COVID-19 Pandemic Is Associated with an Adverse Impact on Burnout and Mood Disorder in Healthcare Professionals.

The coronavirus disease 2019 (COVID-19) pandemic results in a profound physical and mental burden on healthcare professionals. This study aims to evaluate burnout status and mood disorder of healthcare workers during this period. An online questionnaire was voluntarily answered by eligible adult employees in a COVID-19 specialized medical center. The major analysis included the burnout status and mood disorder. Factors related to more severe mood disorder were also identified. A total of 2029 participants completed the questionnaire. There were 901 (44.4%) and 923 (45.5%) participants with moderate to severe personal and work-related burnout status, respectively. Nurses working in the emergency room (ER), intensive care unit (ICU)/isolation wards, and general wards, as well as those with patient contact, had significantly higher scores for personal burnout, work-related burnout, and mood disorder. This investigation identified 271 participants (13.35%) with moderate to severe mood disorder linked to higher personal/work-related burnout scores and a more advanced burnout status. Univariate analysis revealed that nurses working in the ER and ICU/isolation wards were associated with moderate to severe mood disorder risk factors. Multivariate analysis demonstrated that working in the ER (OR, 2.81; 95% CI, 1.14-6.90) was the only independent risk factor. More rest, perquisites, and an adequate supply of personal protection equipment were the most desired assistance from the hospital. Compared with the non-pandemic period (2019), employees working during the COVID-19 pandemic (2020) have higher burnout scores and percentages of severe burnout. In conclusion, this study suggests that the COVID-19 pandemic has had an adverse impact on healthcare professionals. Adequate measures should be adopted as early as possible to support the healthcare system.

The In Vivo Toxicity and Antimicrobial Properties for Electrolyzed Oxidizing (EO) Water-Based Mouthwashes.

The objective of this study was to verify the feasibility of electrolyzed oxidizing (EO) water as a mouthwash through the evaluation of its in vivo toxicity by embryonic zebrafish and antimicrobial efficacy against Streptococcus mutans (S. mutans). METHODOLOGY: Each 1.5-3.0 g of sodium chloride (NaCl), sodium bromide (NaBr), or calcium chloride (CaCl2) were added into an electrolyzer with 300 mL of DD water to produce electrolyzed oxidizing (EO) water. A zebrafish embryo assay was used to evaluate acute toxicity of specimens. Antimicrobial property was conducted with 100 µL microbial count of 1 × 108 cfu/mL S. mutans to blend with each 10 mL specimen of chlorhexidine (CHX) gluconate or hypochlorous acid (HOCl) for various time points. The concentration of viable microorganisms was assessed according to individually standardized inoculum by a plate-count method. RESULTS: Among the EO water produced from NaCl, NaBr, and CaCl2, the EO water from NaCl showed a relatively low mortality rate of zebrafish embryos and was chosen for a detailed investigation. The mortality rates for the groups treated with EO water containing 0.0125% and 0.0250% HOCl were not statically different from those of a negative control, however the mortality rate was 66.7 ± 26.2% in 0.2% CHX gluconate for the same treatment time of 0.5 min. All of the HOCl or 2.0% CHX gluconate groups showed >99.9% antimicrobial effectiveness against S. mutans; while the 0.2% CHX gluconate group showed a bacterial reduction rate of 87.5% and 97.1% for treatment times of 0.5 min and 1.0 min, respectively. CONCLUSIONS: Except for the 0.2% CHX gluconate, all the HOCl specimens and 2.0% CHX gluconate revealed similar antimicrobial properties (>99.9%) against S. mutans. The EO water comprised of both 0.0125% and 0.0250% HOCl showed >99.9% antimicrobial efficacy but with little in vivo toxicity, illuminating the possibility as an alternative mouthwash for dental and oral care.

Anti-metastatic activity of MPT0G211, a novel HDAC6 inhibitor, in human breast cancer cells in vitro and in vivo.

Triple-negative breast cancer (TNBC) is associated with an increased risk of metastasis and a poor prognosis. The invasive ability of TNBC relies on actin reorganization and is regulated by histone deacetylase 6 (HDAC6). The present study aimed to examine the effect of MPT0G211, a novel HDAC6 inhibitor, on cell migration and microtubule association in both in vitro and in vivo models of TNBC. Here MPT0G211 more selectively and potently targeted and inhibited HDAC6, compared with tubastatin A, another selective HDAC6 inhibitor. In vitro, MPT0G211 decreased the migration of the TNBC cell line MDA-MB-231, particularly when administered together with paclitaxel, and increased heat shock protein 90 (Hsp90) acetylation, leading to the dissociation of Hsp90 from aurora-A and proteasomal degradation. Furthermore, MPT0G211 significantly disrupted F-actin polymerization by increasing cortactin acetylation and downregulating slingshot protein phosphatase 1 (SSH1) and active cofilin expression. In vivo, MPT0G211 treatment significantly ameliorated TNBC metastasis. In conclusion, our results demonstrate that MPT0G211 reduces TNBC cell motility by promoting cortactin acetylation and aurora-A degradation, and inhibiting the cofilin-F-actin pathway via HDAC6 activity attenuation. MPT0G211 therefore demonstrates therapeutic potential for invasive TNBC.

Salt Stability - The Effect of pHmax on Salt to Free Base Conversion.

PURPOSE: The aim of this study was to investigate how the disproportionation process can be impacted by the properties of the salt, specifically pHmax. METHODS: Five miconazole salts and four sertraline salts were selected for this study. The extent of conversion was quantified using Raman spectroscopy. A mathematical model was utilized to estimate the theoretical amount of conversion. RESULTS: A trend was observed that for a given series of salts of a particular basic compound (both sertraline and miconazole are bases), the extent of disproportionation increases as pHmax decreases. Miconazole phosphate monohydrate and sertraline mesylate, although exhibiting significantly different pHmax values (more than 2 units apart), underwent a similar extent of disproportionation, which may be attributed to the lower buffering capacity of sertraline salts. CONCLUSION: This work shows that the disproportionation tendency can be influenced by pHmax and buffering capacity and thus highlights the importance of selecting the appropriate salt form during the screening process in order to avoid salt-to-free form conversion.

Salt stability--effect of particle size, relative humidity, temperature and composition on salt to free base conversion.

PURPOSE: The aim of this study was to investigate how factors such as temperature, relative humidity and particle size impact the extent of disproportionation (salt to free base conversion) in powder blends of miconazole, benzocaine or sertraline mesylate salts mixed with a basic additive. METHOD: Raman spectroscopy was used to quantitate the extent of disproportionation. The data was further analyzed by multivariate analysis with partial least squares (PLS) modeling. RESULTS: It was found that salt disproportionation was significantly influenced by % weight gain due to moisture sorption both in terms of the kinetics and the conversion extent, suggesting a solution-mediated reaction. Temperature plays an important role in impacting the value of pHmax which in turn has a significant correlation to the amount of free base formed. The particle size and drug: additive ratio were also found to influence the extent of disproportionation. CONCLUSIONS: This study shows that the extent of salt disproportionation is influenced by multiple factors and the application of PLS modeling demonstrated the feasibility of utilizing multivariate analysis to generate a predictive model for estimating the extent of conversion and thus may serve as a tool for risk assessment.

Postirradiated carotid blowout syndrome in patients with nasopharyngeal carcinoma: a case-control study.

BACKGROUND: Carotid blowout syndrome is one of the most devastating complications of nasopharyngeal carcinoma (NPC) therapy. METHODS: A retrospective review was conducted from January 2004 to April 2013. Thirty-one patients with carotid blowout syndrome were enrolled and a case control study was conducted to analyze the risk factors. RESULTS: When a comparison was made between the carotid blowout syndrome and matched non-bleeding group, there was a significantly higher local recurrence rate and prevalence of skull base osteoradionecrosis (ORN) in the carotid blowout syndrome group compared to those of the control group (both p < .001). The hazard ratio of carotid blowout syndrome was 3.599 between patients with or without reirradiation (95% confidence interval, 1.465-8.839; p = .005, adjusted for nasopharyngectomy and chemotherapy) using a Cox proportional hazard model. CONCLUSION: Reirradiation and skull base ORN are strong predisposing factors for carotid blowout syndrome, and therefore they should be mentioned in the informed consent form before treatment.

Indole-3-ethylsulfamoylphenylacrylamides: potent histone deacetylase inhibitors with anti-inflammatory activity.

A series of 2-methyl-1H-indol-3-ethylsulfamoylphenylacrylamides based on LBH589-PXD101 core have been synthesized and evaluated for their histone deacetylase (HDAC) inhibitory and anti-inflammatory activity. In vitro, compounds 9-12 show 2.6-fold better HDAC inhibition and 3-fold better IL-6 suppression compared to LBH589·HCl (1·HCl). Furthermore, these compounds did not show apparent cell viability suppression on macrophages while in contrast, treatment with 1·HCl resulted in significant reduction in cell viability as demonstrated by an MTT assay. Repressed expression of iNOS, COX-2 and reduced phosphorylation of p65 revealed the inhibitory effect of these analogues on inflammatory mediator release which is related to inhibited NF-ĸB signals. (N-Hydroxy-3-{3-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide) (9), exhibited ability superior to that of 1·HCl, was able to reduce carrageenan-induced acute inflammation in an animal model. Compounds 9-12 have potential anti-inflammatory activity and compound 9 can serve as lead compound for further development.

Assessing the impact of polymers on the pH-induced precipitation behavior of poorly water soluble compounds using synchrotron wide angle X-ray scattering.

The aim of this study was to investigate the pH-induced precipitation behavior of four ionizable compounds (papaverine, dipyridamole, glyburide, and warfarin) in the absence and presence of polymers. Polymers selected included nonionic, anionic, and cationic polymers. Precipitates were analyzed immediately after formation using high-energy radiation wide-angle X-ray scattering analysis and polarized light microscopy. Papaverine immediately crystallized to the original solid-state form upon creation of a highly supersaturated solution and polymers were unable to prevent crystallization. Dipyridamole also crystallized rapidly, forming a metastable polymorph that was stabilized by several of the cellulosic polymers. For glyburide and warfarin, although the compounds readily crystallized in the absence of the polymers, several of the polymers were able to prevent crystallization for more than 6 h. In general, measurements of solution concentration immediately following precipitation corroborated the solid-state analysis results, with the solution phase for the noncrystalline precipitates having a concentration considerably higher than that of the equilibrium solubility value, whereas for the crystalline precipitates, values were closer to the equilibrium solubility. Thus, precipitation to a noncrystalline solid was found to be promoted by the presence of some polymers, resulting in the formation of a supersaturated solution.

Laryngeal electromyography findings of vocal fold immobility in patients after radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: The clinical features of vocal fold immobility (VFI) after radiotherapy for nasopharyngeal carcinoma (NPC) have seldom been reported. METHODS: We retrospectively reviewed laryngeal electromyography (LEMG) and tumor study findings to elucidate the common clinical features of patients who presented with VFI after radiotherapy for NPC. The LEMG signals obtained from the cricothyroid and thyroarytenoid muscles were used to confirm superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) injury. RESULTS: The medical records of 13 patients were reviewed and 11 of them had evidence of RLN injury. Six of the 11 patients also had SLN injury, indicating possible vagus nerve (VN) injury. Two patients had cricoarytenoid joint fixation without evidence of nerve injury. None of the nerve injuries were caused by skull base recurrence or tumor metastasis. CONCLUSION: VFI is usually caused by nerve injury, but it is not a malignant sign of tumor recurrence or metastasis.

Classification of the crystallization behavior of amorphous active pharmaceutical ingredients in aqueous environments.

PURPOSE: To classify the crystallization behavior of amorphous active pharmaceutical ingredients (API) exposed to aqueous environments. METHODS: A set of approximately 50 chemically and physically diverse active pharmaceutical ingredients (APIs) was selected for this study. Two experimental setups were employed to characterize the crystallization behavior of the amorphous API in an aqueous environment. For the first approach, precipitation, as evidenced by the development of turbidity, was induced using the solvent shift method, by mixing concentrated API solutions in DMSO with an aqueous buffer in a capillary. Subsequently, crystallization was monitored in situ over time using synchrotron radiation (simultaneous SAXS/WAXS beamline 12-ID-B at the Advanced Photon Source, Argonne National Laboratories, Argonne, IL). In the second approach, amorphous films were prepared by melt quenching; after adding buffer, crystallization was monitored with time using polarized light microscopy. RESULTS: In general, the crystallization behavior of a given compound was similar irrespective of the experimental method employed. However, the crystallization behavior among different compounds varied significantly, ranging from immediate and complete crystallization to no observable crystallization over biorelevant time scales. Comparison of the observed behavior with previous studies of crystallization tendency in non-aqueous environments revealed that the crystallization tendency of individual APIs was somewhat similar regardless of the crystallization environment. CONCLUSIONS: API properties, rather than the method by which amorphous materials are generated, tend to dictate crystallization behavior in aqueous media.

Impact of sertraline salt form on the oxidative stability in powder blends.

Oxidation of active pharmaceutical ingredients is a common chemical degradation process occurring in solid dosage forms. The aim of this study was to investigate the tendency of various sertraline salts to oxidize in powder blends containing a basic additive. A different extent of conversion of each salt to the free base was observed to occur in the presence of the basic additive, consistent with their respective pHmax values. Sertraline was found to undergo oxidation as the unioinized form, in both solution and powder blends that incorporated an oxidizing agent. In contrast, the ionized form of sertraline remained stable in both cases. Three sertraline salts undergoing a significant extent of conversion from salt to free form in the presence of tribasic sodium phosphate were found to oxidize extensively while sertraline benzoate which had a considerably lower extent of free base formation was more resistant to oxidation. The oxidative degradants were produced through oxidation at the amine functional group of sertraline which is where sertraline is ionized as the salt form. The link between oxidation tendency and the ionization state of sertraline in powder mixtures has thus been demonstrated in this study.

1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines histone deacetylase inhibitors are potent cytokine release suppressors.

A series of 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines (7-15) has been developed; the compounds exhibited potent histone deacetylase (HDAC) inhibitory activities. Notably, almost all of this series exhibited better HDAC-inhibitory and antiproliferative activities than 3-(1-benzenesulfonyl-1H-indol-5-yl)-N-hydroxyacrylamide (6), as reported in a previous study. Among these compounds, 3-[1-(4-methoxybenzenesulfonyl)-2,3-dihydro-1H-indol-5-yl]-N-hydroxyacrylamide (9) showed a two- to tenfold increase in activity compared to SAHA (1) in the suppression of lipopolysaccharide-induced cytokine production. Compound 9 also caused a marked reduction in carrageenan-induced acute inflammation in a rat model. Taken together, these data indicated that 1-arylsulfonyl-5-(N-hydroxyacrylamide)indolines HDAC inhibitors exhibit potent anti-inflammatory activity.

BCRP/ABCG2 inhibition sensitizes hepatocellular carcinoma cells to sorafenib.

The multikinase inhibitor, sorafenib (Nexavar®, BAY43-9006), which inhibits both the Raf/MEK/ERK pathway and several receptor tyrosine kinases (RTKs), has shown significantly therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond to sorafenib well and new therapeutic strategies to optimize the efficacy of sorafenib are urgently required. Overexpression of breast cancer resistance protein (BCRP/ABCG2) mediates the drug-efflux of several tyrosine kinase inhibitors (TKIs) to attenuate their efficacy. This study aimed to investigate the role of BCRP/ABCG2 in the sensitivity of HCC to sorafenib. Our data showed that BCRP/ABCG2 mediated the efflux of sorafenib. Co-treatment with a BCRP/ABCG2 inhibitor greatly augmented the cytotoxicity of sorafenib in HCC cells. Similar results were also achieved by the competitive inhibitor of BCRP/ABCG2, gefitinib, in combination with sorafenib. These results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of BCRP/ABCG2 may be a potential strategy to increase the response of HCC cells to sorafenib.

Rhodiola: an ordinary plant or a promising future therapy for pulmonary hypertension? a brief review.

Abstract Pulmonary hypertension (PH) is a chronic, complex, and progressive disease that eventuates in fatality. Research efforts over the past decades have resulted in therapeutic options that improve quality of life and prolong survival of patients, but they do not offer a cure. We propose a philosophical model that a disturbed balance of yin and yang results in pulmonary vascular remodeling, the hallmark of PH pathology. The model may be useful in exploring the wisdom of traditional Chinese medicine and incorporating it into mainstream PH research. In this context, the medicinal plant Rhodiola can be of profound interest owing to its variety of health-friendly attributes. Rhodiola has been shown to be beneficial in high-altitude-related symptoms and acute exacerbation of PH; moreover, improvement of PH has been demonstrated experimentally in chronically hypoxic rats. The beneficial effects of Rhodiola in PH may be attributable to its potential targeting of the signaling pathways, such as endothelin-1, nitric oxide, vascular endothelial growth factor, angiotensin-converting enzyme, nuclear factor κ-B, tumor necrosis factor α, and interleukin-6. Alterations in these mediators are implicated in PH pathogenesis, the characteristics of which include chronic pulmonary vasoconstriction, vasoproliferation, and vascular inflammation. Salidroside, one of the compounds extracted from Rhodiola, has been found to provide therapeutic benefits in experimental PH. As the data are limited and the field is in its infancy, further studies including in-depth analysis of the therapeutic effects on various animal models of PH are desirable. We believe that future PH research should place an adequate and special emphasis on exploring and promoting the potential of traditional Chinese medicine, and to this end, the medicinal plant Rhodiola offers a promising field on which to embark.

pH-Induced precipitation behavior of weakly basic compounds: determination of extent and duration of supersaturation using potentiometric titration and correlation to solid state properties.

PURPOSE: To examine the precipitation and supersaturation behavior of ten weak bases in terms of the relationship between pH-concentration-time profiles and the solid state properties of the precipitated material. METHODS: Initially the compound was dissolved at low pH, followed by titration with base to induce precipitation. Upon precipitation, small aliquots of acid or base were added to induce slight subsaturation and supersaturation respectively and the resultant pH gradient was determined. The concentration of the unionized species was calculated as a function of time and pH using mass and charge balance equations. RESULTS: Two patterns of behavior were observed in terms of the extent and duration of supersaturation arising following an increase in pH and this behavior could be rationalized based on the crystallization tendency of the compound. For compounds that did not readily crystallize, an amorphous precipitate was formed and a prolonged duration of supersaturation was observed. For compounds that precipitated to crystalline forms, the observed supersaturation was short-lived. CONCLUSION: This study showed that supersaturation behavior has significant correlation with the solid-state properties of the precipitate and that pH-metric titration methods can be utilized to evaluate the supersaturation behavior.

Complex dielectric properties of microcrystalline cellulose, anhydrous lactose, and α-lactose monohydrate powders using a microwave-based open-reflection resonator sensor.

The real (ε') and imaginary (ε″) components of the complex permittivity of anhydrous lactose and microcrystalline cellulose (MCC) under different bulk densities, moisture contents (MCs), and times of hydration (for anhydrous lactose) were measured nondestructively using a microwave resonator sensor operating in the range of 700-800 MHz. Measurements of sensor resonant frequency and conductance allow, through calibration, determination of the complex dielectric properties ε' (relative permittivity) and ε″ (relative dielectric loss) of the test material. Characteristic graphs of ε″ versus ε' - 1 curve for each powder were generated as a function of bulk density and MC. Such data can be used to develop empirical models for the simultaneous in situ measurement of the bulk density and MC of the powders. Unlike MCC, anhydrous lactose is converted to its hydrate form in the presence of moisture, which causes a reduction in the amount of physisorbed and "free" water and a subsequent change in the dielectric properties. For powders such as anhydrous lactose that can form a crystal hydrate in the presence of moisture, a combination of techniques such as vibrational spectroscopy together with microwave resonator measurements are appropriate to characterize, in situ, the physical and chemical properties of the powder.

Capillary electrochromatographic separation of proteins on a column coated with titanium dioxide nanoparticles.

A TiO2 nanoparticle (TiO2 NP)-coated open-tubular column for the capillary electrochromatographic separation of proteins is described. The surface chemistry of the TiO2 NPs on the inner wall of the fused silica was significantly affected by the running buffer. By varying of the phosphate buffer pH, only cathodic EOF was indicated. The results showed that TiO2 NPs are existed as a complexed form with the buffer ligand. Good separation of conalbumin (ConA), apo-transferrin (apoTf), ovalbumin (OVA), and BSA could be achieved with phosphate buffer (40 mM, pH 8.0) and an applied voltage of 15 kV. Five peaks of glycoisoforms of OVA were observed under these conditions. In comparison with the retention behavior of the analytes on the bare fused-silica column, the new column's high resolving power seems to be predominantly derived from the ligand exchange of the analytes with the phosphate adsorbed onto the TiO2 NPs. The method was also used to separate egg-white proteins. Both acidic and basic proteins in egg white were separated in a single run. The microheterogeneities of OVA could also be found in it. The separation efficiency for the main peak of OVA in egg white was around 10,000 plates/m.

Titanium dioxide nanoparticles-coated column for capillary electrochromatographic separation of oligopeptides.

A novel column made through the condensation reaction of TiO2 nanoparticles (TiO2 NPs) with silanol groups of the fused-silica capillary is described. EOF measurements under various buffer constitutions were used to monitor the completion of reactions. The results indicated that the EOF was dependent on the interactions between buffers and the bonded TiO2 NPs. With formate/Tris buffer, EOF reversal at pH below 5 and cathodic EOF at pH above 5 were indicated. The pI of the bonded TiO2 NPs was found at approximately ph 5. Only cathodic EOF was illustrated by substituting the mobile phase with either glutamate or phosphate buffer. It was elucidated that both glutamate and phosphate buffer yield a negative charge layer on the surface of TiO2 NPs attributable to the formation of a titanium complex. The CEC performance of the column was tested with angiotensin-type oligopeptides. Some parameters that would affect the retention behavior were investigated. The interactions between the bonded phases and the analytes were explicated by epitomized acid-base functional groups of the oligopepetides and the speciation of the surface oxide in different pH ranges. The average separation efficiencies of 3.1 x 10(4) plates/m is readily achieved with a column of 70 cm (50 cm) x 50 mum ID under an applied voltage of 15 kV, phosphate buffer (pH 6.0, 40 mM), and UV detection at 214 nm.

Development of fungal mycelia as a skin substitute: characterization of keratinocyte proliferation and matrix metalloproteinase expression during improvement in the wound-healing process.

SACCHACHITIN membranes, prepared from the waste residue of the fruiting body of Ganoderma taugae, were used in our previous study to enhance skin wound healing in animal models. In the present study, the effects of the membrane on the growth of keratinocytes and the activity of matrix metalloproteinases (MMPs), as well as on the healing of skin wounds in humans, were estimated. Fresh human foreskin was employed as the source of the keratinocyte culture, and a modified keratinocyte-SFM medium supplemented with 0.2 ng/mL of recombinant epidermal growth factor and 30 microg/mL bovine pituitary extract was used to enhance the successful growth of keratinocytes under an atmosphere of 5% CO2, at 37 degrees C. The results indicated that 0.01% SACCHACHITIN enhanced the proliferation of keratinocytes in the culture on the fourth and fifth days, and cells showed neither morphological alteration nor disordered proliferation. This evidence clearly indicated that SACCHACHITIN was not cytotoxic to and was safe for the growth of keratinocytes. Thus, SACCHACHITIN might play a positive role in the proliferation and differentiation of keratinocytes around wounds and in accelerated wound healing of epidermal tissue. In addition, microscopic observations during the growth of keratinocytes showed that normal proliferation and differentiation took place along the margin of the SACCHACHITIN membrane. This indicates that SACCHACHITIN is possibly cytocompatible with keratinocytes. Electrophoretic analysis and inhibition tests for the binding effect of SACCHACHITIN on MMPs showed that SACCHACHITIN reduced MMPs in extracellular matrix degradation and facilitated establishment of an extracellular matrix around wounds; these effects resulted in rapid wound healing. SACCHACHITIN was used as a skin dressing for patients who had skin chronicle ulcer, which had not healed for over 7 months. Preliminary clinical observations showed that the wound improved and began to heal. An analysis of MMPs by ELISA in tissue of the wound indicated a significant decrease in MMP levels.