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Assessment of Surgical Salvage Outcomes for Exposed Cranial Neuromodulating Devices.

OBJECTIVES: Implanted neuromodulating devices (NMDs) such as cochlear implants (CIs) and deep brain stimulators (DBSs) are commonly used in modern medicine. Rarely, complications arise post-operatively, including hardware exposure. Traditional teaching suggests that these devices require removal if exposed; however, surgical salvage is a high risk, high reward alternative. We review our single institution experience managing NMD exposure with surgical salvage. METHODS: Retrospective chart review was performed on individuals who had a NMD implanted and underwent an attempt at surgical salvage for exposure during the study period (January 01, 2021 through December 31, 2023). Study outcome success was defined as maintaining a functional NMD 1 year after salvage was attempted. Surgical techniques associated with successful salvage were compared. RESULTS: Nine of 729 patients (1.2%) implanted with NMDs experienced hardware exposure during this 2-year study period. Nine subjects were referred for NMD salvage; however, only 6 of 9 subjects (66.7%, CI = 3; DBS = 3) underwent NMD salvage attempts. Four of the subjects had successful salvage demonstrated successful salvage with a functioning NMD and without wound healing concerns 1 year after their salvage procedure. CONCLUSIONS: Classic teaching states that exposed NMDs require explantation. However, this approach necessarily imposes time without benefit from the NMD between explantation and reimplantation. Our experience demonstrates that surgical salvage can be a successful alternative for the majority (66.7%) of individuals.

Humans

Effects of automated massage chair therapy on mental health and physical health: A comprehensive study.

BACKGROUND AND OBJECTIVE: Automated massage chair therapy is a non-pharmacological intervention widely believed to enhance wellness, yet evidence regarding its effects remains limited. This 3-part study evaluated the effects of automated massage chair therapy on mental and physical health. METHODS: In Part 1, 20 moderately stressed students were randomized to receive a 20-minute automated massage chair therapy session followed by a 20-minute control session, or vice versa, with a 48-hour washout period. Blood pressure (BP), heart rate (HR), electroencephalogram (EEG), State-Trait Anxiety Inventory (STAI), and Visual Analog Scale (VAS) were measured. In Part 2, 20 hypertensive hospital staff received three 20-minute automated massage chair therapy sessions on alternate days. BP, HR, and skin blood flow (SBF) were measured. In Part 3, 20 hospital staff with chronic low back pain received three 20-minute automated massage chair therapy sessions on alternate days. Electromyogram (EMG) and VAS were measured. RESULTS: Automated massage chair therapy significantly reduced diastolic blood pressure (DBP), HR, stress, and anxiety among moderately stressed students. In hospital staff with hypertension, SBF did not change significantly, whereas BP and HR decreased significantly after automated massage chair therapy. In hospital staff with chronic low back pain, low back function improved, and pain was significantly reduced after automated massage chair therapy. CONCLUSION: These findings indicate that automated massage chair therapy may help reduce stress, lower blood pressure, and alleviate low back pain.

Humans

Ceftriaxone for methicillin-susceptible Staphylococcus aureus bloodstream infections is associated with increased short-term mortality: a systematic review and meta-analysis.

BACKGROUND: Bloodstream infections (BSIs) by methicillin-susceptible Staphylococcus aureus (MSSA) are a significant cause of morbidity and mortality, traditionally treated with antistaphylococcal penicillins (ASPs) or cefazolin. Ceftriaxone has emerged as an alternative due to its once-daily dosing regimen and favourable safety profile; however, its efficacy compared to the standard of care (SoC) remains controversial. This evidence synthesis aimed to assess the role of ceftriaxone in treating MSSA-BSIs. METHODS: A systematic literature search was conducted in PubMed, Embase, and Scopus up to December 31, 2025 (PROSPERO protocol CRD42024595748). Studies comparing ceftriaxone to ASPs or cefazolin for MSSA-BSIs were included. Primary outcomes were 30-day and 90-day all-cause mortality . Pooled effect sizes with their 95% confidence intervals (CIs), were calculated using random-effects models, odds ratios (ORs) and mean differences (MDs) according to the type of outcome. RESULTS: Eleven studies totalling 2,568 patients were included. Ceftriaxone was associated with significantly increased 30-day mortality (OR 3.33; 95% CI: 2.17-5.10), although differences at 90 days were not significant (OR 1.71; 95% CI: 0.75-3.90). No significant differences were noted for clinical success (OR 0.49; 95% CI: 0.19-1.26), microbiological clearance (OR 1.66; 95% CI: 0.73-3.82). Adverse event rates were similar between groups. CONCLUSION: Given the availability of various alternatives and the consistent short-term mortality signal observed, routine use of ceftriaxone for MSSA-BSIs, especially as initial therapy, is not supported by current evidence. Only novel findings from randomized studies may change the place in therapy of the drug in this context.

Humans

"Clinical efficacy and expression of antimicrobial resistance genes after using a novel herbal mouthwash compared to chlorhexidine: A Randomised controlled trial in generalised gingivitis patients".

OBJECTIVES: Chlorhexidine, the gold-standard mouthwash, has several disadvantages, like promotion of antimicrobial resistance. Herbal mouthwashes are emerging as alternatives to chlorhexidine. However, its impact on antimicrobial resistance remains unclear. The aim of the study was to compare the clinical efficacy and the expression of antimicrobial resistance genes of chlorhexidine with a novel herbal mouthwash. DESIGN: Sixty patients with generalised gingivitis were randomly assigned to two groups using block randomisation. After professional mechanical plaque removal patients were instructed to use either chlorhexidine or a novel herbal mouthwash (patented composition) for two weeks. Tetracycline resistance (tetM) and macrolide efflux (mefI) gene expression in subgingival plaque were analysed using real-time polymerase chain reaction. Intragroup comparisons were performed with a paired t-test and Wilcoxon signed-rank test for parametric and nonparametric data. Intergroup comparisons employed unpaired t-test, chi-square test, and Mann-Whitney test. RESULTS: A significant reduction in bleeding, plaque, pocket depth and and patient reported outcomes were noticed in both groups. But reduction in plaque was more significant in chlorhexidine group. tetM and mefI genes significantly upregulated in the chlorhexidine group, while it was downregulated with herbal mouthwash (fold change 1.79 ± 0.74 and 0.60 ± 0.43 for tetM, and 1.83 ± 0.87 and 0.51 ± 0.44 for mefI). However, patients' perception of taste, freshness, and overall satisfaction was better in the chlorhexidine group. CONCLUSIONS: The increased expression of antimicrobial resistance genes following chlorhexidine use warrants careful consideration. Herbal mouthwash is an effective, safer alternative with comparable clinical benefits and less impact on antimicrobial resistance.

Humans

Soft Tissue Volume Augmentation at Single Implant Sites Applying Collagen Matrices or Connective Tissue Grafts: 10-Year Follow-Up of a Randomized Controlled Trial.

AIM: To compare up to 10 years clinical, profilometric and patient-reported outcomes of implant sites previously augmented using a volume-stable collagen matrix (VCMX) or connective tissue graft (SCTG) in the aesthetic zone. METHODS: The original non-inferiority randomized controlled trial (RCT) enrolled 20 patients who received soft tissue volume augmentation with VCMX or SCTG at single implant sites. Clinical assessments and standardized measurements were performed at baseline after crown insertion and at 6 months, 1, 3, 5, 7.5, and 10 years. The primary outcome was mucosal thickness. Secondary outcomes included marginal bone levels (MBL), probing depth (PD), bleeding on probing (BOP), plaque control record, Pink Aesthetic Score (PES), OHIP-14 and buccal profilometric changes. Group comparisons were performed using mixed-effects and generalized estimating equation (GEE) models, which account for within-patient correlations due to repeated measurements and allow inclusion of all available data without requiring imputation for missing observations. RESULTS: Of the 20 originally enrolled patients, 10 (5 in the SCTG group and 5 in the VCMX group) were available for re-examination at 10 years. The adjusted between-group difference in mucosal thickness was -0.02 mm (95% CI -0.99 to 0.96). As the lower bound of the confidence interval remained above the prespecified non-inferiority margin of -1 mm, non-inferiority of VCMX was shown. Buccal contour changes were comparable during the early follow-up, while a trend toward a greater long-term contour decrease was observed in group VCMX (-0.31 mm [95% CI, -0.65 to 0.03]; p = 0.07). Mean PES values were 10.6 in the SCTG group and 9.6 in the VCMX group, with no significant between-group differences (p = 0.45). Both groups revealed high levels of oral health-related quality of life, with low median OHIP-14 scores (SCTG, 0.0; VCMX, 1.0; p = 0.26). CONCLUSION: These preliminary long-term findings showed no clinically relevant differences between SCTG and VCMX in terms of clinical, profilometric and patient-reported outcomes. While SCTG remains the reference standard, VCMX represents a less invasive alternative but with a slight tendency toward greater long-term contour reduction. CLINICAL SIGNIFICANCE: Volume-stable collagen matrices serve as a viable alternative to autogenous connective tissue grafts for peri-implant soft tissue volume augmentation, particularly in patients seeking a reduced morbidity, without compromising long-term clinical or aesthetic outcomes. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017484.

Humans

First Report of Fibromyxoma in a Greater Amberjack (Seriola dumerili) From Aquarium of Genoa.

In teleosts, mesenchymal tumours like fibromas are frequently observed, whereas their malignant counterparts, fibrosarcomas, occur only sporadically. In our study, an adult female greater amberjack (Seriola dumerili) reared at the Aquarium of Genoa developed a slow-growing mass protruding from the ventral right side of the head. The tissue was firm and white greyish with localized cranial haemorrhaging on the external surface. Cut-section examination showed a homogeneous, dry, whitish and richly vascularized tissue layout. Tissue samples from the mass were stained with Masson's Trichrome, Alcian Blue-PAS (pH 2.5), and Toluidine blue for differential diagnosis. Microscopically, it was characterized by alternating collagenous spindle-cell septa and hypocellular metachromatic myxoid areas positive for acidic mucopolysaccharides and glycosaminoglycans. The absence of cellular atypia, mitotic activity and necrosis confirms the diagnosis of fibromyxoma. Documenting rare tumours in aquarium fish expands comparative pathology literature and highlights public aquaria as valuable research platforms for long-term health monitoring under controlled husbandry conditions.

fibromyxoma

Environmentally relevant concentrations of DCOIT impaired lifespan and healthspan in Caenorhabditis elegans.

DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is an antifouling biocide widely used as an alternative to organotin compounds. While previous studies had focused on its effects on energy production, endocrine disruption, and lipid metabolism, its impact on aging and underlying mechanisms remained unclear. Here, we demonstrated that environmentally relevant concentrations of DCOIT (37, 370 and 3700 ng/L) significantly impaired both lifespan and healthspan in Caenorhabditis elegans. RNA-seq and validation assays revealed that DCOIT upregulated comt-4, a key gene in dopamine metabolism, leading to dopamine depletion and subsequent induction of oxidative stress. This redox imbalance critically contributed to accelerated aging phenotypes. Importantly, both genetic (comt-4 RNAi) and pharmacological (opicapone) interventions restored dopamine levels, alleviated oxidative stress, and reversed DCOIT-induced aging deficits. Our study established the comt-4/dopamine/oxidative stress axis as a central mechanism in DCOIT toxicity, suggesting dopamine modulation as a potential countermeasure against environmental toxicant-induced aging.

Animals

Comparison of posterior cellular bonegraft options for single-level lumbar spinal fusion: a randomized trial.

BACKGROUND: Iliac bone autograft (IBG) is osteoinductive/osteogenic/osteoconductive but requires an additional harvesting procedure with known morbidities. Bone morphogenic protein (BMP) is osteoinductive and effective in obtaining fusion but is used off label for posterior fusion, has multiple side effects, and is expensive. Stem cell bone products, both auto- and allograft are attractive osteoinductive alternatives that avoid morbidity related to the graft donor site and may have a better safety profile than BMP. Morcelized allograft bone is osteoconductive but not osteoinductive or osteogenic. PURPOSE: Evaluate and compare the effectiveness of 6 types of viable or osteoinductive bone graft material in obtaining a solid posterior spinal fusion (PSF) for single level anterior/posterior lumbar spinal fusion. The bone grafts were IBG, BMP, autogenous stem cells (MSC) from concentrated bone marrow aspirate (BMA), allograft MSC from bone marrow, adipose tissue, or amniotic fluid, combined with inert cancellous allograft (Allo). STUDY DESIGN/SETTING: Prospective, single-blinded randomized study of 6 cohorts and inert historical control. PATIENT SAMPLE: Elective anterior-posterior lumbar spinal fusion of 175 patients. OUTCOME MEASURES: Assessments included pre and postoperative back and leg pain (VAS) scores, pain drawing, disability (ODI) scores, pain medication usage, and 1-year postoperative thin-cut CT scans (read by blinded radiologists). METHODS: Patients who were surgical candidates for a 1-level anterior/posterior lumbar fusion were randomized to 1 of 6 types of posterior bone graft alternatives: IBG, BMP, BMA, allograft MSC derived from bone marrow combined with morcelized Allo (cAlloBone), adipose derived MSC combined with morcelized Allo (cAlloFat), or amnion derived MSC combined with morcelized Allo (cAlloAm). Historical Allo patients served as a negative control group. Each group (n 27) had prospective outcomes and were followed for a minimum of 2 years. Fusion rate and outcomes were compared and referenced to Allo group. RESULTS: All but 5 patients had a solid ASF. The posterior fusion rates were 98% for IBG, 94% for BMP, 85% for BMA, 67% for cAlloBone, 64% for cAlloFat, 62% for cAlloAm, and 50% for Allo. Outcomes were significantly improved for all measures for all groups and there was no difference between groups except cAlloFat had slightly greater improvement in back pain in the 7-12 month follow-up period. BMP was the most expensive graft material; cellular allografts had a high-cost relative to fusion rate. CONCLUSIONS: For single level ASF/PSF, the PSF fusion rate was significantly greater for IBG and BMP followed by BMA. Various allograft MSC bone graft options resulted in lower fusion rates but may be greater than Allo. Outcomes were uniformly improved regardless of the type of graft used or the fusion status of the posterior fusion as long as the interbody fusion was solid. If bone graft cost savings is a consideration for PSF, then IBG has the greatest radiographic value, and Allo the greatest clinical value as long as the anterior interbody fusion is solid.

Humans

A point-of-use SERS assay for rapid detecting difenoconazole and flusilazole residues in fruit juices using Au/COF substrate.

We developed a ready-to-use surface-enhanced Raman scattering (SERS) sensor for rapid, pretreatment-free detection of difenoconazole (DIF) and flusilazole (FLU) in peach and lychee juices. The substrate combines Au nanoparticles (AuNPs) with covalent organic frameworks (COF) and is implemented on a portable 25-well plate, enabling in situ testing. Juices can be directly applied to the SERS-active Au/COF composite, allowing simultaneous adsorption and signal generation. The correlation between SERS intensity and logarithmic concentration yielded R-values between 0.925 and 0.986, meeting the monitoring needs of non-laboratory scenarios. The entire workflow completes within 12 min, offering a faster alternative to conventional methods while maintaining high sensitivity and reproducibility. Detection limits reach 0.96-1.22 ppb for DIF and FLU, both of which are below the regulatory maximum residue limits. Distinct SERS fingerprints enable reliable discrimination of mixed residues across juice matrices, supporting rapid on-site monitoring and cost-effective pesticide surveillance.

Triazoles

Flux rewiring enables native D-glucosamine production in Escherichia coli.

D-Glucosamine is an industrially important amino sugar used in pharmaceuticals, nutraceuticals, and functional materials, yet its production remains dominated by chemical extraction from chitinous biomass, raising sustainability and allergen concerns. Escherichia coli natively synthesizes D-glucosamine directly from D-glucose through endogenous metabolism, revealing an underutilized amino sugar biosynthetic capability. Building on this native pathway, D-glucosamine production was enhanced through targeted genetic modifications and systematic optimization of nitrogen metabolism and cultivation conditions, reaching 9.2 g L-1 under shake-flask conditions. This work extends a phosphorylation-dephosphorylation strategy previously developed for neutral rare sugars to amino sugar biosynthesis, demonstrating the broader applicability of this metabolic design principle. Phosphatase identity emerged as a key control point for product formation: YbiV was the most effective phosphatase for selective D-glucosamine production, whereas alternative phosphatases redirected flux toward D-sedoheptulose. This enzyme-dependent flux partitioning further enabled tunable co-production of D-glucosamine and D-sedoheptulose. Native amino sugar biosynthesis in E. coli provides a controllable framework for producing chemically distinct sugars through endogenous metabolism and establishes a generalizable strategy for engineering amino sugar and other nitrogen-containing metabolite biosynthesis.

Escherichia coli

Association between hepatic steatosis index and female infertility: a cross-sectional study using NHANES 2013-2018.

Female infertility is a major reproductive health concern. Hepatic steatosis index (HSI), a non-invasive marker of liver-related metabolic burden, has not been well studied in relation to infertility across its distribution. We analyzed women aged 20-49 years from three NHANES cycles (2013-2018). HSI was examined as both a continuous variable and in quartiles, and restricted cubic spline models were used to assess potential nonlinearity. Sensitivity analyses using alternative infertility definitions and exploratory interaction analyses were also performed. Among 3,007 women, 416 (13.8%) were classified as having infertility. In the fully adjusted model, women in the highest HSI quartile had higher odds of infertility than those in the lowest quartile (OR 1.66, 95% CI 1.08-2.57; P = 0.031), with a significant trend across quartiles (P for trend = 0.010). Restricted cubic spline analysis showed a nonlinear association between HSI and infertility (P for overall association = 0.005), which was more evident at higher HSI levels. Higher HSI was associated with greater odds of infertility among reproductive-aged women.

Humans

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans

Assessing the effects of non-invasive transcranial electrical stimulation (tACS and tDCS) on electrophysiological sleep parameters - a systematic review.

Transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), is considered a safe method to modulate cortical activity and endogenous brain oscillations. Given the therapeutic potential of tES across various clinical conditions and the central role of sleep in restoration and memory consolidation, numerous studies have investigated its effects on sleep and sleep-related parameters, yielding inconsistent results. This systematic review provides an up-to-date synthesis of 51 studies assessing the impact of tES on objectively measured electrophysiological sleep outcomes in both healthy individuals and clinical populations. The reviewed studies demonstrate heterogeneous effects, reflecting substantial variability in study designs. Nonetheless, consistent trends emerge, including reduced NREM1 and increases in total sleep time, NREM2, and NREM3 following tES. Moreover, slow-oscillatory tES increased slow-wave power during sleep. Here we show that tES, particularly slow-oscillatory tES, may positively influence sleep architecture and continuity by modulating endogenous brain oscillations. However, due to heterogeneous stimulation protocols, inconsistent findings, the limited number of significant effects and substantial risk of bias the current evidence remains inconclusive. Well-designed, large-scale trials targeting specific sleep outcomes are needed to clarify the therapeutic potential of tES.

Humans

Multiomic insights into fungal polylactic acid degradation: Metabolic adaptation and hydrolytic mechanisms of Sporobolomyces pararoseus.

Polylactic acid (PLA), a biodegradable polyester from renewable resources, is a sustainable alternative to petrochemical plastics. However, its environmental degradation is inefficient naturally, requiring specific microbial activities. While bacterial PLA-degrading mechanisms are well documented, fungal degrading systems-particularly their molecular mechanisms-are underexplored.We isolated Sporobolomyces pararoseus ZRQ01 from the gut microbiota of PLA-fed mealworms. This fungal strain noticeably degraded PLA in PLA-containing medium supplemented with 2% glucose. Biodegradation assays revealed 22.8% loss of the PLA film weight after 35 days of incubation, and scanning electron microscopy confirmed extensive surface erosion and pore formation. Integrated transcriptomic and proteomic analyses, together with the reference genome of S. pararoseus ZRQ01, revealed that S. pararoseus ZRQ01 upregulates hydrolytic enzymes at both transcript and protein levels to cleave PLA into lactic acid. After lactic acid is transferred into S. pararoseus ZRQ01 cells by monocarboxylate transporters with increased abundance, it is assimilated by pathways of pyruvate metabolism and the TCA cycle with increased protein abundance. Intriguingly, upregulation of genes in autophagy-related and MAPK signaling pathways underscores an adaptive stress response potentially supporting cellular homeostasis and degradation-related gene expression. Our results highlight S. pararoseus ZRQ01's metabolic potential for bioremediation and offer insights into fungal bioplastic degradation pathways.

Polyesters

Post-exercise rehydration: a randomized cross-over trial comparing a 100% fruit juice, a glucose-based sports drink, and water.

BACKGROUND: Previous studies indicate that sports drinks may improve rehydration, compared to water, an effect likely achieved by manufacturing sports drinks to contain carbohydrates and sodium. However, there is a growing preference for natural products and a "food first" approach to sports nutrition. Fruit juices naturally contain similar concentrations of carbohydrates to sports drinks, but fruit juices may produce a more stable blood glucose profile. Fruit juices also naturally contain electrolytes, particularly potassium, but their potential as effective rehydration alternatives to sports drinks, which have higher sodium concentrations, is not well understood. This study compared the rehydration efficacy and glucose responses following consumption of a 100% fruit juice (Raw Hydrate&#xae;; FRU), a glucose-based sports drink (SPO), and water (WAT) after exercise-induced hypohydration. Importantly, rehydration beverages were matched for water volume, rather than total volume, to ensure that any potential differences in water balance were not due to unequal water volumes between trials, a limitation affecting previous rehydration research. METHODS: After familiarization, 17 adults (age: 28&#x2009;&#xb1;&#x2009;8&#x2009; years; BMI: 23.8&#x2009;&#xb1;&#x2009;2.9&#x2009;kg/m2) completed three trials in a randomized cross-over design. The participants cycled in the heat (~35&#xb0;C) to induce ~2% body mass loss (BML), then rehydrated over a 1&#x2009;h period in a laboratory (~21&#xb0;C) with a water volume equivalent to 150% of BML from either FRU, SPO, or WAT. This was followed by an additional 4&#x2009;h of seated rest (5&#x2009;h rehydration period), when blood glucose was measured (0, 0.25, 0.5, 0.75, 1, 1.5, and 2&#x2009;h after beverage consumption), and all urine produced was collected. RESULTS: During the 5&#x2009;h rehydration period, there was no effect of trial on total urine volume (FRU: 1266&#x2009;&#xb1;&#x2009;403&#x2009;mL, SPO: 1338&#x2009;&#xb1;&#x2009;361&#x2009;mL, WAT: 1394&#x2009;&#xb1;&#x2009;360&#x2009;mL; P&#x2009;=&#x2009;0.156) or water retention (FRU: 42&#x2009;&#xb1;&#x2009;12%, SPO: 37&#x2009;&#xb1;&#x2009;10%, WAT: 35&#x2009;&#xb1;&#x2009;11%; P&#x2009;=&#x2009;0.059). The blood glucose area under the curve differed by trial (P&#x2009;<&#x2009;0.001), with all beverages significantly different from each other (FRU: 10.12&#x2009;&#xb1;&#x2009;0.72 mmol/L/2h, SPO: 12.48&#x2009;&#xb1;&#x2009;1.34 mmol/L/2h, WAT: 7.90&#x2009;&#xb1;&#x2009;0.47 mmol/L/2h; P&#x2009;<&#x2009;0.003). CONCLUSION: Rehydration efficacy was similar between all beverages, but each elicited a distinct glycemic response. For sports drink consumers seeking a natural alternative or implementing a "food first" nutritional strategy, switching to a 100% fruit juice will not compromise rehydration effectiveness, but may elicit a lower blood glucose response. Although, it should be noted that an additional three participants were withdrawn from the study because of gastrointestinal issues after consuming the 100% fruit juice. This was likely a product of the present study's design, where a large volume of 100% fruit juice (average ~2,300 mL) was consumed in a short period of time (1&#x2009;h). Whilst this is a commonly used study design to robustly assess the rehydration efficacy of different beverages, future studies should distribute fluid intake over a longer duration, in order to improve ecological validity and reduce the risk of gastrointestinal issues.

Humans

Malaria rapid diagnostic tests: performance, pitfalls, and progress.

PURPOSE OF REVIEW: Malaria rapid diagnostic tests (RDTs) have revolutionized malaria diagnosis in endemic settings. RDTs are simple to use and accurate for clinical cases, although sensitivity is reduced at parasite densities below 200&#x200a;parasites/&#x3bc;l. However, increasing prevalence of hrp2/3 gene deletions in certain areas threaten utility of histidine-rich protein 2 (HRP2)-based RDTs, and lingering HRP2 antigenemia can generate false-positive results after parasite clearance. This review summarizes current performance of malaria RDTs, threats to their validity, and recent innovations to improve their performance and continued role in malaria diagnosis. RECENT FINDINGS: Most World Health Organization (WHO) prequalified RDTs perform well for clinical diagnosis, with only occasional exceptions, including a recently reported issue affecting several countries. RDT sensitivity is generally related to malaria transmission intensity, with higher proportions of false-negative results in lower-transmission areas. Newly prequalified lactate dehydrogenase (pLDH)-based RDTs perform well for both Plasmodium falciparum in areas with >5% hrp2/3 gene deletions&#xa0;and for Plasmodium vivax diagnosis. Several point-of-care alternatives to RDTs, including micro-fluidic devices, hemozoin-detecting devices, and automated hematology analyzers, have shown promising results in small studies, but require larger-scale trials before widespread use. SUMMARY: RDTs remain a critical tool in clinical diagnosis of malaria, and newer pLDH-based tests perform well in areas where hrp2/3 gene deletions threaten validity of HRP2-based RDTs.

Humans

Access Block and Ambulance Ramping: The Canaries of the Healthcare System.

OBJECTIVE: To identify evidence-based factors leading to the global challenge of hospital access block and inform strategies to improve emergency access performance. METHODS: A mixed methods approach was followed comprising an umbrella review of published systematic reviews, qualitative analysis of the perspectives of patients and healthcare workers, and quantitative analysis of contextual factors and 6&#x2009;years of ambulance, emergency inpatient and ward movement records for the 25 largest public hospitals in Queensland, Australia. RESULTS: A key set of findings and recommendations were identified to improve emergency access that are practical and actionable. These comprise the introduction of inpatient discharge metrics and monitoring to shift focus from the front door of hospitals to the 'back door'; increasing support for primary care, community care, aged care, NDIS and vulnerable groups; maintaining demand-side strategies such as increasing inpatient-equivalent care alternatives (e.g., hospital in the home, acute care within nursing home services); investment in prehospital flow; improving hospital processes such as extended-hour discharge lounges; improving workforce; and revising funding policies. CONCLUSIONS: The study findings fill a gap in the evidence regarding challenges and recommendations for improving patient flow within hospital emergency departments and across the broader health system. Focussing efforts at the 'back end' of the inpatient journey is a critical step to improve emergency care outcomes.

Humans

Inducible flocculation in Komagataella phaffii enables enhanced biomass separation for biopharmaceutical production.

Biomass separation represents a critical bottleneck in Komagataella phaffii-based biopharmaceutical processes, as typically high cell densities of 40 - 50&#x202f;% create significant operational, technical and economic challenges for harvest operations. Yeast cell aggregation (flocculation) provides a solution to accelerate cell sedimentation by increasing particle size, thus allowing to improve biomass-supernatant separation efficiency during both natural gravity settling and (continuous) centrifugation operations. This study demonstrates successful engineering of K. phaffii strains with an inducible flocculation phenotype using CRISPR/Cas9-based genome editing to integrate the Saccharomyces cerevisiae FLO1 (ScFLO1) gene under control of various regulatory elements, including methanol-inducible and derepressible promoters. Flocculation strength could be enhanced by implementing transcriptional positive feedback circuits based on the methanol-inducible AOX1 promoter. To address methanol-free production requirements, we developed alternative systems to retrofit PAOX1-based ScFLO1 expression and exploited the derepressible PDF promoter, offering broader compatibility with biopharmaceutical manufacturing facilities. Flocculating cells cultivated in a bioreactor demonstrated significantly improved sedimentation behavior, with considerably lower supernatant turbidity after short low-speed centrifugation or gravity sedimentation compared to non-flocculating controls. Crucially, cell flocculation had no negative impact on product amount and quality when expressing a multivalent NANOBODY&#xae; VHH molecule with pharmaceutical relevance. Thus, this work establishes the first genetically engineered flocculation system in K. phaffii compatible with recombinant protein production, providing the basis for an innovative approach to streamline harvest operations in biopharmaceutical processes.

Flocculation