Effect of Novel and Traditional Intracanal Medicaments on Biofilm Viability and Composition.

INTRODUCTION: The aim of this study was to test the hypothesis that a combination of D-amino acids (DAA) and trans-cinnamaldehyde (TC) demonstrates superior antibiofilm activity to calcium hydroxide (CH) and untreated controls. METHODS: In this 3-part in vitro study, the concentration of DAAs (D-methionine, D-leucine, D-tyrosine, and D-tryptophan) that would significantly decrease Enterococcus faecalis and Actinomyces naeslundii biofilm biomass was first determined. Then, the effect of TC + selected DAAs on polymicrobial biofilms was characterized by quantifying the biomass and biofilm viability. Finally, the antibiofilm effects of TC+DAA was compared with CH and untreated controls by (i) determining bacterial viability and (ii) quantifying biofilm matrix composition using selective fluorescence-binding analysis. Statistical analysis was performed using one-way ANOVA and appropriate multiple comparisons test, with P<.05 considered as statistically significant. RESULTS: TC (0.06%) + D-tyrosine (1 mM) + D-tryptophan (25 mM) significantly reduced the biomass and biofilm viability compared to the control (P<.05). While no significant difference was observed between TC+DAA and CH in the cultivable bacterial counts (P>.05), confocal microscopy demonstrated a significantly greater percentage of dead bacteria in TC+DAA-treated biofilms compared to CH and the control (P<.05). TC+DAA significantly decreased the biovolume and all the examined components of the biofilm matrix quantity compared to the control, while CH significantly reduced only the exopolysaccharide quantity (P<.05). CONCLUSION: TC + D-tyrosine + D-tryptophan demonstrated superior antibiofilm activity (biofilm bacterial killing and reduction of matrix quantity) to CH and has potential to be developed as an intracanal medicament.

Investigation of a foodborne outbreak at a mass gathering in Petaling District, Selangor, Malaysia.

Objective: On 6 October 2019, Petaling District Health Office received notification of a possible foodborne outbreak involving a mass gathering event. This report presents the processes of diagnosis verification, case identification, determination of associated risk factors and commencement of control measures in managing the outbreak. Methods: Cases were defined as those who attended the mass gathering event on 6 October 2019, consumed the pre-packaged food and subsequently developed vomiting, abdominal pain, diarrhoea or other symptoms (e.g. fever, nausea and dizziness). Epidemiological, environmental and laboratory investigations were performed. Data were analysed using SPSS software (version 24.0). Results: A total of 169 cases were identified. The attack rate was 7.2%, and cases ranged in age from 7 to 50 years, with a median of 20 years. A total of 156 (92.3%) cases had vomiting, 137 (81.1%) had abdominal pain and 83 (49.1%) had diarrhoea. Consuming nasi lemak at the mass gathering was found to be significantly associated with developing illness (odds ratio: 9.90, 95% confidence interval: 6.46-15.16). The samples from suspected food, food handlers and the environment were positive for Bacillus cereus, Staphylococcus aureus or coliforms. Discussion: The outbreak at this mass gathering was probably caused by food contaminated with B. cereus and S. aureus. To prevent future outbreaks, we recommend mass gathering events use certified catering services that have adequate food safety training.

Potential limitations of diagnostic standard codes to distinguish polycythemia vera and secondary erythrocytosis.

Red cell overproduction is seen in polycythemia vera (PV), a bone marrow myeloproliferative neoplasm characterized by trilinear cell proliferation (WBC, platelets), as well as in secondary erythrocytosis (SE), a group of heterogeneous disorders characterized by elevated EPO gene transcription. We aimed to verify the concordance of the International Classification of Diseases (ICD) code-based diagnosis of "polycythemia" or "erythrocytosis" with the true clinical diagnosis of these conditions. We retrospectively reviewed the electronic medical records (January 1, 2005, to December 31, 2016) of adult patients with ICD codes of polycythemia and/or erythrocytosis who had testing done for the presence of the JAK2V617F mutation. We verified the accuracy of the ICD code-based diagnoses by meticulous chart review and established whether these patients fulfilled the criteria by the evaluating physician for PV or SE and according to the World Health Organization 2016 diagnostic guidelines. The reliability of ICD coding was calculated using Cohen's kappa. We identified and chart reviewed a total of 578 patient records. Remarkably, 11% of the patients had concurrent diagnosis codes for PV and SE and were unable to be classified appropriately without individual chart review. The ICD code-based diagnostic system led to misidentification in an important fraction of cases. This represents a problem for the detection of PV or SE cases by ICD-based registries and their derived studies. Research based exclusively on ICD codes could have a potential impact on patient care and public health, and limitations must be weighed when research findings are conveyed.

Cyclobis[2,5-(thiophenedimethane)-4,4'-(triphenylamine)] versus Its S,S-Dioxidized Macrocycle: Global Antiaromaticity and Intramolecular Dynamics.

Fully conjugated macrocycles containing benzenoid rings rarely show global aromaticity/antiaromaticity. Herein, we report an annulene-like macrocycle CBTT and its S,S-dioxidized macrocycle DOCBTT with alternative quinoidal thiophene/1,1-dioxide thiophene and triphenyl amine moieties. They both showed temperature-dependent intramolecular dynamics and global antiaromatic character with 32π electrons at low temperature. However, CBTT and DOCBTT have different conjugated pathways.

A Tetraindeno-Fused Bis(anthraoxa)quinodimethane with Nine Consecutively Fused Six-Membered Rings.

A tetraindeno-fused bis(anthraoxa)quinodimethane RBR with nine consecutively fused six-membered rings in a row was synthesized. Its structure was confirmed by X-ray crystallographic analysis and NMR measurement. Compared with an unfused analogue ABA, the indeno fusion onto the zigzag edges not only enhanced the photostability but also dramatically tuned the electronic properties. Due to the existence of two rubicene units, RBR can also be readily reduced to form a radical anion and dianion.

Zinc supplement augments the suppressive effects of repurposed drugs of NF-kappa B inhibitor on ACE2 expression in human lung cell lines in vitro.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a vast number of infections and fatalities worldwide. As the development and safety validation of effective vaccines are ongoing, drug repurposing is most efficient approach to search FDA approved agents against coronavirus disease 2019 (COVID-19). In the present study, we found that endogenous ACE2 expressions could be detected in H322M and Calu-3 cell lines, as well as their ACE2 mRNA and protein expressions were suppressed by pyrrolidine dithiocarbamate (PDTC), a NF-kappa B inhibitor, in dose- and time-dependent manners. Moreover, N-acetyl-cysteine (NAC) pretreatment reversed PDTC-induced ACE2 suppression, as well as the combined treatment of hydrogen peroxide and knockdown of p50 subunit of NF-kappa B by siRNA reduced ACE2 expression in H322M cells. In addition, anthelmintic drug triclabendazole and antiprotozoal drug emetine, repurposed drugs of NF-kappa B inhibitor, also inhibited ACE2 mRNA and protein expressions in H322M cells. Moreover, zinc supplement augmented the suppressive effects of triclabendazole and emetine on ACE2 suppression in H322M and Calu-3 cells. Taken together, these results indicate that ACE2 expression is modulated by reactive oxygen species (ROS) and NF-kappa B signal in human lung cell lines, and zinc combination with triclabendazole or emetine has the clinical potential for the prevention and treatment of COVID-19.

Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry

Large-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccine preparations have recently been clinically distributed based on accelerated approval. We revisited the early but inconclusive clinical interest in the combination of azithromycin and zinc sulfate repurposing with safety advantages. In vitro proof of concept was provided for rapid and synergistic suppression of ACE2 expression following treatments in human airway cells, Calu-3 and H322M. The two representative ACE2-expressing human airway cells indicate the upper and lower respiratory tracts. Prophylactic and early therapeutic roles of azithromycin combined with zinc are proposed for virus cellular entry prevention potential bridging to effective antibody production.

Diagnostic Performance of Erythropoietin Levels in Polycythemia Vera: Experience at a Comprehensive Cancer Center.

INTRODUCTION: Considering the evolving diagnostic criteria of polycythemia vera (PV), we analyzed the utility of serum erythropoietin (EPO) as a predictive marker for differentiating polycythemia vera (PV) from other etiologies of erythrocytosis. PATIENTS AND METHODS: We conducted a retrospective study after a review of electronical medical records from January 2005 to December 2016 with diagnosis of erythrocytosis using International Classification of Disease-specific codes. To evaluate the diagnostic performance of EPO levels and JAK2-V617F mutation, we constructed a receiver-operated characteristic curve of sensitivity versus 1-specificity for serum EPO levels and JAK2-V617F mutation as predictive markers for differentiating PV from other causes of erythrocytosis. RESULTS: We surveyed 577 patients with erythrocytosis. Median patient age was 59.2 years, 57.72% (n = 329) were male, 86.3% (n = 491) were white, and only 3.3% (n = 19) were African American. A total of 80.88% (n = 351) of those diagnosed with PV had a JAK2-V617F mutation compared to only 1.47% (n = 2) whose primary diagnosis was secondary polycythemia. When comparing JAK2-V617 mutation to the EPO level, the area under the curve of JAK2-V617 (0.8970) was statistically larger than that of EPO test (0.6765). Therefore, the PV diagnostic methodology using JAK2-V617 is better than the EPO test. An EPO level of < 2 mIU/mL was > 99% specific to predict PV but was only 12% sensitive. CONCLUSION: In the appropriate clinical setting, cytogenetic and molecular studies such as JAK2 mutation status prevail as the most useful tools for PV case identification. The use of isolated EPO to screen patients with erythrocytosis is not a good diagnostic approach.

Reasons for Frequent Psychiatric Emergency Service Use in a Large Urban Center.

OBJECTIVE: Reasons for frequent use of psychiatric emergency services are complex and numerous, but research has largely depended on quantitative methods to describe the phenomenon. The goal of this study was to describe the reasons for frequent use in Singapore and the ways service seekers changed because of frequent use. METHODS: Semistructured qualitative interviews were conducted with 44 adults between July 2016 and December 2017. These people visited the psychiatric emergency department of a large tertiary care institute in Singapore five or more times in 12 months. Thematic analysis was conducted to categorize the reasons for frequent use. RESULTS: Participants were 39 years old on average, and their median length of contact with emergency services was 3.5 years. Psychotic, depressive, adjustment, and personality disorders were most common. Reasons for frequent use included seeking psychiatric services outside of office hours, seeking the safety of admission, seeking the comfort of speaking with an empathetic professional, intoxication, contact with police, and families seeking respite. Because their frequent use gave them knowledge of standard operating procedures, participants censored their disclosure of symptoms instead of reporting the full depth of their crisis in order to reach their desired outcome of the visit. CONCLUSIONS: Frequent use of emergency services led to changes in people's willingness to disclose important details of their crisis. These adjustments allowed service users to reach their desired outcome. Service providers and policy makers must be mindful that the package of care they deliver may prescribe medical solutions to social distress because of a lack of better alternatives.

New insights into the synergistic effect of active radicals and adsorptive ability on the photodegradation of gaseous acetaldehyde over reduced graphene Oxide/P25 composite.

Although coupling reduced graphene oxide (RGO) with TiO2 is believed to enhance the photocatalysis through the light utilization, studies on its photothermal conversion effect are rarely reported. Herein, RGOP (reduced graphene oxide/P25) was synthesized to explore roles of the enhanced light adsorption and photothermal conversion in the photocatalytic process. It was found that although RGOP had increased absorbance, it actually possessed lower available light utilization compared with P25. In the synergistic effect of available light utilization, transfer resistance and hydrophilicity, RGOP exhibited less superoxide radicals but more hydroxyl radicals. In the presence of scavenger experiments, O2- was proved to play the predominant role in the photocatalytic process, while OH was the secondary one. In comparison to P25, the change of active radicals of RGOP was adverse to its photocatalysis. However, due to the superior adsorptive property of RGOP, it exhibited higher photocatalytic activity than P25. The improved photocatalytic activity of RGOP was ascribed to its superior adsorptive ability aside from active radicals (O2-, OH).

Stereotactic body radiotherapy for bone oligometastatic disease in prostate cancer.

PURPOSE: There are sparse data describing outcomes of bone-only oligometastatic prostate cancer in comparison with lymph node disease treated with stereotactic body radiotherapy (SBRT). The primary aim of this study was to report progression-free survival (PFS) data for patients with bone-only disease. Influence of hormone sensitivity and androgen deprivation therapy use was also assessed. METHODS: This is a single-centre retrospective cohort study. Hormone-sensitive and castrate-resistant patients with oligometastatic (≤ 3) bone-only prostate cancer treated with SBRT were included. Data were collected using electronic records. Kaplan-Meier survivor function, log rank test, as well as Cox regression were used to calculate PFS and overall survival. RESULTS: In total, 51 patients with 64 bone metastases treated with SBRT were included. Nine patients were castrate resistant and 42 patient's hormone sensitive at the time of SBRT. Median follow-up was 23 months. Median PFS was 24 months in hormone-sensitive patients and 3 months in castrate-resistant patients. No patients experienced grade 3 or 4 toxicities. There were three in-field recurrences. CONCLUSIONS: In this study, patients with bone oligometastatic disease showed potential benefit from SBRT with a median PFS of 11 months. Hormone-sensitive patients showed the greatest benefit, with results similar to that published for oligometastatic pelvic nodal disease treated with SBRT. Prospective randomised control trials are needed to determine the survival benefit of SBRT in oligometastatic bone-only prostate cancer and to determine prognostic indicators.

Multivariate Cryptography Based on Clipped Hopfield Neural Network.

Designing secure and efficient multivariate public key cryptosystems [multivariate cryptography (MVC)] to strengthen the security of RSA and ECC in conventional and quantum computational environment continues to be a challenging research in recent years. In this paper, we will describe multivariate public key cryptosystems based on extended Clipped Hopfield Neural Network (CHNN) and implement it using the MVC (CHNN-MVC) framework operated in space. The Diffie-Hellman key exchange algorithm is extended into the matrix field, which illustrates the feasibility of its new applications in both classic and postquantum cryptography. The efficiency and security of our proposed new public key cryptosystem CHNN-MVC are simulated and found to be NP-hard. The proposed algorithm will strengthen multivariate public key cryptosystems and allows hardware realization practicality.

Using Laboratory Test Results at Hospital Admission to Predict Short-term Survival in Critically Ill Patients With Metastatic or Advanced Cancer.

CONTEXT: Accurately estimating the life expectancy of critically ill patients with metastatic or advanced cancer is a crucial step in planning appropriate palliative or supportive care. OBJECTIVES: We evaluated the results of laboratory tests performed within two days of hospital admission to predict the likelihood of death within 14 days. METHODS: We retrospectively selected patients 18 years or older with metastatic or advanced cancer who were admitted to intensive care units or palliative and supportive care services in our hospital. We evaluated whether the following are independent predictors in a logistic regression model: age, sex, comorbidities, and the results of seven commonly available laboratory tests. The end point was death within 14 days in or out of the hospital. RESULTS: Of 901 patients in the development cohort and 45% died within 14 days. The risk of death within 14 days after admission increased with increasing age, lactate dehydrogenase levels, and white blood cell counts and decreasing albumin levels and platelet counts (P < 0.01). The model predictions were confirmed using a separate validation cohort. The areas under the receiver operating characteristic curves were 0.74 and 0.70 for the development and validation cohorts, respectively, indicating good discriminatory ability for the model. CONCLUSIONS: Our results suggest that laboratory test results performed within two days of admission are valuable in predicting death within 14 days for patients with metastatic or advanced cancer. Such results may provide an objective assessment tool for physicians and help them initiate conversations with patients and families about end-of-life care.

Which skills boost service provider confidence when managing people presenting with psychiatric emergencies?

The way service seekers interact with the staff at emergency services has been shown to influence the standard of care, especially in the case of certain psychiatric manifestations. Staff reactions to psychiatric complaints have been linked to their comfort dealing with these types of service users as well as their competencies understanding the illness. It is therefore vital to understand which skills increase confidence in treating psychiatric emergencies. Twenty-six open-ended convergent interviews were conducted with staff working in a psychiatric emergency department. Thematic analysis was used to analyze the data. Participants reported several non-technical skills which developed from exclusively serving people with psychiatric emergencies: 1) Vigilance allowed staff to be sensitive to minor changes in behavior which precede psychiatric emergencies. 2) The ability to negotiate and find tangible solutions was particularly important when dealing with psychiatric complaints which may not have tangible resolutions. 3) The ability to appraise social support networks allowed staff to plan follow-up actions and ensure continuity of care when support was available. 4) The ability to self-reflect allowed participants to learn from their experience and avoid burnout, frustration, and fatigue. Participants also reported several other clinical skills which they gained during training, including teamwork, de-escalating techniques and risk assessment. Tentatively speaking, these skills improve staff's confidence when treating psychiatric emergencies. Certain skills may be generalized to staff working in medical emergency departments who frequently encounter psychiatric complaints.

Provider and Patient Gender Influence on Timing of Do-Not-Resuscitate Orders in Hospitalized Patients with Cancer.

BACKGROUND: End-of-life decisions and advance directives require timely physician-patient discussions but barriers exist to these discussions. OBJECTIVE: To evaluate the influence of physician and patient gender on the timing of inpatient do-not-resuscitate (DNR) orders. DESIGN: Retrospective cohort study. SETTING/SUBJECTS: All adult patients (≥18 years) with cancer who received inpatient DNR orders at The University of Texas MD Anderson Cancer Center between January 2011 and December 2013. MEASUREMENTS: Gender interaction between physicians and patients towards timing of the DNR order. RESULTS: We identified 4,157 unique patients with a cancer diagnosis. These patients were treated by 353 physicians, of whom 123 (34.8%) were females and 230 (65.2%) were males. Multivariate analysis showed female patients were 1.3 times more likely to have early DNR orders written during hospital admission than were male patients (odds ratio [OR] 1.27; 95% confidence interval [CI] 1.07-1.50). When comparing gender interaction between physicians and patients, our results showed that female physicians were 1.5 times more likely to write early DNR orders with their female patients than for their male patients (OR, 1.48; 95% CI, 1.13-1.94). Same gender physician-patient dyads were not found between male physician and their patients (OR, 1.09; 95% CI, 0.91-1.31). Higher age, more comorbid conditions, and progression of diseases were also associated with early DNR orders (all p < 0.01). CONCLUSION: Female patients are more likely to receive early DNR orders from their female physicians. Gender and gender interaction between physician and patients may potentially influence the timing of receiving DNR order.

Flavonoids and phenylethanoid glycosides from Lippia nodiflora as promising antihyperuricemic agents and elucidation of their mechanism of action.

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia nodiflora has been traditionally used in the Ayurvedic, Unani, and Sidha systems, as well as Traditional Chinese Medicine (TCM) for the treatment of knee joint pain, lithiasis, diuresis, urinary disorder and swelling. AIM OF THE STUDY: The present study aims to investigate the antihyperuricemic effect of the L. nodiflora methanol extract, fractions, and chemical constituents and their mechanism of action in the rat model. MATERIALS AND METHODS: The mechanisms were investigated by performing xanthine oxidase inhibitory, uricosuric, and liver xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitory studies in potassium oxonate- and hypoxanthine-induced hyperuricemic rats. The plant safety profile was determined using acute toxicity study. The molecular docking of the active compound to the xanthine oxidase was simulated using computer aided molecular modeling analysis. RESULTS: Oral administration of methanol extract showed a dose-dependent reduction effect on the serum uric acid level of hyperuricemic rats. F3 was the most potent fraction in lowering the serum uric acid level of hyperuricemic rats. Bioactivity-guided purification of F3 afforded two phenylethanoid glycosides, arenarioside (1) and verbascoside (2) and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). The highest serum uric acid reduction effect was exhibited by 3 (66.94%) in hyperuricemic rats, followed by 5 (55.97%), 4 (49.16%), 2 (29.03%), and 1 (22.08%) at 0.2 mmol/kg. Dose-response investigation on 3 at doses of 0.05, 0.1, and 0.3 mmol/kg produced a significant dose-dependent reduction on the serum uric acid level of hyperuricemic rats. Repeated administration of F3 or 3 to the hyperuricemic rats for 10 continuous days resulted in a significant and progressive serum uric acid lowering effect in hyperuricemic rats. In contrast, methanol extract and F3 did not reduce serum uric acid level of normoruricemic rats. In addition, F4 significantly increased the uric acid excretion of hyperuricemic rats at 200mg/kg. No toxic effect was observed in rats administered with 5000 mg/kg of methanol extract or F3. CONCLUSION: The potential application of L. nodiflora against hyperuricemia in the animal in accordance with its traditional uses has been demonstrated in the present study for the first time. The antihyperuricemic effect possessed by L. nodiflora was contributed mainly by liver XOD/XDH inhibitory activities and partially by uricosuric effect. Flavonoids mainly accountable for the uric acid lowering effect of L. nodiflora through the inhibition of XOD/XDH activities.

In vitro Xanthine Oxidase Inhibitory Studies of Lippia nodiflora and Isolated Flavonoids and Phenylethanoid Glycosides as Potential Uric Acid-lowering Agents.

Lippia nodiflora has been traditionally used for treatment of knee joint pain. Hitherto, no studies have been reported on the effective use of L. nodiflora against hyperuricemia, gout or other metabolic disorders. In this present study, L. nodiflora was examined for its ability to lower uric acid levels using an in vitro xanthine oxidase inhibitory assay. The whole plant methanolic extract was subjected to bioactivity-guided fractionation to yield 4 fractions (F1-F4). F3 displayed the highest potency and was further purified by column chromatography to afford two phenylethanoid glycosides, arenarioside (1) and verbascoside (2), and three flavonoids, 6-hydroxyluteolin (3), 6-hydroxyluteolin-7-O-glycoside (4), and nodifloretin (5). These compounds inhibited xanthine oxidase activity, with IC50 values between 7.52 ± 0.01 and 130.00 ± 2.25 µM, of which 3 was the most potent. In contrast, allopurinol, serving as a positive control, was 0.22 ± 0.00 µM. Thus, L. nodiflora, and its chemical constituents are worthy of further studies as potential anti-hyperuricemic agents.

The role of palliative radiotherapy for haemostasis in unresectable gastric cancer: a single-institution experience.

PURPOSE: To evaluate the outcomes of patients with gastric cancer bleeding who had been treated with palliative radiotherapy with haemostatic intent. METHODS AND MATERIALS: Fifty-two gastric cancer patients aged 52-92 years (median 78 years) with active bleeding or anaemia resulting from inoperable gastric cancer were treated with short-course radiotherapy. Responses to radiotherapy treatment were evaluated based on the changes of haemoglobin level, number of transfusions received before and after radiotherapy, and overall median survival. RESULTS: Thirty-nine (75%) patients received single 8 Gy fraction, and 13 (25%) patients received 20 Gy in five daily fractions. The need for transfusion was evaluable in 44 patients, and the response rate was 50%, with less requirement for blood transfusions within four weeks of radiotherapy. There was also an increase in mean haemoglobin level (0.66 ± 1.12 g/dl, p < 0.01) after radiotherapy in 35 evaluable patients. The overall median survival (calculated from last day of treatment to date of death) was 160 days (95% CI of 119-201 days), making actuarial 12-month survival 15%. CONCLUSION: Palliative short-course radiotherapy is a reasonably effective treatment that can provide durable palliation of bleeding in gastric cancer.