Long-term follow-up of G3T1 transitional cell carcinoma of the bladder treated with intravesical bacille Calmette-Guérin: 18-year experience.
Immunotherapy with bacille Calmette-Guérin (BCG) has been proposed in the past decade as first-line treatment for high-grade superficial bladder cancer (G3T1). We report our 18-year experience in the treatment of patients with G3T1 bladder cancer. From January 1989 to July 1997, 670 patients underwent transurethral resection for superficial bladder cancer. Eighty-one patients (12%) had G3T1 tumors. All of these patients were treated with an innovative schedule of Pasteur strain BCG followed by maintenance BCG therapy. Treatment consisted of four cycles of 6 instillations per cycle of BCG. The first cycle was administered weekly x 6, the second was given every 2 weeks x 6, the third cycle was given monthly x 6, and the fourth was given every 3 months x 6 instillations. Sixty-nine patients (84%) completed at least the first two cycles. At a median follow-up of 76 months (range 30 to 197), the overall recurrence rate was 33% (27 of 81). The median time to recurrence was 20 months (range 5 to 128). Of these patients, 12 (15%) had progression at a median follow-up of 16 months (range 8 to 58). Cystectomy was required in 7 patients (8%). Death from disease occurred in 5 (6%) of 81 patients. One patient died of adenocarcinoma at the ureterosigmoidostomy site. Sixty patients (74%) were alive at a median follow-up of 79+ months (range 15 to 182). Of these, 56 (69%) were alive with a functioning bladder. Conservative treatment with BCG is a reasonable approach for patients with primary G3T1 transitional cell carcinoma of the bladder. The long-term results of BCG therapy are good. Cystectomy may not be justified as the therapy of choice in first-line treatment of high-grade superficial carcinoma of the bladder.


PCR-based markers for the powdery mildew resistance gene Pm4a in wheat.
Gene tagging is the basis of marker-assisted selection and map-based cloning. To develop PCR-based markers for Pm4a, a dominant powdery mildew resistance gene of wheat, we surveyed 46 group 2 microsatellite markers between Pm4a near-isogenic line (NIL) CI 14124 and the recurrent parent Chancellor (Cc). One of the markers, gwm356, detected polymorphism and was used for genotyping an F(2) population of 85 plants derived from CI 14124 x Cc. Linkage mapping indicated that Xgwm356 was linked to Pm4a at a distance of 4.8 cM. To identify more PCR-based markers for Pm4a, we also converted the restriction fragment length polymorphism marker BCD1231 linked to it into a sequence-tagged site (STS) marker. The STS primer designed based on the end sequences of BCD1231 amplified an approximately 1.6-kb monomorphic band in both parents. Following digestion of the products with the four-cutter enzymes HaeIII and MspI, it was discovered that the band from CI 14124 consisted of at least two products, one of which had a digestion pattern different from the band from Cc. In the F(2) population, the cleaved polymorphism revealed by the STS marker between the parents co-segregated with powdery mildew resistance. To design Pm4a-specific PCR markers, the 1.6-kb band from Cc and the fragment associated with Pm4a in CI 14124 were sequenced and compared. Based on these sequences a new PCR marker was identified, which detected a 470-bp product only in the Pm4a-containing lines. These PCR-based markers provide a cost-saving option for marker-assisted selection of Pm4a.


Harmonic dynamics of a DNA hexamer in the absence and presence of the intercalator ethidium.
Vibrational normal mode calculations are presented for a DNA hexanucleoside pentaphosphate, d(CpGpCpGpCpG)2, and for its complex with the cationic intercalator ethidium. Two intercalation sites are modeled that differ in DNA backbone torsion angles. Normal mode frequencies for the DNA fragment itself are significantly lower than those reported earlier using different force fields, but an analysis of "effective" frequencies suggests that somewhat higher frequencies are more appropriate. Intercalation leads to significant lowering of mobility for the base pairs adjacent to the drug; in this sequence, the ethidium binding affects the guanosine atoms more strongly than the cytosine atoms. Motions of the bases and the intercalator are analyzed in terms of "twist" about the local helix axis and a "tilt" angle relative to this axis, and the results are compared to fluorescence studies of ethidium-DNA complexes.


Organ and tissue donation: a survey of nurse's knowledge and educational needs in an adult ITU.
The aim of this paper is to present the results of a survey that was undertaken to assess nurses' knowledge and educational needs towards organ donation within one adult general intensive care unit. The survey consists of 31 registered nurses who completed a confidential questionnaire that aimed to assess their existing knowledge and deficits in organ and tissue donation. The survey highlights the sample lacked confidence in approaching relatives for donation consent, deficits in brain stem death testing and donor criteria. It was also apparent that a significant number of nurses could not identify which tissues can be donated and the contraindications for tissue donation. A majority of the sample stated their knowledge of donation issues would improve if an educational programme were developed on organ donation. This is further supported by previous work by [Bidigare S, Oermann M, 1991. Attitudes and knowledge of nurses regarding organ procurement. Heart & lung 1:20-3; Smith-Brew S, Yanai L, 1996. The organ donation process through a review of the literature. Part 1. Accident & emergency nursing 4:5-11; Roark D, 2000. Overhauling the organ donation system. Am J Nurs 6:44-9] who suggest that educational programmes covering donation issues should enhance nurses' knowledge and confidence in the organ donation process and ultimately increase the number of potential donors.


Decreased warfarin clearance associated with the CYP2C9 R150H (*8) polymorphism.
The cytochrome P450 (CYP) 2C9 R150H (*8) allele occurs commonly in African Americans and is associated with lower warfarin dose requirements. We conducted a pharmacokinetic study to examine whether the CYP2C9*8 allele impacts warfarin clearance in African-American patients. We also conducted an in vitro kinetic study of S-warfarin 7-hydroxylation using complementary DNA (cDNA)-expressed CYP2C9 enzymes. We observed a 30% reduction in the unbound oral clearance of S-warfarin and a 25% lower R- to S-warfarin plasma concentration ratio in patients with the CYP2C9*8 allele (n = 12) as compared to CYP2C9*1 homozygotes (n = 26). Consistent with these findings, the in vitro intrinsic clearance of S-warfarin was 30% lower with the cDNA-expressed R150H protein as compared to the wild-type protein. These data show that the R150H variant protein expressed by the CYP2C9*8 allele is associated with lower S-warfarin clearance. This finding provides clinical and experimental evidence to explain the lower warfarin dose requirements in patients with the CYP2C9*8 allele.


Factors associated with psychological impact of celebrity suicide media coverage: An online survey study.
We investigated factors associated with vulnerability to the psychological impact of celebrity suicide news reporting after the suicide of an emerging Taiwanese novelist, Ms Yi-Han Lin. We conducted a cross-sectional online survey. Participants completed a questionnaire which asked whether they were affected by the media coverage of Lin's suicide and whether they would seek help if affected. Logistic regression was used to identify factors associated with being affected by the celebrity suicide media reporting and, among those affected, factors associated with feeling suicidal or not seeking help. A total of 1258 respondents (81% females) completed the survey. Affected individuals (n=907; 70%) were more likely to be females, younger (age < 40 years), have past psychiatric treatment, and show increased interest in the incident (e.g., spending more time on reading the celebrity suicide news) than non-affected individuals. Among those affected, negative views of the media reporting impact, pessimistic attitude toward both depression treatment and suicide prevention, and having a history of past psychiatric treatment were associated with feeling suicidal, while low education attainment, increased interest in the celebrity suicide, and permissive attitude toward inappropriate media reporting were additionally associated with not seeking help. Selection bias of participants through internet-based surveying should be considered. Individuals affected by the media coverage of celebrity suicide showed similar demographic and mental health characteristics as those of the deceased celebrity. Poor mental health and suicide prevention literacy may increase the risk of psychological impact and not seeking help. Future interventions could target at enhancing mental health literacy and help seeking intention in vulnerable individuals.


MOF-derived N-doped ZnO carbon skeleton@hierarchical Bi2MoO6 S-scheme heterojunction for photodegradation of SMX: Mechanism, pathways and DFT calculation.
Semiconductor photocatalytic degradation of pollutants is considered to be one of the promising sustainable energy routes. Nevertheless, it is challenging for photocatalysts to have excellent visible light absorption and suppress photo-generated electron-hole recombination at the same time. Here, we prepared nitrogen-doped ZnO carbon skeleton by directly calcining the metal-organic framework. Then hierarchical Bi2MoO6 nanosheets are grown in situ on its surface to synthesize S-scheme heterojunction. This special 3D layered and oxygen vacancies work together to make photo-generated electrons and holes easier to separate and migrate. Therefore, the pseudo-first-order kinetic constant of N-doped ZnO carbon skeleton@Bi2MoO6 degradation of sulfamethoxazole reaches 0.022 min-1, which is almost 10 times that of ZIF-8 derived ZnO and 27.5 times Bi2MoO6 under visible light irradiation. Meanwhile, the mechanism of driving charge transfer of S-scheme heterojunction, and the photocatalytic degradation pathway of sulfamethoxazole are also analyzed. This work will provide a new way to construct S-scheme heterojunction photocatalyst to degrade antibiotic pollutants.


Changes and relations of photosynthesis and iron cycling in anoxic paddy soil amended with high concentrations of sulfate.
Sulfate contamination is an increasingly serious environmental problem related to microbial reduction processes in anoxic paddy soil. This study revealed the changes and interrelations of ferric iron [Fe(III)] reduction, ferrous iron [Fe(II)] oxidation, and oxygenic photosynthesis in an anoxic paddy soil (Fe-accumuli-Stagnic Anthrosols) amended with a range of high sulfate concentrations. Soil slurries mixed with 0 (control), 50, 100, 200, and 400 mmol kg-1 Na2SO4 were incubated anaerobically under dark and light conditions. The changes in chlorophyll a (Chl a), Fe(II), pH levels, and the chlorophyll absorption spectrum were determined over a 42-day period. Fe(II) concentrations increased with the addition of sulfate under dark conditions, while Fe(III) reduction potential was enhanced by increasing sulfate addition. The effect of light on Fe(II) concentration was observed after 16 days of incubation, when Fe(II) started to decrease markedly in the control. The decrease in Fe(II) slowed with increasing sulfate addition. The concentrations of Chl a increased in all treatments after 16 days of incubation under light conditions. There was a reduction in Chl a accumulation with increasing sulfate at the same incubation time. The absorption peaks of chlorophyll remained shorter than the 700-nm wavelength throughout the incubation period. The pH of all treatments decreased in the first week and then increased thereafter. The pH increased with sulfate addition and light conditions. In conclusion, contamination with high concentrations of sulfate could accelerate Fe(III) reduction while inhibiting oxygenic photosynthesis, which correspondingly slows chemical Fe(II) oxidation in an anoxic paddy soil.


The DASH complex and Klp5/Klp6 kinesin coordinate bipolar chromosome attachment in fission yeast.
We identified a truncated allele of dam1 as a multicopy suppressor of the sensitivity of cdc13-117 (cyclin B) and mal3-1 (EB-1) cells to thiabendazole, a microtubule poison. We find that Dam1 binds to the plus end of spindle microtubules and kinetochores as cells enter mitosis and this is dependent on other components of the fission yeast DASH complex, including Ask1, Duo1, Spc34 and Dad1. By contrast, Dad1 remains bound to kinetochores throughout the cell cycle and its association is dependent on the Mis6 and Mal2, but not Mis12, Nuf2 or Cnp1, kinetochore proteins. In cells lacking Dam1, or other components of the DASH complex, anaphase is delayed due to activation of the spindle assembly checkpoint and lagging sister chromatids are frequently observed and occasionally sister chromatid pairs segregate to the same spindle pole. We find that the mitotic centromere-associated Klp5/Klp6 kinesin complex is essential in cells lacking components of the DASH complex. Cells lacking both Dam1 and Klp5 undergo a first cell cycle arrest in mitosis due to a failure to establish bipolar chromosome attachment.


Standardization of Galleria mellonella as an Infection Model for Malassezia furfur and Malassezia pachydermatis.
Galleria mellonella larva has been widely exploited as an infection model for bacteria and fungi. Our laboratory uses this insect as a model for fungal infection caused by the genus Malassezia, in particular, systemic infections caused by Malassezia furfur and Malassezia pachydermatis, which are poorly understood. Here, we describe the G. mellonella larva inoculation process with M. furfur and M. pachydermatis and the posterior assessment of the establishment and dissemination of the infection in the larvae. This assessment was done through the evaluation of larval survival, melanization, fungal burden, hemocytes populations, and histological changes. This methodology allows for the identification of virulence patterns between Malassezia species and the impact of inoculum concentration and temperature.


Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations.
Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Here, we describe the first characterization and neuronal differentiation of induced pluripotent stem (iPS) cells derived from Mecp2-deficient mice. Fully reprogrammed wild-type (WT) and heterozygous female iPS cells express endogenous pluripotency markers, reactivate the X-chromosome and differentiate into the three germ layers. We directed iPS cells to produce glutamatergic neurons, which generated action potentials and formed functional excitatory synapses. iPS cell-derived neurons from heterozygous Mecp2(308) mice showed defects in the generation of evoked action potentials and glutamatergic synaptic transmission, as previously reported in brain slices. Further, we examined electrophysiology features not yet studied with the RTT iPS cell system and discovered that MeCP2-deficient neurons fired fewer action potentials, and displayed decreased action potential amplitude, diminished peak inward currents and higher input resistance relative to WT iPS-derived neurons. Deficiencies in action potential firing and inward currents suggest that disturbed Na(+) channel function may contribute to the dysfunctional RTT neuronal network. These phenotypes were additionally confirmed in neurons derived from independent WT and hemizygous mutant iPS cell lines, indicating that these reproducible deficits are attributable to MeCP2 deficiency. Taken together, these results demonstrate that neuronally differentiated MeCP2-deficient iPS cells recapitulate deficits observed previously in primary neurons, and these identified phenotypes further illustrate the requirement of MeCP2 in neuronal development and/or in the maintenance of normal function. By validating the use of iPS cells to delineate mechanisms underlying RTT pathogenesis, we identify deficiencies that can be targeted for in vitro translational screens.


Vascular anatomy of flexor tendons. I. Vincular system and blood supply of the profundus tendon in the digital sheath.
The detailed blood supply of the flexor tendons in the digital canal was studied in 35 fresh human hands by means of an India ink-latex vascular injection technique. The specimens were examined by first exposing the pulley system, followed by examination of the intact tendon which had been rendered transparent by immersion in a solution of tributyl and tricresyl phosphate. Five annular and three cruciform pulleys were shown. There were five types of long vincula to the profundus (VLP) and three types of long vincula to the superficialis (VLS). The vincular systems of index and little fingers were symmetrical. Occasionally, neither the VLP nor the VLS was found in either the long or the ring fingers. The vincula received blood supply from four transverse branches of the digital arteries. A volar avascular area of the profundus tendon was seen in the cleared cross-sections, and the cross-over zone of its intrinsic vessels was found to be at the midproximal phalanx.


STAT3 phosphorylation inhibition for treating inflammation and new bone formation in ankylosing spondylitis.
AS is a rheumatic disease characterized by chronic inflammation and bony ankylosis. This study was to evaluate whether a signal transducer and activator of transcription 3 phosphorylation inhibitor (stat3-p Inh) could treat both chronic inflammation and bone formation in AS. Primary AS osteoprogenitor cells and spinal entheseal cells were examined for osteogenic differentiation. SF mononuclear cells (SFMCs) and lamina propria mononuclear cells (LPMCs) were obtained from AS patients. Inflammatory cytokine-producing cells were analysed using flow cytometry and ELISA. Female SKG mice were treated with stat3-p Inh, IL-17A blocker or vehicle. Inflammation and new bone formation were evaluated using immunohistochemistry, PET and micro-CT. In the SKG mouse model, stat3-p Inh significantly suppressed arthritis, enthesitis, spondylitis and ileitis. In experiments culturing SFMCs and LPMCs, the frequencies of IFN-γ-, IL-17A- and TNF-α-producing cells were significantly decreased after stat3-p Inh treatment. When comparing current treatments for AS, stat3-p Inh showed a comparable suppression effect on osteogenesis to Janus kinase inhibitor or IL-17A blocker in AS-osteoprogenitor cells. Stat3-p Inh suppressed differentiation and mineralization of AS-osteoprogenitor cells and entheseal cells toward osteoblasts. Micro-CT analysis of hind paws revealed less new bone formation in stat3-p Inh-treated mice than vehicle-treated mice (P = 0.005). Hind paw and spinal new bone formation were similar between stat3-p Inh- and anti-IL-17A-treated SKG mice (P = 0.874 and P = 0.117, respectively). Stat-3p inhibition is a promising treatment for both inflammation and new bone formation in AS.


A cost-aware framework for the development of AI models for healthcare applications.
Accurate artificial intelligence (AI) for disease diagnosis could lower healthcare workloads. However, when time or financial resources for gathering input data are limited, as in emergency and critical-care medicine, developing accurate AI models, which typically require inputs for many clinical variables, may be impractical. Here we report a model-agnostic cost-aware AI (CoAI) framework for the development of predictive models that optimize the trade-off between prediction performance and feature cost. By using three datasets, each including thousands of patients, we show that relative to clinical risk scores, CoAI substantially reduces the cost and improves the accuracy of predicting acute traumatic coagulopathy in a pre-hospital setting, mortality in intensive-care patients and mortality in outpatient settings. We also show that CoAI outperforms state-of-the-art cost-aware prediction strategies in terms of predictive performance, model cost, training time and robustness to feature-cost perturbations. CoAI uses axiomatic feature-attribution methods for the estimation of feature importance and decouples feature selection from model training, thus allowing for a faster and more flexible adaptation of AI models to new feature costs and prediction budgets.


Biomechanical Implications of Mandibular Flexion on Implant-Supported Full-Arch Rehabilitations: A Systematic Literature Review.
Mandibular flexion (MF) is a complex biomechanical phenomenon, which involves a deformation of the mandible, due mainly to the contraction of the masticatory muscles, and it can have numerous clinical effects. The deformation of the lower jaw caused by mandibular flexion is generally very small, and it is often overlooked and considered irrelevant from a clinical point of view by many authors; however, it should be important to remember that median mandibular flexure (MMF) has a multifactorial aetiology. The main aim of the current systematic review is to highlight the different factors that can increase MF in order to help clinicians identify patients to whom they should pay more attention. As a secondary outcome, we wanted to analyse the preventive measures and suitable techniques to be adopted to minimise the negative effects of this phenomenon on oral fixed rehabilitations. The review, which was carried out in accordance with the "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) flowchart, was recorded in the "International Prospective Register of Systematic Reviews" (PROSPERO). As research questions, "Patient/Population, Intervention, Comparison and Outcomes" (PICO) questions were employed. Using the ROBINS-I technique, the risk of bias in non-randomised clinical studies was evaluated. The initial electronic search identified over 1300 potential articles, of which 54 studies were included in this systematic review. Information regarding the relationship between MF and individual factors, mandibular movements, impression taking, and fixed rehabilitations were obtained. The studies included in this systematic review showed that MF is greater during protrusive movements, in the posterior areas of the lower jaw, and in patients with brachial facial type, greater jaw length; small gonial angle; and less density, length, and bone surface of the symphysis. The biomechanical effects of mandibular flexion on fixed restorations are debated. Prospective clinical and radiological observational studies should be conducted to evaluate the potential short-, medium-, and long-term consequences of MF.


Intracavity hyperthermia in nasopharyngeal cancer: a phase III clinical study.
To compare the local tumour control, survival, and acute mucous toxicity of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy (RT) combined with intracavity hyperthermia versus conventional RT alone. Previously untreated NPC patients were assigned randomly into the conventional RT group and the hyperthermia group. In addition to curative RT, hyperthermia group patients received intracavity hyperthermia before or after RT; T90 was 42.5°-43°C for 50 min twice a week for 7 weeks. From August 2001 to July 2006, 180 eligible patients with NPC were enrolled in this study. The complete response (CR) rate in the two arms (RT plus hyperthermia versus conventional RT) was 95.6% and 81.1%, respectively (p = 0.003, χ² test). CR rates for T2 and T3 patients in the hyperthermia group were 97.1% and 96.9%, respectively, while in the conventional RT group they were 79.5% and 76.7%, respectively. The difference between the two groups was statistically significant (p = 0.03 and p = 0.024, respectively). The 5-year local control rate was 91.1% and 78.9% for the two arms, respectively (p = 0.022). Oral mucous toxicity in both arms was comparable. The 5-year PFS and 5-year OS rate for the hyperthermia arm vs. the conventional arm were 72.7% versus 63.1% (p = 0.039) and 78.2% versus 70.3% (p = 0.14), respectively. Conventional RT treatment followed by intracavity hyperthermia was well tolerated by the NPC patients. The addition of hyperthermia improved the local tumour control, and our results indicated a positive impact on PFS of NPC patients.


Economics at the FCC 2021-22: 5G Spectrum Auctions, Affordable Connectivity, Broadband Data Collection, and Merger Review.
The Federal Communications Commission (FCC) is responsible for regulation in the communications marketplace and for management of the nation's non-federal radio spectrum. During the past year, FCC economists continued to work on auctions so as to repurpose mid-band spectrum for advanced wireless services - including 5G - as well as initiatives to close the connectivity gap and make broadband more affordable. FCC economists also evaluated the likely competitive effects of Verizon's proposed acquisition of prepaid competitor TracFone Wireless. Finally, FCC economists helped in setting up the novel Broadband Data Collection.


ClC-3B, a novel ClC-3 splicing variant that interacts with EBP50 and facilitates expression of CFTR-regulated ORCC.
We have cloned ClC-3B, a novel alternative splicing variant of ClC-3 (ClC-3A) that is expressed predominantly in epithelial cells. ClC-3B has a different, slightly longer C-terminal end than ClC-3A and contains a consensus motif for binding to the second PDZ (PSD95/Dlg/ZO-1) domain of the epithelium-specific scaffolding protein EBP50. Both in vitro and in vivo binding assays demonstrate interaction between ClC-3B and EBP50. C127 mouse mammary epithelial cells transfected with ClC-3B alone showed diffuse immunoreactivity for ClC-3B in the cytoplasmic region. In contrast, when EBP50 was cotransfected with ClC-3B, strong immunoreactivity for ClC-3B appeared at the leading edges of membrane ruffles. Patch-clamp experiments revealed that cotransfection of ClC-3B and EBP50 resulted in a remarkable increase in outwardly rectifying Cl- channel (ORCC) activities at the leading edges of membrane ruffles in C127 cells. The electrophysiological properties of the ClC-3B-induced ORCCs are similar to those of ORCCs described in native epithelial cells. When cystic fibrosis transmembrane conductance regulator (CFTR) was cotransfected with ClC-3B and EBP50, ClC-3B-dependent ORCCs were activated via the protein kinase A-dependent pathway. These findings indicate that ClC-3B is itself a CFTR-regulated ORCC molecule or its activator.


Circulating leptin and adiponectin concentrations in healthy exceptional longevity.
People reaching exceptional longevity free of major age-related diseases represent the paradigm of successful aging. Adipose tissue function declines as we age, potentially resulting in changes of circulating adipokines (e.g., leptin and adiponectin). Here, we measured circulating levels of leptin and adiponectin in healthy centenarians (n=81; 100-104 years) and younger elderly controls (n=46; 70-80 years). Centenarians had significant higher serum levels of leptin compared with controls (p<0.001), whereas no significant differences were observed for adiponectin. Further research including also other blood variables will be needed to elucidate whether high leptin levels could serve as a hallmark of healthy exceptional longevity.


Early Invasive Strategy for Unstable Angina: a New Meta-Analysis of Old Clinical Trials.
Randomized controlled trials (RCTs) were conflicting to support whether unstable angina versus non-ST-elevation myocardial infarction (UA/NSTEMI) patients best undergo early invasive or a conservative revascularization strategy. RCTs with cardiac biomarkers, in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from 1975-2013 were reviewed considering all cause mortality, recurrent non-fatal myocardial infarction (MI) and their combination. Follow-up lasted from 6-24 months and the use of routine invasive strategy up to its end was associated with a significantly lower composite of all-cause mortality and recurrent non-fatal MI (Relative Risk [RR] 0.79; 95% confidence interval [CI], 0.70-0.90) in UA/NSTEMI. In NSTEMI, by the invasive strategy, there was no benefit (RR 1.19; 95% CI, 1.03-1.38). In the shorter time period, from randomization to discharge, a routine invasive strategy was associated with significantly higher odds of the combined end-point among UA/NSTEMI (RR 1.29; 95% CI, 1.05-1.58) and NSTEMI (RR 1.82; 95% CI, 1.34-2.48) patients. Therefore, in trials recruiting a large number of UA patients, by routine invasive strategy the largest benefit was seen, whereas in NSTEMI patients death and non-fatal MI were not lowered. Routine invasive treatment in UA patients is accordingly supported by the present study.


Mobile sensors based platform of Human Physical Activities Recognition for COVID-19 spread minimization.
The development of smartphones technologies has determined the abundant and prevalent computation. An activity recognition system using mobile sensors enables continuous monitoring of human behavior and assisted living. This paper proposes the mobile sensors-based Epidemic Watch System (EWS) leveraging the AI models to recognize a new set of activities for effective social distance monitoring, probability of infection estimation, and COVID-19 spread prevention. The research focuses on user activities recognition and behavior concerning risks and effectiveness in the COVID-19 pandemic. The proposed EWS consists of a smartphone application for COVID-19 related activities sensors data collection, features extraction, classifying the activities, and providing alerts for spread presentation. We collect the novel dataset of COVID-19 associated activities such as hand washing, hand sanitizing, nose-eyes touching, and handshaking using the proposed EWS smartphone application. We evaluate several classifiers such as random forests, decision trees, support vector machine, and Long Short-Term Memory for the collected dataset and attain the highest overall classification accuracy of 97.33%. We provide the Contact Tracing of the COVID-19 infected person using GPS sensor data. The EWS activities monitoring, identification, and classification system examine the infection risk of another person from COVID-19 infected person. It determines some everyday activities between COVID-19 infected person and normal person, such as sitting together, standing together, or walking together to minimize the spread of pandemic diseases.


On the mechanistic derivation of various discrete-time population models.
We present a derivation of various discrete-time population models within a single unifying mechanistic context. By systematically varying the within-year patterns of reproduction and aggression between individuals we can derive various discrete-time population models. These models include classical examples such as the Ricker model, the Beverton-Holt model, the Skellam model, the Hassell model, and others. Some of these models until now lacked a good mechanistic interpretation or have been derived in a different context. By using this mechanistic approach, the model parameters can be interpreted in terms of individual behavior.


Colposcopic evaluation of abnormal Papanicolaou smears in pregnancy.
Colposcopy was used to examine 401 pregnant patients with cytologic or clinical abnormalities of the cervix to determine if routine biopsy could be safely omitted except where the colposcopic impression was one of possible invasive carcinoma. A comparison of the antepartum colposcopic impressions with the postpartum histologic diagnosis revealed agreement to within one degree in 87% of patients, with 3% of patients showing a more advanced lesion than that anticipated. Only 2% of patients showed a progression of cytologic abnormalities at postpartum examination; 39% showed marked improvement. Four of nine patients with invasive carcinoma were diagnosed at antepartum colposcopy, with an additional two patients recognized as having invasive cancer at the postpartum colposcopic examination. The omission of routine biopsy is less than ideal if only one antepartum colposcopy is performed, since a considerable period of time may elapse before the patient is seen again postpartum. Those situations in which it may be omitted, together with guidelines for the management of pregnant patients with abnormal cervical cytologic findings, are presented.


Identification and characterization of an indazole-3-carboxamide class synthetic cannabinoid: 2-[1-(cyclohexylmethyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoic acid (DMBA-CHMINACA).
Illicit psychoactive substances have threatened public health worldwide. An active metabolite of ADB-CHMINACA and MDMB-CHMINACA was identified for the first time in a powder-type product found in an airmail package. The structure of compound 1 was elucidated by a combination of gas chromatography-mass spectrometry (GC-MS), liquid chromatography-high resolution mass spectrometry (LC-HRMS), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. Compound 1 was proven to be an analogue of MDMB-CHMINACA, an indazole-based synthetic cannabinoid. The methyl ester group in MDMB-CHMINACA was replaced with a carboxylic acid group in compound 1. Compound 1 was determined as 2-[1-(cyclohexylmethyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoic acid and named as DMBA-CHMINACA.


Outbreak of contact sensitization to methylisothiazolinone: an analysis of French data from the REVIDAL-GERDA network.
The preservative methylisothiazolinone (MI) is used in combination with methylchloroisothiazolinone (MCI), but the MCI/MI mixture has been identified as highly allergenic. MI is considered to be less allergenic, and since the mid-2000s has been widely used alone, but is now clearly identified as a contact allergen. The French Vigilance Network for Dermatology and Allergy of the Study and Research Group on Contact Dermatitis (REVIDAL-GERDA) added MI to its baseline patch testing series in 2010. To evaluate the change in the proportion of MI-positive tests in France between 2010 and 2012. We conducted a nationwide, multicentre, retrospective study of all MI-tested patients between 2010 and 2012. Sixteen centres participated in the study (7874 patients were tested). Patch tests were performed mainly at a concentration of MI 200 ppm aq. We observed a significant increase in the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%, 3.3%, and 1.5%, respectively; p < 0.001). We report a significant increase in the number of MI-positive tests. MI is confirmed to be a rapidly emerging allergen, as also observed in other European countries.


BAP1 links metabolic regulation of ferroptosis to tumour suppression.
The roles and regulatory mechanisms of ferroptosis (a non-apoptotic form of cell death) in cancer remain unclear. The tumour suppressor BRCA1-associated protein 1 (BAP1) encodes a nuclear deubiquitinating enzyme to reduce histone 2A ubiquitination (H2Aub) on chromatin. Here, integrated transcriptomic, epigenomic and cancer genomic analyses link BAP1 to metabolism-related biological processes, and identify cystine transporter SLC7A11 as a key BAP1 target gene in human cancers. Functional studies reveal that BAP1 decreases H2Aub occupancy on the SLC7A11 promoter and represses SLC7A11 expression in a deubiquitinating-dependent manner, and that BAP1 inhibits cystine uptake by repressing SLC7A11 expression, leading to elevated lipid peroxidation and ferroptosis. Furthermore, we show that BAP1 inhibits tumour development partly through SLC7A11 and ferroptosis, and that cancer-associated BAP1 mutants lose their abilities to repress SLC7A11 and to promote ferroptosis. Together, our results uncover a previously unappreciated epigenetic mechanism coupling ferroptosis to tumour suppression.


Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of nateglinide, cilostazol and its active metabolite 3,4-dehydro-cilostazol in Wistar rat plasma and its application to pharmacokinetic study.
Nateglinide (NTG), an insulin secretogogue, has been studied in rats for drug-drug interaction with cilostazol (CLZ), an antiplatelet agent commonly used in diabetics. We developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) based method that is capable of simultaneous monitoring plasma levels of nateglinide, cilostazol, and its active metabolite 3,4-dehydro-cilostazol (DCLZ). All analytes including the internal standard (Repaglinide) were chromatographed on reverse phase C(18) column (50 mm x 4.6mm i.d., 5 microm) using acetonitrile: 2mM ammonium acetate buffer, pH 3.4 (90:10, v/v) as mobile phase at a flow rate 0.4 ml/min in an isocratic mode. The detection of analyte was performed on LC-MS/MS system in the multiple reaction monitoring (MRM) mode. The quantitations for analytes were based on relative concentration. The method was validated over the concentration range of 20-2000 ng/ml and the lower limit of quantitation was 20 ng/ml. The recoveries from spiked control samples were >79% for all analytes and internal standard. Intra- and inter-day accuracy and precision of validated method were with in the acceptable limits of <15% at all concentration. The quantitation method was successfully applied for simultaneous estimation of NTG, CLZ and DCLZ in a pharmacokinetic drug-drug interaction study in Wistar rats.


Production of chicken ovalbumin in Escherichia coli.
For better understanding of the structure-function relationship in serine proteinase inhibitors, a protein engineering approach for converting non-inhibitory chicken ovalbumin (Ova) to the inhibitory form would be a highly useful model system. A prerequisite expression system for the Ova-encoding gene (Ova) was established in this study. The Ova gene was expressed in Escherichia coli with high yield using the T7 phage promoter; the amount of the recombinant Ova (re-Ova) was 29.4% of cellular proteins. SDS-PAGE and Western blotting analysis revealed that re-Ova immunoreacting with the egg ovalbumin antibody is not glycosylated. The re-Ova was purified by anion exchange chromatography into homogeneity, as evaluated by SDS-PAGE. Amino-acid and N-terminal sequence analyses confirmed that the purified product had the correct sequence designed for Ova production. As for secondary structure, re-Ova showed a far-UV circular dichroism spectrum indistinguishable from natural egg Ova. Furthermore, the proteolytic fragmentation pattern that should reflect protein conformation was exactly the same for the natural egg and re-Ova. Using the proteolytic fragments, the identity of the internal sequences for the natural and re- proteins was confirmed.


Medicalizing normality? Management of irritability in babies.
The aims of this project were to identify the scources and quality of the health advice provided to parents with irritable infants; to assess the efficacy of a residential programme in the diagnosis and management of irritable infants; and to assess the intermediate term outcome for such infants and their mothers. All mother-infant pairs admitted during a 3 month period to a residential setting with the primary concern of infant irritability were asked to participate in the study. Pre-admission and 3 month post-discharge health-care advice, investigations and treatment details were collected. Maternal mood at admission and 3 months post-discharge was measured using the Edinburgh Postnatal Depression Scale (EPDS). On admission, infant medication for proposed cause of excess irritability was ceased, with parental consent, if it was appropriate and following full medical assessment. Individual case plans were designed by the admitting child health nurse in consultation with the mother. These included education as to normal infant behaviour, settling techniques, and establishment of routine; family issues were also explored. Fifty-one consecutive mother-infant pairs consented to participate and formed the cohort, 48 (94%) were available for follow-up interview 3 months post-discharge. The average age on admission was 13 weeks (range 4-28 weeks), 32 (62.7%) were male, 34 (66.7%) were first born and 45 (88.2%) lived with both their parents. A multiplicity of health professionals had been involved in the pre-admission care, and 48 of the infants had been or were currently on medication for gastro-oesophageal reflux disease and or colic. At the end of admission, diagnoses made were predominantly behavioural (22) and feeding problems (20). Nine infants were felt to have an organic cause for their irritability. Maternal mood improved significantly on EPDS from the time of admission (45 (86.2%) of mothers with scores > or = 12, mean score 16.5) to post-admission follow up (9 (18. 8%) with scores > or = 12, mean score 7.2). There is evidence that a proportion of babies with 'normal' irritability are being incorrectly diagnosed as having an organic disorder exposing them inappropriately to medication, which may be harmful, and potentially creating lifelong problems for these infants and their families.


SERS-based lateral flow assay combined with machine learning for highly sensitive quantitative analysis of Escherichia coli O157:H7.
In the present study, surface-enhanced Raman scattering-based lateral flow assay (SERS-LFA) strips were applied to promptly and sensitively detect Escherichia coli O157:H7 (E. coli O157:H7) to ensure food safety. The SERS nanotags were prepared by connecting peculiar monoclonal antibody (McAb) against E. coli O157:H7 directly onto the surfaces of gold-silver core-shell nanostructures loaded with two-layer Raman reporter molecules of 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB). The Raman signal intensity at 1335 cm-1 on the test line (T line) of SERS-LFA strips was detected in the wide range of 101-109 colony-forming units/mL (CFU/mL), and regression models based on machine learning were combined to accurately and quantitatively analyze E. coli O157:H7. The limit of detection (LOD) of the extreme gradient boosting regression (XGBR) based on the Raman signal intensity of DTNB was 6.94 × 101 CFU/mL for E. coli O157:H7, which was approximately four orders of magnitude lower than that of visual limits. In addition, although E. coli O157:H7 was spiked into the food matrices including milk and beef at an ultra-low dose of 10 CFU/mL, the SERS-LFA combined with XGBR was able to successfully explore E. coli O157:H7 from the mixture that was incubated for only 2 h, in which the recoveries were mainly distributed between 86.41 and 128.25%. In summary, these results demonstrated that the SERS-LFA had a significant potential as a powerful tool for the point-of-care testing (POCT) of E. coli O157:H7 in the early food contamination stage.


Primary closure after laparoscopic common bile duct exploration is safe and feasible for patients with non-severe acute cholangitis.
The safety and feasibility of primary closure after laparoscopic common bile duct exploration (LCBDE) have been confirmed in elective settings. However, the suitability of primary closure after LCBDE in the treatment of patients with non-severe acute cholangitis in emergency settings remains unclear. The aim of the present study was to explore the safety and feasibility of LCBDE with primary closure in patients with non-severe acute cholangitis. Consecutive patients with choledocholithiasis combined with gallbladder stones treated by LCBDE with primary closure at our institution from January 2015 to April 2021 were retrospectively reviewed. These patients were divided into two groups: emergency group (patients with non-severe acute cholangitis) and elective group (patients without acute cholangitis). The demographic and perioperative data of the two groups were compared. One hundred twenty-two patients received LCBDE combined with primary closure during this period, including 70 in the emergency group and 52 in the elective group. Baseline characteristics were balanced in both groups, except for higher levels of white blood cells (WBC), C-reactive protein (CRP), total bilirubin, alkaline phosphatase (ALP), and albumin in the emergency group. No postoperative mortality occurred in either group. Compared to the elective group, the emergency group had a longer operation time (P = 0.011), and more estimated blood loss (P < 0.001). No significant differences were found between the two groups in terms of conversion (2.9% vs. 0.0%, P = 0.507), use of baskets (84.2% vs. 78.8%, P = 0.481), use of electrohydraulic lithotripsy (EHL) (2.9% vs. 1.9%, P = 1.000), or postoperative hospital stay (P = 0.214). The incidence of postoperative complications was comparable between the two groups. During the follow-up period, none of the patients experienced biliary stricture, and 1 case of stone recurrence occurred in the elective group. LCBDE with primary closure for choledocholithiasis patients with non-severe acute cholangitis has the equivalent efficacy and morbidity to elective surgery. Primary closure after LCBDE is a safe and feasible option for choledocholithiasis patients with non-severe acute cholangitis.


Metabolic memory and all-cause death in community-based patients with type 2 diabetes: the Fremantle Diabetes Study.
To validate the findings, in a usual care setting, of glycaemic intervention trials, which have shown that tight control in patients with recently diagnosed type 2 diabetes protects against death during post-study monitoring, but that it may be deleterious in long-duration diabetes with vascular complications. A subset of 531 patients with type 2 diabetes from the community-based observational Fremantle Diabetes Study Phase 1, who attended ≥5 annual reviews (mean follow-up 15.9 years), were categorized by baseline diabetes duration [<1 year (Group 1); 1 to <5 years (Group 2); and ≥5 years (Group 3)]. Glycated haemoglobin (HbA1c) trajectories over the first 5 years were determined [low, medium and high; equivalent to mean HbA1c ≤6.6% (<49 mmol/mol), 6.7-8.0% (50-64 mmol/mol) and ≥8.0% (>64 mmol/mol), respectively]. Kaplan-Meier analysis was used to assess survival by duration and HbA1c trajectory. Cox proportional hazards modelling identified predictors of all-cause death. There was greater mortality in patients with a medium versus those with a low trajectory in Group 1: hazard ratio (HR) 1.99 [95% confidence interval (CI) 1.003-3.94; p = 0.049], and in patients with a high versus a low trajectory in Group 2: HR 2.02 (95% CI 1.11-3.71; p = 0.022). In Group 3, both medium [HR 0.57 (95% CI 0.35-0.92; p = 0.022)] and high [HR 0.56 (95% CI 0.32-0.96); p = 0.035] trajectories were independently and inversely associated with death. In community-based patients with newly or recently diagnosed type 2 diabetes, poor glycaemic control was an adverse prognostic indicator. Tight control was independently associated with death in patients with diabetes duration ≥5 years. These data parallel intervention trial findings and support individualization of HbA1c targets.


[THE REMNANTS OF THE POWERS OF THE PHYSICIAN CONCERNING MEDICAL INFORMATION].
The aim of the reporting obligation laid down by the law on the physician is to allow the patient to express their free and informed consent to health care and to be more concerned about their own health. However, the legislator has left particularly extensive pieces of power, making information a tool to. secure the misfit of medical conference. Furthermore, in practice the physician holds significant influential power on the patient's decision, sometimes unconscious, often controlled, and which the works of sociologists have highlighted.


Use of a dodecadeoxynucleotide to study repair of the O4-methylthymine lesion.
A dodecadeoxynucleotide of defined sequence containing O4-methylthymine was labeled at the 5' end with [32P] by the reaction with (gamma-32P]ATP and polynucleotide kinase. Extracts prepared from bacterial and mammalian sources such as the human cell lines, HeLa and HT29, and rat liver were incubated with the labeled, methylated dodecamer to determine the extent of repair of the lesion. The labeled, demethylated dodecamer was separated from the labeled methylated dodecamer on a reverse-phase column using a shallow methanol gradient. There was complete repair of O4-methylthymine by the E. coli alkyltransferase upon incubation for 4 h at 37 degrees C. There was no detectable amount of demethylated product formed upon incubation with HeLa or HT29 cell extract for the same incubation period. There was also no repair of the O4-methylthymine lesion in the presence of crude rat-liver extract. However, the rat-liver extract alone degraded the methylated substrate completely, and the assay had to be conducted in the presence of NaF, AMP and unlabeled, nonmethylated dodecamer to prevent this. The results obtained from this assay, which is at least an order of magnitude more sensitive than previous methods, are in agreement with previous results that the mammalian alkyltransferase is specific for O6-alkylguanine repair.


Preoperative quantitative pivot shift does not correlate with in vivo kinematics following ACL reconstruction with or without lateral extraarticular tenodesis.
Quantitative pivot shift (QPS) testing using PIVOT technology can detect high- and low-grade rotatory knee instability following anterior cruciate ligament injury or reconstruction (ACLR). The aim of this project was to determine if preoperative QPS correlates with postoperative knee kinematics in the operative and contralateral, healthy extremity following ACLR with or without lateral extraarticular tenodesis (LET) using a highly precise in vivo analysis system. A positive correlation between preoperative QPS and postoperative tibial translation and rotation following ACLR with or without LET in the operative and healthy, contralateral extremity was hypothesized. Twenty patients with ACL injury and high-grade rotatory knee instability were randomized to undergo anatomic ACLR with or without LET as part of a prospective randomized trial. At 6 and 12 months postoperatively, in vivo kinematic data were collected using dynamic biplanar radiography superimposed with high-resolution computed tomography scans of patients' knees during downhill running. Total anterior-posterior (AP) tibial translation and internal-external tibial rotation were measured during the gait cycle. Spearman's rho was calculated for preoperative QPS and postoperative kinematics. In the contralateral, healthy extremity, a significant positive correlation was seen between preoperative QPS and total AP tibial translation at 12 months postoperatively (rs = 0.6, p < 0.05). There were no additional significant correlations observed between preoperative QPS and postoperative knee kinematics at 6 and 12 months postoperatively in the operative and contralateral, healthy extremity for combined isolated ACLR and ACLR with LET patients as well as isolated ACLR patients or ACLR with LET patients analyzed separately. The main finding of this study was that there was a significant positive correlation between preoperative QPS and total AP tibial translation at 12 months postoperatively in the contralateral, healthy extremity. There were no significant correlations between preoperative QPS and postoperative in vivo kinematics at 6 and 12 months following ACLR with or without LET. This suggests that QPS as measured with PIVOT technology does correlate with healthy in vivo knee kinematics, but QPS does not correlate with in vivo kinematics following ACLR with or without LET.


Preeclampsia is associated with reduced serum levels of placenta growth factor.
Adequate vascular development of the placental bed is essential for normal pregnancy. We assessed serum levels of placenta growth factor, an angiogenic factor, throughout normal pregnancy and determined its association with preeclampsia. Serum samples were collected from (1) 308 healthy pregnant women throughout normal gestation, (2) at delivery from 30 each gestational age-matched patients with normal pregnancy and preeclampsia, and (3) maternal and cord blood samples from normal deliveries with and without labor (n = 37 each). Placenta growth factor levels were determined with an antigen-capture enzyme-linked immunosorbent assay. Maternal placenta growth factor levels during normal pregnancy increased from the first trimester to the late second trimester; they subsequently declined from 30 weeks' gestation to delivery. Significantly less maternal placenta growth factor (P <.0001) was found in pregnancies complicated by preeclampsia, and labor significantly lowered placenta growth factor levels in both maternal (P =.0189) and cord serum samples (P <.0001). Decreased levels of placenta growth factor during preeclampsia could influence endothelial cell and trophoblast function, thereby contributing to the pathogenesis of the disease.


Molecular Stabilization of Sub-Nanometer Cu Clusters for Selective CO2 Electromethanation.
Electrochemical CO2 methanation powered by renewable electricity provides a promising approach to utilizing CO2 in the form of a high-energy-density, clean fuel. Cu nanoclusters have been predicted by theoretical calculations to improve methane selectivity. Direct electrochemical reduction of Cu-based metal-organic frameworks (MOFs) results in large-size Cu nanoparticles which favor multi-carbon products. This study concerns an electrochemical oxidation-reduction method to prepare Cu clusters from MOFs. The derived Cu clusters exhibit a faradaic efficiency of 51.2 % for CH4 with a partial current density of >150 mA cm-2 . High-resolution microscopy, in situ X-ray absorption spectroscopy, in situ Raman spectroscopy, and a range of ex situ spectroscopies indicate that the distinctive CH4 selectivity is due to the sub-nanometer size of the derived materials, as well as stabilization of the clusters by residual ligands of the pristine MOF. This work offers a new insight into steering product selectivity of Cu by an electrochemical processing method.


Measuring fast neutrons in Hiroshima at distances relevant to atomic-bomb survivors.
Data from the survivors of the atomic bombs serve as the major basis for risk calculations of radiation-induced cancer in humans. A controversy has existed for almost two decades, however, concerning the possibility that neutron doses in Hiroshima may have been much larger than estimated. This controversy was based on measurements of radioisotopes activated by thermal neutrons that suggested much higher fluences at larger distances than expected. For fast neutrons, which contributed almost all the neutron dose, clear measurement validation has so far proved impossible at the large distances (900 to 1,500 m) most relevant to survivor locations. Here, the first results are reported for the detection of 63Ni produced predominantly by fast neutrons (above about 1 MeV) in copper samples from Hiroshima. This breakthrough was made possible by the development of chemical extraction methods and major improvements in the sensitivity of accelerator mass spectrometry for detection of 63Ni atoms (refs 8-11). When results are compared with 63Ni activation predicted by neutron doses for Hiroshima survivors, good agreement is observed at the distances most relevant to survivor data. These findings provide, for the first time, clear measurement validation of the neutron doses to survivors in Hiroshima.


Ultrasound-guided bilateral brachial plexus blockade with propofol-ketamine sedation.
We report the use of ultrasound-guided bilateral brachial plexus block in a patient with bilateral radius fractures. An axillary block was performed on the patient's right and a supraclavicular block on her left using an in-plane (long-axis) needle insertion technique. Into each side was injected 20 ml 0.5% ropivacaine, giving a total volume (dose) of 40 ml (200 mg). Provisions were made for rescue analgesia or unplanned conversion to general anesthesia during the operation, but these were not needed; furthermore, no perioperative complications were observed. General anesthesia has traditionally been used for simultaneous surgery involving the bilateral upper extremities because of concerns relating to local anesthetic toxicity, phrenic nerve blockade, and pneumothorax. The ultrasound-guided technique facilitates a reduction in the minimal effective volume of local anesthetic and can prevent potentially critical complications. Moreover, the technique can be performed within the recommended safe dose limits of the anesthetic, rendering it an important option for bilateral upper extremity surgery.


Tolerability and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) for warfarin and non-warfarin reversals.
Current guidelines favor 4F-PCC over plasma for warfarin reversal. Uncertainty remains on its thrombotic risk and hemostatic effectiveness when used for direct-acting oral anticoagulants (DOACs), transplants, massive transfusion protocols (MTP), and non-anticoagulated patients. This study sought to evaluate the tolerability and effectiveness of 4F-PCC in a real-world setting. This was a retrospective study of adults who received 4F-PCC from March 2014 to December 2015. The primary outcome was thromboembolic events within 14 days. The secondary outcome was hemostatic effectiveness within 24 h. The final analysis included 212 patients. Primary reversal indication was major bleed in 165 patients (77.8%) and emergent surgery in 47 patients (22.2%). Thromboembolism occurred in 22 patients (10.4%), more in emergent surgery than major bleed reversals (17% and 8.5%, respectively). MTP and heart transplant patients had the highest thromboembolic event rates (44.4% and 28.6%, respectively). Hemostatic effectiveness was 65.8% (68% in major bleed and 58.1% in emergent surgery). DOAC patients achieved hemostasis most often (78.9%). Administration of any reversal agent, major surgery within 14 days, and MTP activation were significant predictors of thromboembolism. Use of 4F-PCC in this real-world setting was associated with variable thromboembolic and hemostatic effectiveness rates based on the indication for reversal.


Effects of glazing methods on the optical and surface properties of silicate ceramics.
This study aims to evaluate the effect of different glazing methods on translucency parameter (TP), contrast ratio (CR), opalescence parameter (OP), surface roughness (Ra) and topography of the silicate ceramics. Seventy specimens (10×10×1mm) were fabricated from lithium disilicate (IPS e.max CAD, abbreviated as E) and zirconia-reinforced lithium silicate (Vita Suprinity, abbreviated as VS) ceramics and divided into 7 subgroups (n=10) according to the polishing and glazing procedures: (1) mechanical polishing before-crystallization (m-BC), (2) mechanical polishing after-crystallization (m-AC), (3) glaze powder/liquid after-crystallization (pl-AC), (4) glaze-paste before-crystallization (gp-BC), (5) glaze-paste after-crystallization (gp-AC), (6) glaze-spray before-crystallization (gs-BC), (7) glaze-spray after-crystallization (gs-AC). Color and Ra measurements were performed. CIEL*a*b* and CIEXYZ parameters were recorded and TP, CR, and OP values were calculated. Data were analyzed using two-way ANOVA and Tukey HSD tests (α=0.05). In E groups, the highest Ra value was found in gs-AC (1.66±0.14μm) while the lowest value was found in pl-AC (0.68±0.08μm). In VS groups, the highest Ra value was found in gp-BC (1.64±0.25μm) while the lowest value was found in m-AC (0.77±0.06μm) (p<0.05). The mean TP value of E (17.62±0.73) was found to be higher than VS (15.37±1.16). The CR (0.72±0.030) and OP (12.06±0.74) values of VS were found higher than CR (0.57±0.02) and OP (6.72±0.40) values of E. Zirconia-reinforced silicate ceramics have higher opalescence and lower translucency values than lithium disilicate ceramics. Increase in surface roughness reduces translucency. Glaze powder/liquid after-crystallization is the most effective way to reduce surface roughness of lithium disilicate ceramics while that is mechanical polishing after-crystallization for zirconia-reinforced silicate ceramics.


Another glimpse over the salting-out assisted liquid-liquid extraction in acetonitrile/water mixtures.
The use of the salting-out effect in analytical chemistry is very diverse and can be applied to increase the volatility of the analytes in headspace extractions, to cause the precipitation of proteins in biological samples or to improve the recoveries in liquid-liquid extractions. In the latter, the salting-out process can be used to create a phase separation between water-miscible organic solvents and water. Salting-out assisted liquid-liquid extraction (SALLE) is an advantageous sample preparation technique aiming HPLC-UV analysis when developing analytical methodologies. In fact, some new extraction methodologies like QuEChERS include the SALLE concept. This manuscript discusses another point of view over SALLE with particular emphasis over acetonitrile-water mixtures for HPLC-UV analysis; the influence of the salting-out agents, their concentration and the water-acetonitrile volume ratios were the studied parameters. α-dicarbonyl compounds and beer were used as test analytes and test samples, respectively. The influence of the studied parameters was characterized by the obtained phase separation volume ratio and the fraction of α-dicarbonyls extracted to the acetonitrile phase. Results allowed the distribution of salts within three groups according to the phase separation and their extractability: (1) chlorides and acetates, (2) carbonates and sulfates and (3) magnesium sulfate; of all tested salts, sodium chloride had the highest influence on the α-dicarbonyls fraction extracted.


Congenital abdominal aortic aneurysms in the young. Case report and review of the literature.
Aneurysms of the aorta are rare in children and young adults. We report a case of a 19-year-old man with a saccular abdominal aortic aneurysm (AAA). No associated disorders were discovered in this patient. The aneurysm was resected and a Dacron aortic graft was implanted. Nine years after operation the patient was in good health without evidence of other aneurysms. Thirty-two cases of probable congenital abdominal aortic aneurysms were collected from the literature. In 19 cases, the cause of aneurysm was not ascertained. We identified two groups of patients with probably congenital AAAs: type I congenital AAA, in which there is a generalized disorder of the arterial tissue and usually aneurysms are present in other areas and type II congenital AAA, in which there is a localized defect of the abdominal aorta, without aneurysms in other areas. We speculate that a congenital defect localized to the wall of the abdominal aorta was the cause of the aneurysm in this patient (type II congenital AAA).


Synthetic Fe-rich nontronite as a novel activator of bisulfite for the efficient removal of tetracycline.
In this work, the iron-containing smectite nontronite (NNT) was artificially prepared by hydrothermal process and used as a heterogeneous catalyst to activate bisulfite (BS) for degradation of tetracycline (TC). Two NNT samples with different iron content (NNT1 and NNT2) were characterized by XRD, FTIR, XPS and SEM-EDS analysis. Under dark condition, the TC removal rates of NNT1/BS and NNT2/BS reached about 91.7% and 95.5% respectively at 60 min. Due to the heterogeneous catalysis of structural Fe(III), the NNT catalysts showed great catalytic activity and low iron leaching at the pH range 3.0-7.5. In addition, NNT particles were also stable and reusable in activating BS for TC removal. According to the EPR and radical quenching experiments, it could be proved that the precursor radical •SO3- was first generated in NNT/BS system, then •SO4- and •OH were the active species that played a role in TC degradation. The synthetic NNT clay is a promising Fe-based catalyst for treatment of TC wastewater thanks to its high activity, good stability and effective reusability.


Monoexponential and Biexponential Fitting of Diffusional Magnetic Resonance Imaging Signal Analysis for Prediction of Liver Fibrosis Severity.
The objective of this study is to compare the value of monoexponential and biexponential approach to the diffusion-weighted magnetic resonance imaging signal in the prediction of the liver fibrosis. Forty patients with hepatitis C were included. Quantification of the apparent diffusion coefficient (ADC) and pure molecular diffusion (D), pseudodiffusion (D*), and perfusion fraction (f) was performed using 9 b values (b = 0, 20, 50, 100, 200, 400, 600, 800, 1000 s/mm). Significant fibrosis was found in 14 subjects. Monoexponentally derived ADC parameters were significantly correlated. Apparent diffusion coefficient calculated from all b values and ADC based on high b values were significantly related to the fibrosis grade (P < 0.02), and none of intravoxel incoherent motion parameters presented such an association. Apparent diffusion coefficient based on high b values was the best predictor of significant fibrosis with area under the curve of 0.81, sensitivity of 0.57, and specificity of 0.92. Intravoxel incoherent motion parameters did not allow for prediction of the liver fibrosis. Apparent diffusion coefficient calculated based on high b values presents considerable specificity in predicting significant fibrosis.


LC/MS-based untargeted lipidomics reveals lipid signatures of nonpuerperal mastitis.
Nonpuerperal mastitis (NPM) is a disease that presents with redness, swelling, heat, and pain during nonlactation and can often be confused with breast cancer. The etiology of NPM remains elusive; however, emerging clinical evidence suggests a potential involvement of lipid metabolism. Liquid chromatography‒mass spectrometry (LC/MS)-based untargeted lipidomics analysis combined with multivariate statistics was performed to investigate the NPM lipid change in breast tissue. Twenty patients with NPM and 10 controls were enrolled in this study. The results revealed significant differences in lipidomics profiles, and a total of 16 subclasses with 14,012 different lipids were identified in positive and negative ion modes. Among these lipids, triglycerides (TGs), phosphatidylethanolamines (PEs) and cardiolipins (CLs) were the top three lipid components between the NPM and control groups. Subsequently, a total of 35 lipids were subjected to screening as potential biomarkers, and the chosen lipid biomarkers exhibited enhanced discriminatory capability between the two groups. Furthermore, pathway analysis elucidated that the aforementioned alterations in lipids were primarily associated with the arachidonic acid metabolic pathway. The correlation between distinct lipid populations and clinical phenotypes was assessed through weighted gene coexpression network analysis (WGCNA). This study demonstrates that untargeted lipidomics assays conducted on breast tissue samples from patients with NPM exhibit noteworthy alterations in lipidomes. The findings of this study highlight the substantial involvement of arachidonic acid metabolism in lipid metabolism within the context of NPM. Consequently, this study offers valuable insights that can contribute to a more comprehensive comprehension of NPM in subsequent investigations. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Number: 2019-702-57; Date: July 2019).


Antimicrobial activity and synergy of antibiotics with two biphenyl compounds, protosappanins A and B from Sappan Lignum against methicillin-resistant Staphylococcus aureus strains.
This study aims to investigate antimicrobial ingredients from Sappan Lignum and to evaluate their synergy on methicillin-resistant Staphylococcus aureus strains with antibiotics. Bioactivity-guided phytochemical procedures were used to screen the active compounds. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were assayed by broth microdilution. The synergy was evaluated through checkerboard microdilution and loss of viability assays. Protosappanins A (PsA) and B (PsB) were identified from Sappan Lignum extracts. They showed active against both S. aureus and MRSA with MIC or MIC50 at 64 (PsA) and 128 (PsB) mg/L alone. When they were used in combination with antibiotics, they showed best synergy with amikacin and gentamicin with MIC50 (mg/L) of amikacin reduced more significantly from 32 to four (with PsA) and eight (with PsB), and the fractional inhibitory concentration index (FICI) ranged between 0.078 and 0.500 (FICI50 = 0.375). Moreover, the resistance of MRSA towards amikacin and gentamicin could be reversed by the Clinical and Laboratory Standards Institute criteria. The combined bactericidal mode could as well be synergy. PsA and PsB showed very low cytotoxicity in comparison with their promising activity against MRSA. Protosappanins A and B showed both alone activities and resistance reversal effects of amikacin and gentamicin against MRSA, which warrant further investigations for potential combinatory therapy of MRSA infection.


Importance of complete system removal of infected cardioverter-defibrillators.
We describe a case of device infection after implantable cardioverter-defibrillator implantation managed by removal of all hardware except a portion of the epicardial sensing electrodes. Recurrent septic complications developed until all residual foreign material was eliminated. Despite anecdotal reports of successful management without device removal, extraction of all hardware components should be considered standard treatment for this complication.


High-performance liquid chromatography-fluorescent assay of catechol-O-methyltransferase activity in rat brain.
A method to measure catechol- O-methyltransferase (COMT) activity using high performance liquid chromatography-fluorescence detection with norepinephrine (NE) as a natural substrate was optimized for both soluble (S-) and membrane-bound (MB-) COMT activities in rat brain areas, cerebral cortex, cerebellum, hippocampus, brain stem, hypophysis, and hypothalamus. The highest S-COMT activity in Sprague-Dawley rat brain was found in hippocampus. MB-COMT activities in all brain areas were about 3-8 times lower than S-COMT activities. However, considering Vmax/ Km values, specificity constants for NE to S- and MB-COMT contributes mainly to the metabolism of NE in cerebral cortex and cerebellum.


Plasma ghrelin levels are closely associated with severity and morphology of angiographically-detected coronary atherosclerosis in Chineses patients with diabetes mellitus.
Low plasma ghrelin level was found to be associated with diabetes, and ghrelin was shown to inhibit pro-atherogenic changes in experimental models of atherosclerosis. The aim of this study was to investigate the relationship between plasma ghrelin levels and coronary atherosclerotic lesions in Chinese patients with diabetes. Plasma ghrelin levels were measured using an ELISA kit. The severity of coronary artery disease (CAD) was determined via angiography. Composition of atherosclerotic plaques was detected via coronary CT angiography. A total of 178 patients with diabetes were recruited. Among the patients, 70 were diagnosed with acute coronary syndrome (ACS), 82 with stable angina pectoris (SAP) and 26 without coronary angiographic finding (controls). A negative correlation was found between ghrelin levels and the severity of the CAD, as determined via the Gensini score (r=-0.2434; P=0.0217). In diabetic patients with CAD and a complex lesion, the plasma ghrelin levels were significantly lower than in those with a simple lesion (ACS group: 3.81 ± 0.49 ng/mL vs 4.72 ± 0.50 ng/mL, P<0.0001; SAP group: 4.21 ± 0.52 ng/mL vs 4.76 ± 0.59 ng/mL, P=0.0397). Angiographically-detected complex lesion was an independent factor associated with ghrelin levels (adjusted beta coefficient=-0.67, 95% CI -0.97 to -0.37, P<0.0001). Low plasma ghrelin level is closely related to angiographically-detected severity and the complex lesion morphology in Chinese diabetic patients with CAD.


Identification of the non-ribosomal peptide synthetase responsible for biosynthesis of the potential anti-cancer drug sansalvamide in Fusarium solani.
Sansalvamide is a cyclic pentadepsipeptide produced by Fusarium solani and has shown promising results as potential anti-cancer drug. The biosynthetic pathway has until now remained unidentified, but here we used an Agrobacterium tumefaciens-mediated transformation (ATMT) approach to generate knockout mutants of two candidate non-ribosomal peptide synthetases (NRPS29 and NRPS30). Comparative studies of secondary metabolites in the two deletion mutants and wild type confirmed the absence of sansalvamide in the NRPS30 deletion mutant, implicating this synthetase in the biosynthetic pathway for sansalvamide. Sansalvamide is structurally related to the cyclic hexadepsipeptide destruxin, which both contain an α-hydroxyisocaproic acid (HICA) unit. A gene cluster responsible for destruxin production has previously been identified in Metarhizium robertsii together with a hypothetical biosynthetic pathway. Using comparative bioinformatic analyses of the catalytic domains in the destruxin and sansalvamide NRPSs, we were able to propose a model for sansalvamide biosynthesis. Orthologues of the gene clusters were also identified in species from several other genera including Acremonium chrysogenum and Trichoderma virens, which suggests that the ability to produce compounds related to destruxin and sansalvamide is widespread.


Glutathione mobilization during cerebral ischemia and reperfusion in the rat.
1. Cerebral ischemia applied for 15 min and followed by a 30 min reperfusion did not change the glutathione (GSH) levels and beta-adrenoceptor density (Bmax) in brain cortex. 2. A significant increase in erythrocyte-lysate GSH concentration (vs control) and a significant decrease of Bmax values in erythrocyte membranes (vs control) was found at the same time. 3. Pretreatment with the alpha-adrenoceptor antagonist phentolamine (5 mg/kg i.p.) prevented the erythrocyte GSH increase but not the decrease of Bmax value. Pretreatment with the beta-antagonist propranolol (2 mg/kg i.p.) did not influence the increase in erythrocyte GSH but circumvented the decrease of Bmax.


Cardiac output monitoring during the acute phase of myocardial infarction: accuracy and precision of the thermodilution method.
A triple human catheter was used for the determination of cardiac output during the acute phase of moycardial infarction in 23 patients. The correlation coefficient between thermodilution and the Fick method was 0.91. Precision of the method assessed by multiple repeated determinations was 4.8 or 5.6%. Quadruplicate determinations allowed to detect variations of cardiac output in the range of 0.465 1/min. Variation between two successive determinations of more than 9.4% can probably be attributed to a technical error.


Non-coding RNAs as emerging targets for crop improvement.
Food security is affected by climate change, population growth, as well as abiotic and biotic stresses. Conventional and molecular marker assisted breeding and genetic engineering techniques have been employed extensively for improving resistance to biotic stress in crop plants. Advances in next-generation sequencing technologies have permitted the exploration and identification of parts of the genome that extend beyond the regions with protein coding potential. These non-coding regions of the genome are transcribed to generate many types of non-coding RNAs (ncRNAs). These ncRNAs are involved in the regulation of growth, development, and response to stresses at transcriptional and translational levels. ncRNAs, including long ncRNAs (lncRNAs), small RNAs and circular RNAs have been recognized as important regulators of gene expression in plants and have been suggested to play important roles in plant immunity and adaptation to abiotic and biotic stresses. In this article, we have reviewed the current state of knowledge with respect to lncRNAs and their mechanism(s) of action as well as their regulatory functions, specifically within the context of biotic stresses. Additionally, we have provided insights into how our increased knowledge about lncRNAs may be used to improve crop tolerance to these devastating biotic stresses.


Quantifying the Economic and Clinical Value of Reducing Antimicrobial Resistance in Gram-negative Pathogens Causing Hospital-Acquired Infections in Australia.
Antimicrobial resistance (AMR) is a global public health challenge requiring a global response to which Australia has issued a National Antimicrobial Resistance Strategy. The necessity for continued-development of new effective antimicrobials is required to tackle this immediate health threat is clear, but current market conditions may undervalue antimicrobials. We aimed to estimate the health-economic benefits of reducing AMR levels for drug-resistant gram-negative pathogens in Australia, to inform health policy decision-making. A published and validated-dynamic health economic model was adapted to the Australian setting. Over a 10-year time horizon, the model estimates the clinical and economic outcomes associated with reducing current AMR levels, by up to 95%, of three gram-negative pathogens in three hospital-acquired infections, from the perspective of healthcare payers. A willingness-to-pay threshold of AUD$15,000-$45,000 per quality-adjusted life-year (QALY) gained and a 5% discount rate (for costs and benefits) were applied. Over ten years, reducing AMR for gram-negative pathogens in Australia is associated with up to 10,251 life-years and 8924 QALYs gained, 9041 bed-days saved and 6644 defined-daily doses of antibiotics avoided. The resulting savings are estimated to be $10.5 million in hospitalisation costs, and the monetary benefit at up to $412.1 million. Our results demonstrate the clinical and economic value of reducing AMR impact in Australia. Of note, since our analysis only considered a limited number of pathogens in the hospital setting only and for a limited number of infection types, the benefits of counteracting AMR are likely to extend well beyond the ones demonstrated here. These estimates demonstrate the consequences of failure to combat AMR in the Australian context. The benefits in mortality and health system costs justify consideration of innovative reimbursement schemes to encourage the development and commercialisation of new effective antimicrobials.


A melatonin-based fluorescence method for the measurement of mitochondrial complex III function in intact cells.
Mitochondrial complex III (MC-3) plays a pivotal role in electron transfer and oxidative phosphorylation. Impaired MC-3 functions may contribute to a variety of diseases by interrupting normal bioenergetics and increasing reactive oxygen production and oxidative stress. Currently, MC-3 function is assessed by measuring the cytochrome c reductase activity spectrophotometrically in isolated mitochondria or MC-3. The cytoplasmic microenvironment critical for mitochondrial complex functions may be depleted during these isolation processes. The development of a reliable method to measure MC-3 activities in intact cells or tissues is highly desirable. This report describes a novel fluorescence-based method to assess MC-3 functions, i.e., Qi site electron transfer, in the intact cells. Human mesangial and teratocarcinoma NT2 cells were used to demonstrate that melatonin-induced oxidation of 2',7'-dichlorodihydrofluorescein (H2 DCF) was inhibited by antimycin A, the MC-3 Qi site-specific inhibitor, but not by myxothiazol, the MC-3 Qo site-specific inhibitor, nor rotenone, the mitochondrial complex I inhibitor. These results indicate that melatonin-induced oxidation of H2 DCF is reflecting MC-3 Qi site electron transfer activities. Modifying structures of the side groups at the R3 and R5 positions of the indole ring of melatonin diminished its efficacy for inducing H2 DCF oxidation, suggesting a specific interaction of melatonin with the MC-3 Qi site. These results suggest that the fluorogenic property of melatonin-induced H2 DCF oxidation provides a MC-3 Qi site electron transfer-specific measurement in intact cells. Interestingly, using this method, the Qi site electron transfer activity in transformed or immortalized cells was found to be significantly higher than the nontransformed cells.


Phlebosclerotic colitis: an unusual cause of abdominal pain and hematochezia.
A 64-year-old male presented to our department with right low abdominal pain and intermittent bloody stool of a five-day duration. He had a long history of drinking alcohol. Both wall thickening of the ascending colon and transverse colon and a dense shadow of the vascular wall of the peripheral mesentery were detected by abdominal computed tomography (CT) scans. Abdominal angiography revealed stenosis of the mesenteric artery and multiple calcifications of distal vessels of the ascending colon and transverse colon. Colonoscopy showed multiple ulcers in the ascending colon and transverse colon where the bowel walls were edematous, along with focal hyperplasia. Pathological studies showed inflammatory hyperplasia in the colonic mucosal tissue and a diagnosis of phlebosclerotic colitis (PC) was made.


Fundamentals of Ion Mobility-Mass Spectrometry for the Analysis of Biomolecules.
Ion mobility-mass spectrometry (IM-MS) combines complementary size- and mass-selective separations into a single analytical platform. This chapter provides context for both the instrumental arrangements and key application areas that are commonly encountered in bioanalytical settings. New advances in these high-throughput strategies are described with description of complementary informatics tools to effectively utilize these data-intensive measurements. Rapid separations such as these are especially important in systems, synthetic, and chemical biology in which many small molecules are transient and correspond to various biological classes for integrated omics measurements. This chapter highlights the fundamentals of IM-MS and its applications toward biomolecular separations and discusses methods currently being used in the fields of proteomics, lipidomics, and metabolomics.


A highly specific aptamer probe targeting PD-L1 in tumor tissue sections: Mutation favors specificity.
Although DNA aptamers can show comparable affinity to antibodies and have the advantage of having high batch-to-batch consistency, they often suffer from unsatisfied specificity for complex samples. The limited library size used for aptamer in vitro isolation (SELEX) has been recognized as one of the major reasons. Programmed cell death-ligand 1 (PD-L1) is both a key protein in cancer diagnostics and also immunotherapy. We report here a DNA aptamer that highly specifically binds PD-L1 expressed on the surface of various cancer cells and multiple types of tissue sections. The aptamers were selected from a DNA library containing a type II restriction endonuclease Alu I recognition site in the middle of the 40-nt random sequences, against recombinant PD-L1 rather than the whole cell or tissue section. The library enrichment was achieved by Alu I mediated-SELEX, named as REase-SELEX, in which Alu I cut off the non-binders at the recognition site and, more importantly, induced library mutations to substantially increase the library diversity. 8-60, a representative aptamer with high affinity (KD = 1.4 nM determined by SPR) successfully detected four types of cancer cells with PD-L1 expression levels from low to high by flow cytometry, normal human tonsil (gold standard for PD-L1 antibody evaluation), clinical non-small cell lung cancer (high PD-L1 expression level), and malignant melanoma (low PD-L1 expression level) tissue sections by fluorescence microscopy imaging, showing unprecedented high specificity. The results demonstrate that 8-60 is an advanced probe for PD-L1 cancer diagnostics and mutations in SELEX greatly favor aptamer specificity.


Coaction of Electrostatic and Hydrophobic Interactions: Dynamic Constraints on Disordered TrkA Juxtamembrane Domain.
In the receptor tyrosine kinase family, conformational change induced by ligand binding is transmitted across the membrane via a single transmembrane helix and a flexible juxtamembrane domain (JMD). Membrane dynamics makes it challenging to study the structural mechanism of receptor activation experimentally. In this study, we employ all-atom molecular dynamics with highly mobile membrane mimetic (HMMM) to capture the native conformation of the JMD in tropomyosin receptor kinase A (TrkA). We find that phosphatidylinositol 4,5-bisphosphate (PIP2) lipids engage in stable binding with multiple basic residues. Anionic lipids can compete with salt bridges within the peptide and alter TrkA-JMD conformation. We discover three-residue insertion into the membrane and are able to either enhance or reduce the level of insertion through computationally-designed point mutations. The vesicle-binding experiment supports computational results and indicates that hydrophobic insertion is comparable to electrostatic binding for membrane anchoring. Biochemical assays on cell lines with mutated TrkA show that enhanced TrkA-JMD insertion promotes receptor degradation but does not affect the short-term signaling capacity. Our joint work points to a scenario where lipid headgroups and tails interact with basic and hydrophobic residues on disordered domain, respectively, to restrain flexibility and potentially modulate protein function.


Effect of Face-to-Face vs Virtual Reality Training on Cardiopulmonary Resuscitation Quality: A Randomized Clinical Trial.
Bystander cardiopulmonary resuscitation (CPR) is crucial for survival after cardiac arrest but not performed in most cases. New, low-cost, and easily accessible training methods, such as virtual reality (VR), may reach broader target populations, but data on achieved CPR skills are lacking. To compare CPR quality between VR and face-to-face CPR training. Randomized noninferiority trial with a prospective randomized open blinded end point design. Participants were adult attendees from the science section of the Lowlands Music Festival (August 16 to 18, 2019) in the Netherlands. Analysis began September 2019. Two standardized 20-minute protocols on CPR and automated external defibrillator use: instructor-led face-to-face training or VR training using a smartphone app endorsed by the Resuscitation Council (United Kingdom). During a standardized CPR scenario following the training, we assessed the primary outcome CPR quality, measured as chest compression depth and rate using CPR manikins. Overall CPR performance was assessed by examiners, blinded for study groups, using a European Resuscitation Council-endorsed checklist (maximum score, 13). Additional secondary outcomes were chest compression fraction, proportions of participants with mean depth (50 mm-60 mm) or rate (100 min-1-120 min-1) within guideline ranges, and proportions compressions with full release. A total of 381 participants were randomized: 216 women (57%); median (interquartile range [IQR]) age, 26 (22-31) years. The VR app (n = 190 [49.9%]) was inferior to face-to-face training (n = 191 [50.1%]) for chest compression depth (mean [SD], VR: 49 [10] mm vs face to face: 57 [5] mm; mean [95% CI] difference, -8 [-9 to -6] mm), and noninferior for chest compression rate (mean [SD]: VR: 114 [12] min-1 vs face to face: 109 [12] min-1; mean [95% CI] difference, 6 [3 to 8] min-1). The VR group had lower overall CPR performance scores (median [IQR], 10 [8-12] vs 12 [12-13]; P < .001). Chest compression fraction (median [IQR], 61% [52%-66%] vs 67% [62%-71%]; P < .001) and proportions of participants fulfilling depth (51% [n = 89] vs 75% [n = 133], P < .001) and rate (50% [n = 87] vs 63% [n = 111], P = .01) requirements were also lower in the VR group. The proportion of compressions with full release was higher in the VR group (median [IQR], 98% [59%-100%] vs 88% [55%-99%]; P = .002). In this randomized noninferiority trial, VR training resulted in comparable chest compression rate but inferior compression depth compared with face-to-face training. Given the potential of VR training to reach a larger target population, further development is needed to achieve the compression depth and overall CPR skills acquired by face-to-face training. ClinicalTrials.gov identifier: NCT04013633.


Arrhythmias Associated with Inflammatory Cardiomyopathies.
To provide an approach to the diagnosis and treatment of arrhythmias associated with inflammatory cardiomyopathies. Inflammatory cardiomyopathies are increasingly recognized as the etiology of both ventricular and supraventricular arrhythmias. There have been recent studies providing novel insights into the pathogenesis of arrhythmias in inflammatory cardiomyopathies and exploring the role of various diagnostic tools and treatment strategies. Patients with inflammatory cardiomyopathies often present with one or more arrhythmias, including atrioventricular block, atrial and ventricular tachyarrhythmias, and occasionally sudden cardiac death. Given dynamic pathophysiology and heterogeneous presentation, the management of arrhythmias in these patients presents unique challenges. We review the current approach to the diagnosis and treatment of arrhythmias in this challenging cohort of patients with an emphasis on cardiac sarcoidosis. The online version of this article (10.1007/s11936-020-00871-5) contains supplementary material, which is available to authorized users.


Swallowing disorders post orotracheal intubation in the elderly.
The purpose of this study was to assess the prevalence and recovery time of swallowing dysfunction after prolonged endotracheal intubation in critically ill elderly patients compared to a younger cohort. This was a prospective, interventional, clinical study set in a medical intensive care unit in a university-affiliated hospital. The study involved 42 consecutive elderly patients (>/=65 years old) and 42 controls (<65 years) matched for severity of illness requiring endotracheal intubation for more than 48 h. A fiberoptic endoscopic evaluation of swallowing (FEES) was performed within 48 h post-extubation and on days 5, 9, and 14 for those with evidence of aspiration. RESULTS. Swallowing dysfunction was assessed by the detection of test material below the true vocal cords. Aspiration was documented in 52% of the elderly and 36% of the control group (P=0.2). No significant difference in the co-morbidity index and the length of mechanical ventilation was found between aspirators and non-aspirators. None of the control group had swallowing deficits after 2 weeks, while 13% of the elderly participants showed persistent impairment in the swallowing reflex. By multivariate analysis, the preadmission functional status was the only determinant of a slowly resolving swallowing deficit (hazard ratio 1.68; 95% confidence interval 1.26-3.97). No post-extubation aspiration pneumonia was identified in either group. Critically ill elderly patients exhibit delayed resolution of swallowing impairment post extubation. FEES should be considered for those with impaired preadmission functional status.


Twenty years of experience with less radical fertility-sparing surgery in early-stage cervical cancer: Pregnancy outcomes.
The standard procedure in cervical cancer is radical hysterectomy and pelvic lymphadenectomy (PLND). Because of the increasing age of women bearing children, fertility has become a major challenge. We present pregnancy results after less radical fertility-sparing surgery in women with IA1, LVSI positive, IA2 and IB1 (<2 cm, infiltration less than half of the cervical stroma). All women (n = 91) underwent laparoscopic sentinel lymph node mapping with frozen section followed by PLND and "selective parametrectomy" (removal of afferent lymphatic channels from the paracervix) if sentinel nodes (SLN) are negative. If lymph nodes were verified negative by definitive histopathology, patients were treated by simple trachelectomy (IB1) or large cone (IA1/IA2) biopsy 1 week after primary surgery. From 1999 to 2018, 91 women were enrolled in the study (median age 29.1 years, range 21-40). Fertility was spared in 76 (83.5%) women; 13 (17.1%) women did not plan future pregnancy and 63 (82.9%) had pregnancy desires. Fifty-four of 63 women conceived (pregnancy rate 85.7%) and 48 of 63 delivered 58 babies (delivery rate 76.2%). Thirty-nine women delivered in term (67.2%): 13 women between 32 and 36 + 6 weeks of pregnancy, 3 between 28 and 31 + 6 weeks and 3 between 24 and 27 + 6 weeks. Only one woman still plans pregnancy. One woman is currently pregnant. The goal of fertility-sparing surgery is to produce good oncological results and promising pregnancy outcomes. Pregnancy results after less radical fertility-sparing procedures show promise (pregnancy rate 82.9% and delivery rate 76.2%).


Radiofrequency-assisted subcision combined with polycaprolactone-based dermal fillers in the management of atrophic facial acne scars: A pilot investigative study.
The scar's appearance and psychological burden are the most esthetically challenging issues in acne vulgaris. This study investigated the effectiveness and safety profile of combined radiofrequency-assisted subcision, which, even though effective on both Icepeak and Rolling subtypes, is only mildly effective on boxcar lesions, and polycaprolactone-based dermal filler with collagen stimulation potency in managing atrophic postacne scars. Our quasi-experimental single-arm study, after the inclusion of 10 cases over the age of 18 with moderate to severe mixed atrophic facial acne scarring, was carried out in two 3-month separate sessions, during and after the intended intervention of which the experienced lesion improvements and also adverse events were documented. Moreover, all cases were followed for 3 months after the last session, evaluating the differences in the mentioned outcomes. We found the combined intervention to be highly effective in improving the intended outcomes, with the total number of acne lesions (p-value < 0.001), along with the total number of Ice peak (p-value = 0.002), Rolling (p-value < 0.001), and boxcar (p-value = 0.023) lesions demonstrating statistically significant changes. Radiofrequency-assisted subcision combined with polycaprolactone-based dermal fillers can be an effective intervention in managing postacne scars. However, we recommend that randomized clinical trials with larger sample sizes be carried out for a more precise conclusion.


[The prevalence of cataract in Doumen County, Guangdong Province].
To investigate the prevalence of cataract, cataract blindness and the cataract burden in population aged >or= 50 years in Doumen County. 5,759 individuals aged >or= 50 were identified from sampling units. The definition of cataract was the vision < 0.7 caused by lens opacity in either eye, among them the person whose vision in both eyes was < 0.1 was cataract burden and whose vision in both eyes was < 0.05 was cataract blindness. The response rate was 92.76%. The prevalence of cataract, cataract blindness and cataract burden was 20.93%, 1.67% and 3.86%, respectively. The huge community necessary for cataract surgery still remains as a great challenge in China.


Mineral characteristics of the leaves of 166 plant species with different phylogeny in the temperate region.
The P-N regression coefficient was moderate in Magnoliales, Coniferopsidae, Pteridophyta, and Asterids, but very high in Caryophyllids, and very low in Rosids. The K-N regression coefficient in trees remained constant regardless of evolution, and that in grasses was high except for Rosids compared with that in trees. The coefficient was very high in Caryophyllids and was very low in Rosids. The N-Ca and N-Mg relationship was not estimated at all, suggesting that the mechanism of Ca and Mg accumulation was completely different from that of N related accumulation. The Zn and Cu concentrations were related to the N concentration. The Al concentration in leaves was negatively correlated with the N, P, K, Ca, Mg, Na, Cu, Zn, Mn, and Fe concentrations, while the N, P, K, and Mn concentrations in leaves increased slightly with the increase of Al concentration in the high Al concentration. The Na concentration in leaves related negatively to the P, Ca, Cu, Zn, Mn and Al concentration range. Thus, it was demonstrated that most of the minerals in leaves accumulate negatively Al and Na indicating that there are antagonistic mechanisms for mineral accumulation in leaves among Al or Na and other mineral elements.


[Survey of medical treatment in primary open-angle glaucoma].
To survey patient understanding of primary open-angle glaucoma (POAG) and difficulties associated with medical treatment of POAG patients, to determine patient compliance rates with medical therapy, to study factors influencing compliance rates, and to formulate suggestions to improve patient compliance. Our descriptive prospective study was carried out at the ophthalmology clinic of the Hubert K. Maga national university medical center and in the "La Lumière" ophthalmology clinic in Cotonou, from January 5 through April 25, 2009. The study included all glaucoma patients under medical treatment for at least 1 year with no surgical POAG intervention, seen in consultation during the study period, i.e. 120 patients. The following parameters were studied: whether the patient took or forgot to take his or her medication within the week preceding the survey, the patient's statement of whether or not voluntary interruption of antiglaucoma treatment occurred for more than 1 day, and the regularity of follow-up appointments with the doctor over the preceding 2 years. The median age of the patients was 56.5 ± 11.9years. A percentage of 90.8 of patients understood the chronic nature of POAG. A percentage of 91.7 knew that, in the absence of treatment, POAG can result in irreversible blindness. A percentage of 90 knew that medical treatment is intended to be lifelong. A percentage of 84.2 knew that the dosing schedule must be adhered to. The rate of total compliance was 53.3%. Only regularity of follow-up visits and adherence to dosing schedules were found as significant factors (P<0.05). Compliance is a dynamic variable which ophthalmologists need to evaluate throughout the follow-up of POAG patients, in order to reduce the prevalence of glaucoma blindness in Bénin.