Differential Diagnosis: Hepatic Complications in Inborn Errors of Immunity.

Inborn errors of immunity (IEIs) are a heterogeneous group of diverse clinical and genetic phenotypes that have an estimated combined prevalence as high as 1/1000. Increased risk of frequent, severe, or opportunistic infections is a common feature of IEIs, but there are also diverse immune-mediated, non-infective complications that are associated with significant morbidity and mortality. As patient survival increases, these are becoming more apparent within the liver. Hepatic involvement of IEIs may not only manifest as infections, but also nodular regenerative hyperplasia, granulomatous disease, autoimmune hepatitis and malignancy. As therapeutic options for patients are expanding, with both pharmaceutical treatments as well as haematopoietic stem cell transplant (HSCT), iatrogenic liver injury is increasingly common and important to identify. This review article summarises the spectrum of hepatic complications seen in IEIs, and highlights the challenges of management within this patient cohort, where immunosuppression is poorly tolerated. Early recognition and prompt diagnosis of potential hepatic complications is therefore crucial in ensuring potentially reversible causes are treated, but significant uncertainty remains regarding best practice for many features of immune dysregulation with limited high-quality evidence.

Fabrication and Performance Evaluation of a Cation Exchange Membrane Using Graphene Oxide/Polyethersulfone Composite Nanofibers.

Ion exchange membranes, especially cation exchange membranes (CEMs), are an important component in membrane-based energy generation and storage because of their ability to transport cations via the electrochemical potential gradient while preventing electron transport. However, developing a CEM with low areal resistance, high permselectivity, and stability remains difficult. In this study, electrospun graphene oxide/polyethersulfone (GO/PES) composite nanofibers were prepared with varying concentrations of GO. To fabricate a CEM, the pores of the electrospun GO/PES nanofiber substrates were filled with a Nafion ionomer. The pore-filled PES nanofiber loaded with 1% GO revealed a noticeable improvement in hydrophilicity, structural morphology, and mechanical properties. The 1% GO/PES pore-filled CEM was compared to a Nafion membrane of a varying thickness and without a nanofiber substrate. The CEM with a nanofiber substrate showed permselectivity of 85.75%, toughness of 111 J/m3, and areal resistance of 3.7 Ω cm2, which were 12.8%, 4.3 times, and 4.0 times better, respectively, than those of the Nafion membrane at the same thickness. The development of a reinforced concrete-like GO/PES nanofiber structure containing stretchable ionomer-enhanced membrane surfaces exhibited suitable areal resistance and reduced the thickness of the composite membrane without compromising the mechanical strength, suggesting its potential application as a cation exchange membrane in electrochemical membrane-based systems.

Control of Tire Wear Particulate Matter through Tire Tread Prescription.

This study aims to analyze tire wear particulate matter (TWP) from tread rubber with different formulations and to compare the concentration of TWP with different wear devices. The TWP generated during the abrasion of truck and bus radial (TBR) tires were examined, and the effect of using different types of rubber and carbon black (CB) were investigated. When natural rubber (NR) was solely used as the tire tread rubber material, there was a higher concentration of 5-10 µm TWP. However, when the tread formulation consisted of NR mixed with butadiene rubber, the TWP concentration decreased. Changing the type of CB also reduced the amount of TWP in the 2.5 µm size range. The TWP concentration in the specimens increased with increasing speed and vertical load. The TWP generated during the abrasion tests using wear testers and tire simulators exhibited similar trends. These findings suggest that modifying tire tread formulations can effectively control the distribution and amount of TWP generation.

Anti-Müllerian hormone levels in serum and testes of male dogs: relations with neuter status and bilateral abdominal cryptorchidism.

Anti-Müllerian hormone (AMH) analysis has contributed to new information in the reproductive endocrinology of domestic animals, due to clinically available diagnostic tools. An accurate and rapid diagnostic method to distinguish between neutered and bilateral abdominal cryptorchid dogs is needed in veterinary practice. Therefore, this study uses an enzyme-linked immunosorbent assay to evaluate the clinical relevance of AMH analysis in peripheral blood as a diagnostic tool for dogs with suspected bilateral abdominal cryptorchidism. The possible alteration of the AMH localization in testicular tissue caused by this pathologic condition was also investigated using immunohistochemistry. Male dogs were divided into three groups of healthy intact (n = 14), healthy castrated (n = 14), and bilateral abdominal cryptorchid (n = 14) dogs. The results demonstrated a higher level of serum AMH in the cryptorchid group compared to the intact group (P < 0.01), while serum AMH levels of all castrated dogs were below the limit of detection (<0.05 ng/mL). Moreover, the percentage of positive AMH immunostaining of the intact group was less than that of the cryptorchid group (P < 0.01). A significantly positive correlation was found between serum AMH concentration and localization in testicular tissues (r = 0.93, P < 0.01). Our findings suggest that AMH levels in the peripheral blood could be used as an alternative and rapid screening method for detecting dogs with abdominal cryptorchidism.

Sulfonated graphene oxide-based pervaporation membranes inspired by a tortuous brick and mortar structure for enhanced resilience against silica scaling and organic fouling.

A novel tortuous brick-and-mortar structure utilizing intercalation of polyvinyl alcohol (PVA) on sulfonated graphene oxide (SGO) membranes was specifically tailored for brine treatment by pervaporation to ensure excessive resistance to silica scaling and organic fouling, as well as ultrafast water transport without compromising salt rejection. The synthesized SGO membrane showed a smoother surface morphology, improved zeta potential, and a higher hydration capacity than the graphene oxide (GO) membrane. Further intercalation of PVA through glutaraldehyde (GA) crosslinking, confirmed by Fourier transform infrared spectroscopy and X-ray diffraction analysis, conferred increased cohesiveness, and the SGO-PVA-GA membrane was therefore able to withstand ultrasonication tests without any erosion of the coating layer. According to a pervaporative desalination test, the SGO-PVA-GA membrane exhibited 62 kg m-2 h-1 of permeate flux, with an extraordinary salt rejection of 99.99% for a 10 wt% NaCl feed solution at 65 °C. The 72 h organic fouling, silica scaling, and combined fouling and scaling tests proved that the SGO-PVA-GA membrane sustains a stable flux with less scaling and fouling than the GO-PVA-GA membrane, attributable to dense surface negative charges and great hydration capacities caused by sulfonic acid. Thus, the SGO-PVA-GA membrane offers superlative advantages for long-term brine treatment by pervaporation, related to its ability to withstand silica scaling and organic fouling.

Protective Effect of Bojungikki-Tang against Radiation-Induced Intestinal Injury in Mice: Experimental Verification and Compound-Target Prediction.

Bojungikki-tang (BJIT) is a traditional herbal medicine used in Korea, Japan, and China to treat gastrointestinal disorders. In this study, we aimed to investigate whether BJIT has protective effects against radiation-induced intestinal injury and to predict the underlying therapeutic mechanisms and related pathways via network pharmacological analyses. BJIT was injected intraperitoneally (50 mg/kg body weight) to C3H/HeN mice at 36 and 12 h before exposure to partial abdominal irradiation (5 Gy and 13 Gy) to evaluate the apoptotic changes and the histological changes and variations in inflammatory cytokine mRNA levels in the jejunum, respectively. Through in silico network analysis, we predicted the mechanisms underlying BJIT-mediated regulation of radiation-induced intestinal injury. BJIT reduced the level of apoptosis in the jejunal crypts 12 h post 5-Gy irradiation. Histological assessment revealed intestinal morphological changes in irradiated mice 3.5 days post 13-Gy irradiation. Furthermore, BJIT decreased inflammatory cytokine levels following radiation exposure. Apoptosis, TNF, p53, VEGF, toll-like receptor, PPAR, PI3K-Akt, and MAPK signaling pathways, as well as inflammatory bowel disease (IBD), were found to be linked to the radioprotective effects of BJIT against intestinal injury. According to our results, BJIT exerted its potential protective effects by attenuating histopathological changes in jejunal crypts and suppressing inflammatory mediator levels. Therefore, BJIT is a potential therapeutic agent that can treat radiation-induced intestinal injury and its associated symptoms.

Sphenopalatine ganglion block ... a new treatment for burning mouth syndrome?: a case report.

Burning mouth syndrome is a poorly understood entity for which current treatment modalities fail to provide effective relieve. Branches of the maxillary and mandibular nerves are responsible for the innervation of the affected area. These are also the nerves involved in trigeminal neuralgia, an entity where sphenopalatine block has proved to be effective. We present a case of a patient with burning mouth syndrome in whom a bilateral sphenopalatine ganglion block was successfully performed for pain treatment. It is an easy and safe technique that can be a valuable treatment option for these patients, although more studies are needed.

Quadratus Lumborum block as primary anesthetic technique for colostomy procedure: a case report.

An elderly patient was admitted to the hospital due to an enterovesical fistula and a terminal colostomy was proposed. The patient had a high anesthetic risk and thus a quadratus lumborum block was chosen as the sole anesthetic technique. This block has been described to provide both somatic and visceral analgesia to the abdomen. In fact, it yielded good anesthetic conditions to perform the procedure and allowed the patient to be hemodynamically stable and comfortable throughout the case. The postoperative period was uneventful.

Open Pore Ultrafiltration Hollow Fiber Membrane Fabrication Method via Dual Pore Former with Dual Dope Solution Phase.

Hollow-fiber membranes are widely used in various fields of membrane processes because of their numerous properties, e.g., large surface area, high packing density, mass production with uniform quality, obvious end-of-life indicators, and so on. However, it is difficult to control the pores and internal properties of hollow-fiber membranes due to their inherent structure: a hollow inside surrounded by a wall membrane. Herein, we aimed to control pores and the internal structure of hollow-fiber membranes by fabricating a dual layer using a dual nozzle. Two different pore formers, polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP), were separately prepared in the dope solutions and used for spinning the dual layer. Our results show that nanoscale pores could be formed on the lumen side (26.8-33.2 nm), and the open pores continuously increased in size toward the shell side. Due to robust pore structure, our fabricated membrane exhibited a remarkable water permeability of 296.2 ± 5.7 L/m2·h·bar and an extremely low BSA loss rate of 0.06 ± 0.02%, i.e., a high BSA retention of 99.94%. In consideration of these properties, the studied membranes are well-suited for use in either water treatment or hemodialysis. Overall, our membranes could be considered for the latter application with a high urea clearance of 257.6 mL/min, which is comparable with commercial membranes.

Enhancing the Dye-Rejection Efficiencies and Stability of Graphene Oxide-Based Nanofiltration Membranes via Divalent Cation Intercalation and Mild Reduction.

Laminar graphene oxide (GO) membranes have demonstrated great potential as next-generation water-treatment membranes because of their outstanding performance and physicochemical properties. However, solute rejection and stability deterioration in aqueous solutions, which are caused by enlarged nanochannels due to hydration and swelling, are regarded as serious issues in the use of GO membranes. In this study, we attempt to use the crosslinking of divalent cations to improve resistance against swelling in partially reduced GO membranes. The partially reduced GO membranes intercalated by divalent cations (i.e., Mg2+) exhibited improved dye-rejection efficiencies of up to 98.40%, 98.88%, and 86.41% for methyl orange, methylene blue, and rhodamine B, respectively. In addition, it was confirmed that divalent cation crosslinking and partial reduction could strengthen mechanical stability during testing under harsh aqueous conditions (i.e., strong sonication).

Anatomical changes of the ligamentum flavum and the epidural space after spinal surgery: a retrospective magnetic resonance imaging study.

BACKGROUND: Anatomical changes of the ligamentum flavum (LF) and epidural space (ES) after spinal surgery may affect the loss-of-resistance during interlaminar epidural procedure and distribution of drug administered into the ES. This study aims to investigate clinically relevant anatomical changes of the LF and ES after spinal surgery. METHODS: We reviewed pre- and postoperative lumbar magnetic resonance imaging data from 34 patients who underwent spinal surgeries at two vertebral body levels. The presence and thickness of LF (midline, right, and left) and the cross-sectional area of the ES were checked at L2, L3, L4, L5, and S1 levels. RESULTS: Intact LF was observed in only 4/34 (12%) and 9/27 (33%) patients at the upper and lower vertebral level of surgery, respectively. Intact LF was observed in 30/30 (100%), 28/33 (75%), and 2/4 (50%) patients, at two levels above, one level above, and one level below the segment level of surgery, respectively. Intact ES was observed in only 4/34 (12%) and 8/27(30%) patients at the upper and lower vertebral level of surgery, respectively. Intact ES was observed in 30/30 (100%), 29/33 (88%), and 3/4 (75%) patients, at two levels above, one level above, and one level below the segment level of surgery, respectively. The thickness of LF and the cross-sectional area of ES significantly decreased at the levels of spinal surgery. CONCLUSIONS: For epidural anesthesia in patients who have previously undergone spinal surgery, it is reasonable to select a needle insertion site other than the level of spinal surgery.

Differentiation of multiple visceral artery aneurysm rupture from major bleeding after coronary artery bypass grafting.

BACKGROUND: Visceral artery aneurysm is a very rare disease, but it is clinically important because of the high risk of rupture involved. These ruptures must be differentiated from those that occur during hospitalization after extra-abdominal surgery. METHODS: During hospitalization after off-pump coronary artery bypass grafting, a 77-year-old woman developed hypovolemic symptoms and had decreased hemoglobin. There was no obvious bleeding, but while screening for possible complications after cardiac surgery, abdominal computed tomographic angiography showed multiple visceral artery aneurysms of the gastroduodenal and pancreaticoduodenal arteries along with hemoperitoneum. RESULTS: The patient underwent coil embolization of the visceral artery aneurysm and was discharged without any complications. CONCLUSIONS: In patients with coronary artery disease with risk factors for atherosclerosis, if anemia occurs without apparent bleeding after surgery, visceral artery aneurysm should be considered as a differential diagnosis.

Acute biological mitral valve thrombosis after the left atrial venting in a patient with a venoarterial extracorporeal membrane oxygenator.

BACKGROUND: Left atrial venting through atrial septotomy in patients with decreased left ventricular (LV) contractility after venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a simple and effective method for treating LV decompression. MATERIALS & METHODS: We report a case of prosthetic mitral valve thrombosis after left atrial venting in a patient with VA-ECMO. RESULTS: In patients undergoing mitral valve replacement, left atrial venting reduces the flow through the mitral valve and forms a prosthetic thrombosis. DISCUSSION: Therefore, excessive left atrial venting should be avoided. Other venting methods that can maintain the flow through the mitral valve should be considered after mitral valve replacement.

Artificial Neural Networks and Response Surface Methodology Approach for Optimization of an Eco-Friendly and Detergent-Stable Lipase Production from Actinomadura Keratinilytica Strain Cpt29.

This work mainly focused on the production of an efficient, economical, and eco-friendly lipase (AKL29) from Actinomadura keratinilytica strain Cpt29 isolated from poultry compost in north east of Algeria, for use in detergent industries. AKL29 shows a significant lipase activity (45 U/mL) towards hydrolyzed triacylglycerols, indicating that it is a true lipase. For maximum lipase production the modeling and optimization of potential culture parameters such as incubation temperature, cultivation time, and Tween 80 (v/v) were built using RSM and ANN approaches. The results show that both the two models provided good quality predictions, yet the ANN showed a clear superiority over RSM for both data fitting and estimation capabilities. A 4.1-fold increase in lipase production was recorded under the following optimal condition: incubation temperature (37.9 °C), cultivation time (111 h), and Tween 80 (3.27%, v/v). Furthermore, the partially purified lipase showed good stability, high compatibility, and significant wash performance with various commercial laundry detergents, making this novel lipase a promising potential candidate for detergent industries.

Consensus Statement on Ethical & Safety Practices for Conducting Digital Monitoring Studies with People at Risk of Suicide and Related Behaviors.

OBJECTIVE: Digital monitoring technologies (e.g., smart-phones and wearable devices) provide unprecedented opportunities to study potentially harmful behaviors such as suicide, violence, and alcohol/substance use in real-time. The use of these new technologies has the potential to significantly advance the understanding, prediction, and prevention of these behaviors. However, such technologies also introduce myriad ethical and safety concerns, such as deciding when and how to intervene if a participant's responses indicate elevated risk during the study? METHODS: We used a modified Delphi process to develop a consensus among a diverse panel of experts on the ethical and safety practices for conducting digital monitoring studies with those at risk for suicide and related behaviors. Twenty-four experts including scientists, clinicians, ethicists, legal experts, and those with lived experience provided input into an iterative, multi-stage survey, and discussion process. RESULTS: Consensus was reached on multiple aspects of such studies, including: inclusion criteria, informed consent elements, technical and safety procedures, data review practices during the study, responding to various levels of participant risk in real-time, and data and safety monitoring. CONCLUSIONS: This consensus statement provides guidance for researchers, funding agencies, and institutional review boards regarding expert views on current best practices for conducting digital monitoring studies with those at risk for suicide-with relevance to the study of a range of other potentially harmful behaviors (e.g., alcohol/substance use and violence). This statement also highlights areas in which more data are needed before consensus can be reached regarding best ethical and safety practices for digital monitoring studies.

Antiviral Nanomaterials for Designing Mixed Matrix Membranes.

Membranes are helpful tools to prevent airborne and waterborne pathogenic microorganisms, including viruses and bacteria. A membrane filter can physically separate pathogens from air or water. Moreover, incorporating antiviral and antibacterial nanoparticles into the matrix of membrane filters can render composite structures capable of killing pathogenic viruses and bacteria. Such membranes incorporated with antiviral and antibacterial nanoparticles have a great potential for being applied in various application scenarios. Therefore, in this perspective article, we attempt to explore the fundamental mechanisms and recent progress of designing antiviral membrane filters, challenges to be addressed, and outlook.

Promoter engineering-mediated Tuning of esterase and transaminase expression for the chemoenzymatic synthesis of sitagliptin phosphate at the kilogram-scale.

Here, we report a bienzymatic cascade to produce ß-amino acids as an intermediate for the synthesis of the leading oral antidiabetic drug, sitagliptin. A whole-cell biotransformation using recombinant Escherichia coli coexpressing a esterase and transaminase were developed, wherein the desired expression level of each enzyme was achieved by promotor engineering. The small-scale reactions (30 ml) performed under optimized conditions at varying amounts of substrate (100-300 mM) resulted in excellent conversions of 82%-95% for the desired product. Finally, a kilogram-scale enzymatic reaction (250 mM substrate, 220 L) was carried out to produce ß-amino acid (229 mM). Sitagliptin phosphate was chemically synthesized from ß-amino acids with 82% yield and > 99% purity.

Practical Considerations of Wastewater-Seawater Integrated Reverse Osmosis: Design Constraint by Boron Removal.

The wastewater-seawater (WW-SW) integrated reverse osmosis (RO) process has gained much attention in and out of academia due to its energy saving capability, economic benefits, and sustainability. The other advantage of this process is to reduce boron concentration in the RO permeate that can exclude the post-treatment process. However, there are multiple design constraints regarding boron removal that restrict process design in the WW-SW integrated system. In this study, uncertainties in design factors of the WW-SW integrated system in consideration of boron removal have been explored. In comprehensive consideration of the blending ratio of between WW and SW, regulatory water quality standard, specific energy consumption (SEC), specific water cost, and RO recovery rate, a range of 15,000~20,000 mg/L feed turned out to be the most appropriate. Furthermore, boron rejection tests with SWRO (seawater reverse osmosis) and BWRO (brackish water reverse osmosis) membranes under actual WW-SW integration found a critical reduction in boron rejection at less than 20 bar of operating pressure. These findings emphasize the importance of caution in the use of BWRO membranes in the WW-SW integrated RO system.

Beneficial Effects of Milk Having A2 ß-Casein Protein: Myth or Reality?

Diet has been shown to play an important role in maintaining normal homeostasis in the human body. Milk and milk products are a major component of the Western diet, but their consumption may predispose sensitive individuals to adverse health outcomes. Current literature about milk products recognizes various bioactive components including lactate, whey protein, and ß-casein protein. Specifically, cow milk has 2 major subvariants of its ß-casein protein, A1 and A2, due to a single nucleotide difference that changes the codon at position 67. Whereas the A2 polymorphism is unlikely to undergo enzymatic cleavage during digestion, the A1 polymorphism is more likely to undergo enzymatic cleavage resulting in the product peptide ß-casomorphin-7, a known µ-opioid receptor agonist. The objective of this article is to review the current understanding of the 2 major ß-casein subvariants and their effects on various organ systems that may have an impact on the health of an individual. Synthesis of the current existing literature on this topic is relevant given the increased association of milk consumption with adverse effects in susceptible individuals resulting in a rising interest in consuming milk alternatives. We discuss the influence of the ß-casein protein on the gastrointestinal system, endocrine system, nervous system, and cardiovascular system as well as its role in antioxidants and methylation. A1 milk consumption has been associated with enhanced inflammatory markers. It has also been reported to have an opioid-like response that can lead to manifestations of clinical symptoms of neurological disorders such as autism spectrum disorder. On the other hand, A2 milk consumption has been associated with beneficial effects and is easier to digest in sensitive individuals. Further research is warranted to investigate the short- and long-term effects of consumption of A1 ß-casein in comparison with milk with A2 ß-casein proteins.