síndrome de Dificultad Respiratoria/patología , Pérdida de Peso , Ratones Transgénicos , Modelos Animales de EnfermedadRESUMEN
The impacts of accumulating atmospheric greenhouse gases on the earth's climate are now well established. As a result, there have been increases in ambient temperatures and resultant higher frequency and duration of temperature extremes and other extreme weather events, which have been linked to a wide range of adverse health outcomes. This topical narrative review provides a summary of published evidence on the links between climate change and stroke. There is consistent evidence of associations between stroke incidence and mortality and increasing ambient temperature and air pollution. Associations have also been shown for changes in barometric pressure, wildfires, and desert dust and sandstorms, but current evidence is limited. Flooding and other extreme weather events appear to primarily cause service disruption, but more direct links to stroke may emerge. Synergies between dietary changes that reduce stroke risk and may also reduce carbon footprint are being explored. We also discuss the impact on vulnerable populations, proposed pathophysiologic mechanisms, mitigation strategies, and current research priorities. In conclusion, climate change increasingly impacts the stroke community, warranting elevated attention.
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Contaminación del Aire , Gases de Efecto Invernadero , Humanos , Cambio Climático , Contaminación del Aire/efectos adversos , Gases de Efecto Invernadero/efectos adversosRESUMEN
Electrochemical conversion of nitrate, a prevalent water pollutant, to ammonia (NH3) is a delocalized and green path for NH3 production. Despite the existence of different nitrate reduction pathways, selectively directing the reaction pathway on the road to NH3 is now hindered by the absence of efficient catalysts. Single-atom catalysts (SACs) are extensively investigated in a wide range of catalytic processes. However, their application in electrocatalytic nitrate reduction reaction (NO3 -RR) to NH3 is infrequent, mostly due to their pronounced inclination toward hydrogen evolution reaction (HER). Here, Ni single atoms on the electrochemically active carrier boron, nitrogen doped-graphene (BNG) matrix to modulate the atomic coordination structure through a boron-spanning strategy to enhance the performance of NO3 -RR is designed. Density functional theory (DFT) study proposes that BNG supports with ionic characteristics, offer a surplus electric field effect as compared to N-doped graphene, which can ease the nitrate adsorption. Consistent with the theoretical studies, the as-obtained NiSA@BNG shows higher catalytic activity with a maximal NH3 yield rate of 168 µg h-1 cm-2 along with Faradaic efficiency of 95% and promising electrochemical stability. This study reveals novel ways to rationally fabricate SACs' atomic coordination structure with tunable electronic properties to enhance electrocatalytic performance.
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PURPOSE OF REVIEW: The overwhelming majority of stroke burden can be prevented through the pillars of lifestyle medicine: diet, exercise, sleep, substance abuse, stress management, and healthy relationships. Among these, diet confers the greatest attributable risk. RECENT FINDINGS: Despite abundant data and integration of lifestyle medicine within major stroke prevention guidelines, several barriers to effective implementation remain. These include lack of emphasis in medical education, integration in hospital certification metrics, reimbursement from medical insurance, and health policy that inadequately addresses social determinants of health. However, both top-down and bottom-up solutions introduced within the last few years are helping to break down these barriers. This review highlights recent literature and interventions that are closing the gap between the theory and practice of stroke prevention through lifestyle risk factors from a US perspective. By strategically targeting the various institutional barriers, it is possible and essential to substantially reduce stroke burden.
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Anode materials with high-rate performances and good electrochemical stabilities are urgently required for the grid-scale application of lithium-ion batteries (LIBs). Theoretically, transition metal borides are desirable candidates because of their appropriate working potentials and good conductivities. However, the reported metal borides exhibit poor performances owing to their lack of favorable Li+ storage sites and poor structural stabilities during long-term charging/discharging. In this work, a ternary alkali metal boride, Li1.2 Ni2.5 B2 , which displays a high Li+ storage capacity and remarkable electrochemical stability and an excellent rate performance is studied. In contrast to conventional transition metal borides, the introduction of Li atoms facilitates the formation of 1D Ni/B-based honeycomb channels during synthesis. This Ni/B framework successfully sustains the strain during Li+ intercalation and deintercalation, and thus, the optimized Li1.2 Ni2.5 B2 anode exhibits an excellent cycle stability over 500 charge/discharge cycles. This electrode also exhibits superior reversible capacities of 350, 183, and 80 mA h g-1 at 0.1, 1, and 5 A g-1 , respectively, indicating the considerable potential of the 1D Ni/B framework as a commercially available fast-charging LIB anode.
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INTRODUCTION: Herpes Simplex Virus-1 (HSV-1) is a neurotropic DNA virus with neural latency and stereotypic viral encephalitis. It has been reported to conceal underlying glioblastoma (GBM) due to similar radiographic imaging and clinical presentation. Limited data exist on the co-occurrence of GBM and HSV-1. To better describe the pathophysiology of HSV-1 superinfections in GBM, we performed a comprehensive review of GBM cases with superimposed HSV-1. METHODS: A comprehensive literature search of six electronic databases with apriori search criteria was performed to identify eligible cases of GBM with HSV-1. Relevant clinic-radiographic data were collected, Kaplan-Meier estimates, Fisher's exact test, and logistic regression analyses were used. RESULTS: We identified 20 cases of HSE in GBM with an overall survival (OS) of 8.0 months. The median age of presentation was 63 years (range: 24-78 years) and the median interval between GBM or HSE diagnosis was 2 months (range: 0.05-25 months). HSE diagnosis before GBM diagnosis was a predictor for improved survival (HR: 0.06; 95% CI: [0.01-0.54]; p < 0.01). There is a significant reduction in OS in patients with concomitant HSE and GBM compared to the cancer genome atlas (TCGA) cohort (median OS: 8 months vs. 14.2 months; p < 0.05). Finally, HSV does not directly infect GBM cells but indirectly activates a local immune response in the tumor microenvironment. CONCLUSIONS: Superimposed HSE in GBM may contribute to a significant reduction in OS compared to uninfected controls, potentially activating proto-oncogenes during active infection and latency. Preoperative HSE may induce an antiviral immune response, which may serve as a positive prognostic factor. Prompt antiviral treatment upon co-occurrence is necessary.
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Encefalitis por Herpes Simple , Glioblastoma , Herpes Simple , Herpesvirus Humano 1 , Humanos , Preescolar , Niño , Herpesvirus Humano 1/genética , Glioblastoma/complicaciones , Glioblastoma/tratamiento farmacológico , Encefalitis por Herpes Simple/complicaciones , Encefalitis por Herpes Simple/diagnóstico , Encefalitis por Herpes Simple/tratamiento farmacológico , Herpes Simple/complicaciones , Antivirales/farmacología , Microambiente TumoralRESUMEN
BACKGROUND: Forty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic. METHODS: To determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed. RESULTS: Cytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in the SRY gene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients. CONCLUSION: Rare or novel pathogenic variants were identified in the AR, SRD5A2, ZNRF3, SOX8, SOX9 and HHAT genes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.
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Aciltransferasas , Disgenesia Gonadal 46 XY , Factores de Transcripción SOXE , Desarrollo Sexual , Testículo , Ubiquitina-Proteína Ligasas , Femenino , Humanos , Masculino , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Aciltransferasas/genética , Disgenesia Gonadal 46 XY/genética , Proteínas de la Membrana/genética , Mutación , Fenotipo , Diferenciación Sexual , Desarrollo Sexual/genética , Factores de Transcripción SOXE/genética , Testículo/crecimiento & desarrollo , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Psoriasis is a deleterious auto-immune disorder which seriously harms the patients physical and mental health. CD44 are found to be over-expressed on psoriatic lesions which are highly responsible for epidermal hyperproliferation and inflammation. Gallic acid (GA), a phenolic acid natural compound has potential inhibitory impact on pro-inflammatory transcription factors. However, the penetration across skin and availability is low when applied topically, making the treatment extremely challenging. Considering such factors, we developed GA loaded chitosan nanoparticles and modified with hyaluronic acid (HA) (HA@CS-GA NP) to assess the therapeutic potential against psoriasis. The formulations were characterized by DSC, zetasizer and TEM for assuring the development of nanosystems. GA loaded CS NP had a particle size of 207.2 ± 0.08 nm while after coating with HA, the size increased to 220.1 ± 0.18 nm. The entrapment efficiency was 93.24 ± 0.132% and drug loading of 73.17 ± 0.23%. The in vitro cell viability assessment study confirmed enhanced anti-proliferative effect of HA@CS-GA NP over plain GA which is due to high sensitivity towards HaCaT cell. The in vivo results on imiquimod induced psoriasis model indicated that CD44 receptor mediated targeted approach of HA@CS-GA NP gel had great potential in restricting the keratinocyte hyperproliferation and circumventing psoriasis. For the therapy of further skin-related conditions, HA modified nanoparticles should be investigated extensively employing genes, antibodies, chemotherapeutics, or natural substances.
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Quitosano , Nanopartículas , Psoriasis , Humanos , Ácido Hialurónico/uso terapéutico , Ácido Gálico , Psoriasis/tratamiento farmacológicoRESUMEN
Lyotropic liquid crystals are self-assembled, non-lamellar, and mesophase nanostructured materials that have garnered significant attention as drug carriers. Cubosomes, a subtype of lyotropic liquid crystalline nanoparticles, possess three-dimensional structures that display bicontinuous cubic liquid-crystalline patterns. These patterns are formed through the self-organization of unsaturated monoglycerides (amphphilic lipids such as glyceryl monooleate or phytantriol), followed by stabilization using steric polymers (poloxamers). Owing to their bicontinuous structure and steric polymer-based stabilization, cubosomes have been demonstrated to possess greater entrapment efficiency for hydrophobic drugs compared to liposomes, while also exhibiting high stability. In the past decade, there has been significant interest in cubosomes due to their ability to deliver therapeutic and contrast agents for cancer treatment and imaging with minimal side effects, establishing them as a safe and effective approach. Concerning these advantages, the present review elaborates on the general aspects, composition, and preparation techniques of cubosomes, followed by explanations of their mechanisms of drug loading and release patterns. Furthermore, the review provides meticulous discussions on the use of cubosomes in the treatment and imaging of various types of cancer, culminating in the enumeration of patents related to cubosome-based drug delivery systems.
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BACKGROUND: Alport syndrome (AS) is caused by mutations in type IV collagen genes that typically target and compromise the integrity of basement membranes in kidney, ocular, and sensorineural cochlear tissues. Type IV and V collagens are also integral components of arterial walls, and whereas collagenopathies including AS are implicated in aortic disease, the incidence of aortic aneurysm in AS is unknown probably because of underreporting. Consequently, AS is not presently considered an independent risk factor for aortic aneurysm and more detailed case studies including histological evidence of basement membrane abnormalities are needed to determine such a possible linkage. CASE PRESENTATION: Here, we present unique histopathological findings of an ascending aortic aneurysm collected at the time of surgery from an AS patient wherein hypertension was the only other known risk factor. CONCLUSIONS: The studies reveal classical histological features of aortic aneurysm, including atheroma, lymphocytic infiltration, elastin disruption, and myxoid degeneration with probable AS association.
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Aneurisma de la Aorta Ascendente , Aneurisma de la Aorta , Nefritis Hereditaria , Humanos , Nefritis Hereditaria/complicaciones , Nefritis Hereditaria/genética , Nefritis Hereditaria/patología , Riñón/patología , Colágeno Tipo IV/genética , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/genéticaRESUMEN
BACKGROUND: Acceptance of COVID-19 vaccination was noticed to be less common among parents of children with autism spectrum disorder (ASD) and other neurodevelopmental disorders. This study aimed to explore the beliefs and willingness of parents of children with neurodevelopmental disorders about COVID-19 vaccine and understand how certain factors influencing the vaccine decision-making process differ between them and other parents' groups. METHODS: A cross-sectional study was conducted between August to November 2021. An Arabic online survey was distributed in August 2021 to collect the study's data. 400 parents from all the major regions in Saudi Arabia participated in and shared their beliefs about the new COVID-19 vaccination for their children. RESULTS: Out of 400 participants, 381 of them were eligible to answer the survey (95.2%). The total number of parents of children with neurodevelopmental disorder was 158 (41.5%), was compared to responses of parents of heathy children 223 (58.5%). 85 (53.8%) of them were ready to vaccinate their children with COVID-19 vaccine. While 36 (22.8%) were hesitant, the rest 37 (23.4%) did not want to vaccinate their children at all. Only a small number 16 (10.1%) have beliefs of vaccines as a cause of their child's neurodevelopmental disorder. A total of 79 out of 131 responses were received from both parents' groups. Fear of long-term side-effects was the most common reason reported by 41 responders out of 64 (64.06%) from parents of healthy children and 38 responders out of 67 (56.71%) from parents of diagnosed children. Another reason reported by parents of younger children in both groups was the child's age. Having a healthcare relative worker was significantly associated with the vaccine decision making (p < .001). CONCLUSION: The acceptance rate of COVID-19 vaccination of parents of children with neurodevelopmental disorders was low compared to the parents of healthy children in Saudi Arabia. Authorities can benefit from this study results to offer more accessible information about the vaccine importance and safety to the targeted population.
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Trastorno del Espectro Autista , Trastorno Autístico , COVID-19 , Trastornos del Neurodesarrollo , Niño , Humanos , Vacunas contra la COVID-19/uso terapéutico , Estudios Transversales , Arabia Saudita/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación , Trastornos del Neurodesarrollo/epidemiología , PadresRESUMEN
Intrusion detection systems (IDS) play a crucial role in securing networks and identifying malicious activity. This is a critical problem in cyber security. In recent years, metaheuristic optimization algorithms and deep learning techniques have been applied to IDS to improve their accuracy and efficiency. Generally, optimization algorithms can be used to boost the performance of IDS models. Deep learning methods, such as convolutional neural networks, have also been used to improve the ability of IDS to detect and classify intrusions. In this paper, we propose a new IDS model based on the combination of deep learning and optimization methods. First, a feature extraction method based on CNNs is developed. Then, a new feature selection method is used based on a modified version of Growth Optimizer (GO), called MGO. We use the Whale Optimization Algorithm (WOA) to boost the search process of the GO. Extensive evaluation and comparisons have been conducted to assess the quality of the suggested method using public datasets of cloud and Internet of Things (IoT) environments. The applied techniques have shown promising results in identifying previously unknown attacks with high accuracy rates. The MGO performed better than several previous methods in all experimental comparisons.
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Infectious diseases caused by viruses and bacteria are a major public health concern worldwide, with the emergence of antibiotic resistance, biofilm-forming bacteria, viral epidemics, and the lack of effective antibacterial and antiviral agents exacerbating the problem. In an effort to search for new antimicrobial agents, this study aimed to screen antibacterial and antiviral activity of the total methanol extract and its various fractions of Pulicaria crispa (P. crispa) aerial parts. The P. crispa hexane fraction (HF) was found to have the strongest antibacterial effect against both Gram-positive and Gram-negative bacteria, including biofilm producers. The HF fraction reduced the expression levels of penicillin binding protein (PBP2A) and DNA gyrase B enzymes in Staphylococcus aureus and Pseudomonas aeruginosa, respectively. Additionally, the HF fraction displayed the most potent antiviral activity, especially against influenza A virus, affecting different stages of the virus lifecycle. Gas chromatography/mass spectrometry (GC/MS) analysis of the HF fraction identified 27 compounds, mainly belonging to the sterol class, with ß-sitosterol, phytol, stigmasterol, and lupeol as the most abundant compounds. The in silico study revealed that these compounds were active against influenza A nucleoprotein and polymerase, PBP2A, and DNA gyrase B. Overall, this study provides valuable insights into the chemical composition and mechanism of action of the P. crispa HF fraction, which may lead to the development of more effective treatments for bacterial and viral infections.
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Asteraceae , Pulicaria , Virus , Antibacterianos/farmacología , Antibacterianos/química , Antivirales/farmacología , Pulicaria/química , Girasa de ADN/farmacología , Bacterias Gramnegativas , Bacterias Grampositivas , Pruebas de Sensibilidad Microbiana , Bacterias , Biopelículas , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
Objective: To evaluate the diagnostic accuracy of different imaging modalities in patients with partial biliary obstruction with no obvious aetiology on initial imaging. Methods: This is a prospective single-centre cohort study carried out at Pak Emirates Military Hospital, Rawalpindi from June 2019 to June 2021 with non-probability consecutive sampling. Patients with ages 16 to 75 years, presenting with partial biliary obstruction and undetermined aetiology on initial imaging (TUS and MRCP) were enrolled. EUS was performed for each of these patients and the case was regarded as "true positive" or "true negative" if the findings of imaging modality correlated to those of ERCP. ROC curve, sensitivity, specificity, PPV, NPV and AUC (with 95% confidence interval) were drawn for all the diagnostic tools using SPSS V. 21. Results: A total of 65 patients were enrolled over a period of two years with male to female ratio of 1.4:1. Forty-four patients had an intermediate risk of choledocholithiasis upon preliminary evaluation whereas, 48(74%) of the participants had CBD calculi or sludge confirmed upon subsequent ERCP. Trans-abdominal ultrasound showed the lowest sensitivity (29.2%), specificity (85%), NPV 12% and PPV 93% for diagnosing CBD calculi. This was followed by MRCP with a sensitivity of 37.5%, specificity of 100%, NPV of 36.2% and PPV of 100%. EUS showed the maximum diagnostic accuracy with AUC of 1.0 and a 100% sensitivity and specificity when compared with ERCP as gold standard. Conclusion: EUS is superior to MRCP in terms of diagnostic accuracy as minimally invasive diagnostic tool and EUS superiority is particularly relevant in patients with intermediate risk of choledocholithiasis.
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Objective: To compare the efficacy and safety of left lateral decubitus versus prone position during endoscopic retrograde cholangio-pancreaticography (ERCP). Methods: This prospective single-centre cohort study was carried out at Pak Emirates Military Hospital from January to June 2021. Patients requiring ERCP were subsequently allotted LL or PP group randomly (unequal randomization) except patients with recent abdominal surgery, in-dwelling catheters, raised intra-abdominal pressure, cervical spine abnormalities and limb contractures. Qualitative data was analysed using frequencies and chi square statistics whereas, quantitative data was analysed using mean±SD and student T or Mann Whitney U-test. Results: A total of 114 patients were enrolled according to the inclusion criteria with 62(54%) males and majority of the patients (42%) belonging to the age group 31-45 years. The most common ERCP indication was choledocholithiasis (36%). Technical success was achieved in 109(96%) patients with no statistically significant difference between the two groups. The total time of procedure, time for deep cannulation, time for acquiring therapeutic goal and ERCP complexity level were all similar between the two groups. The rate of inadvertent PD cannulation and PEP were relatively higher for the PP group but were statistically non-significant through univariate and logistic regression analyses and the only outcome measure that showed significance was multiple cannulations in the PP group. Conclusion: The study concludes that LL is non-inferior to PP and both positions have comparable outcomes with non-significant differences in terms of technical success rate, complications (specifically PEP), total procedure time, time required for deep cannulation and attainment of goal, ERCP complexity level and inadvertent PD cannulation.
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Objective: To determine that early needle-knife sphincterotomy does not increase post-ERCP pancreatitis in patients with difficult biliary cannulation as compared to standard cannulation. Method: This prospective single-centre cohort study was carried out at Pak Emirates Military Hospital from January 2021 to June 2021. Patients requiring ERCP were enrolled in the study (according to inclusion and exclusion criteria) and were subsequently allotted different groups according to the technique used for deep biliary cannulation. Qualitative data was analysed using frequencies and chi square statistics whereas, quantitative data was analysed using mean±SD and one way ANOVA test. Result: The cohort included 114 patients with 52.6% male patients and predominance of relatively younger age group (31-45 years). The most common indication for ERCP was choledocholithiasis (36%) with an overall technical success rate of 96%. Deep cannulation was achieved either through standard cannulation (56%), double guidewire and/or pancreatic stent assisted (10.5%), use of early Needle-Knife Sphincterotomy (19%), NKS as a last resort (3.5%) or Transpancreatic Stenting and/or combined sphincterotomy (6%). Pancreatitis as a complication occurred in 4(3.5%) patients, bleeding in 2(1.8%), on-table desaturation in 2(1.8%) and perforation in 1(0.9%) patient. The occurrence of pancreatitis was only related significantly to inadvertent PD cannulation through univariate and logistic regression analysis whereas, multiple cannulations (>5), gender, age, classification of papilla and the use of early NKS had no impact on pancreatitis or the occurrence of other complications. Conclusion: NKS is an effective and safe modality for deep biliary cannulation and achieving technical success where cannulation is deemed difficult and does not increase the risk of PEP if done by experienced endoscopists in high volume centres.
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Ex vivo expanded decidua-basalis(DB)-derived mesenchymal stem cells (MSCs) obtained from single donors have demonstrated therapeutic benefits in in vitro and in vivo studies. In this report, the intravenous and subcutaneous administration of DB-MSCs obtained from five healthy donors was assessed considering clinical grade proliferation, accessibility, and toxic effects in Wistar albino rats. The ability of the obtained DB-MSCs for differentiating, as well as their expression of several cell surface markers and immunomodulatory activities, were all assessed. Clinical standard proliferated cells were administered to animals intravenously and subcutaneously in a series of preclinical models in order to assess their in vivo toxicity, general safety, and tumorigenic possibilities. We established that DB cells exhibit structural and functional traits with MSCs. At various doses supplied intravenously or subcutaneously, the research showed no fatality, abnormal response to therapy, or substantial pathological modifications in the rats. Furthermore, there was no indication of prenatal damage in the same animal species when the rats were repeatedly treated with DBMSCs. Thus, DBMSCs were demonstrated to be non-toxic, non-teratogenic, and non-tumorigenic. To determine whether they can be administrated to human patients without risk, more investigation is recommended.
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Here, the synthesis of a series of pure phase metal borides is reported, including WB, CoB, WCoB, and W2 CoB2 , and their surface reconstruction is studied under the electrochemical activation in alkaline solution. A cyclic voltammetric activation is found to enhance the activity of the CoB and W2 CoB2 precatalysts due to the transformation of their surfaces into the amorphous CoOOH layer with a thickness of 3-4 nm. However, such surface transformation does not happen on the WB and WCoB due to their superior structure stability under the applied voltage, highlighting the importance of metal components for the surface reconstruction process. It is found that, compared with CoB, the W2 CoB2 surface shows a quicker reconstruction with a larger active surface area due to the selective leaching of the W from its surface. In the meantime, the metallic W2 CoB2 core underneath the CoOOH layer shows a better promotion of its oxygen evolution reaction (OER) performance than CoB. Therefore, the ternary W2 CoB2 shows better OER performance than the CoB, as well as the WB and WCoB. It is also found that the mixture of W2 CoB2 with Pt/C as the catalysts in air electrode for rechargeable Zn-air battery (ZAB), shows better performance than the IrO2 -Pt/C couple-based ZAB.
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Transition metal borides are considered as promising electrocatalysts for water splitting due to their metallic conductivity and good durability. However, the currently reported monometallic and noncrystalline multimetallic borides only show generic and monofunctional catalytic activity. In this work, the authors design and successfully synthesize highly crystalline ternary borides, Mo2 NiB2 , via a facile solid-state reaction from pure elemental powders. The as-synthesized Mo2 NiB2 exhibits very low overpotentials for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), that is, 280 and 160 mV to reach a current density of 10 mA cm-2 , in alkaline media. These values are much lower from the ones observed over monometallic borides, that is, Ni2 B and MoB, and the lowest among all nonprecious metal borides. By loading Mo2 NiB2 onto Ni foams as both cathode and anode electrode for overall water splitting applications, a low cell voltage of 1.57 V is required to achieve a current density of 10 mA cm-2 , comparable with the value required from the Pt/C||IrO2 /C couple (1.56 V). The proposed synthesis strategy can be used for the preparation of cost-effective, multi-metallic crystalline borides, as multifunctional electrocatalysts.