Metabolomic profiles of ovariectomized mice and their associations with body composition and frailty-related parameters in postmenopausal women.

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

In Situ Photo-Crosslinkable Protein Bioadhesive for Bone Graft Fixation.

Bone grafting is a fundamental dental surgery procedure widely used for implant placement and periodontal disease management treatments. Despite its broad applications, vertical bone augmentation presents unique challenges, including the risk of graft displacement due to gravitational and masticatory forces. Traditional physical stabilization methods introduce additional complexities and risks, underscoring the need for innovative fixation technologies. This study aimed to develop an in situ photo-crosslinkable bioadhesive hydrogel (iPBAH) as a multifunctional bone graft binder to enhance the process of bone reconstruction. The bioadhesive is composed of mussel-derived adhesive protein (MAP) fused with the cell-adhesive peptide RGD. The numerous tyrosine residues in MAP facilitate rapid photo-crosslinking, enabling efficient hydrogel formation using visible blue light. Subsequently, iPBAH underwent comprehensive characterization to evaluate its suitability as a multifunctional bone graft binder. iPBAH efficiently underwent in situ crosslinking through harmless exposure to visible light within minutes and displayed several exceptional properties, including a microporous structure, underwater adhesion, extended durability, high compressive strength, and biocompatibility. In vivo assessments, using male Sprague-Dawley rats, demonstrated that iPBAH binder significantly enhanced bone regeneration in a rat calvarial bone defect model. The in situ crosslinking of the iPBAH binder during bone graft transplantation can effectively fill irregular and complex defect shapes while simultaneously preventing graft material leakage. The improved physical attributes of the bound graft material can enhance its resistance to external forces, thereby ensuring sustained retention over time. Moreover, the interaction between iPBAH and surrounding tissues promotes adhesion and integration of the graft material with host tissues in the defect area. In addition, the included RGD peptide in iPBAH can augment inherent cell recruitment, adhesion, and growth, consequently expediting osteogenesis.

Hemorrhagic morbidity in nulliparous patients with placenta previa without placenta accrete spectrum disorders.

Background: Placental adhesion spectrum (PAS) is a disease in which the trophoblast invades the myometrium, and is a well-known high-risk condition associated with placental previa. Aim: The morbidity of nulliparous women with placenta previa without PAS disorders is unknown. Patients and Methods: The data from nulliparous women who underwent cesarean delivery were collected retrospectively. The women were dichotomized into malpresentation (MP) and placenta previa groups. The placenta previa group was categorized into previa (PS) and low-lying (LL) groups. When the placenta covers the internal cervical os, it is called placenta previa, when the placenta is near the cervical os, it is called the low-lying placenta. Their maternal hemorrhagic morbidity and neonatal outcomes were analyzed and adjusted using multivariate analysis based on univariate analysis. Results: A total of 1269 women were enrolled: 781 women in the MP group and 488 women in the PP-LL group. Regarding packed red blood cell transfusion, PP and LL had adjusted odds ratio (aOR) of 14.7 (95% confidence interval (CI): 6.6 - 32.5), and 11.3 (95% CI: 4.9 - 26) during admission, and 51.2 (95% CI: 22.1 - 122.7) and 10.3 (95% CI: 3.9 - 26.6) during operation, respectively. For intensive care unit admission, PS and LL had aOR of 15.9 (95% CI: 6.5 - 39.1) and 3.5 (95% CI: 1.1 - 10.9), respectively. No women had cesarean hysterectomy, major surgical complications, or maternal death. Conclusion: Despite placenta previa without PAS disorders, maternal hemorrhagic morbidity was significantly increased. Thus, our results highlight the need for resources for those women with evidence of placenta previa including a low-lying placenta, even if those women do not meet PAS disorder criteria. In addition, placenta previa without PAS disorder was not associated with critical maternal complications.

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial.

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.

Magnetocaloric effect and Griffiths phase analysis in a nanocrystalline Ho2NiMnO6 and Ho2CoMnO6 double perovskite.

Rare-earth double perovskite oxides have intriguing magnetocaloric properties at cryogenic temperatures. In this study, Ho2NiMnO6 and Ho2CoMnO6 were synthesized using the sol-gel method, which crystallized in a monoclinic structure in the P21/n space group. The magnetic phase transition was observed at 81.2 K for Ho2NiMnO6 and 73.5 K for Ho2CoMnO6. The presence of a paramagnetic matrix and short-range ferromagnetic clusters causes magnetic disorder in these double perovskites, resulting in Griffiths phase formation. The Arrott plot confirms that compounds undergo second-order phase transition. At an applied magnetic field of 5 T, the maximum magnetic entropy change (-ΔS) for the studied compounds is 1.7 and 2.2 J kg-1 K-1, respectively. The transition metals Ni and Co in a double perovskite cause lattice distortion in the structural parameters and oxidation states of manganese (Mn3+/Mn4+), which changes the magnetic and magnetocaloric properties. The quantitative approach provides a systematic study of magnetocaloric properties of the rare earth double perovskite compounds with ferromagnetic 3d transition elements.

Comparative efficacy evaluation of disinfectants against severe acute respiratory syndrome coronavirus-2.

BACKGROUND: Disinfection is one of the most effective ways to block the rapid transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the prolonged coronavirus disease 2019 (COVID-19) pandemic, disinfectants have become crucial to prevent person-to-person transmission and decontaminate hands, clothes, facilities and equipment. However, there is a lack of accurate information on the virucidal activity of commercial disinfectants. AIM: To evaluate the virucidal efficacy of 72 commercially available disinfectants constituting 16 types of ingredients against SARS-CoV-2. METHODS: SARS-CoV-2 was tested with various concentrations of disinfectants at indicated exposure time points as recommended by the manufacturers. The 50% tissue culture infectious dose assay was used to calculate virus titre, and trypan blue staining and CCK-8 were used to assess cell viability after 3-5 days of SARS-CoV-2 infection. FINDINGS: This study found that disinfectants based on 83% ethanol, 60% propanol/ethanol, 0.00108-0.0011% sodium dichloroisocyanurate and 0.497% potassium peroxymonosulfate inactivated SARS-CoV-2 effectively and safely. Although disinfectants based on 0.05-0.4% benzalkonium chloride (BAC), 0.02-0.07% quaternary ammonium compound (QAC; 1:1), 0.4% BAC/didecyldimethylammonium chloride (DDAC), 0.28% benzethonium chloride concentrate/2-propanol, 0.0205-0.14% DDAC/polyhexamethylene biguanide hydrochloride (PHMB) and 0.5% hydrogen peroxide inactivated SARS-CoV-2 effectively, they exhibited cytotoxicity. Conversely, disinfectants based on 0.04-4% QAC (2:3), 0.00625% BAC/DDAC/PHMB, and 0.0205-0.14% and 0.0173% peracetic acid showed approximately 50% virucidal efficacy with no cytotoxicity. Citric acid (0.4%) did not inactivate SARS-CoV-2. CONCLUSION: These results indicate that most commercially available disinfectants exert a disinfectant effect against SARS-CoV-2. However, re-evaluation of the effective concentration and exposure time of certain disinfectants is needed, especially citric acid and peracetic acid.

The effect of flash vacuum cooling on the flavor of ultrapasteurized milk.

Ultrapasteurization (UP) extends the shelf life of milk. Direct steam injection (DSI) is commonly used for UP because milk is quickly heated and cooled. During this process, steam is directly injected into milk and removed by a vacuum cooler. Consumers do not prefer the flavor of DSI-UP milk compared with traditional high temperature short time (HTST) milk due to the higher cooked and eggy flavors of DSI-UP milk. The objective of this research was to characterize the effect of the vacuum cooler on the flavor of DSI-UP milk. Raw skim milk was pasteurized at 140°C for 2.3 s by DSI and homogenized at 20.7 MPa. By using a liquid sample port, steam-infused pasteurized milk was sampled after heating but before reaching the vacuum chamber. A septum was installed in the vacuum chamber to allow sampling of the removed volatiles by solid-phase microextraction (SPME) fiber followed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) combined with a sulfur-selective flame photometric detector. Steam-infused milk and vacuum-cooled milk diluted to the same solids contents were evaluated by descriptive sensory analysis and volatile compound analysis. The entire experiment was replicated 3 times. Milks cooled by the vacuum cooler were lower in sweet aromatic, sulfur/eggy, and cooked flavors than milk sampled before the vacuum cooler. Volatile compounds removed by the vacuum cooler included the sweet aromatic flavor contributors furaneol, maltol, furfural, sotolon, 2-heptanone, γ-dodecalactone, γ-decalactone, and δ-decalactone, as well as the cooked and sulfur/eggy contributors hydrogen sulfide and dimethyl sulfide. The vacuum cooler applied during DSI-UP of milk is effective at removing steam and cooling UP milk, but this process may also remove important flavor compounds from fluid milk.

Cellular Mechanisms Mediating the Antinociceptive Effect of Botulinum Toxin A in a Rodent Model of Trigeminal Irritation by a Foreign Body.

Although numerous studies have described botulinum toxin type A (BTX-A) efficacy against trigeminal neuralgia (TN), the underlying cellular mechanisms remain unclear. We have investigated cellular mechanisms that mediate the antinociceptive effect of BTX-A in a rodent model of TN produced by compression of the trigeminal nerve root (TNR). Anesthetized male Sprague-Dawley rats were fixed in a stereotaxic instrument and compression of the TNR was then achieved with a 4% agar solution. This model produced a significant mechanical allodynia and increased the expression of hypoxia-inducible factor (HIF)-1α and cytokines levels including interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the trigeminal ganglion (TG) by postoperative day (POD) 7. Single or double treatments with a high BTX-A dose (3 U/kg) led to significantly prolonged antinociceptive effects. Furthermore, a single treatment with BTX-A (3 U/kg) significantly suppressed the upregulation of HIF-1α expression and IL-1ß, IL-6, and TNF-α concentrations in the TG. Intraganglionic injection of PX-12, a HIF-1α inhibitor, led to significant anti-allodynic effects and lowered the IL-1ß, IL-6, and TNF-α levels in the TG. These findings indicate that the antinociceptive effect of BTX-A is mediated via HIF-1α associated cytokines modulation in the TG and is therefore a potentially relevant treatment strategy for TN. PERSPECTIVE: The antinociceptive properties of BTX-A in a rat model of trigeminal neuralgia are mediated through the regulation of the HIF-1α associated cytokine pathway in the trigeminal ganglion. BTX-A is therefore a potentially effective treatment strategy for trigeminal neuralgia.

Structural, magnetic, and magnetocaloric properties of R2NiMnO6 (R = Eu, Gd, Tb).

The crystal structure, cryogenic magnetic properties, and magnetocaloric performance of double perovskite Eu2NiMnO6 (ENMO), Gd2NiMnO6 (GNMO), and Tb2NiMnO6 (TNMO) ceramic powder samples synthesized by solid-state method have been investigated. X-ray diffraction structural investigation reveal that all compounds crystallize in the monoclinic structure with a P21/n space group. A ferromagnetic to paramagnetic (FM-PM) second-order phase transition occurred in ENMO, GNMO, and TNMO at 143, 130, and 112 K, respectively. Maximum magnetic entropy changes and relative cooling power with a 5 T applied magnetic field are determined to be 3.2, 3.8, 3.5 J/kgK and 150, 182, 176 J/kg for the investigated samples, respectively. The change in structural, magnetic, and magnetocaloric effect attributed to the superexchange mechanism of Ni2+-O-Mn3+ and Ni2+-O-Mn4+. The various atomic sizes of Eu, Gd, and Tb affect the ratio of Mn4+/Mn3+, which is responsible for the considerable change in properties of double perovskite.

Health-related quality of life of inpatients and outpatients with TB in rural Malawi.

INTRODUCTION: Patients being treated for TB may suffer reductions in health-related quality of life (HRQoL). This study aims to assess the extent of such reductions and the trajectory of HRQoL over the course of treatment in rural Malawi.METHODS: We collected patient demographic and socioeconomic status, TB-related characteristics, and HRQoL data (i.e., EQ-5D and a visual analogue scale VAS) from adults (age ≥18 years) being treated for TB in 12 primary health centers and one hospital in rural Thyolo District, Malawi, from 2014 to 2016. Associations between HRQoL and patient characteristics were estimated using multivariable linear regression.RESULTS: Inpatients (n = 197) consistently showed lower median HRQoL scores and suffered more severe health impairments during hospitalization than outpatients (n = 156) (EQ5D and VAS: 0.79, 55 vs. 0.84, 70). Longer treatment duration was associated with higher HRQoL among outpatients (EQ5D: 0.034 increase per 2 months, 95%CI 0.012-0.057). We found no substantial associations between patients´ demographic and socioeconomic characteristics and HRQoL in this setting.CONCLUSION: HRQoL scores among patients receiving treatment for TB in rural Malawi differ by clinical setting and duration of treatment, with greater impairment among inpatients and those early in their treatment course.

Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

Disrupted Functional and Structural Connectivity in Angelman Syndrome.

BACKGROUND AND PURPOSE: This work investigated alterations in functional connectivity (FC) and associated structures in patients with Angelman syndrome (AS) by using integrated quantitative imaging analysis and connectivity measures. MATERIALS AND METHODS: We obtained 3T brain MR imaging, including resting-state functional MR imaging, diffusion tensor imaging, and 3D T1-weighted imaging from children with AS (n = 14) and age- and sex-matched controls (n = 28). The brains of patients with AS were analyzed by measuring FC, white matter microstructural analysis, cortical thickness, and brain volumes; these were compared with brains of controls. RESULTS: Interregional FC analysis revealed significantly reduced intra- and interhemispheric FC, especially in the basal ganglia and thalamus, in patients with AS. Significant reductions in fractional anisotropy were found in the corpus callosum, cingulum, posterior limb of the internal capsules, and arcuate fasciculus in patients with AS. Quantitative structural analysis also showed gray matter volume loss of the basal ganglia and diffuse WM volume reduction in AS compared with the control group. CONCLUSIONS: This integrated quantitative MR imaging analysis demonstrated poor functional and structural connectivity, as well as brain volume reduction, in children with AS, which may explain the motor and language dysfunction observed in this well-characterized neurobehavioral phenotype.

Identification of heat shock protein gene expression in hair follicles as a novel indicator of heat stress in beef calves.

Heat shock proteins (HSPs) consist of highly preserved stress proteins that are expressed in response to stress. Two studies were carried out to investigate whether HSP genes in hair follicles from beef calves can be suggested as indicators of heat stress (HS). In study 1, hair follicles were harvested from three male Hanwoo calves (aged 172.2 ± 7.20 days) on six dates over the period of 10 April to 9 August 2017. These days provided varying temperature-humidity indices (THIs). In study 2, 16 Hanwoo male calves (aged 169.6 ± 4.60 days, with a BW of 136.9 ± 6.23 kg) were maintained (4 calves per experiment) in environmentally controlled chambers. A completely randomized design with a 2 × 4 factorial arrangement involving two periods (thermoneutral: TN; HS) and four THI treatment groups (threshold: THI = 68 to 70; mild: THI = 74 to 76; moderate THI = 81 to 83; severe: THI = 88 to 90). The calves in the different group were subjected to ambient temperature (22°C) for 7 days (TN) and subsequently to the temperature and humidity corresponding to the target THI level for 21 days (HS). Every three days (at 1400 h) during both the TN and HS periods, the heart rate (HR) and rectal temperature (RT) of each individual were measured, and hair follicles were subsequently collected from the tails of each individual. In study 1, the high variation (P < 0.0001) in THI indicated that the external environment influenced the HS to different extents. The expression levels of the HSP70 and HSP90 genes at the high-THI level were higher (P = 0.0120, P = 0.0002) than those at the low-THI level. In study 2, no differences in the THI (P = 0.2638), HR (P = 0.2181) or RT (P = 0.3846) were found among the groups during the TN period, whereas differences in these indices (P < 0.0001, P < 0.0001 and P < 0.0001, respectively) were observed during the HS period. The expression levels of the HSP70 (P = 0.0010, moderate; P = 0.0065, severe) and HSP90 (P = 0.0040, severe) genes were increased after rapid exposure to heat-stress conditions (moderate and severe levels). We conclude that HSP gene expression in hair follicles provides precise and accurate data for evaluating HS and can be considered a novel indicator of HS in Hanwoo calves maintained in both external and climatic chambers.

Comparison of a central location test versus a home usage test for consumer perception of ready-to-mix protein beverages.

Ready-to-mix (RTM) whey protein beverages are an expanding product category, and sensory properties strongly affect consumer acceptance and purchase intent. Because consumers themselves prepare RTM whey protein beverages, understanding possible gaps between central location test (CLT) and home usage test (HUT) results is critical. The objectives of this study were to compare results obtained from a CLT and a HUT and to identify the drivers of liking and disliking vanilla-flavored RTM whey protein beverages. Fourteen commercial vanilla-flavored RTM whey protein beverages were rehydrated with spring water at 15% solids (wt/vol) and evaluated by a trained panel (n = 8). Ten representative products were selected for consumer testing. Rehydrated beverages were subsequently evaluated by protein beverage consumers (n = 160) in a CLT. Nine representative products were selected for the HUT. Consumers prepared and evaluated individual beverages over 3 consecutive weeks, trying 3 samples each week. Overall liking and other attributes were scored by consumers in both tests. Data were evaluated by univariate and multivariate statistical analyses. Overall liking scores from the HUT were higher than scores from the CLT. The products with the highest and lowest overall liking scores were consistent between the CLT and HUT. More differences were observed among beverages by CLT compared with HUT when liking was averaged across all consumers. Both methods identified 2 distinct consumer clusters. Fruity flavor and sweet taste were drivers of liking, whereas cardboard flavor and bitter taste were drivers of disliking in both methods. The HUT exclusively identified thickness (viscosity) as a driver of liking and astringency as a driver of disliking. These results suggest that a CLT can be used to differentiate consumer acceptance among vanilla-flavored RTM whey protein beverages. A HUT should be used to provide more intensive insights for mouthfeel and mixing experience-related attributes.

Influence of green light illumination at night on biological characteristics of the oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae).

The oriental armyworm, Mythimna separata is an important crop pest in eastern Asia. Nocturnal insects, including nocturnal moths, have phototactic behavior to an artificial light source. Phototactic behavior in insects is species-specific in response to different wavelengths of light sources. Our previous study showed that green (520 nm) light emitting diode (LED) light resulted in a significantly higher phototactic behavior in M. separata moths compared to the other wavelength LED lights. The goal of the present study is to investigate the influence of green light illumination on biological characteristics of different developmental stages in M. separata. Our results revealed that when different developmental stages of M. separata were exposed to the green light illumination in a dark period, several biological characteristics in all developmental stages except for egg stage were positively changed, but those of F1 generation M. separata which are next generation of the adults exposed to the green light did not significantly change compared with the control level. These findings suggest that green light illumination at night (or dark period) has a positive effect on the development and longevity of M. separata.

Co-Administered Low Doses Of Ibuprofen And Dexamethasone Produce Synergistic Antinociceptive Effects On Neuropathic Mechanical Allodynia In Rats.

BACKGROUND: The traditional analgesics used to treat neuropathic pain such as anticonvulsants, opioids, and nonsteroidal anti-inflammatory drugs (NSAIDs) lack efficacy and/or carry unpleasant side effects. The present study aimed to investigate the synergistic antinociceptive effects of co-administered low doses of ibuprofen and dexamethasone in rats with trigeminal neuropathic pain. MATERIALS AND METHODS: A Sprague-Dawley rat model for trigeminal neuropathic pain was produced using mal-positioned dental implants. The left mandibular second molar was extracted under anesthesia and replaced with a miniature dental implant to induce injury to the inferior alveolar nerve. RESULTS: Monotherapy with intraperitoneal injection of high-dose ibuprofen (30 mg/kg) or dexamethasone (10 mg/kg) but not low-dose ibuprofen (1, 5, 10 mg/kg) or dexamethasone (0.01, 1 mg/kg) attenuated the neuropathic mechanical allodynia in the rats with inferior alveolar nerve injury. We examined the synergistic antinociceptive effects of co-administered ibuprofen (5 mg/kg) and dexamethasone (0.01, 0.1, 1 mg/kg). The early co-administration of ibuprofen (5 mg/kg) with dexamethasone (0.1, 1 mg/kg) on postoperative days (POD) 1-3 significantly inhibited mechanical allodynia before the pain had been established. We also observed the synergistic antinociceptive effects of the same doses the combined treatment on mechanical allodynia on POD 7-9, when the pain had already been established. The attenuation of c-fos immuno-positive cells in the ipsilateral trigeminal subnucleus caudalis after the intraperitoneal co-administration of ibuprofen (5 mg/kg) with dexamethasone (1 mg/kg) confirmed these synergistic antinociceptive effects. Moreover, the magnitude of the effects of this co-administration was comparable with that of gabapentin both before and after the pain had been established. CONCLUSION: These results suggest that a combination of ibuprofen and dexamethasone at low doses is an alternative therapeutic strategy for neuropathic pain and provide a rationale for the use of such drug combinations in patients who are unable to tolerate high-dose monotherapy.

Identification of the source of volatile sulfur compounds produced in milk during thermal processing.

Volatile sulfur compounds in ultra-pasteurized (UP) milk are the major contributors to sulfur/burnt and eggy flavors, and these flavors are disliked by consumers. Previous research has established distinct differences in flavor profiles of fluid milk processed by high temperature, short time pasteurization (HTST) and UP by direct steam injection (DSI-UP) or indirect heat (IND-UP). An understanding of the contribution of the individual milk proteins to sulfur off-flavors would clarify the source of sulfur flavors in UP milks. The objective of this study was to determine the source of volatile sulfur compounds in fluid milk with a specific focus on the comparison of heat treatment effects on milks by HTST and UP. Formulated skim milks (FSM) were manufactured by blending micellar casein concentrate and serum protein isolate (SPI). Three different caseins as a percentage of true protein (FSM95, FSM80, and FSM60) were formulated to determine the source of sulfur/burnt and eggy flavors. Freshly processed micellar casein concentrate or SPI were blended to achieve a true protein content of about 3.2%. Raw skim milk served as a control. Skim milk and FSM were pasteurized at 78°C for 15 s (HTST) or 140°C for 2.3 s by IND-UP or DSI-UP. The experiment was replicated twice. Sensory properties of milks and FSM were documented by descriptive sensory analysis. Volatile sulfur compounds in milks and FSM were evaluated using solid-phase microextraction followed by gas chromatography-triple quadrupole mass spectrometry combined with a sulfur selective flame photometric detector. The FSM with higher SPI as a percent of true protein had higher sensory sulfur/burnt and eggy flavors along with elevated concentrations of hydrogen sulfide and carbon disulfide compared with skim milk or FSM with lower proportions of SPI. Sulfur compounds including dimethyl sulfide, dimethyl disulfide, dimethyl trisulfide, dimethyl sulfoxide, and methional were not associated with sulfur/burnt and eggy flavors, which suggests that these compounds may not specifically contribute to the sulfur/burnt and eggy off-flavors of UP milks. Sensory panelists found higher overall aroma impact, and cooked, sulfur/burnt, and eggy flavors for DSI-UP, followed by IND-UP and HTST. The combination of sensory and instrumental methods used in the current study effectively identified that milk serum proteins are the source of sulfur compounds in milk, and further confirmed the contribution of hydrogen sulfide and carbon disulfide to eggy and sulfur/burnt flavors, respectively.

FCC to BCC transformation-induced plasticity based on thermodynamic phase stability in novel V10Cr10Fe45CoxNi35-x medium-entropy alloys.

We introduce a novel transformation-induced plasticity mechanism, i.e., a martensitic transformation from fcc phase to bcc phase, in medium-entropy alloys (MEAs). A VCrFeCoNi MEA system is designed by thermodynamic calculations in consideration of phase stability between bcc and fcc phases. The resultantly formed bcc martensite favorably contributes to the transformation-induced plasticity, thereby leading to a significant enhancement in both strength and ductility as well as strain hardening. We reveal the microstructural evolutions according to the Co-Ni balance and their contributions to a mechanical response. The Co-Ni balance plays a leading role in phase stability and consequently tunes the cryogenic-temperature strength-ductility balance. The main difference from recently-reported metastable high-entropy dual-phase alloys is the formation of bcc martensite as a daughter phase, which shows significant effects on strain hardening. The hcp phase in the present MEA mostly acts as a nucleation site for the bcc martensite. Our findings demonstrate that the fcc to bcc transformation can be an attractive route to a new MEA design strategy for improving cryogenic strength-ductility.