Paediatric testicular torsion in low- and middle-income countries: an OxPLORE scoping study.

BACKGROUND: Literature on paediatric surgical conditions in low- and middle-income countries (LMICs) remains limited. As a common emergency, timely treatment of testicular torsion acts as a benchmark of adequate emergency service delivery in paediatric surgery. This scoping study aims to synthesise all existing literature on paediatric testicular torsion in LMICs. METHODS: A database search was conducted by the OxPLORE global paediatric surgery research group to identify studies containing the terms 'testicular torsion' or 'acute scrotum' originating from LMICs. A thematic analysis was applied to the results of the search and the quality of evidence was appraised for all included articles. RESULTS: This review included 17 studies with 1798 patients. All studies originated from middle-income countries and the majority (76%) had sample sizes smaller than 100 patients. All studies were appraised as providing less than adequate evidence. Included studies identified long delays to treatment and highlighted ongoing debates on the value of scoring systems and Doppler ultrasonography in diagnosing torsion. Major heterogeneity in surgical approaches to treatment of testicular torsion in children was also observed. CONCLUSIONS: Literature on paediatric testicular torsion in LMICs is scarce and heterogeneous. Prospective, multi-centre research on the management of this common paediatric surgical emergency is urgently required.

Nafamostat reduces systemic inflammation in TLR7-mediated virus-like illness.

BACKGROUND: The serine protease inhibitor nafamostat has been proposed as a treatment for COVID-19, by inhibiting TMPRSS2-mediated viral cell entry. Nafamostat has been shown to have other, immunomodulatory effects, which may be beneficial for treatment, however animal models of ssRNA virus infection are lacking. In this study, we examined the potential of the dual TLR7/8 agonist R848 to mimic the host response to an ssRNA virus infection and the associated behavioural response. In addition, we evaluated the anti-inflammatory effects of nafamostat in this model. METHODS: CD-1 mice received an intraperitoneal injection of R848 (200 µg, prepared in DMSO, diluted 1:10 in saline) or diluted DMSO alone, and an intravenous injection of either nafamostat (100 µL, 3 mg/kg in 5% dextrose) or 5% dextrose alone. Sickness behaviour was determined by temperature, food intake, sucrose preference test, open field and forced swim test. Blood and fresh liver, lung and brain were collected 6 h post-challenge to measure markers of peripheral and central inflammation by blood analysis, immunohistochemistry and qPCR. RESULTS: R848 induced a robust inflammatory response, as evidenced by increased expression of TNF, IFN-γ, CXCL1 and CXCL10 in the liver, lung and brain, as well as a sickness behaviour phenotype. Exogenous administration of nafamostat suppressed the hepatic inflammatory response, significantly reducing TNF and IFN-γ expression, but had no effect on lung or brain cytokine production. R848 administration depleted circulating leukocytes, which was restored by nafamostat treatment. CONCLUSIONS: Our data indicate that R848 administration provides a useful model of ssRNA virus infection, which induces inflammation in the periphery and CNS, and virus infection-like illness. In turn, we show that nafamostat has a systemic anti-inflammatory effect in the presence of the TLR7/8 agonist. Therefore, the results indicate that nafamostat has anti-inflammatory actions, beyond its ability to inhibit TMPRSS2, that might potentiate its anti-viral actions in pathologies such as COVID-19.

Asymmetrically synchronous reduction and assembly of graphene oxide film on metal foil for moisture responsive actuator.

Graphene has drawn tremendous attention for the fabrication of actuators because of its unique chemical and structural features. Traditional graphene actuators need integration with polymers or other responsive components for shape-changeable behaviour. Searching for a sole material with asymmetric properties is difficult and challenging for actuators that are responsive to external stimulus. Herein, asymmetrically synchronous reduction and assembly of a graphene oxide (GO) film with oxygen-containing group gradients was prepared on various metal foils. Such film possessed asymmetric surface chemical components on both sides, which showed reversible deformation via alternating moisture. Importantly, we can detect the moisture change via recording the voltage pulse during self-deformation on the basis of spontaneous H3O+ ions diffusion across the GO film without the need of power input. Finally, a smart gripper was developed using a moisture responsive GO film. Present work opens a new avenue for developing smart actuator using a sole material and simultaneously realizing the detection of deformation in self-powered mode.

Immunocompromised individuals are at increased risk of COVID-19 breakthrough infection, hospitalization, and death in the post-vaccination era: A systematic review.

INTRODUCTION: Immunocompromised individuals have been shown to mount a reduced response to vaccination, resulting in reduced vaccine effectiveness in this cohort. Therefore, in the postvaccination era, immunocompromised individuals remain at high risk of breakthrough infection and COVID-19 related hospitalization and death, which persist despite vaccination efforts. There has been a marked paucity of systematic reviews evaluating existing data describing the clinical measures of efficacy of COVID-19 vaccination, specifically in immunocompromised populations. In particular, there is a scarcity of comprehensive evaluations exploring breakthrough infections and severe COVID-19 in this patient population. METHODS: To address this gap, we conducted a systematic review which aimed to provide a summary of current clinical evidence of the effectiveness of COVID-19 vaccination in the immunocompromised population. Using PRISMA guidelines, we conducted a literature search on PubMed and the Cochrane database published between January 1, 2021 to September 1, 2022. RESULTS: Our findings demonstrated that despite vaccination, immunocompromised patients remained at high risk of new breakthrough COVID-19 infection and severe COVID-19 outcomes compared to the general population. We found increased average relative risk (RR) of breakthrough infections in the immunocompromised population, including patients with cancer (RR = 1.4), HIV (RR = 1.92), chronic kidney disease (RR = 2.26), immunodeficiency (RR = 2.55), and organ transplant recipients (RR = 6.94). These patients are also at greater risk for hospitalizations and death following COVID-19 breakthrough infection. We found that the RR of hospitalization and death in Cancer patients was 1.08 and 2.82, respectively. CONCLUSION: This demonstrated that vaccination does not offer an adequate level of protection in these groups, necessitating further measures such as Evusheld and further boosters.

Genome-Wide Identification and Characterization of the Salvia miltiorrhiza Histone Deacetylase (HDAC) Family in Response to Multiple Abiotic Stresses.

Salvia miltiorrhiza is a plant commonly used in traditional Chinese medicine. Its material bases for treating diseases are tanshinones and phenolic acids, including salvianolic acids. Histone deacetylase proteins (HDACs) are a class of specific functional enzymes that interact with acetylation groups on the N-terminal lysine of histone proteins further regulate gene transcription through structural changes at the chromatin level. HDACs involved in the growth and development of various plants, and induced by plant hormones to regulate the internal environment of plants to resist stress, at the same time affect the accumulation of some secondary metabolites. However, the role of SmHDACs on the accumulation of salvianolic acid in S. miltiorrhiza remains unclear. In this study, 16 SmHDACs genes were identified from the high-quality S. miltiorrhiza genome, their physicochemical properties were predicted. In phylogenetic trees co-constructed with HDACs proteins from other plants, SmHDACs was divided into three subfamilies, each with similar motif and conserved domain composition. The distribution of the three subfamilies is similar to that of dicotyledonous plants. Chromosome localization analysis showed that SmHDACs genes were randomly located. Cis-acting element analysis predicted that SmHDACs gene expression may be related to and induced by various phytohormones, such as MeJA and ABA. By combining the expression pattern and co-expression network induced by phytohormones, we speculate that SmHDACs may further influence the synthesis of salvianolic acid, and identified SmHDA5, a potential functional gene, then speculate its downstream target based on the co-expression network. In summary, we analyzed the SmHDACs gene family of S. miltiorrhiza and screened out the potential functional gene SmHDA5. From the perspective of epigenetics, we proposed the molecular mechanism of plant hormone promoting salvianolic acid synthesis, which filled the gap in the subdivision of histone deacetylase in S. miltiorrhiza research, provided a theoretical basis for the culture and transformation of S. miltiorrhiza germplasm resources.

Nanoscale Thermal Strain Engineering-Driven Ferroelastic Domain Evolution in CH3NH3PbI3 Perovskites.

A local thermal strain engineering approach via an ac-heated thermal probe was incorporated into methylammonium lead triiodide (MAPbI3) crystals and acts as a driving force for ferroic twin domain dynamics, local ion migration, and property tailoring. Periodically, striped ferroic twin domains and their dynamic evolutions were successfully induced by local thermal strain and high-resolution thermal imaging, giving decisive evidence of the ferroelastic nature in MAPbI3 perovskites at room temperature. Local thermal ionic imaging and chemical mappings demonstrate that domain contrasts are from local methylammonium (MA+) redistribution into the stripes of chemical segregation in response to the local thermal strain fields. The present results reveal an inherent coupling among local thermal strains, ferroelastic twin domains, local chemical-ion segregations, and physical properties and offer a potential path to improve the functionality of metal halide perovskite-based solar cells.