Investigation of alkali and alkaline earth solvation structures in tetraglyme solvent.

This study compares molecular calculations performed with molecular and periodic codes through an investigation of the solvation structures of alkali and alkaline earth metal ions in tetraglyme solution. The two codes are able to produce equivalent structural and energetic information at the same level of theory, and in the presence of the implicit solvation model or not. This comparison reveals that molecular optimisations can be performed with periodic codes and used directly as input models for interface or electrochemistry calculations in order to preserve the solvent-solute interaction and the cavitation energy. By a rigorous comparison, we have demonstrated that equivalent energetic values can be obtained with the conventional PBE-D3 and the newly developed SCAN-rVV10 functionals. Nevertheless, as far as the vibrational features are concerned and when the molecule possesses a highly conjugated system, the SCAN-rVV10 functional is required to describe the vibrational modes properly. The computed IR/Raman spectra can thus be used as essential information to determine the first solvation shell of metal ions in glyme-based solutions. In tetraglyme solution, the alkali and alkaline earth metal ions exhibit a diverse solvation structure. Small ions like Li+ and Mg2+ tend to adopt a coordination number of five or six, while larger ions, Na+, K+, and Ca2+, prefer an eight-coordinated environment, and the metal-ligand interaction increases in the order K+-O < Na+-O < Li+-O < Ca2+-O < Mg2+-O. The solvation spheres play a significant role in the stability and the reactivity of the solvated ions, and can thus be used as input models to construct the solvation structure in more sophisticated electrolytes, such as polyethylene oxide, or perform electrochemical calculations.

Structural, optical and conductivity properties in tetragonal BaTi1-x Co x O3 (0≤ x ≤0.1).

This work investigates the structure, optical and electrical conductivity properties of BaTi1-x Co x O3 (0≤ x ≤0.1) ceramics prepared by the hydrothermal method. The X-ray diffraction and Raman scattering analysis demonstrates that the prepared samples have a single-phase tetragonal structure with P4mm symmetry. The UV-vis diffuse reflectance spectrum confirms the influence of Co concentration on the direct optical band gap of BaTi1-x Co x O3 ceramics. The optical band gap shifts from 3.14 eV to 3.44 eV as the Co concentration increases from 0 to 0.1. The dielectric constant increases with the depletion of frequency according to the Maxwell-Wagner and Koops model. The AC conductivity versus frequency curve indicates that the conduction mechanism is determined by using the correlated barrier hopping (CBH) model. The Cole-Cole plot of the complex impedance was investigated for the prepared samples. The compounds showed dielectric relaxation of the non-Debye type.

Sensitive MnFe2O4-Ag hybrid nanoparticles with photothermal and magnetothermal properties for hyperthermia applications.

In this study, we present an experiment showing that designing multifunctional MnFe2O4-Ag nanoparticles to act as a dual hyperthermia agent is an efficient route for enhancing their heating ability. Interestingly, the specific absorption rate of the heteromeric MnFe2O4-Ag nanoparticles increased 2.7 times under simultaneous irradiation of a 100 Oe magnetic field and 0.14 W cm-2 laser compared to the action by the magnetic field alone, and more interestingly, is 30% higher than the sum of the two individual actions. The synergistic benefit of the magneto- and photo-thermal properties of the heteromeric structure can reduce the strengths of the magnetic field and laser intensities as well as their irradiation time to levels lower than those required in their hyperthermia applications individually. In vitro cytotoxicity analysis performed on HepG2 liver cancer and Hela cervical cancer cell lines showed that IC50 values were 83 ± 5.6 µg mL-1 (for HepG2) and 122.6 ± 19.8 µg mL-1 (for Hela cells) after 48 h of incubation, therefore, the nanoparticles are moderately cytotoxic and nontoxic to HepG2 and Hela cells, respectively; which offers the potential of safe therapy.

Correction: Sensitive MnFe2O4-Ag hybrid nanoparticles with photothermal and magnetothermal properties for hyperthermia applications.

[This corrects the article DOI: 10.1039/D1RA03216J.].

Optimal symptom combinations to aid COVID-19 case identification: Analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Optimal symptom combinations to aid COVID-19 case identification: analysis from a community-based, prospective, observational cohort.

OBJECTIVES: Diagnostic work-up following any COVID-19 associated symptom will lead to extensive testing, potentially overwhelming laboratory capacity whilst primarily yielding negative results. We aimed to identify optimal symptom combinations to capture most cases using fewer tests with implications for COVID-19 vaccine developers across different resource settings and public health. METHODS: UK and US users of the COVID-19 Symptom Study app who reported new-onset symptoms and an RT-PCR test within seven days of symptom onset were included. Sensitivity, specificity, and number of RT-PCR tests needed to identify one case (test per case [TPC]) were calculated for different symptom combinations. A multi-objective evolutionary algorithm was applied to generate combinations with optimal trade-offs between sensitivity and specificity. FINDINGS: UK and US cohorts included 122,305 (1,202 positives) and 3,162 (79 positive) individuals. Within three days of symptom onset, the COVID-19 specific symptom combination (cough, dyspnoea, fever, anosmia/ageusia) identified 69% of cases requiring 47 TPC. The combination with highest sensitivity (fatigue, anosmia/ageusia, cough, diarrhoea, headache, sore throat) identified 96% cases requiring 96 TPC. INTERPRETATION: We confirmed the significance of COVID-19 specific symptoms for triggering RT-PCR and identified additional symptom combinations with optimal trade-offs between sensitivity and specificity that maximize case capture given different resource settings.

Hearing loss in pediatric temporal bone fractures: Evaluating two radiographic classification systems as prognosticators.

INTRODUCTION: Temporal bone fractures (TBF) are traditionally classified by their angle of fracture relative to the petrous ridge, and more recently by whether or not they violate the otic-capsule. This study compared rates of hearing loss (HL) and signs of otologic dysfunction among fracture types of both classification systems, within the pediatric population. METHODS: Pediatric patients were retrospectively characterized from a previously identified cohort of TBF patients, diagnosed from 2000 to 2014. CT scans were reviewed and TBFs were classified first as longitudinal (L), transverse (T) or mixed (M), and then as otic-capsule sparing (OCS) or otic-capsule violating (OCV). Medical records were reviewed, and rates of HL and presenting signs were compared among L, T and M fractures, and OCS and OCV fractures. RESULTS: Forty-three patients with 47 TBFs met the inclusion criteria. Eighteen, 4 and 25 TBFs were classified as L, T and M fractures, respectively. Thirty-three and 9 were classified as OCS, and OCV, respectively. Among 24 cases of HL: 20, 3, and 1 were conductive HL (CHL), sensorineural HL (SNHL) and mixed HL, respectively. Two cases of SNHL were found among OCV fractures, with none in OCS fractures (estimated difference 0.22; 95% confidence interval 0.01-0.60). Similar rates of CHL were found across L, T and M fractures (range 36-50%), and across OCV and OCS fractures (range 42-44%). Hemotympanum was the most common presenting sign, found in 68% of TBFs and 80% of CHL cases. There were no significant differences in the incidence of signs or symptoms between fracture types. CONCLUSIONS: In our cohort, both the traditional and otic-capsule radiographic classification systems failed to predict the incidence of CHL and other otologic signs in the pediatric population. Though OCV fractures conferred an increased risk for developing SNHL, we found a lower incidence than anticipated given violation to the bony labyrinth.

Allergen sensitisation among chronic respiratory diseases in urban and rural areas of the south of Viet Nam.

OBJECTIVE: To evaluate the prevalence of and risk factors for allergen sensitisation among patients with chronic respiratory disease (CRD) in southern Viet Nam. DESIGN: An environmental questionnaire and skin prick tests for airborne and food allergens were administered to patients with CRD, defined as individuals with respiratory symptoms and lung function defects. RESULTS: Of 610 CRD patients, 56% had chronic obstructive pulmonary disease and 31% were asthma patients; 80% were males. The most frequent sensitisers were dust mites (Dermatophagoides farinae 22%, Blomia tropicalis 19%, D. pteronyssinus 18%) and cockroach droppings (13%). Among study participants, 37% were from rural settings and 36% from urban areas, whereas 27% had migrated from rural to urban areas. Compared with people from rural areas, being born in an urban area was a risk factor for sensitisation to mites (OR 1.56, 95%CI 1.11-2.20, P < 0.02). In multivariate analysis, place of birth remained a risk factor for mite sensitisation. Compared with the native urban population, the risk of mite sensitisation was not significantly different among patients born in rural areas and those migrating to urban areas. CONCLUSION: Dust mites and cockroach droppings were the most frequent allergens among people with CRD in the south of Viet Nam. Compared with the urban population, being native to a rural area was protective against mite sensitisation, but this effect ceased to be significant after migration from rural to urban areas.

Transcription factor IIIB generates extended DNA interactions in RNA polymerase III transcription complexes on tRNA genes.

Transcription complexes that assemble on tRNA genes in a crude Saccharomyces cerevisiae cell extract extend over the entire transcription unit and approximately 40 base pairs of contiguous 5'-flanking DNA. We show here that the interaction with 5'-flanking DNA is due to a protein that copurifies with transcription factor TFIIIB through several steps of purification and shares characteristic properties that are normally ascribed to TFIIIB: dependence on prior binding of TFIIIC and great stability once the TFIIIC-TFIIIB-DNA complex is formed. SUP4 gene (tRNATyr) DNA that was cut within the 5'-flanking sequence (either 31 or 28 base pairs upstream of the transcriptional start site) was no longer able to stably incorporate TFIIIB into a transcription complex. The TFIIIB-dependent 5'-flanking DNA protein interaction was predominantly not sequence specific. The extension of the transcription complex into this DNA segment does suggest two possible explanations for highly diverse effects of flanking-sequence substitutions on tRNA gene transcription: either (i) proteins that are capable of binding to these upstream DNA segments are also potentially capable of stimulating or interfering with the incorporation of TFIIIB into transcription complexes or (ii) 5'-flanking sequence influences the rate of assembly of TFIIIB into stable transcription complexes.

Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis.

BACKGROUND: The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad-spectrum antibiotics. AIM: To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP. METHODS: A literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta-analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random-effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs). RESULTS: Five studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16-1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19-0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11-0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis. CONCLUSION: Rifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo.

Securing an OTL-HNS residency: how competitive is it? Comparing medical student perceptions to actual Canadian statistics.

BACKGROUND: The residency match is an important event in an aspiring physician's career. Otolaryngology - Head and Neck Surgery (OTL-HNS) is a surgical specialty that has enjoyed high numbers of applicants to its residency programs. However, recent trends in Canada show a decline in first-choice applicants to several surgical fields. Factors thought to influence a medical student's choice include role models, career opportunities and work-life balance. The notion of perceived competitiveness is a factor that has not yet been explored. This study sought to compare competitiveness of OTL-HNS, as perceived by Canadian medical students to residency match statistics published yearly by CaRMS (Canadian Residency Matching Service), with the hope of informing future decisions of surgical residency programs. METHODS: An electronic survey was created and distributed to all medical students enrolled in the 17 Canadian medical schools. After gathering demographic information, students were asked to rank what they perceived to be the five most competitive disciplines offered by CaRMS. They were also asked to rank surgical specialties from most to least competitive. Publically available data from CaRMS was then collected and analyzed to determine actual competitiveness of admissions to Canadian OTL-HNS residency programs. RESULTS: 1194 students, from first to fourth year of medical school, completed the survey. CaRMS statistics over the period from 2008 to 2014 demonstrated that the five most competitive specialties were Plastic Surgery, Dermatology, Ophthalmology, Emergency Medicine and OTL-HNS. Among surgical disciplines, OTL-HNS was third most competitive, where on average 72% of students match to their first-choice discipline. When students were questioned, 35% ranked OTL-HNS amongst the top five most competitive. On the other hand 72%, 74% and 80% recognized Opthalmology, Dermatology and Plastic Surgery as being among the five most competitive, respectively. We found that fourth-year medical students were significantly more knowledgeable about the competitiveness of both OTL-HNS and Plastic Surgery compared to first-year students (p < 0.01). CONCLUSION: Overall, Canadian medical students may underestimate the competitiveness of OTL-HNS. Furthermore, competitiveness would appear to be a concept that resonates with medical students during the match process.

Pediatric temporal bone fractures: A case series.

OBJECTIVES: Temporal bone fractures are relatively common findings in patients with head trauma. The aim of this study was to evaluate the characteristics of temporal bone fractures in the pediatric population. STUDY DESIGN: Retrospective case series. Tertiary care pediatric academic medical center. METHODS: The medical records of patients aged 18 years or less diagnosed with a temporal bone fracture at the Montreal Children's Hospital from January 2000 to August 2014 were reviewed. Patient demographics, clinical presentation, mechanism of injury and complications were analyzed. Imaging studies and audiograms were also evaluated. RESULTS: Out of 323 patients presenting to the emergency department with a skull fracture, 61 presented with a temporal bone fracture. Of these, 5 presented with bilateral fractures. 47 patients had associated fractures, and 3 patients deceased. We observed a male to female ratio of 2.8:1, and the average age was 9.5 years. Motor vehicle accidents were the primary mechanism of injury (53%), followed by falls (21%) and bicycle or skateboard accidents (10%). The most common presenting signs included hemotympanum, decreased or loss of consciousness, facial swelling and nausea and vomiting. 8 patients had otic involvement on computed tomography scans, and 30 patients had documented hearing loss near the time of accident with a majority being conductive hearing loss. 17 patients underwent surgical management of intracranial pressure. CONCLUSION: In children, fractures of the temporal bone were most often caused by motor vehicle accidents and falls. It is common for these patients to have associated fractures.

Ethnic differences in incidence of hepatitis B surface antigen seroclearance in a real-life multicenter clinical cohort of 4737 patients with chronic hepatitis B infection.

BACKGROUND: Hepatitis B surface antigen (HBsAg) positivity is associated with increased risk for cirrhosis and hepatocellular carcinoma (HCC). HBsAg seroclearance is thought to be rare in general, but cohort data from US patients are limited. AIM: To determine the incidence of HBsAg seroclearance in a real-life US cohort. METHODS: In total, 4737 patients with chronic hepatitis B from five primary care, gastroenterology and multispecialty centres, and a university medical centre were retrospectively enrolled between 2001 and 2014 with data obtained by manual review of individual patient medical records. Seroclearance was determined by loss of HBsAg seropositivity. Persistent HBsAg was confirmed by direct serology or by proxy with positive hepatitis B e-antigen (HBeAg) or HBV DNA levels. RESULTS: HBsAg seroclearance occurred in 52 patients over 16 844 person-years (0.31% annually, 1.2% overall). Median follow-up was 32 months, and mean age 45 ± 14 years. Incidence of HBsAg seroclearance was higher in non-Asians, age >45, males, and those with baseline HBV DNA ≤10 000 IU/mL. On multivariate Cox proportional modelling, non-Asian ethnicity (HR 2.8), male sex (HR 2.1), baseline HBVDNA ≤10 000 (HR 2.0) and age >45 (HR 1.8) were significant independent predictors of seroclearance. CONCLUSION: HBsAg seroclearance rates were lower than previously described in this real-life cohort of patients with chronic hepatitis B, especially among Asian, female and younger patients.

Mapping the protein-DNA interface and the metal-binding site of the major human apurinic/apyrimidinic endonuclease.

Apurinic/apyrimidinic (AP) endonuclease Ape1 is a key enzyme in the mammalian base excision repair pathway that corrects AP sites in the genome. Ape1 cleaves the phosphodiester bond immediately 5' to AP sites through a hydrolytic reaction involving a divalent metal co-factor. Here, site-directed mutagenesis, chemical footprinting techniques, and molecular dynamics simulations were employed to gain insights into how Ape1 interacts with its metal cation and AP DNA. It was found that Ape1 binds predominantly to the minor groove of AP DNA, and that residues R156 and Y128 contribute to protein-DNA complex stability. Furthermore, the Ape1-AP DNA footprint does not change along its reaction pathway upon active-site coordination of Mg(2+) or in the presence of DNA polymerase beta (polbeta), an interactive protein partner in AP site repair. The DNA region immediately 5' to the abasic residue was determined to be in close proximity to the Ape1 metal-binding site. Experimental evidence is provided that amino acid residues E96, D70, and D308 of Ape1 are involved in metal coordination. Molecular dynamics simulations, starting from the active site of the Ape1 crystal structure, suggest that D70 and E96 bind directly to the metal, while D308 coordinates the cation through the first hydration shell. These studies define the Ape1-AP DNA interface, determine the effect of polbeta on the Ape1-DNA interaction, and reveal new insights into the Ape1 active site and overall protein dynamics.

Oral acyclovir after penetrating keratoplasty for herpes simplex keratitis.

OBJECTIVE: To determine the efficacy of systemic acyclovir in decreasing complications and improving the outcome of penetrating keratoplasty for herpes simplex virus (HSV) keratitis. METHODS: Retrospective study of 53 primary penetrating keratoplasties for HSV keratitis at an eye hospital from January 1, 1989, through December 31, 1996. Medical records were analyzed for history of HSV keratitis, preoperative neovascularization, and disease activity. Postoperative use of acyclovir, recurrence of HSV keratitis, rejection, uveitis or edema, and graft failure were evaluated. RESULTS: Twenty-four patients (mean +/- SD follow-up, 44.7 +/- 32.6 months) received no acyclovir and were compared with 20 patients, (mean +/- SD follow-up, 28.8 +/- 16.7 months), who received 400 mg acyclovir twice a day for at least 1 year. No patient in the acyclovir group had a recurrence of dendritic keratitis in the first year compared with 5 (21%) of the patients who did not receive acyclovir (P = .03). No patient had graft failure in the acyclovir group compared with 4 (17%) in the group without acyclovir after 1 year of follow-up (P = .06). CONCLUSION: Postoperative systemic acyclovir therapy after penetrating keratoplasty for HSV keratitis is associated with a reduced rate of recurrent HSV dendritic keratitis and possible graft failure at 1 year of follow-up.

Xanthones and triterpenoids from the bark of Garcinia vilersiana.

The hexane extract of the bark of Garcinia vilersiana from Vietnam contained four triterpenoids (olean-12-ene-3beta,11alpha-diol, lupeol, beta-amyrin and oleanolic acid), and six xanthones (globuxanthone, subelliptenone H, subelliptenone B, 12b-hydroxy-des-D-garcigerrin A, 1-O-methylglobuxanthone and symphoxanthone). The structure of 1-O-methylglobuxanthone, the only novel compound, was determined using 1D and 2D NMR techniques and by correlation with globuxanthone.

Recovery of locomotor function after hemisection of the spinal cord in cats.

Cats were subjected to high lumbar hemisection of the spinal cord, on the right side. The initial paralysis of the right hindlimb became rapidly attenuated, and they walked again in one week or less after surgery. Minor residual deficits in gait remained, that may be permanent. Electrical stimulation of the bulbar reticulospinal formation showed residual crossed connections reaching the right lumbosacral cord via the left hemicord. Recovery from Brown-Séquard's syndrome may be primarily due to the survival of low crossing descending projections to the spinal cord.

Transsynaptic degeneration of motoneurones caudal to spinal cord lesions.

We studied the effects of complete transversal section of the spinal cord, at T8-10, in adult rats, upon the number and morphology of identified motoneurones in lumbar segments L4 and L5. In observations by light and electron microscopy many lumbar motoneurones had structural abnormalities when the interval between surgery and perfusion ranged between a few hours and one week. We found also that as many as 25% of the motoneurones distal to a cord transection disappeared as a consequence of the lesions. We did not find comparable changes in the spinal cord at C6 after transection at T8-10. Complete removal of the cerebellum did not reduce the lumbar motoneurone counts. Bilateral ablation of the "motor" cortex did cause a reduction of motoneurone counts at L4-5; these animals showed normal or near normal spontaneous locomotor activity beginning a few days after the lesion was placed. Motoneurone counts were significantly reduced after partial cord lesions that spared the dorsal funiculi (where the corticospinal tract travels in the rat), but in this case the rats were paraplegic as a result of the lesion. Cord transection at 7 days of postnatal age resulted in reduced motoneurone counts when the rats reached adulthood. Intraspinal or subarachnoid administration of colchicine led to reduced motoneurone counts. Prolonged infusion of a GABA agonist, muscimol, into the lumbar CSF did not prevent the loss of motoneurones produced by cord transection. Pretreatment of animals with a Ca2+ channel blocker (nimodipine) did not prevent the effects of cord transection.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer databases for the sentinel lymph node program.

At the University of California San Francisco Comprehensive Cancer Center, a computer database system was created using the FileMaker Pro database program. The system allows the clinical team to bring together data from all aspects of a multidisciplinary effort toward improving daily clinical management, for research, and ultimately, for the clinical standard of care for melanoma patients. With modest objectives during the initiation of the database, its adaptability has allowed it to become an integral link in all the efforts of the melanoma program. For the future, tapping into the immense potential of the Internet has begun to organize multicenter efforts. Through nationwide collaboration, the Sentinel Lymph Node Working Group will be able to follow, on a larger scale, the successes of the FileMaker pro database at the UCSF Comprehensive Cancer Center.