Wake-like skin patterning and neural activity during octopus sleep.

While sleeping, many vertebrate groups alternate between at least two sleep stages: rapid eye movement and slow wave sleep1-4, in part characterized by wake-like and synchronous brain activity, respectively. Here we delineate neural and behavioural correlates of two stages of sleep in octopuses, marine invertebrates that evolutionarily diverged from vertebrates roughly 550 million years ago (ref. 5) and have independently evolved large brains and behavioural sophistication. 'Quiet' sleep in octopuses is rhythmically interrupted by approximately 60-s bouts of pronounced body movements and rapid changes in skin patterning and texture6. We show that these bouts are homeostatically regulated, rapidly reversible and come with increased arousal threshold, representing a distinct 'active' sleep stage. Computational analysis of active sleep skin patterning reveals diverse dynamics through a set of patterns conserved across octopuses and strongly resembling those seen while awake. High-density electrophysiological recordings from the central brain reveal that the local field potential (LFP) activity during active sleep resembles that of waking. LFP activity differs across brain regions, with the strongest activity during active sleep seen in the superior frontal and vertical lobes, anatomically connected regions associated with learning and memory function7-10. During quiet sleep, these regions are relatively silent but generate LFP oscillations resembling mammalian sleep spindles11,12 in frequency and duration. The range of similarities with vertebrates indicates that aspects of two-stage sleep in octopuses may represent convergent features of complex cognition.

Postnatal expression of CD38 in astrocytes regulates synapse formation and adult social memory.

Social behavior is essential for health, survival, and reproduction of animals; however, the role of astrocytes in social behavior remains largely unknown. The transmembrane protein CD38, which acts both as a receptor and ADP-ribosyl cyclase to produce cyclic ADP-ribose (cADPR) regulates social behaviors by promoting oxytocin release from hypothalamic neurons. CD38 is also abundantly expressed in astrocytes in the postnatal brain and is important for astroglial development. Here, we demonstrate that the astroglial-expressed CD38 plays an important role in social behavior during development. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, impairs social memory without any other behavioral abnormalities. Morphological analysis shows that depletion of astroglial CD38 in the postnatal brain interferes with synapse formation in the medial prefrontal cortex (mPFC) and hippocampus. Moreover, astroglial CD38 expression promotes synaptogenesis of excitatory neurons by increasing the level of extracellular SPARCL1 (also known as Hevin), a synaptogenic protein. The release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. These data demonstrate a novel developmental role of astrocytes in neural circuit formation and regulation of social behavior in adults.

Highly adsorptive removal of ciprofloxacin and E. coli inactivation using amino acid tryptophan modified nano-gibbsite.

Adsorption of essential amino acid, Tryptophan (Tryp) on synthesized gibbsite nanoparticles and their applications in eliminating of antibiotic ciprofloxacin (CFX) and bacteria Escherichia coli (E. coli) in aqueous solution. Nano-gibbsite which was successfully fabricated, was characterized by XRD, TEM-SAED, FT-IR, SEM-EDX and zeta potential measurements. The selected parameters for Tryp adsorption on nano-gibbsite to form biomaterial, Tryp/gibbsite were pH 11, gibbsite dosage 20 mg/mL and 1400 mg/L Tryp. The optimum conditions for CFX removal using Tryp/gibbsite were adsorption time 60 min, pH 5, and 20 mg/mL Tryp/gibbsite dosage. The CFX removal significantly raised from 63 to 90% when using Tryp/gibbsite. The Freundlich and pseudo-second-order models achieved the best fits for CFX adsorption isotherm and kinetic on Tryp/gibbsite, respectively. The amount of CFX increased with increasing ionic strength, suggesting that both electrostatic and non-electrostatic interactions were important. After four reused time, CFX removal was greater than 66%, demonstrating that Tryp/gibbsite is reusable with high performance in removing CFX. The application in bacterial activity in term of E. coli reached greater than 98% that was the best material for bacteria inactivation. The present study reveals that Tryp/gibbsite is an excellent bio-material for removing CFX and E. coli.

Use of infant simulators as an aid in pregnancy and parenting educational interventions for school-aged students: a scoping review.

Schools and school teachers often focus on content aimed at delaying sexual debut and preventing teenage pregnancy, and address the impacts of risky behaviours on infant health. Infant simulators are increasingly used in health education courses. However, it is unclear how effective this education is. In this review, we examined the evidence for the effectiveness and use of pregnancy/parenting education programmes for school-aged students using infant simulators. Infant simulators are lifelike replicas of human newborn babies that have electronic capacity to mimic a range of infant behaviours. These may include feeding, comfort needs and nappy changing. Responses to these replicated behaviours may be recorded to provide feedback of the adequacy of the response for educational purposes and provide feedback to prospective parents and caregivers. This review followed the guidelines for conducting a scoping review developed by Joanna Briggs Institute (JBI). After following the process as recommended by the JBI, 32 eligible articles were selected for inclusion. Eight themes emerged from the analysis and it was found that the use of infant simulators in terms of effectiveness was not conclusive. This may be due to lack of longitudinal studies examining the impact of the education provided. Furthermore, the literature did not address innovations of infant simulators that replicate infants with particular characteristics, those with fetal alcohol spectrum disorder, shaken baby syndrome or challenges from parental substance use. Further research is required to determine the long-term impact of using infant simulators on reducing risky behaviours. Given these challenges, it is important to support initiatives for sex, pregnancy and parenting education among all students.

Labdane-type diterpenoids and sesquiterpenes from Curcuma aromatica and their nitric oxide inhibitory activity in lipopolysaccharide-stimulated RAW264.7 macrophages.

One new labdane-type diterpenoid, 3ß,15-dihydroxylabda-8(17),12E-dien-16,15-olide (1) named curcumatin and twelve known compounds, coronarin D (2), isocoronarin D (3), (E)-labda-8(17),12-diene-15,16-dial (4), zerumin A (5), (E)-labda-8(17),12-dien-15,16-dioic acid (6), furanodiene (7), linderazulene (8), zedoarol (9), zedoarondiol (10), germacrone-1,10-epoxide (11), germacrone-4,5-epoxide (12), and zingiberenol (13) were isolated from the ethanol extract of the roots of Curcuma aromatica Salisb. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, and comparing with the NMR data reported in the literature. Compounds 2, 5, and 13 significantly inhibited the nitric oxide production effect in LPS-stimulated RAW 264.7 macrophages with IC50 values of 8.8 ± 1.7, 4.0 ± 0.9, and 6.2 ± 0.4 µM, respectively.

Burden of Postinfectious Symptoms after Acute Dengue, Vietnam.

We assessed predominantly pediatric patients in Vietnam with dengue and other febrile illness 3 months after acute illness. Among dengue patients, 47% reported >1 postacute symptom. Most resolved by 3 months, but alopecia and vision problems often persisted. Our findings provide additional evidence on postacute dengue burden and confirm children are affected.

Spatio-temporal dynamics of the metabolome of climacteric fruit during ripening and post-harvest storage.

Fruit quality traits are determined to a large extent by their metabolome. The metabolite content of climacteric fruit changes drastically during ripening and post-harvest storage, and has been investigated extensively. However, the spatial distribution of metabolites and how it changes in time has received much less attention as fruit are usually considered as homogenous plant organs. Yet, spatio-temporal changes of starch, which is hydrolyzed during ripening, has been used for a long time as a ripening index. As vascular transport of water, and hence convective transport of metabolites, slows down in mature fruit and even stalls after detachment, spatio-temporal changes in their concentration are probably affected by diffusive transport of gaseous molecules that act as substrate (O2), inhibitor (CO2), or regulator (ethylene and NO) of the metabolic pathways that are active during climacteric ripening. In this review, we discuss such spatio-temporal changes of the metabolome and how they are affected by transport of metabolic gases and gaseous hormones. As there are currently no techniques available to measure the metabolite distribution repeatedly by non-destructive means, we introduce reaction-diffusion models as an in silico tool to compute it. We show how the different components of such a model can be integrated and used to better understand the role of spatio-temporal changes of the metabolome in ripening and post-harvest storage of climacteric fruit that is detached from the plant, and discuss future research needs.

ATF6ß Deficiency Elicits Anxiety-like Behavior and Hyperactivity Under Stress Conditions.

Activating transcription factor 6 (ATF6) is an endoplasmic reticulum (ER) stress-regulated transcription factor that induces expression of major molecular chaperones in the ER. We recently reported that ATF6ß, a subtype of ATF6, promoted survival of hippocampal neurons exposed to ER stress and excitotoxicity, at least in part by inducing expression of calreticulin, an ER molecular chaperone with high Ca2+-binding capacity. In the present study, we demonstrate that ATF6ß deficiency in mice also decreases calreticulin expression and increases expression of glucose-regulated protein 78, another ER molecular chaperone, in emotional brain regions such as the prefrontal cortex (PFC), hypothalamus, hippocampus, and amygdala. Comprehensive behavioral analyses revealed that Atf6b-/- mice exhibit anxiety-like behavior in the light/dark transition test and hyperactivity in the forced swim test. Consistent with these results, PFC and hypothalamic corticotropin-releasing hormone (CRH) expression was increased in Atf6b-/- mice, as was circulating corticosterone. Moreover, CRH receptor 1 antagonism alleviated anxiety-like behavior in Atf6b-/- mice. These findings suggest that ATF6ß deficiency produces anxiety-like behavior and hyperactivity via a CRH receptor 1-dependent mechanism. ATF6ß could play a role in psychiatric conditions in the emotional centers of the brain.

Multi-pollutants (organic and inorganic) removal potential of scenedesmus species on municipal sewage water and analyzed their phycoremediation mechanisms.

Municipal sledge water is a combination of residential wastewater, industrial effluent, and precipitation water. The water quality parameters analyses results demonstrated that most of the parameters (pH: 5.6 ± 0.3, Turbidity: 102.31 ± 2.8 mg L-1, TH: 946.38 ± 3.7 mg L-1, BOD: 295.63 ± 5.4 mg L-1, COD: 482.41 ± 4.9 mg L-1, Ca: 278.74 ± 1.8 mg L-1, SO42-: 559.64 ± 11.4 mg L-1, Cd: 18.56 ± 1.37 mg L-1, Cr: 31.25 ± 1.49 mg L-1, Pb: 21.45 ± 1.12 mg L-1, and Zn: 48.65 ± 1.56 mg L-1) were considerably increased in quantities with slightly acidic in condition. The in-vitro phycoremediation study was carried out for two weeks with pre-identified Scenedesmus sp. Biomass in different groups of treatments (A, B, C, and D). Interestingly, most of the physicochemical parameters were significantly reduced in group C (4 × 103 cells mL-1) treated municipal sludge water in a shorter treatment period than in the other treatment groups. The phycoremediation percentage of group C were found as pH: 32.85%, EC: 52.81%, TDS: 31.32%, TH: 25.58%, BOD: 34.02%, COD: 26.47%, Ni: 58.94%, Ca: 44.75%, K: 42.74%, Mg: 39.52%, Na: 36.55%, Fe: 68%, Cl: 37.03%, SO42-: 16.77%, PO43-: 43.15%, F: 55.55%, Cd:44.88%, Cr:37.21%, Pb:43.8%, and Zn:33.17%. These findings suggest that increased biomass from Scenedesmus sp. can be used to significantly remediate municipal sludge water and that the obtained biomass and treated sludge can be used as feedstock's for bio fuel as well as bio fertilizer, respectively.

Phytoremediation proficiency of Jatropha gossypifolia under the influence of Pseudomonas aeruginosa on metal contaminated soil.

This investigation was performed to evaluate the metal pollution and possible phytoremediation on bauxite mine surrounding farmland soil. The quality analysis results revealed that, the soil has been polluted with metals such as Al (13.25 ± 0.54 mg kg-1), Pb (336.18 ± 7.17 mg kg-1), Zn (382.18 ± 3.05 mg kg-1), and Cd (11.32 ± 0.28 mg kg-1) and possess poor essential element content. The test bacterium Pseudomonas aeroginosa showed considerable metal tolerance up to 100 mg kg-1 concentration of metals such as Al, Pb, Zn, and Cd. Besides that, it also possesses essential plant growth promoting traits such as sederophore, IAA, nitrogen fixation, and phosphate solubilization. The test bacterium P. aeroginosa demonstrated optimistic influence on the growth and phytoremediation ability of Jatropha gossypifolia on metal-polluted soil under greenhouse experiment with different treatment groups (I-V). Group I (J. gossypifolia seeds coated with P. aeroginosa) showed outstanding phytoremediation potential on metal polluted soil than other treatment groups. The group I reduced considerable quantity of metals (Al 42.79%, Pb 36.57%, Zn 47.06%, and Cd 39.57%) from the treated soil. It was significantly higher than the remediation potential of other treatment groups (II-V). These findings suggest that P. aeroginosa's metal tolerant and PGP characters can effectively influence the growth and phytoremediation potential of J. gossypifolia on metal polluted soil.

Biosorption potential of viable and dead Aspergillus flavus biomass on polluted pond water.

The State Industries Promotion Corporation of Tamil Nadu Ltd (SIPCOT) Lake is never dry; it is always full of water and was recently used as a waste reservoir by the native peoples and industrialists. Thus, this investigation was performed to assess the quality of the lake water and evaluate the possible biosorption potential of Aspergillus flavus on this lake water sample through batch model biosorption study. The water quality parameters analyses revealed that the lake water has been polluted with number of contaminates which including organic and inorganic. The most of the parameters such as pH (9.5 ± 0.7), turbidity (38 ± 1.1 NT unit), TDS (2350.12 ± 31.24 mg L-1), BOD (40.21 ± 3.27 mg L-1), and COD (278.61 ± 11.84 mg L-1), Ca (212.85 ± 9.64 mg L-1), Fe (3.1 ± 0.8 mg L-1), NH3 (15.62 ± 0.5 mg L-1), NO3-(5.84 ± 0.14 mg L-1), Cl- (1257.85 ± 4.6 mg L-1),Cd (15.64 ± 0.29 mg L-1), Cr (6.86 ± 0.34 mg L-1), Pb (25.61 ± 3.41 mg L-1), and Hg (1.8 ± 0.024 mg L-1) content of water sample were beyond the acceptable limits. Fortunately, the A. flavus dead biomass showed considerable biosorption potential (Cd: 27.5 ± 1.1%, Cr: 13.48 ± 1.2%, Pb: 21.27 ± 1.5%, and Hg: 6.49 ± 0.86% in 180 min of contact time) than viable form on polluted lake water. Since, reduced the quantities of most of the parameters which beyond the permissible limit and also increased remarkable percentage of DO in the water sample in a short period of contact time. These findings suggest that A. flavus dead biomass can be used for bioremediation of polluted water in a sustainable manner.

Determination of tacrolimus in human whole blood in kidney transplant recipients using a rapid and specific LC-MS/MS method.

OBJECTIVE: To develop and validate an LC-M/SMS method for the determination of tacrolimus in human whole blood. METHOD: The LC-MS/MS method for the determination of tacrolimus in whole blood was developed and validated according to the guidelines. Concentrations of TAC in 100 kidney transplant patients measured by LC-MS/MS were compared with CMIA using correlation analysis and Bland-Altman plots. RESULTS: The method had a total chromatographic run time of 5 min. The calibration curves were linear over the range of 0.5-100.0 ng/mL with a lower limit of quantification of 1 ng/mL. The intra- and interday accuracy was within the range of 93.3%-109.2% and 96.0%-108.4%, respectively, with precision ranging from 0.8 to 9.4%. The mean extraction recoveries of TAC ranged from 102.6 to 107.8%. The mean concentrations of TAC in whole blood of kidney transplant patients measured by the two assays were different at 1, 3 months and all time points (p < 0.001), but no significant difference was observed at 6 months (p = 0.094). The correlation of data was good with the correlation coefficients (r2 ) of 0.7581, 0.8811, 0.8777, and 0.8077, respectively. Passing-Bablok regression analysis demonstrated good correlations with r2 values higher than 0.88 between TAC levels measured by LC-MS/MS and CMIA. Using Bland-Altman plots yielded average biases of 1.29, 0.79, 0.11, and 0.65 ng/mL at 1, 3, and 6 months and all time points. CONCLUSION: The LC-MS/MS method was validated for the accurate determination of TAC in human whole blood. The comparison of tacrolimus concentrations measured by the LC-MS/MS with CMIA showed a good correlation and agreement of two methods, suggesting LC-MS/MS should be used routinely to monitor TAC concentrations in kidney transplant patients.

Exploring the relationships between health literacy, social support, self-efficacy and self-management in adults with multiple chronic diseases.

BACKGROUND: Self-management in chronic diseases is essential to slowing disease progression and preventing complications. However, empirical research on the associations of critical factors, such as health literacy, social support, and self-efficacy with self-management in the context of multiple chronic diseases is scarce. This study aimed to investigate these associations and provides insights for healthcare providers to develop effective educational strategies for people with multiple chronic diseases. METHODS: Using a cross-sectional survey design, adults (n = 600) diagnosed with at least two chronic diseases were conveniently recruited. To measure health literacy, social support, self-efficacy, and chronic disease self-management behaviours, the Health Literacy Questionnaire (HLQ), Medical Outcome Study - Social Support Survey, Self-efficacy in Managing Chronic Disease, and Self-management in Chronic Diseases instruments were utilized respectively. Comorbidity status was assessed using Age-adjusted Charlson Comorbidity Index (ACCI). A generalised linear regression model was used with a backward technique to identify variables associated with self-management. RESULTS: Participants' mean age was 61 years (SD = 15.3), 46% were female, and most had up to 12 years of education (82.3%). Mean scores for HLQ domains 1-5 varied from 2.61 to 3.24 (possible score 1-4); domains 6-9 from 3.29 to 3.65 (possible score 1-5). The mean scores were 52.7 (SD = 10.4, possible score 0-95), 5.46 (SD = 1.9, possible score 0-10) and 82.1 (SD = 12.4, possible score 30-120) for social support, self-efficacy, and self-management, respectively. Mean ACCI was 6.7 (SD = 2.1). Eight factors (age > 65 years, being female, 4 health literacy domains, greater social support, and higher self-efficacy levels) were significantly associated with greater self-management behaviours while comorbidity status was not. The factors that showed the strongest associations with self-management were critical health literacy domains: appraisal of health information, social support for health, and healthcare provider support. CONCLUSIONS: Developing critical health literacy abilities is a more effective way to enhance self-management behaviours than relying solely on self-confidence or social support, especially for people with multiple chronic diseases. By facilitating communication and patient education, healthcare providers can help patients improve their critical health literacy, which in turn can enhance their self-management behaviours.

Traditional Vietnamese medicine Kovir capsule for non-severe COVID-19 patients: A phase III double-blind randomized controlled trial.

The number of COVID-19 infections is still increasing with the omicron variant. Although vaccination has shown its effectiveness, efficacious treatments are still required. Kovir, a Vietnamese herbal medicine, has shown potential effects for non-severe COVID-19 patients in terms of symptom resolution and prevention of disease progression in previous studies. This phase-3 trial evaluated the safety and efficacy of Kovir for non-severe COVID-19 adults. Participants were randomized to the Kovir (381 patients) or placebo (192 patients) groups. Outcomes were progression to severe/critical COVID-19, a daily symptom score based on 11 pre-defined symptoms, time to symptom resolution, a negative reverse transcription polymerase chain reaction, an EQ-5D-5L quality of life (QOL) score, and serious adverse events. Only one patient (in the placebo group) progressed to severe COVID-19, thus we could not conclude the effect of Kovir on the prevention of disease progression. Kovir significantly reduced time to symptom resolution (median: 7 vs. 11 days, hazard ratio [95% confidence interval]: 2.03 [1.66-2.48]) compared to placebo. Kovir also increased the QOL score on days 7 and 14. No safety concerns were observed. To conclude, Kovir is safe and facilitates symptom relief for non-severe COVID-19 patients. We advocate using Kovir in the early phase of COVID-19 for non-severe adult patients.

New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti-Inflammatory Activity.

A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3-16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC50 value of 6.16±0.14 µM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 µM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 µM) toward TNF-α production, respectively.

Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions.

This review aims to provide a comprehensive understanding of the molecular mechanisms underlying autophagy and mitophagy in hepatocellular carcinoma (HCC). Autophagy is an essential cellular process in maintaining cell homeostasis. Still, its dysregulation is associated with the development of liver diseases, including HCC, which is one of leading causes of cancer-related death worldwide. We focus on elucidating the dual role of autophagy in HCC, both in tumor initiation and progression, and highlighting the complex nature involved in the disease. In addition, we present a detailed analysis of a small subset of autophagy- and mitophagy-related molecules, revealing their specific functions during tumorigenesis and the progression of HCC cells. By understanding these mechanisms, we aim to provide valuable insights into potential therapeutic strategies to manipulate autophagy effectively. The goal is to improve the therapeutic response of liver cancer cells and overcome drug resistance, providing new avenues for improved treatment options for HCC patients. Overall, this review serves as a valuable resource for researchers and clinicians interested in the complex role of autophagy in HCC and its potential as a target for innovative therapies aimed to combat this devastating disease.

Component and Content of Lipid Classes and Phospholipid Molecular Species of Eggs and Body of the Vietnamese Sea Urchin Tripneustes gratilla.

Sea urchins (Tripneustes gratilla) are among the most highly prized seafood products in Vietnam because of their nutritional value and medicinal properties. In this research, lipid classes and the phospholipid (PL) molecular species compositions from the body and eggs of T. gratilla collected in Hon Tam, Nha Trang, Khanh Hoa, Vietnam, were investigated. Hydrocarbon and wax (HW), triacylglycerol (TG), mono- and diacylglycerol (MDAG), free fatty acid (FFA), sterol (ST), polar lipid (PoL), and monoalkyl-diacylglycerol are the major lipid classes. In PL, five main glycerophospholipid classes have been identified, in which 137 PL molecular species were detected in the body and eggs of T. gratilla, including 20 inositol glycerophospholipids (PI), 11 serine glycerophospholipids (PS), 22 ethanolamine glycerophospholipids (PE), 11 phosphatidic acids (PA), and 73 choline glycerophospholipids (PC). PI 18:0/20:4, PS 20:1/20:1, PE 18:1e/20:4, PA 20:1/20:1, and PC 18:0e/20:4 are the most abundant species with the highest content values of 38.65-48.19%, 42.48-44.41%, 41.21-40.03%, 52.42-52.60%, and 7.77-7.18% in each class of the body-eggs, respectively. Interestingly, PL molecules predominant in the body sample were also found in the egg sample. The molecular species with the highest content account for more than 40% of the total species in each molecular class. However, in the PC class containing 73 molecular species, the highest content species amounted to only 7.77%. For both the body and egg TL samples of the sea urchin T. gratilla, a substantial portion of C20:4n polyunsaturated fatty acid was found in PI, PE, and PC, but C16, C18, C20, and C22 saturated fatty acids were reported at low levels. The most dominant polyunsaturated fatty acid in PI, PE, and PC was tetracosapolyenoic C20, while unsaturated fatty acid C20:1 was the most dominant in PS and PA. To our knowledge, this is the first time that the chemical properties of TL and phospholipid molecular species of the PoL of Vietnamese sea urchin (T. gratilla) have been studied.

Effectiveness and safety of a cream product containing zinc oxide for alleviating mosquito bite symptoms.

BACKGROUND: People frequently experience discomfort with immediate wheal, delayed papules, and pruritus from mosquito bites. A topical cream product containing zinc oxide is commercially available for the management of insect bites, but there has been no published evidence for its effectiveness and safety. AIMS: To evaluate the effectiveness and safety of this product in symptoms caused by mosquito bites. METHODS: An open-label, controlled study was performed on 41 healthy participants. All subjects received Aedes aegypti mosquito bites on the forearm. Then test product was randomly applied to the bitten areas of the left or right arm. The other arm was left untreated (control). The onset of pruritus relief was noted. The severity of pruritus was assessed using a visual analogue scale (VAS), ranging from 0 mm (no pruritus) to 100 mm (severe pruritus), and a 4-point pruritus score (0 = none; 1 = mild, not affecting normal activities; 2 = moderate, affecting normal activities to some extent; 3 = severe, significantly affecting activities) at four time points: 15 minutes after the mosquito bite (baseline), as well as 1 hour, 24 hours, and 48 hours after initiating treatment. The size of the bite reaction lesion was also measured at all time points. Any local cutaneous adverse reactions observed during the study were documented. RESULTS: The onset of pruritus relief in the treated group (25 ± 21.7 minutes) was significantly faster compared to the untreated group (118.7 ± 304.8 minutes). The reduction in VAS score at 1 hour was significantly greater in the product group (30.5 ± 16.22) compared to the control group (14.9 ± 9.9). Moreover, there was a significant difference in the reduction of pruritus score at 1 hour, with the product group (1.1 ± 0.5) showing a higher reduction compared to the control group (0.3 ± 0.4). However, there was no significant difference in the reduction of bite lesion size between the two groups. Throughout the study, no adverse events were reported. CONCLUSION: Our preliminary findings indicate that the product effectively reduces pruritus caused by mosquito bites but does not have a significant impact on the size of the bite lesions. The product was found to be safe and may be an option for managing mosquito bites pruritus.

Preventing Risks of Infections and Medication Errors in IV therapy (PRIME): a patient safety initiative.

BACKGROUND: Two major avoidable reasons for adverse events in hospital are medication errors and intravenous therapy-induced infections or complications. Training for clinical staff and compliance to patient safety principles could address these. METHODS: Joint Commission International (JCI) consultants created a standardised, 6-month training programme for clinical staff in hospitals. Twenty-one tertiary care hospitals from across south-east Asia took part. JCI trained the clinical consultants, who trained hospital safety champions, who trained nursing staff. Compliance and knowledge were assessed, and monthly audits were conducted. RESULTS: There was an overall increase of 29% in compliance with parameters around medication preparation and vascular access device management. CONCLUSION: The programme improved safe practice around preparing medications management and managing vascular access devices. The approach could be employed as a continuous quality improvement initiative for the prevention of medication errors and infusion-associated complications.

Profile and Predictors of Blood Tumor Mutational Burden in Advanced Hepatocellular Carcinoma.

Advanced hepatocellular carcinoma (HCC) is responsive to immune checkpoint inhibitors, but there are currently no known biomarkers to predict treatment benefit. Blood TMB (bTMB) estimation via circulating tumor DNA (ctDNA) profiling can provide a convenient means to estimate HCC TMB. Here we provide the first landscape of bTMB in advanced HCC using a commercially available next-generation sequencing assay, show that it is approximately three times as high as matched tissue TMB, and show that bTMB correlates with NAFLD cirrhosis etiology and the presence of genomic alterations in HTERT and TP53. These results lay the foundation for subsequent studies evaluating bTMB as an immune therapy predictive biomarker in HCC.