7-day Period Research Articles

CVN424, a GPR6 inverse agonist, for Parkinson's disease and motor fluctuations: a double-blind, randomized, phase 2 trial

CVN424 is a GPR6 inverse agonist that provides selective pharmacological control of the indirect striatopallidal pathway. We assessed the safety and efficacy of CVN424 as an adjunctive treatment to levodopa for reducing OFF-time in individuals with Parkinson's disease (PD) experiencing motor-fluctuations. This was a randomised, double-blind, placebo-controlled study conducted at 21 sites across the United States to evaluate two doses of CVN424 (NCT04191577). Patients with PD (Hoehn and Yahr stages 2-4) who were on a stable dose of levodopa and experiencing ≥2h of daily OFF-time were randomised (1:1:1) to receive either once-daily CVN424 (50mg or 150mg) or placebo for a 28-day treatment period. The primary endpoints were safety and tolerability. The key secondary endpoint was the change from baseline to Day 27 in OFF-time. The study was conducted from December 23, 2019, to October 14, 2021. Out of 198 participants screened, 141 eligible participants were randomised to one of the three treatment groups (n=47 per group), and 127 participants completed the 28-day treatment period. The most common treatment emergent adverse events (TEAEs) were headache (2% with CVN424 50mg, 9% with CVN424 150mg, and 2% with placebo) and nausea (4% with CVN424 50mg, 6% with CVN424 150mg and 2% with placebo). No serious treatment-related adverse events were reported. On Day 27, the mean±standard deviation (SD) change from baseline in daily OFF-time was-1.3±3.0h in the CVN424 50mg group,-1.6±2.5h in the CVN424 150mg group, and-0.5±2.9h in the placebo group. The placebo-adjusted LS mean±standard error (SE) treatment difference was significant for the CVN424 150mg dose (1.3±0.56h, [95 CI%-2.41 to-0.19], nominal p=0.02). Treatment with CVN424 was safe and well-tolerated. Despite the short study duration and small sample size, the 150mg CVN424 dose provided a clinically meaningful reduction in daily OFF-time. This study supports the development of CVN424 for the treatment of PD. Cerevance.

Double-walled encapsulation of curcumin in starch and cellulose, its characterization and application as a sensing material to monitor food quality

The curcumin was encapsulated within a double-layered complex shell of nano-sized cellulose as the primary layer and the native starch (MDC) or the nano-sized starch (NDC) as the secondary layer to improve its stability, decreasing its release rate, while masking bitterness. The double-walled curcumin capsules were studied for encapsulation efficiency, colour behaviour at different pH and characterization using FTIR, DSC & FESEM. The encapsulation efficiency for NDC and MDC was 97.11 % & 90.46 %. The FTIR showed a shift of peaks to higher wavelength particularly at 1043 cm −1 and most of the curcumin peaks disappeared or had low intensity as enclosed within the layers of the capsules. Further, fish fillets were coated in starch paste containing 20 % double-walled curcumin capsules and the visible colour change was observed during a 7-day storage period at refrigerated conditions that could confirm the spoilage of fish to consumers without opening the package.

Career Advancement Insights from Certified Pharmacy Technicians: Enhanced Opportunities for the Pharmacy Technician Workforce

Sustainable career advancement opportunities for pharmacy technicians will be a critical part of patient-centered community pharmacy environments as the role of the pharmacist provider expands. (1) To determine the impact of a Pharmacy Technician Certification Board pharmacy (PTCB) certification on career advancement and professional growth metrics; (2) To assess technicians' role in advanced pharmacy services before and after certification; and (3) To identify changes in pharmacist services when a certified pharmacy technician (CPhT) was added to the provider team. A 73-question web-based survey was distributed to all PTCB certified pharmacy technicians (CPhT) in the United States, Washing D.C., Puerto Rico, Guam, and the US Virgin Islands. The survey was distributed by PTCB in April 2021 with a 28-day collection period. The survey included multiple choice, rating scale, and free text questions centered on five domains: Practice experience, Career aspirations, Compensation, Pharmacy practice motivations, and Impact of COVID-19 pandemic. 23,007 CPhTs completed the survey. Respondents were primarily female (85.5%), age 30-39 (32.8%), and ≥ 10 years CPhT experience (42.8%). The majority of respondents cited improvement of patient health (77.4%), career advancement opportunities (53.5%), the ability to expand their role during emergencies (e.g., COVID-19) (52.6%), and future career advancement opportunities (51.7%) as benefits of CPhT certification. Increases in job responsibility after certification included changes occurring in roles related to clinical pharmacy services, patient education, preventive health services, provider communication, and staff training. Respondents agreed that PTCB-certification allowed for the expansion of pharmacists' services where they practiced, including clinical services (18.5%), patient education (18.3%), and preventive health services (18.1%). CPhT's value certification for its benefits on career advancement, personal growth, and salary enhancement. Affirmation of skill and training through certification is also recognized to positively influence patient care and the pharmacy's ability to provide advanced patient care and services.

Synergising tradition and innovation: Fortification of milk kefir with date syrup, a novel functional beverage

AbstractMilk kefir is gaining popularity due to its high probiotic content. This study focuses on fortifying milk kefir with date syrup to enhance its sensory attributes, with the goal of encouraging consumption among the younger generation. Date syrup was added to milk kefir in specific proportions (2, 4, 6, 8, and 10% per 100 mL of milk). The selection of the most suitable percentage (10%, 74 °Bx) was determined based on sensory preferences indicated by the panellists. The newly developed fermented beverage underwent physicochemical and biochemical analyses over a 14-day fermentation period. Results revealed that the addition of date syrup led to a significant (P ≤ 0.001) decrease in pH and total soluble solids (TSS) content, accompanied by a noteworthy increase in total phenolic, flavonoids, condensed tannins contents and antioxidant activity (almost 2-fold). Liquid chromatography - heated electrospray ionisation - mass spectrometry (LC-HESI-MS/MS) results identified the presence of a newly formed and important antifungal compound, p-hydroxyphenyllactic acid (HPLA), showing a progressive increase in quantity during the fermentation process (13.8-fold on the 14th day of fermentation). Hence, the outcomes of this study offer compelling evidence that a novel category of functional beverage can be developed by employing milk kefir as an appropriate starter with the incorporation of date syrup.

Effect of single parenteral administration of marbofloxacin on bacterial load and selection of resistant Enterobacteriaceae in the fecal microbiota of healthy pigs

BackgroundAntimicrobial resistance (AMR) is a global concern impacting both humans, animals and their environment. The use of oral antimicrobials in livestock, particularly in pigs, has been identified as a driver in the selection of AMR bacteria. The aim of the present study was to evaluate the effects of a single intramuscular (IM) dose of marbofloxacin (8 mg/kg) on Enterobacteriaceae and E. coli populations, as well as on fluoroquinolone resistance within the fecal microbiota of pigs. Twenty healthy pigs, 60-days old, were divided into two groups: a treated group (n = 13) and a control group (n = 7) and were monitored over a 28-day experimental period. Fecal samples were collected from all animals for the isolation of E. coli and Salmonella strains. The minimum inhibitory concentration (MIC) of marbofloxacin for the isolates recovered on MacConkey agar supplemented with 1 or 4 µg/mL of marbofloxacin and for some generic E. coli isolates (recovered from MacConkey agar not supplemented with marbofloxacin) was determined using the broth microdilution method. Genomic DNA was extracted from the confirmed bacterial strains and sequenced using the Sanger method to identify mutations in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes.ResultsThe single IM administration of marbofloxacin resulted in a significant decrease in Enterobacteriaceae and E. coli fecal populations from days 1 to 3 post- treatment. No Salmonella isolates were detected in either group, and no marbofloxacin-resistant E. coli isolates were identified. The MIC of the selected generic E. coli strains (n = 100) showed an increase to up to 0.5 µg/mL between days 1 and 3 post-treatment but remained below the clinical breakpoint of marbofloxacin resistance (4 µg/mL). Sequencing of these isolates revealed no mutations in gyrA and parC genes.ConclusionsThe present study showed that this dosing regimen of marbofloxacin significantly decreases the fecal shedding of Enterobacteriaceae and E. coli populations in pigs, while limiting the selection of marbofloxacin-resistant E. coli isolates. These findings warrant validation in sick pigs to support the selective use of this antibiotic solely in cases of clinical disease, thereby minimizing the reliance on conventional (metaphylactic) group treatments in pigs.

Evaluation of Toxicity of Feed Additive for Highly Productive Animals

The study of new feed additives requires toxicological research to assess their safety for further use. This research presents the results of an acute toxicity study of the feed additive "Bodrivin," developed for highly productive animals of dairy, meat-dairy, and meat breeds. The aim is to prevent stress of various etiologies, enhance the nutritional value of the diet, especially during periods of energy deficiency, and consequently improve productivity and profitability in production. Non-linear laboratory rats were used for the experiment. The first experimental group received a single oral dose of the feed additive via syringe and atraumatic needle with a bulbous end at a dosage of 2000 mg/kg. After obtaining the results of the experiment over a 14-day period, a similar experiment was conducted on the second experimental group. At the conclusion of the experiment, no signs indicating toxic effects of the studied feed additive were observed in the animals, and the body weight of the experimental animals remained unchanged in both the first and second series of the experiment. The acute toxicity study of the feed additive "Bodrivin" indicated that the evaluated feed additive belongs to Class V of danger according to GOST 32644-2014.

Zinc oxide nanoparticles at low dose mitigate lead toxicity in pea (Pisum sativum L.) seeds during germination by modulating metabolic and cellular defense systems

Addressing lead (Pb) pollution and contamination in soil and agriculture is urgent due to its widespread and long-lasting impacts on human health, food safety, and the environment. In the current study, we assessed the potential use of Zinc oxide nanoparticles (ZnONPs) in alleviating Pb toxicity in germinating seedlings. Pea (Pisum sativum L.) seedlings were exposed to Pb (83 mg/L) over a 7-day period, without and with ZnONPs amendment. Our results showed that the application of ZnONPs at 10 mg/L restored the morphological parameters affected by Pb, 34 %, 26 % and 23 %, for the length, fresh, and dry biomass of embryonic axis, respectively. ZnONPs decreased the activities of antioxidative enzymes of catalase (87.5 %), guaiacol peroxidase (60 %), and glutathione peroxidase (25 %), but increased the activities of ascorbate peroxidase (60 %) and glutathione reductase (25 %). These changes were associated with the increase (7 %) in the thiol groups, and reductions in the malondialdehyde (23 %), hydrogen peroxide (33 %), and carbonyl group levels (78 %), in addition to the stimulation of the activities of ROS-associated enzymes, including glycolate oxidase (40 %) and NADPH oxidase (by 89 %). Consequently, cell viability was increased by 66 %, while cellular death was reduced by 10 %, with ZnONPs, relative to the Pb-stressed seedlings. These findings highlight the mechanisms surrounding the ability of nanosized ZnO to mitigate the harmful effects of Pb on the growth and physiology of plants. Further investigation is needed to understand the mitigating effects of ZnONPs on Pb on the molecular and genomic levels in seedlings and plants, and ensure the sustainability of agricultural practices and food safety. Besides, site and source-specific integrated approaches must be practiced to formulate suitable remediation strategies.

A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Immunological and Safety Parameters in Healthy Adults.

Recombinant human lactoferrin (rhLF) is of commercial interest for immune support as a food ingredient. The objective was to evaluate the immunogenicity/alloimmunization potential of Helaina rhLF (effera™) from K. phaffii over a 28-day period compared to bovine LF (bLF). Study 1 was a randomized, double-blind, parallel arm, controlled trial where 66 healthy adults were randomly allocated to 1 of 3 groups: high-dose rhLF (3.4g/d), low-dose rhLF (0.34g/d), or bLF (3.4g/d). Participants completed a 28-day supplementation period with follow-up visits on Days 28, 56, and 84. Study 2 was a 12-week observational study with no intervention that enrolled 24 healthy adults. In both studies, serum was obtained for analysis of anti-LF antibody levels as the primary endpoint. In Study 1, change from baseline to Day 56 in serum anti-bLF antibodies in the bLF group (least squares geometric mean and 95% confidence interval for the post/pre ratio: 3.01; 2.08, 4.35) was greater than the changes in serum anti-hLF antibodies in the low-dose rhLF (1.07; 0.77, 1.49; P < 0.001) and high-dose rhLF (1.02; 0.62, 1.70; P < 0.001) groups. The rhLF groups had similar changes to the observational study, indicating no change in anti-hLF antibodies and no evidence of alloimmunization following ingestion. Changes in safety outcomes were similar between groups and within normal ranges. These results show that under the conditions of the protocol, no increased anti-hLF antibodies or adverse events were identified following ingestion of effera™ as a food ingredient at an intake level up to 3.4g/d in healthy adults (clinicaltrials.gov: NCT06012669).

Varying levels of natural light intensity affect the phyto-biochemical compounds, antioxidant indices and genes involved in the monoterpene biosynthetic pathway of Origanum majorana L.

BackgroundLight is a critical environmental factor in plants, encompassing two vital aspects: intensity and quality. To assess the influence of different light intensities on Origanum majorana L., pots containing the herb were subjected to four levels of light intensity: 20, 50, 70, and 100% natural light. After a 60-day treatment period, the plants were evaluated for metabolite production, including total sugar content, protein, dry weight, antioxidant indices, expression of monoterpenes biosynthesis genes, and essential oil compounds. The experimental design followed a randomized complete blocks format, and statistical analysis of variance was conducted.ResultsThe results indicated a correlation between increased light intensity and elevated total sugar and protein content, which contributed to improved plant dry weight. The highest levels of hydrogen peroxide and malondialdehyde (MDA) were observed under 100% light intensity. Catalase and superoxide dismutase enzymes exhibited increased activity, with a 4.23-fold and 2.14-fold increase, respectively, under full light. In contrast, peroxidase and polyphenol oxidase enzyme activities decreased by 3.29-fold and 3.24-fold, respectively. As light intensity increases, the expression level of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) gene increases. However, beyond a light intensity of 70%, the DXR gene expression level decreased. Furthermore, the expression levels of the cytochrome P450 genes CYP71D178 and CYP71D179 exhibited an increasing trend in response to elevated light intensity. Essential oil content increased from 0.02 to 0.5% until reaching 70% light intensity. However, with further increases in light intensity, the essential oil content decreased by 54 to 0.23%.ConclusionsThese findings emphasize the importance of balancing plant growth promotion and stress management under different light conditions. The research suggests that sweet marjoram plants thrive best in unshaded open spaces, resulting in maximum biomass. However, essential oil production decreases under the same conditions. For farmers in areas with an average light intensity of approximately 1700 µmol m−2s−1, it is recommended to cultivate sweet marjoram in shade-free fields to optimize biomass and essential oil production. Towards the end of the growth cycle, it is advisable to use shades that allow 70% of light to pass through. The specific duration of shade implementation can be further explored in future research.

Supplementation of Chlorella vulgaris Extracts During Brewing: The Effects on Fermentation Properties, Phytochemical Activity and the Abundance of Volatile Organic Compounds

Chlorella vulgaris, a microalga rich in secondary metabolites and nutrients, offers a promising alternative for promoting microbial growth in food fermentation processes. This study aimed to evaluate the effects of C. vulgaris extracts on fermentation kinetics, sensory characteristics, phytochemical composition, antioxidant activity, and the abundance of volatile organic compounds (VOCs) in treated versus control beers. The bioactive compounds from C. vulgaris were extracted using an ultrasound-assisted method with water as the solvent. A German Pilsner-style lager beer (GPB) was brewed and supplemented with 0.5, 1, and 5 g/L of C. vulgaris extracts prior to primary fermentation. Yeast viability, °Brix, and pH levels were monitored to assess fermentation progress. Phytochemical composition was analyzed by quantifying total polyphenols and flavonoids. The antioxidant activity of the beer was evaluated using both the 2,2-diphenyl-1-picrylhydrazyl (DPPH●) and hydrogen peroxide assays. The addition of C. vulgaris extracts resulted in increased yeast viability and slight variations in gravity during the 7-day fermentation period. Moreover, the beers supplemented with C. vulgaris extracts demonstrated higher levels of total polyphenols, flavonoids, and antioxidant activity compared to the GPB. Specific volatile organic compounds, including 2-methyl-1-propanol, 1-hexanol, isopentyl hexanoate, 2-methylpropyl octanoate, β-myrcene, and geranyl acetate, were significantly more abundant (p &lt; 0.05) in the treated beers than in the control. Sensory evaluations revealed a favorable impact of the treatment on aroma scores compared to the GPB. Overall, the findings indicate that C. vulgaris extracts could be a valuable ingredient for developing functional beers with enhanced health benefits, particularly regarding antioxidant activity. Additionally, the results underscore the importance of exploring innovative approaches that utilize natural sources like Chlorella to enrich the nutritional profile and sensory qualities of fermented products.

Neurotrophic extracellular matrix proteins promote neuronal and iPSC astrocyte progenitor cell- and nano-scale process extension for neural repair applications.

The extracellular matrix plays a critical role in modulating cell behaviour in the developing and adult central nervous system influencing neural cell morphology, function and growth. Neurons and astrocytes, play vital roles in neural signalling and support respectively and respond to cues from the surrounding matrix environment. However, a better understanding of the impact of specific individual extracellular matrix proteins on both neurons and astrocytes is critical for advancing the development of matrix-based scaffolds for neural repair applications. This study aimed to provide an in-depth analysis of how different commonly used extracellular matrix proteins- laminin-1, Fn, collagen IV, and collagen I-affect the morphology and growth of trophic induced pluripotent stem cell (iPSC)-derived astrocyte progenitors and mouse motor neuron-like cells. Following a 7-day culture period, morphological assessments revealed that laminin-1, fibronectin, and collagen-IV, but not collagen I, promoted increased process extension and a stellate morphology in astrocytes, with collagen-IV yielding the greatest increases. Subsequent analysis of neurons grown on the different extracellular matrix proteins revealed a similar pattern with laminin-1, fibronectin, and collagen-IV supporting robust neurite outgrowth. fibronectin promoted the greatest increase in neurite extension, while collagen-I did not enhance neurite growth compared to poly-L-lysine controls. Super-resolution microscopy highlighted extracellular matrix-specific nanoscale changes in cytoskeletal organization, with distinct patterns of actin filament distribution where the three basement membrane-associated proteins (laminin-1, fibronectin, and collagen-IV) promoted the extension of fine cellular processes. Overall, this study demonstrates the potent effect of laminin-1, fibronectin and collagen-IV to promote both iPSC-derived astrocyte progenitor and neuronal growth, yielding detailed insights into the effect of extracellular matrix proteins on neural cell morphology at both the whole cell and nanoscale levels. The ability of laminin-1, collagen-IV and fibronectin to elicit strong growth-promoting effects highlight their suitability as optimal extracellular matrix proteins to incorporate into neurotrophic biomaterial scaffolds for the delivery of cell cargoes for neural repair.

Long-term administration of atorvastatin had no effect on the occurrence and progression of spontaneous hypertensive intracerebral hemorrhage in mice

Abstract Background Intracerebral hemorrhage (ICH) is a catastrophic disease with limited treatment options. Statins and low low-density lipoprotein cholesterol (LDL-C) levels have been reported to be associated with increased risk of ICH. Safety concerns of statins were raised as statins become the cornerstone of anti-atherosclerosis therapy. To date, the effect of statins on the incidence of ICH still remains a controversial topic. Purpose The aim of this study was to investigate the effect of atorvastatin on the occurrence and progression of hypertensive ICH in mice. Methods Male wild-type C57BL/6J mice, 13 months old, were randomly divided into atorvastatin (Ato, n=20) group and vehicle (Veh, n=20) group. The atorvastatin group and vehicle group were given atorvastatin (20 mg/kg) and same volume of 0.5% sodium carboxymethylcellulose by oral gavage for 8 weeks, separately. Angiotensin II (Ang II) and L-NAME were then used to induce hypertensive ICH. The time of stroke symptom onset was documented. Hemorrhage volumes were measured by spectrophotometric hemoglobin assay. Results After 8 weeks of atorvastatin or vehicle administration, serum LDL-C levels were significantly lower in the mice treated with atorvastatin than vehicle controls (0.705 vs. 1.008 mmol/L, P&amp;lt;0.001). The administration of atorvastatin did not show significant effects on the systolic blood pressure (SBP) levels when compared with the vehicle group (164 vs. 166 mmHg, P=0.497) after the induction of Ang II and L-NAME. Hemorrhage was observed in brain morphology, and was further verified by hematoxylin and eosin staining or MRI scans in mice that showed signs of stroke. During the 28-day experimental period, 75% (15/20) of mice in the atorvastatin group developed signs of ICH, and 70% (14/20) of mice in the vehicle group developed in the similar time window. The incidence of hypertensive ICH had no significant difference between atorvastatin and vehicle groups (Log-rank P=0.761). Hemorrhage volumes were also comparable between the two groups (1.462 vs. 1.392 uL, P=0.788). Conclusion Reducing serum LDL-C levels by long-term administration of atorvastatin had no effect on the occurrence and progression of spontaneous hypertensive ICH in middle-aged mice.

Dynamic QTc interval changes observed in real-world patients with implanted insertable cardiac monitors taking class III antiarrhythmic drugs

Abstract Background QT prolongation can lead to sustained ventricular arrhythmias . Class III Antiarrhythmic drugs (AAD) are known to cause QT prolongation. Insertable cardiac monitors (ICM) have the capability to continuously monitor and detect dynamic changes in QT. Purpose To investigate the characteristics of QTc interval changes before and after antiarrhythmic drug loading in real-world ICM patients administered with Sotalol, Amiodarone, and Dofetilide in hospital. Methods The QT detection algorithm detects the T-waves and determines the QTc intervals for every beat, thus providing continuous long-term QTc trends from ICM ECG. Real-world patients from de-identified Electronic Health Record (EHR) database linked with ICM device data warehouse with implanted ICM being administered sotalol, amiodarone or dofetilide AAD for the first time in the hospital were analyzed. The patients were broken down into groups based on the AAD taken. Patients not taking AAD were selected as control. QTc intervals 7-days pre and post administered AAD are reported, and a random 14-day period was used for control patients. The paired difference in median QTc 7 days pre and post administered AAD were analyzed using the Wilcoxon signed rank test. The Wilcoxon rank-sum test was used to analyze QTc between the different groups. Results A total of 487 patients with ICM were included in this analysis: 56 sotalol patients (avg. age: 67±10 years, 50% male), 100 amiodarone patients (avg. age: 72±10 years, 50% male), 52 dofetilide patients (avg. age: 66±12 years, 50% male), and 248 control patients (avg. age: 70±13 years, 50% male). Sotalol, amiodarone, and dofetilide patients showed significant increase in QTc 1-7 days post AAD compared to 1-7 days pre AAD (figure 1). For sotalol (post AAD median[IQR] = 426.5[408.8,446.6] msec, pre AAD median[IQR] = 415.9[391,437.3] msec, p=0.004); Dofetilide (post median[IQR] = 432.4[413,458.7] msec; pre median[IQR] = 409.3[397.5,435.2] msec, p&amp;lt;0.001); Amiodarone (post median[IQR] = 426.3[400.9,449] msec, pre median[IQR] = 415.5[397.5,435.2] msec, p = 0.037). The QTc 1-7 days pre AAD compared to 1-7 days post AAD for control patients was insignificant p&amp;gt;0.05. The median change in QTc 1-7 days post AAD from 1-7 days pre AAD was 13.0, 7.5, 21.25 and -1.0 msec for sotalol, amiodarone, dofetilide, and control patients respectively (figure 2). Dofetilide patients had a significantly higher change in QTc compared to the amiodarone patients, p=0.018. QTc for all three AAD groups when compared to control group post AAD were significantly higher, p&amp;lt;0.001. QTc was also higher pre AAD compared to control, p=0.003, p&amp;lt;0.001, p=0.009 for sotalol, amiodarone, and dofetilide respectively. Conclusions There is a significant increase in QTc detected by ICM in patients receiving index drug loading of Sotalol, amiodarone and dofetilide. QTc monitoring via ICM can detect these dynamic changes in QTc allowing for early intervention.Figure 1Figure 2

Impact of Biofilms on Surface Properties of Polymethyl Methacrylate (PMMA) Resins.

Poly(methyl methacrylate) (PMMA) resins are widely used in medical and dental applications. Their susceptibility to bacterial biofilm formation poses significant challenges related to material degradation and infection risk. This study investigated the effects of Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) biofilms on PMMA resin surface properties over a 45-day period at 35°C. The study examined various parameters including biofilm adhesion, morphology, surface roughness, hydrophobicity, solid fraction, and zeta potential. PMMA resin specimens were inoculated with bacteria and incubated for 45 days. Biofilm adhesion was visually assessed, while surface characterization was conducted using scanning electron microscopy (SEM), atomic force microscopy (AFM), roughness analysis, contact angle measurements, solid fraction determination, and zeta potential analysis. The P. aeruginosa and S. aureus isolates were selected based on their biofilm-positive characteristics, which were further confirmed using Congo red and biofilm formation assays through crystal violet staining and spectrophotometric analysis. The results demonstrated robust biofilm adhesion on PMMA surfaces. SEM and AFM imaging revealed textured surfaces with elevated structures and depressions within the biofilm matrix. Biofilm-exposed resins exhibited significantly increased roughness (Ra = 164.5 nm, Rq = 169.5 nm) and hydrophobicity (mean angle = 85.5°-90.5°) compared to control samples (Ra = 38-50 nm, angle = 55°). Solid fraction measurements indicated a denser biofilm matrix on exposed resins (0.908) compared to controls (0.65). Additionally, zeta potential values were more negative for biofilm-exposed resins (mean = -84.2 mV) than controls (-45.0 mV). These findings underscore the substantial alterations in PMMA resin surface properties induced by bacterial biofilms, emphasizing the critical need for strategies to prevent biofilm formation and mitigate associated risks in healthcare settings. Future research should focus on developing anti-biofilm coatings or treatments to preserve the integrity and functionality of PMMA materials.

Physicochemical Stability of Nab-Paclitaxel (Pazenir) Infusion Dispersions in Original Glass Vials and EVA Infusion Bags

Background/Objectives: The study objective was to determine the physicochemical stability of nab-paclitaxel (Pazenir) ready-to-use (RTU) dispersion for infusion in original glass vials and ready-to-administer (RTA) infusion dispersion in EVA infusion bags. Methods: Triplicate test dispersions were prepared and stored light protected for a maximum of 28 days either in the original glass vials (RTU) at 2–8 °C or in EVA infusion bags (RTA) at 2–8 °C and at 25 °C. Directly after reconstitution and on days 1, 3, 5, 7, 14, 21, and 28 samples were withdrawn and paclitaxel concentrations assayed by a stability-indicating HPLC method. In parallel, pH and osmolality were measured. In a second series, test dispersions were stored over a 14-day period and inspected daily for visible particles and colour changes. Samples were taken daily for particle size analysis. Integrity and particle size distribution of the nanoparticles were determined by dynamic light scattering (DLS) and albumin monomers, dimers, oligomers, or polymers by size-exclusion-chromatography (SEC). Results: Non-redispersible particles were observed in test dispersions on day 5 (RTA 25 °C), day 7 (RTA 2–8 °C), and day 11 (RTU 2–8 °C). DLS analysis revealed out-of-specification results for the polydispersity index from day 7 (RTA 25 °C) and day 12 (RTU, RTA refrigerated). Paclitaxel concentrations remained &gt;95% of the initial concentrations for 7 days (RTU 2–8 °C, RTA 25 °C) and for 14 days (RTA 2–8 °C). All test dispersions met the specifications regarding the oligomeric status of albumin, pH, and osmolality over the investigation periods. Conclusions: Stability of nab-paclitaxel dispersions is limited by the release of water-insoluble paclitaxel from the nanoparticles and subsequent crystallisation and by formation of insoluble albumin aggregates. Based on our overall results, shelf life of refrigerated RTU and RTA nab-paclitaxel dispersions is limited to 7 days. Shelf life of RTA nab-paclitaxel dispersions stored at room temperature is limited to 4 days. Careful visual inspection of nab-paclitaxel dispersions after reconstitution and prior to administration is highly recommended to detect non-redispersible particles.

Opioid receptor and dopaminergic gene expression increase in the brains of dominant medaka Oryzias latipes males after repeated fights.

The central opioid system and dopaminergic activity in mammals play key roles in mediating social reward, impulsivity, cognition, decision making, and motivation for learning and social interactions. Repeated positive fighting experiences enhance the gene expression levels of μ-type opioid receptor (Mor), tyrosine hydroxylase (Th), an enzyme involved in dopamine synthesis, and dopamine receptor type 2 (D2r) in the reward-related brain regions of aggressive mice. However, it remains unclear whether the opioid system and dopaminergic activity are associated with repeated winning in fish. In this study, we investigated changes in the expression levels of Mor, Th1, and D2r in different regions of the brain of adult medaka Oryzias latipes males after intermittent and continuous fight for 3 days. When a pair of males was provided a fighting opportunity for 20 min per day, we noted that within the 3-day observation period, aggressive winning males showed significantly higher expression levels of Mor in telencephalon and diencephalon, Th1 in diencephalon, and D2r in telencephalon than subordinate losing males. However, no such differences in gene expression level were observed between winning and losing males in the 3-day continuous fight. Further, no differences were detected in the total number of aggressive actions among the winners from each fighting test. However, the total number of "chase" actions, with a stronger aggressiveness index, was higher for the repeated winning male in the three-time intermittent fight than for the winner in the 3-day continuous fight. These findings suggest that repeated intermittent winning experiences with strong aggressiveness could be perceived as a reward by O. latipes males.

Lactation-related dynamics of bacterial and fungal microbiomes in feces of sows and gut colonization in suckling and newly weaned piglets.

Changes in the gut microbial composition of the sow during lactation may influence the gut microbial colonization in their offspring, for which less information was available in the literature. This study aimed to assess: 1) the changes that occur in the bacterial and fungal communities in sow feces during the 28-day lactation period as well as in gastric and cecal digesta of piglets until one week after weaning, and 2) bacterial and fungal taxa in cecal digesta of the piglets postweaning that associate with fecal consistency. Aside from sow milk, piglets had access to creep feed from day of life (DoL) 3. Fecal samples from sows for microbial analysis were collected (n=20) on days postpartum (DPP) 1, 6, 13, 20 and 27, as well as from weaned piglets for fecal scoring on DoL 30 and 34. Gastric and cecal digesta of piglets was collected on DoL3, 7, 14, 21, 28, 31 and 35 (n=5/sex/DoL). Progressing lactation affected bacterial and fungal communities in sow feces, including 10.3- and 3.0-fold increases in the relative abundances of Lactobacillus from DPP1 to 6 and Kazachstania from DPP1 to 13, respectively (P < 0.001). Although time- and gut site-related differences existed, bacterial and fungal taxa found in sow feces were also present in gastric and cecal digesta of piglets, which supports their role for gut colonization in neonatal piglets. In piglets, bacterial and fungal alpha-diversities showed certain fluctuations during the suckling period, whereby weaning affected more the fungal than bacterial diversity at both gut sites (P < 0.05). At both gut sites, Lactobacillus largely increased from DoL3 to 7 and remained a dominating taxon until DoL35 (P < 0.05). Postweaning, plant-glycan fermenters (e.g., Prevotella-9) seemed to replace milk-glycan fermenting Fusobacterium and Bacteroides (P < 0.05). In gastric and cecal digesta, Kazachstania, Tausonia, Candida and Blumeria were dominating fungi from DoL3 to 35, with Kazachstania becoming even more dominant postweaning (P < 0.001). Fecal consistency was softer on DoL34 than 30 (P < 0.05). Correlation analysis identified that softer feces were linked to the relative abundances of plant-glycan and proteolytic bacterial taxa including pathobionts (e.g., Clostridium sensu stricto) in the cecum on DoL34. However, the potential association between cecal mold and plant-pathogenic fungi Talaromyces, Mrakia, and Blumeria and softer feces are worth to investigate in the future in relation to (gut) health of piglets.

Effects of meteorological factors on tuberculosis and potential modifiers in Zhejiang Province, China

Although some studies have explored the role of meteorological factors in the development of tuberculosis (TB), the majority have been confined to single regions, leading to inconsistent findings. Consequently, we conducted a multi-city study not only to determine whether meteorological factors significantly influence the risk of developing TB but also to assess the magnitude of these effects and explore potential modifying factors. Data on daily reported TB cases and meteorological factors were collected from January 1, 2013, to December 31, 2022, across 11 cities in Zhejiang Province. A distributed lag non-linear model using a quasi-Poisson distribution was employed. Multivariate meta-regression was used to obtain overall pooled estimates and assess heterogeneity. From 2013 to 2022, 267,932 TB cases were reported in Zhejiang Province. Notably, a nonlinear relationship was observed between temperature and TB, with the relative risk (RR) peaking at 1.0 °C (RR = 1.882, 95% CI 1.173–3.020). The effect of low temperature was immediate and significant for a 13-day lag period, with the maximum effect at lag0 (RR = 1.014, 95% CI 1.008–1.021). The exposure-response curve between relative humidity (RH) and TB exhibited an M-shape, with the RR peaking at 47.7% (RR = 1.642, 95% CI 1.044–2.582). The lag effect of low RH was significant at lag 25–59, with the highest RR observed at lag 32 (RR = 1.011, 95% CI 1.001–1.022). Gross domestic product (GDP) per person, population density, and latitude demonstrated significant modification effects. Our study showed that low temperature and RH were associated with an increased risk of TB. Additionally, GDP per person, population density, and latitude may play important roles in explaining the association between RH and TB. These findings provide scientific evidence for the development of geographically specific public health policies.

Traumatic Optic Neuropathy Treatment Trial 2 (TONTT-2): evaluating the efficacy of different doses of erythropoietin – a multicentre, randomised, double-blind clinical trial

AimThe aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON).MethodsThis study is a multicentre, randomised,...

Promising Anti-Inflammatory Properties of Ursolic Acid Isolated from Atylosia goensis.

Indigenous plants are plant species that are native to a specific region and have evolved naturally and adapted to local environmental conditions over a long period. This study aimed to explore the anti-arthritic effects of Atylosia goensis, an indigenous plant species in the Western Ghats of India. An ethanolic extract of Atylosia goensis was obtained using the Soxhlet extraction method, which revealed a diverse array of phytochemicals through liquid chromatography-mass spectroscopy (LC-MS). Key compounds, including fatty acids, sterols, and potential health-beneficial compounds, were identified, and one prominent phytoconstituent, ursolic acid, was spectroscopically characterized using 1H NMR, 13C NMR, and mass spectrometry. The research also examined the anti-inflammatory activity and in-vitro and in-vivo anti-arthritic activity of ethanolic extract. The ethanol extract exhibited notable inhibition of Cox-2, indicating potential anti-inflammatory effects. The in vivo anti-arthritic activity of ursolic acid was evaluated at different doses (200 and 400 mg/kg) over a 24-day period. Ursolic acid significantly reduced joint edema, particularly at higher doses, thereby emphasizing its anti-inflammatory properties. Biomarker analysis revealed dose-dependent attenuation of disease-associated biomarker levels, supporting the potential therapeutic efficacy of ursolic acid in arthritis management. Moreover, the hepatoprotective potential of ursolic acid was evident in biochemical parameters, including SGPT, SGOT, and ALP levels. Both doses of ursolic acid effectively mitigated liver dysfunction induced in the disease control group, demonstrating its protective role in liver health. Histopathological assessments corroborated these findings, indicating a reduction in inflammatory areas following ursolic acid treatment, especially at higher doses. This experimental work provides valuable information on the therapeutic potential of Atylosia goensis and ursolic acid, emphasizing their roles in anti-inflammatory and hepatoprotective applications. This study contributes to the understanding of plant-derived compounds for potential pharmaceutical use in the management of inflammatory and arthritic conditions.