Exploring the use of rating scales with entrustment anchors in workplace-based assessment.
Competency-based medical education (CBME) has prompted widespread implementation of workplace-based assessment (WBA) tools using entrustment anchors. This study aimed to identify factors that influence faculty's rating choices immediately following assessment and explore their experiences using WBAs with entrustment anchors, specifically the Ottawa Surgical Competency Operating Room Evaluation scale. A convenience sample of 50 semi-structured interviews with Emergency Medicine (EM) physicians from a single Canadian hospital were conducted between July and August 2019. All interviews occurred within two hours of faculty completing a WBA of a trainee. Faculty were asked what they considered when rating the trainee's performance and whether they considered an alternate rating. Two team members independently analysed interview transcripts using conventional content analysis with line-by-line coding to identify themes. Interviews captured interactions between 70% (26/37) of full-time EM faculty and 86% (19/22) of EM trainees. Faculty most commonly identified the amount of guidance the trainee required as influencing their rating. Other variables such as clinical context, trainee experience, past experiences with the trainee, perceived competence and confidence were also identified. While most faculty did not struggle to assign ratings, some had difficulty interpreting the language of entrustment anchors, being unsure whether their assessment should be retrospective or prospective in nature, and if/how the assessment should change whether they were 'in the room' or not. By going to the frontline during WBA encounters, this study captured authentic and honest reflections from physicians immediately engaged in assessment using entrustment anchors. While many of the factors identified are consistent with previous retrospective work, we highlight how some faculty consider factors outside the prescribed approach and struggle with the language of entrustment anchors. These results further our understanding of 'in-the-moment' assessments using entrustment anchors and may facilitate effective faculty development regarding WBA in CBME.


Glycemic Variability and Time in Range During Self-titration of Once Daily Insulin Glargine 300 U/ml Versus Neutral Protamine Hagedorn Insulin in Insulin-naïve Chinese Type 2 Diabetes Patients.
To compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM). This was a 24-week, open-label exploratory study with 1:1 randomization comparing patient-adjusted titration of Gla-300 (n = 23) versus NPH (n = 23) at bedtime in insulin-naïve T2D patients on maximum oral glucose-lowering drugs. The starting dose was 0.2 U/kg/day and with self-titration of one unit per week to achieve a target fasting glucose of 4.4-6 mmol/l, without hypoglycemia. Participants had masked CGM at baseline, weeks 11 and 24. The primary outcome was between-treatment differences in CGM glucose standard deviation (SD) at week 24. HbA1c at week 24 were similar, with 21% of Gla-300 versus 4% of NPH-treated patients achieving HbA1c < 7% without confirmed hypoglycemia. There were no differences in anytime glucose SD at week 24 (LS mean difference - 0.08 mmol/l, 95% CI [- 0.42-0.26], p = 0.63). Anytime %TIRs (3.9-10.0 mmol/l) at week 24 were similar (p = 0.91). Nocturnal % time below range < 3.9 mmol/l was significantly lower in the Gla-300 group (least squares (LS) mean difference - 5.03% [- 9.92 to - 0.14], p = 0.04) with lower % coefficient of variation (LS mean difference - 4.5% [- 8.1 to - 0.8], p = 0.018). Diurnal TIR was higher in Gla-300 patients at week 11 but there were no differences at week 24. Once-daily bedtime Gla-300 was associated with lower nocturnal GV, time below range and self-reported hypoglycemia in insulin-naïve Chinese T2D patients over a 24-week study period, as compared with NPH insulin. ClinicalTrials.gov Identifier: NCT03389490.


Disease-specific eQTL screening reveals an anti-fibrotic effect of AGXT2 in non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) poses an increasing clinical burden. Genome-wide association studies have revealed a limited contribution of genomic variants to the disease, requiring alternative but robust approaches to identify disease-associated variants and genes. We carried out a disease-specific expression quantitative trait loci (eQTL) screen to identify novel genetic factors that specifically act on NAFLD progression on the basis of genotype. We recruited 125 Korean patients (83 with biopsy-proven NAFLD and 42 without NAFLD) and performed eQTL analyses using 21,272 transcripts and 3,234,941 genotyped and imputed single nucleotide polymorphisms. We then selected eQTLs that were detected only in the NAFLD group, but not in the control group (i.e., NAFLD-eQTLs). An additional cohort of 162 Korean individuals with NAFLD was used for replication. The function of the selected eQTL toward NAFLD development was validated using HepG2, primary hepatocytes and NAFLD mouse models. The NAFLD-specific eQTL screening yielded 242 loci. Among them, AGXT2, encoding alanine-glyoxylate aminotransferase 2, displayed decreased expression in patients with NAFLD homozygous for the non-reference allele of rs2291702, compared to no-NAFLD individuals with the same genotype (p = 4.79 × 10-6). This change was replicated in an additional 162 individuals, yielding a combined p value of 8.05 × 10-8 from a total of 245 patients with NAFLD and 42 controls. Knockdown of AGXT2 induced palmitate-overloaded hepatocyte death by increasing endoplasmic reticulum stress, and exacerbated NAFLD diet-induced liver fibrosis in mice, while overexpression of AGXT2 attenuated liver fibrosis and steatosis. We identified a new molecular role for AGXT2 in NAFLD. Our overall approach will serve as an efficient tool for uncovering novel genetic factors that contribute to liver steatosis and fibrosis in patients with NAFLD. Elucidating causal genes for non-alcoholic fatty liver disease (NAFLD) has been challenging due to limited tissue availability and the polygenic nature of the disease. Using liver and blood samples from 125 Korean individuals (83 with NAFLD and 42 without NAFLD), we devised a new analytic method to identify causal genes. Among the candidates, we found that AGXT2-rs2291702 protects against liver fibrosis in a genotype-dependent manner with the potential for therapeutic interventions. Our approach enables the discovery of causal genes that act on the basis of genotype.


Facet-Dependent Oxidative Strong Metal-Support Interactions of Palladium-TiO2 Determined by In Situ Transmission Electron Microscopy.
The strong metal-support interaction (SMSI) is widely used in supported metal catalysts and extensive studies have been performed to understand it. Although considerable progress has been achieved, the surface structure of the support, as an important influencing factor, is usually ignored. We report a facet-dependent SMSI of Pd-TiO2 in oxygen by using in situ atmospheric pressure TEM. Pd NPs supported on TiO2 (101) and (100) surfaces showed encapsulation. In contrast, no such cover layer was observed in Pd-TiO2 (001) catalyst under the same conditions. This facet-dependent SMSI, which originates from the variable surface structure of the support, was demonstrated in a probe reaction of methane combustion catalyzed by Pd-TiO2 . Our discovery of the oxidative facet-dependent SMSI gives direct evidence of the important role of the support surface structure in SMSI and provides a new way to tune the interaction between metal NPs and the support as well as catalytic activity.


ENVIRONMENTAL AND GENETIC CONSTRAINTS ON ADAPTIVE POPULATION DIFFERENTIATION IN ANTHOXANTHUM ODORATUM.
Maximum-likelihood estimates of environmental and broad sense genetic (co)variance components were obtained for the growth and reproductive output of clones of the grass Anthoxanthum odoratum. The clones were transplanted between a mesic and a xeric field site and across-environment genetic correlations were used to estimate the strength of genotype-environment interaction. Significant across-environment clonal covariance matrices were found for several traits, including lifetime reproductive output in one population. None of the matrices differed significantly between populations. Significant within-site clonal variation was found, but there was no significant across-environment clonal covariation. Most broad sense heritability estimates of character states within sites were small (median = 0.12), suggesting that only a slow response to selection is possible. All significant within-site clonal correlations between growth and reproductive output were positive, although the pattern of negative clonal correlations suggests that there may be a cost to first year reproduction, which might constrain future selection response.


Two new species of Myxobolus (Myxozoa: Myxosporea: Bivalvulida) infecting an Indian major carp and a cat fish in wetlands of Punjab, India.
A survey of parasites of freshwater fishes in Kanjali and Harike wetlands of Punjab (India) revealed the presence of two new myxosporean species belonging to the genus Myxobolus Bütschli (Winter (ed): Protozoa, 1882). Spores of the first species, M. saugati sp. nov. parasitizing scales of Labeo rohita (Cypriniformis: Cyprinidae) vern. rohu are characterized in having 'spores measuring 8.3 × 6.6 μm in size, oval to spherical in valvular view having rounded anterior and posterior ends; polar capsules are two, equal, measuring 4.0 × 2.4 μm, pyriform with distinct neck at the anterior end; an intercapsular process is absent'. Spores of the second species, Myxobolus szekeli sp. nov. parasitizing internal wall of stomach of Wallago attu (Cypriniformis: Siluridae) vern. mulle are '8.7 × 4.1 μm in size, elongately ovoidal in valvular view having tapering, bluntly pointed anterior end and rounded posterior end; polar capsules are two, equal, measuring 4.4 × 1.5 μm, tubular with blunt anterior and rounded posterior ends; polar capsules converge anteriorly but are placed at a distance posteriorly and occupies nearly half of the spore body cavity; an intercapsular process is absent'.


Identification of distinct receptors for two hemopoietic growth factors (granulocyte colony-stimulating factor and multipotential colony-stimulating factor) by chemical cross-linking.
Granulocyte colony-stimulating factor (G-CSF) and multipotential colony-stimulating factor (multi-CSF or interleukin 3) are two members of a family of hemopoietic growth and differentiation factors. Using biologically active radioiodinated derivatives and chemical cross-linking (predominantly with the homobifunctional reagent disuccinimidyl suberate) followed by gel electrophoresis and autoradiography, receptors for these two factors have been identified. The G-CSF receptor was identified as a single subunit protein of Mr approximately 150,000 while two molecular species able to specifically cross-link to 125I-multi-CSF were identified of Mr approximately 75,000 and 60,000. For both CSFs specificity of formation of cross-linked species was demonstrated by showing that the homologous unlabeled CSF (but not other CSFs) competed for formation of the complexes with the appropriate dose-response relation, by showing that saturation occurred over the appropriate range of 125I-CSF concentration and by showing that the cellular specificity of CSF binding paralleled that for cross-linked complex formation. The formation of cross-linked complexes was dependent on the concentration and type of chemical cross-linker, especially for cross-linking of 125I-multi-CSF. Based on a number of criteria it is suggested that the two species cross-linked to 125I-multi-CSF do not represent receptors of different affinity but, rather, two noncovalently associated subunits of a receptor complex.


Cranial nerve involvement in patients with immune-mediated neuropathy: An observational blink reflex study.
This study aimed to assess cranial nerve involvement in a large adult cohort of patients with immune-mediated neuropathy undergoing immunoglobulin treatment by measuring blink reflex R1 latency prolongation in correlation with clinical findings and nerve conduction studies. 104 patients underwent blink reflex examination and ulnar nerve conduction studies and were assessed by the Inflammatory Neuropathy Cause and Treatment disability score, the revised Amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and focused clinical examination. Prolonged R1 latencies were identified in 23 of 104 patients (22.1 %). These patients had more severe functional impairments according to the ALSFRS-R, yet only five clinically presented with bulbar dysfunction, facial- or trigeminal nerve impairment. Overall R1 latency was inversely correlated to ulnar motor conduction velocity. In preliminary follow-up assessments under continuous immunoglobulin treatment, prolonged R1 latencies partially improved. Cranial nerve involvement is a common feature in immune-mediated neuropathies and is associated with a more severe disease stage. Here, R1 prolongation was detected less frequently compared to previously reported untreated cohorts. Blink reflex studies can detect subclinical cranial nerve involvement in immune-mediated neuropathies. Further studies are needed to evaluate the clinical utility of measuring R1 latency.


Apta-biosensors for nonlabeled real time detection of human IgE based on carbon nanotube field effect transistors.
In this study, we demonstrated the aptamer-based biosensor (apta-biosensor) using CNT-FET devices for label free detection of allergy diagnosis by IgE detection. In order to detect the IgE, two kinds of receptor (monoclonal IgE antibody and anti-IgE aptamer)-modified CNT-FET devices were fabricated. The binding event of the target IgE onto receptors was detected by monitoring the gating effect caused by the charges of the target proteins. Since the CNT-FET biosensors were used in buffer solution, it was crucial to use small-size receptors like aptamers than whole antibodies so that the charged target IgE could approach the CNT surface within the Debye length distance to give a large gating effect. The results show that CNT-FET biosensors using monoclonal IgE antibody had very low sensitivity (minimum detectable level 1000 ng/mL), while those based on anti-IgE aptamer could detect 50 ng/mL. Moreover, the aptamer-modified CNT-FET herein could successfully block non-target proteins and could selectively detect the target protein in an environment similar to human serum electrolyte. Therefore, aptamer-based CNT-FET devices enable the production of label-free ultrasensitive electronic biosensors to detect clinically important biomarkers for disease diagnosis.


How signs function in the process of meaning construction: an exemplification from Gitai-go in the Japanese language.
In this paper, I will examine the semiotic mediation process of meaning construction and the functioning of signs, focusing on a group of characteristic words, Gitai-go in the Japanese language. Mimic words in the Japanese language, including Gitai-go are applicable to various subjects based on their inter-sensory nature, and appear frequently in informal communication among Japanese, not only for young children but also in adults' communication. When I consider their functioning from the viewpoint of meaning construction, their characteristic feature is their indefiniteness that is open to diverse forms of extension, including that of no further elaboration and continuous diffusion of the affective flavor within the current setting. Though the process is interpretable in terms of the Japanese culture that is characterized by vagueness, it is also a clear exemplification of how the indefiniteness of signs works in the process of meaning construction and in our communication.


Immunoglobulin G4-Related Disease: What an Allergist Should Know.
Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory disorder that begins in 1 or more organs as inflammatory tumors that progress toward fibrosis. It is often accompanied by elevated serum IgG4. IgG4-RD was first described in 2003 as a new concept encompassing a number of immunoallergic diseases that had previously been considered unrelated. IgG4-RD mainly affects middleaged and older men. It consists of upregulation and expansion of CD4+ cytotoxic T lymphocytes, oligoclonal plasmablasts, and other inflammatory cells that infiltrate affected tissues and induce inflammation, organ dysfunction, and fibrosis. Symptoms depend on the location, severity, and extent of the disease. Virtually any organ can be affected, including the pancreas, salivary glands, lacrimal glands, thyroid gland, retro-orbital tissue, lymph nodes, retroperitoneum, mediastinum, lung, kidney, aorta, serosal surfaces, and meninges. Patients with widespread disease may present general symptoms. At least 30%-40% of patients are atopic or display atopic traits such as eosinophilia and elevated serum IgE levels. Additional laboratory features include increased serum IgG4 concentrations, increased blood IgG4-plasmablasts, hypergammaglobulinemia, and hypocomplementemia. Diagnosis of IgG4-RD is based on a clinicopathological correlation. Lymphoplasmacytic infiltrate with abundant IgG4-positive plasma cells, storiform-type fibrosis, obliterative phlebitis, and tissue eosinophilia are the pathological hallmarks. Therapy for IgG4-RD is based primarily on corticosteroids but may include additional immunomodulatory drugs and monoclonal antibodies such as rituximab. In individuals with allergic features, IgG4-RD should be suspected when a history of unexplained swelling is observed in 1 or more organs, particularly if they respond to corticosteroids and the patients are men in the sixth decade of life and beyond.


Inhibition of vitamin B12-dependent microbial growth by nitrous oxide.
In methionine-free media, nitrous oxide inhibits the growth of an auxotrophic strain of Escherichia coli lacking a cobalamin-independent pathway for the de novo synthesis of methionine. Prototrophic E. coli is similarly inhibited by nitrous oxide if the cobalamin-independent pathway is selectively depressed by sulfanilamide. Nitrous oxide thus effectively inactivates cobalamin-dependent 5-methyltetrahydrofolate--homocysteine methyltransferase (methionine synthase, EC 184.108.40.206) in intact bacteria.


Technical report. Processing to achieve high-contrast images with computed dental radiography.
To determine the effects of equalization on image contrast and signal-to-noise ratio (SNR) with Computed Dental Radiography (CDR). Pixel value distributions were measured for various tissue thicknesses of a dental quality assurance jaw phantom and the average pixel values and SNR calculated. Equalization resulted in enhanced image contrast of underexposed images by effecting pixel value adjustment with little change in SNR. Overexposed images demonstrated minimal difference in contrast or SNR when equalization was applied. The equalize function of CDR is a convenient method to provide high-contrast images from underexposed images without detriment to the SNR. As it does not compensate for overexposure, the function will not lead to inappropriate overdosage of the patient.


Antenatal diagnosis and treatment of fetal hydrops secondary to pulmonary extralobar sequestration.
Bronchopulmonary sequestration with associated non-immune hydrops has been previously reported with generally poor prognosis for the neonate. The vast majority of sequestrations are discovered postnatally, and less than half are correctly identified as sequestration before birth.Until recently, treatment for pulmonary sequestration was limited to postnatal respiratory support and resection of the sequestered lung. But aggressive respiratory support does not succeed in salvaging infants with underlying pulmonary hypoplasia. In our report, we describe the antenatal treatment of pleural effusions complicated by hydrops fetalis secondary to a bronchopulmonary sequestration, successfully managed with a transthoracic catheter placement. This therapy resulted in the resolution of pleural effusion, polyhydramnios and hydrops, with a good fetal outcome.


Short-term effects of ambient air pollution on emergency department visits for urolithiasis: A time-series study in Wuhan, China.
Previous studies have explored the correlation between short-term exposure to air pollution and urinary system diseases, but lack of evidence on the correlation between air pollution and urolithiasis. Daily data of emergency department visits (EDVs), concentrations of six air pollutants (SO2, NO2, PM2.5, PM10, CO, and O3) and meteorological variables were collected in Wuhan, China, from 2016 to 2018. And a time-series study was conducted to investigate short-term effects of air pollutants on urolithiasis EDVs. In addition, stratified analyses by season, age and gender were also conducted. A total of 7,483 urolithiasis EDVs were included during the study period. A 10-μg/m3 increase of SO2, NO2, PM2.5, CO, PM10, and O3 corresponded to 15.02% (95% confidence interval [CI]: 1.69%, 30.11%), 1.96% (95% CI: 0.19%, 3.76%), 1.09% (95% CI:-0.24%, 2.43%), 0.14% (95% CI: 0.02%, 0.26%), 0.72% (95% CI: 0.02%, 1.43%), and 1.17% (95% CI: 0.40%, 1.94%) increases in daily urolithiasis EDVs. Significant positive correlations were observed between SO2, NO2, CO, and O3 and urolithiasis EDVs. The correlations were mainly among females (especially PM2.5 and CO) and younger people (especially SO2, NO2, and PM10) but the effect of CO was more obvious in elders. Furthermore, the effects of SO2 and CO were stronger in warm seasons, while the effects of NO2 were stronger in cool seasons. Our time-series study indicates that short-term exposure to air pollution (especially SO2, NO2, CO, and O3) was positively correlated with EDVs for urolithiasis in Wuhan, China, and the effects varied by season, age and gender.


Positively-charged microcrystalline cellulose microparticles: Rapid killing effect on bacteria, trapping behavior and excellent elimination efficiency of biofilm matrix from water environment.
Pathogen and biofilm contamination in aqueous systems leave millions of people at risk of waterborne diseases. Herein, to address this issue, a green and highly efficient strategy is developed to concurrently trap and kill bacteria, eliminate the debris and the existing biofilm matrix in water environment via magnetic microparticles. The particles (TPFPs) were prepared from the in-situ deposition of Fe3O4 nanoparticles onto the surface of antibacterial functionalized microcrystalline cellulose (MCC). Noticeably, TPFPs can completely inactivate both S. aureus and E. coli once contacting for 30 min by disrupting the bacterial membrane. Meanwhile, the MCC-based magnetic particles retained 100% biocidal efficiency against E. coli (5 * 104E. coli/mg particles) during ten recycling procedures without any treatment. More importantly, according to the results of trapping behavior and antibiofilm assays, not only bacteria could be captured by the particles (trapping rate was over 85%), but also the residual debris from dead bacteria and fragmented biofilm was together removed based on the special structure and functions of the antibacterial particles (~ 80%), including extremely rough surfaces, surficial positive charge and magneto-responsive property. This study presents an efficient approach for microorganism management in water system which can be expectantly applied to improve the water safety.


Quercetin upregulates CREM gene expression in cyanide-induced endocrine dysfunction.
Cyanide is among the ubiquitous chemicals that humans are usually exposed to and it is well documented that cyanide induces infertility in humans and experimental rodents. However, the pathogenesis remains unknown. Likewise, quercetin is an important nutraceutical that detoxifies reactive oxygen species, but its effects on testicular damage is not clear. The present study investigated the role of nutraceutical, quercetin on cyanide-induced testicular toxicity and probable involvement of cAMP-response-element modulator (CREM) which is a transcription factor necessary for the process of spermatogenesis. Thus, this work hypothesized that quercetin will mitigate endocrine dysfunction induced by cyanide. Seventy-two adult male Wistar rats were divided into seven groups (A to G). Groups A, B, C, F and G comprised of eight (8) rats per group while groups D and E comprised of sixteen (16) rats per group. Group A was designated as control while Groups B and C were given 0.5 and 1 mg/kg of cyanide respectively for 56 days. Group D and E received 0.5 and 1 mg/kg body weight cyanide respectively for 30 days. At day 30, eight animals were sacrificed from Group D and E and the remaining eight (8) rats were subdivided into sub-groups (D1 and E1) and were given 20 and 40 mg/kg of quercetin respectively for twenty-six (26) days. Group F and G were given concurrent administration of cyanide and quercetin at a dose of 0.5 + 20 mg/kg and 1 + 40 mg/kg respectively for 56 days. Body and testicular weight were significantly reduced in cyanide treated groups while quercetin modulates the reduction. Significant down-regulation of CREM gene and reduction in serum level of follicle stimulating hormone (FSH), Luteinizing hormone (LH), testosterone, glutathione peroxidase (GPx) and zinc in cyanide-treated groups, whereas administration of quercetin concomitantly with cyanide exposure or post-treated significantly reversed the alterations.


Non-invasive measurements of ductus arteriosus flow directly after birth.
To assess ductus arteriosus (DA) blood flow directly after birth in healthy term infants after elective caesarean section. In healthy term newborns, echocardiography was performed at 2, 5 and 10 min after birth to monitor cardiac output and DA blood flow. Heart rate (HR) was assessed using ECG. The delivery rooms of the Leiden University Medical Center. 24 healthy term infants born after a caesarean section were included in this study. Mean (SD) HR did not change (158 (18) beats per minute (bpm), 5 min (159 (23) bpm) and 10 min (156 (19) bpm). DA diameter decreased from 5.2 (1.3) mm at 2 min to 4.6 (1.3) mm at 5 min (p=0.01) to (3.9 (1.2) mm) (p=0.01) at 10 min. Right-to-left DA shunting was unaltered (median (IQR) 95 (64-154) mL/kg/min to 90 (56-168) mL/kg/min and 80 (64-120) mL/kg/min, respectively (ns)), whereas left-to-right shunting significantly increased between 2 and 5 min (41 (31-70) mL/kg/min vs 67 (37-102) mL/kg/min (p=0.01)) and increased significantly between 2 and 10 min (93 (67-125)) mL/kg/min (p<0.001). Right-to-left/left-to-right shunting ratio decreased significantly from 2.1 (1.4-3.1) at 2 min to 1.4 (1.0-1.8) at 5 min (p<0.0001) and to 0.9 (0.6-1.1) at 10 min (p<0.0001). DA shunting changes swiftly from predominantly right-to-left shunting to predominantly left-to-right shunting at 10 min after birth, reflecting differential changes in pulmonary and systemic vascular resistance.


Comparative Analysis of Chitin SynthaseA dsRNA Mediated RNA Interference for Management of Crop Pests of Different Families of Lepidoptera.
RNA interference (RNAi) is a sequence-specific down-regulation in the expression of a particular gene, induced by double-stranded RNA (dsRNA). Feeding of dsRNA either directly or through transgenic plants expressing dsRNA of insect genes has been proven successful against lepidopteran and coleopteran pests, establishing an additional alternative to control insect pests. Lepidopteran crop pests including Spodoptera litura (Fabricius) (Noctuidae), Chilo partellus (Swinhoe) (Crambidae), Plutella xylostella (Linnaeus) (Plutellidae), and Maruca vitrata (Fabricius) (Pyralidae) are the devastating pests of a variety of crops. To tap the potential of RNAi against insect pests, a gene coding for the key enzyme in chitin biosynthesis in arthropods, the chitin synthaseA (CHSA), has been targeted through an exogenous delivery of dsRNA and plant-mediated RNAi. The introduction of dsCHSA caused "Half ecdysis" and "Black body" type lethal phenotypes and a significant reduction in larval body weight. Subsequent RT-qPCR analysis demonstrated the down-regulation of CHSA gene transcripts from 1.38- to 8.33-fold in the four target species. Meanwhile, when S. litura larvae fed with leaves of transgenic tobacco plants expressing dsSlCHSA, the mRNA abundance of CHSA gene was significantly decreased resulting in lethal phenotypes like "Double head formation," "Half ecdysis," and "Black body." In addition, abnormalities in pupal-adult and adult stage were also documented, strongly suggesting the RNAi effect of CHSA gene at late developmental stages. Overall, the results demonstrated that CHSA gene expression in Lepidopteran crop pests could be suppressed by application of dsRNA either as feeding or through transgenic crop plants.


A review of technical advances in interventional magnetic resonance imaging.
Initial research in the development of interventional magnetic resonance (MR) imaging in the late 1980s and early to mid-1990s focused on pulse sequences, devices, and clinical applications. This focus was largely a result of the limited number of areas in which the academic research community leading the development could provide innovation on the MR systems of the time. However, during the past decade, computational power, higher bandwidth graphical displays, faster computer networks, improved pulse sequence architectures, and improved technical specifications have accelerated the pace of development on modern MR systems. Today, it is the combination of multiple system factors that are enabling the future of interventional MR. These developments, their impact on the field, and newly emerging applications are described.


Antimicrobial consumption in intensive care unit patients at level 1 trauma centre in India.
Increase in the antimicrobial resistance causes a concern globally. To mitigate the rapidly rising antimicrobial resistance in the health system globally antimicrobial stewardship programs (AMSP) have been advocated. Therefore, we aim to measure aggregate antibiotic consumption by both Defined Daily Dosage (DDD) and Days of Therapy (DOT) methods. As a part of Indian Council of Medical Research initiative to develop local AMSP, this prospective study of six months was conducted at a level -1 Trauma Centre of AIIMS, New Delhi. In this, we have included all the patients of polytrauma and neurosurgical Intensive care units between April to October 2019. Consumption of antibiotics data were collected manually daily by infection control practitioners. Data were presented as Days of Therapy (DOT) and Defined Daily Dose (DDD). During the six months of study, antimicrobial consumption of ICU was compared with empirical therapy v/s culture-based therapy. Overall average antimicrobial consumption for the six months for both empirical therapy and culture-based therapy DDD/1000 patient days was 531.8 and 460.7 whereas DOT/1000 patient days 489.9 and 426.04 respectively. Antimicrobial Stewardship activities aim to ensure judicious consumption of antimicrobials. Such data will be of value in establishing, evaluating and monitoring the function of the AMSP in the healthcare settings.


Nurses and doctors in prime time series: the dynamics of depicting professional power.
This essay sketches a comparison of 1960s' television portrayals with those of the present to show that a limited and incomplete portrayal of nurses has been an enduring feature of prime-time medical television programs. They have depicted physicians then and now as captains of the medical ship and nurses then and now their ancillary and ill-defined helpers. As the comparison makes clear, part of nurses' lack of clear power in TV medical scenarios has to do with the explicit and implicit clout exercised by physicians' organizations to present doctor images effectively. That clout contrasts with nursing organizations' lack of attempts or ability (it's hard to gauge which) to influence network television's most prominent representations of their roles and the environments in which they work.


Bio-computational model of object-recognition: quantum Hebbian processing with neurally shaped Gabor wavelets.
Theoretical and simulational evidence, as well as experimental indications, are accumulating that quantum associative memory and imaging are possible. We compare these data with biological evidence, since we find them to a significant extent compatible. This paper presents a computationally implementable integrative model of appearance-based viewpoint-invariant recognition of objects. The neuro-quantum hybrid model incorporates neural processing up to V1 and quantum associative processing in V1, achieving together an object-recognition result in V2 and ITC. Results of our simulation of the central quantum-like parts of the bio-model, receiving neurally pre-processed inputs, are presented. This part contains our original simulated storage by multiple quantum interference of image-encoding Gabor wavelets done in a Hebbian way, especially using the Griniasty et al. pose-sequence learning rule.


Low-temperature selective catalytic reduction of N2O by CO over Fe-ZSM-5 catalysts in the presence of O2.
Nitrous oxide (N2O) is an important ozone-depletion substance and greenhouse gas. Selective catalytic reduction (SCR) of N2O by CO is considered an effective method for N2O elimination. However, O2 exhibited a significant inhibition effect on the catalytic performance of N2O reduction by CO. A series of iron-based catalysts were prepared to investigate the effect of O2 in SCR of N2O by CO. The Fe-Z-pH2 (Fe-ZSM-5 ion-exchanged under pH of 2) catalyst manifested superior activity at low temperature and excellent O2 resistance in N2O reduction process. The characterization results from UV-vis DR spectra and XPS indicated that α-sites are the main active sites in Fe-Z-pH2, and they were inert to O2 but highly active to N2O. It could be concluded that the competition effect between N2O and O2 was very important over different catalysts. O2 is more prevalent over α-Fe2O3 catalyst, while N2O dominates over Fe-Z-pH2 catalyst. Moreover, in the presence of O2, Fe-Z-pH2 exhibited better performance for N2O removal than non-noble mixed oxide catalysts, which might broaden the application of low-temperature SCR of N2O by CO.


Blastopore formation inAmbystoma mexicanum.
UsingAmbystoma mexicanum blastulae (Harrison 7 2/3 to 10-), a study was made of the morphogenetic behaviour of the endoderm, both in isolation and upon recombination with marginal zone material.It was shown that the endoderm autonomously forms "flask cells" and thus a blastoporal groove, when isolated at or after the mid-blastula stage (8+). The frequency of blastopore formation decreases as the endoderm is isolated at successively younger stages. At the youngest operable stage (7 2/3) a blastoporal groove is formed in 30% of the isolates.Recombination with marginal zone material promoted blastopore formation in endoderm isolated at stage 7 2/3; the frequency of blastopore formation was maximal (90%) in recombinates with dorsal marginal zone from stages 7 2/3 and 8 1/2, while in recombinates with older dorsal (stages 9 and 10-) or with ventral marginal zone (stages 7 2/3 to 10-) it was lower (60%). Blastopore formation could only be evoked on the dorsal side of the endoderm.Ventral halves of stage 10- endoderm are unable to form flask cells, whereas the complete endoderm forms flask cells ventrally as well as dorsally, demonstrating the leading role of the dorsal endoderm in flask cell formation.Only the left half of the dorsal or ventral marginal zone was used in the recombinates, the corresponding right half being culturedin vitro. Differentiation of mesoderm in these control explants was used as a criterion for the presence of induced mesoderm in the marginal zone material at the time of recombination. Differentiation was poor, however, which affects the reliability of this criterion. No relation could be found between the presence of induced mesoderm in the isolated marginal zone material and the incidence of gastrulation phenomena in the endoderm/marginal zone recombinates.Thus the results of these experiments provide no evidence for a gastrulation-inducing role of the induced mesoderm, as proposed by Nieuwkoop (1969a). Alternatively, the results suggest that the endoderm may acquire its capacity for blastopore formation as a direct consequence of the earlier dorso-ventral polarization of the embryo, without the intervention of the induced mesoderm. Synchronization of endodermal and mesodermal gastrulation movements must be established during mesoderm induction.


Targeted treatments for fragile X syndrome.
Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet full criteria for ASD. Recent major advances have been made in the understanding of the neurobiology and functions of FMRP, the FMR1 (fragile X mental retardation 1) gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to the dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to the dysregulated translational pathway. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model at multiple stages of development. Clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess cognitive change that might be associated with treatment. Genes known to be causes of ASD interact with the translational pathway defective in FXS, and it has been hypothesized that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction between FXS and ASD. Therefore, targeted treatments developed for FXS may also target subgroups of ASD, and clinical trials in FXS may serve as a model for the development of clinical trial strategies for ASD and other cognitive disorders.


Mechanical characteristics and functional length of canine expiratory muscles.
The expiratory muscles of the abdominal region actively contribute to breathing. In dogs, the transversus abdominis appears to be the main abdominal muscle of expiration. The in vitro mechanical properties of the transversus abdominis have not been reported to date, and formed the basis of the present investigation. Moreover, in order to understand better the nature of the mechanical interplay between the various abdominal muscle groups, we also evaluated the effects of posture on the operational length of canine transversus abdominis and external oblique muscles and related their in situ length to optimal length. The experiments were performed on twelve mongrel dogs, anesthetized with pentobarbital sodium. Contractile properties of excised transversus abdominis muscle strips were evaluated at 37 degrees C and revealed similar twitch, force-frequency and length-tension properties as previously reported in canine external oblique (Farkas and Rochester, J. Appl. Physiol. 65: 2427-2433, 1988). In the supine posture, we noted that external oblique was operating at 88% Lo, while the transversus abdominis was operating at a significantly shorter length of 74% Lo. Thus, in the supine posture, the external oblique is better situated than the transversus abdominis to generate tension. In the prone posture, however, we noted that both abdominal muscles were located at similar positions along their length-tension curve, operating at a length of roughly 77% Lo. Since both muscles share common length-tension characteristics, the present results indicate that the tension generating potential of both muscles in prone dogs is equal for a given neural input. However, we conclude that the preferential recruitment of the transversus abdominis in prone animals must be related to factors other than simple tension generation.


Assessment of the in vivo genotoxicity of new lead compounds to treat sickle cell disease.
The compounds 1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl nitrate (C1), (1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl nitrate (C2), 3-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C3), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-hydroxy-benzenesulfonamide (C4), 4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)benzyl nitrate (C5), and 2-[4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)phenyl]ethyl nitrate (C6) were evaluated with a micronucleus test using mouse peripheral blood to identify new candidate drugs for the treatment of sickle cell disease (SCD) that are safer than hydroxyurea. The compounds induced an average frequency of micronucleated reticulocytes (MNRET) of less than six per 1,000 cells at 12.5, 25, 50, and 100 mg/kg, whereas hydroxyurea induced an average MNRET frequency of 7.8, 9.8, 15, and 33.7 per 1000 cells respectively, at the same concentrations. Compounds C1-C6 are new non-genotoxic in vivo candidate drugs for the treatment of SCD symptoms.


Association of post-anaesthetic hyperthermia with abnormal muscle characteristics: a case report.
A previously healthy 18-year-old male, following appendectomy developed post-anaesthetic hyperthermia (42.1 degrees C) with an elevation of serum creatine kinase and activated partial thromboplastin time. Repeated arterial blood gases were normal. Cooling and anti-pyretic medication did not control the fever. In contrast, sodium dantrolene appeared effective in lowering the patient's temperature and normalizing the vital signs, both acutely and over the following three days. Subsequent muscle biopsy revealed a normal contracture response to caffeine alone or in the presence of halothane. However, the muscle had a larger than normal potentiation of evoked twitch tension in the presence of caffeine and halothane. Electrophoresis of the muscle revealed a marked increase of an unidentified low molecular weight protein. The patient's clinical course, and the results of the muscle studies, suggest that an abnormality of skeletal muscle.


Infliximab in inflammatory bowel disease. Is premedication necessary?
The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.


Anatomical coupling of sensory and motor nerve trajectory via axon tracking.
It is a long-standing question how developing motor and sensory neuron projections cooperatively form a common principal grid of peripheral nerve pathways relaying behavioral outputs and somatosensory inputs. Here, we explored this issue through targeted cell lineage and gene manipulation in mouse, combined with in vitro live axon imaging. In the absence of motor projections, dorsal (epaxial) and ventral (hypaxial) sensory projections form in a randomized manner, while removal of EphA3/4 receptor tyrosine kinases expressed by epaxial motor axons triggers selective failure to form epaxial sensory projections. EphA3/4 act non-cell-autonomously by inducing sensory axons to track along preformed epaxial motor projections. This involves cognate ephrin-A proteins on sensory axons but is independent from EphA3/4 signaling in motor axons proper. Assembly of peripheral nerve pathways thus involves motor axon subtype-specific signals that couple sensory projections to discrete motor pathways.


Reflux symptom index and reflux finding score in otolaryngologic practice.
To evaluate whether patients with abnormal Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) benefit from proton pump inhibitor (PPI) therapy. Open, multicenter, prospective longitudinal cohort study. Patients with suspected reflux-associated laryngologic symptoms were evaluated by 40 community practice otolaryngologists using RSI and RFS. Patients were treated with pantoprazole 40-80 mg/d for 8-12 weeks if RSI was greater than 9 and RFS greater than 7. Pre- and posttherapeutic RSI and RFS were compared using Wilcoxon signed rank test and additionally controlled with the symmetry test of Bowker. A total of 1044 patients were included over a period of 20 months. Median total score of RSI before therapy was 12 and decreased to 3 (P≪0.001). Median total score of RFS before therapy was 16 and decreased to 6 (P≪0.001). Assessment of the treatment effect by otolaryngologists and patients was judged as being excellent in at least 50%. In 2% of the patients, gastrointestinal side effects were documented. RSI and RSF are easy to administer in the routine care of patients suspected of having laryngopharyngeal reflux. Patients identified by positive results of these tests have a high likelihood of excellent improvement after 8-12 weeks of PPI treatment. By implementation of RFS and RSI in daily use, most patients may not need time-consuming and cost-intensive examinations in the first-line assessment of LPR. These examinations can be reserved for nonresponders, and uncontrolled prescription of PPIs can be restricted.


Health-related quality of life in patients with cleft palate: Validity and reliability of the VPI Effects on Life Outcomes (VELO) questionnaire translated to Dutch.
Disease-specific health-related quality of life (HRQOL) questionnaires provide the clinician with important information regarding the impact of the disease on functioning and well-being. For patients with velopharyngeal insufficiency (VPI), the VPI Effects on Life Outcomes (VELO) questionnaire was developed and validated in English by Skirko et al. (2012). However, a valid and reliable Dutch translation of this questionnaire is not available yet. The English questionnaire was translated to Dutch following a forward-backward translation procedure. A linguistic validation and the evaluation of the internal consistency (Cronbach's α) of this Dutch version were performed based on the responses of 39 parents of patients with cleft (lip and) palate (mean age: 6.8 years) (parent report) and the responses of 14 patients older than 8 years (mean age: 9.5 years) (child report). Additionally, the concurrent validity was assessed by comparing the scores on the parent report to those on the pediatric voice handicap index. Furthermore, the validity of the parent proxy assessment and the relationship between age and responses on the VELO questionnaire were investigated. Based on the responses of an age and gender matched control group without cleft palate, the discriminant validity was evaluated. The parent report was easy to complete for all parents. Nine of the fourteen (64%) patients were able to complete the child report independently. The median scores on the parent report and the child report were 82.7 and 95.1 respectively. The patient group had a significantly worse perception of HRQOL compared to the control group (p < 0.001; p = 0.029). There were no significant differences between the responses of the parent and their child's (p = 0.345). A significant positive correlation was found between the score on the parent report and the age of the patients (p = 0.001). Furthermore, a significant negative correlation was found between the parent report and the P-VHI (p < 0.001). Cronbach's α was 0.955 and 0.817 for the parent report and the child report respectively. The Dutch VELO questionnaire is a valid, reliable and user-friendly tool that provides important information about HRQOL in patients with cleft (lip and) palate.


Effect of Quorum Sensing Inducers and Inhibitors on Cytoplasmic Incompatibility Induced by Wolbachia (Rickettsiales: Anaplasmataceae) in American Serpentine Leafminer (Diptera: Agromyzidae): Potential Tool for the Incompatible Insect Technique.
Agricultural crops around the world are attacked by approximately 3,000-10,000 species of pest insect. There is increasing interest in resolving this problem using environmentally friendly approaches. Wolbachia (Hertig), an insect endosymbiont, can modulate host reproduction and offspring sex through cytoplasmic incompatibility (CI). The incompatible insect technique (IIT) based on CI-Wolbachia is a promising biological control method. Previous studies have reported an association between CI and Wolbachia density, which may involve a quorum sensing (QS) mechanism. In this study, we investigated the effect of manipulating QS in Wolbachia using several chemicals including 3O-C12-HSL; C2HSL; spermidine (QS inducers), 4-phenylbutanoyl; and 4-NPO (QS inhibitors) on American serpentine leafminer (Liriomyza trifolii [Burgess]), an agricultural pest. The results showed that inducing QS with 3O-C12-HSL decreased the proportion of hatched eggs and increased Wolbachia density, whereas QS inhibition with 4-phenylbutanoyl had the opposite effects. Thus, manipulating QS in Wolbachia can alter cell density and the proportion of hatched eggs in the host L. trifolii, thereby reducing the number of insect progeny. These findings provide evidence supporting the potential efficacy of the IIT based on CI-Wolbachia for the environmentally friendly control of insect pest populations.


Testing Behavioral Nudges and Prompts in Digital Courses for the Self-guided Treatment of Depression and Anxiety: Protocol for a 3-Arm Randomized Controlled Trial.
Despite showing strong evidence of positive outcomes, a common problem in the field of digital health is poor engagement and adherence. Non-health care, for-profit digital ventures, such as Facebook, LinkedIn, and Twitter, conduct behavioral experiments to increase user engagement. To our knowledge, digital health organizations have not published similar types of experiments in ad libitum environments, and there are limited published data indicating whether nudges and prompts can be leveraged to increase engagement with digital health interventions. The main objective of our 3-arm randomized controlled trial is to test whether registered members in two well-established digital health courses for anxiety and depression will engage with four different types of nudges and prompts, and whether engaging with nudges and prompts increases engagement within the courses. New members who register for the self-guided anxiety and depression courses on the Evolution Health platform will be randomized into 1 of 3 arms. The first control arm will feature a member home page without any behavioral nudges or prompts. The second arm will feature a member home page with a Tip-of-the-Day section containing directive content. Arm 3 will feature a member home page with a Tip-of-the-Day section containing social proof and present bias content. The third arm will also feature a to-do item checklist. The experiment was designed in August 2021 and was launched in November 2021. Initially, we will measure engagement with the tips and the to-do checklist by calculating the frequency of use by age and gender. If members do engage, we will then, according to age and gender, examine whether nudges and prompts result in higher course completion rates and whether specific types of prompts and nudges are more popular than others. Our 3-arm randomized controlled trial will be the first to compare four distinct types of behavioral prompts and nudges in two self-guided digital health courses that were designed to treat mental health issues. We expect the results to generate insights into which types of behavioral prompts and nudges work best in the population. If they are shown to increase engagement, the insights will then be used to apply prompts and nudges to the platform's addiction-focused courses. Based on the results of the experiment, the insights will be applied to using artificial intelligence to train the platform to recognize different usage patterns and provide specific engagement recommendations to stratified users. DERR1-10.2196/37231.


Photo-responsive oxidase-like nanozyme based on a vanadium-docked porphyrinic covalent organic framework for colorimetric L-Arginine sensing.
This study reports the development of a vanadium-docked porphyrinic covalent organic framework as a novel class of highly polar photoactive materials. Thanks to its extended π-electron conjugation and high chemical stabilities, this framework can serve as an oxidase-Like photo-nanozyme for photocatalytic oxidation of o-phenylenediamine (o-PDA) and a colorimetric substrate for the production of the yellow-colored oxidized o-PDA (o-PDAox). The physicochemical properties of the as-prepared photo-nanozyme were characterized by several analytical techniques. Its enhanced light harvesting and charge separation and transfer were also verified by electrochemical and spectroscopic analysis. This photo-nonenzymatic colorimetric assay was applied for the sensitive L-Arginine (L-Arg) detection as a typical amino acid in the linear range of 8.1 nM-330 μM with a limit of detection (LOD) of 3.5 nM. The findings of this research confirmed the safety and feasibility of the proposed photo-nonenzymatic colorimetric sensing strategy for the detection of L-Arg and other similar biomolecules in food samples. Kinetic investigation revealed that the photo-responsive oxidase mimic exhibits satisfactory Km (0.47 mM) and Vmax (42.0 μM/s) values. This work broadened our insight into the development of modified porphyrinic-COF-based visible light-responsive oxidase-like photo-nanozyme for environmentally friendly colorimetric biosensing.


Sleep-promoting effects of intraperitoneally administered uridine in unrestrained rats.
An intraperitoneal injection of 0.1 nmol uridine in rats resulted in a transient excess slow-wave sleep if administered shortly before onset of the dark period. The sleep latency was remarkably shortened. A small dose (0.01 nmol) and larger doses (1, 10, 100 nmol) caused no effect. Uridine at a dose of 0.1 nmol was entirely ineffective if injected shortly before onset of the light period, while it resulted in transient excess paradoxical sleep if injected at an early phase of the light period. It is concluded that uridine, if timely administered through a systemic route, may pass the blood-brain barrier to modulate sleep in rats.


Simple and biodegradable mesoporous silica nanocarriers for enhancing antitumor therapy through photochemical synergism.
The biosafety and degradability of nanocarriers have always been an important factor restricting their entry into the clinic. In this work, a new nano-system was prepared by coating the photothermal effect of dopamine-doped mesoporous silica nanoparticles with carboxymethyl chitin through electrostatic interaction, and is further anchored with folic acid on the surface for targeted delivery of anti-cancer the drug doxorubicin (DOX). The nano-system (DOX@PDA/MSN-CMCS-FA) is simply modified CMCS after being loaded with DOX and has good dispersibility, and the drug loading is 10.6%. In vitro release studies have shown that the release rate of PDA/MSN-CMCS-FA is 40% in pH 5.5. Effective degradation is debris in 14 d acidic environments. Due to the anti-infrared photothermal effects of PDA doping and DOX chemotherapy, the semi-lethal concentration (IC50) of nanoparticles (NPS) was 14.95 μg/mL, which can inhibit tumor cell growth by photochemical synergistic treatment, and have certain degradation performance.


Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock.
Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock. Retrospective, multicenter, database study between January 2010 and March 2017. Premier Healthcare Database hospitals. Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included. The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression. Among 294,733 patients (mean age, 66 ± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35-0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29-0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ± 1,130 vs $77 ± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73-78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017. After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.


Mathematical modeling of hydrolysate diffusion and utilization in cellulolytic biofilms of the extreme thermophile Caldicellulosiruptor obsidiansis.
In this study, a hydrolysate diffusion and utilization model was developed to examine factors influencing cellulolytic biofilm morphology. Model simulations using Caldicellulosiruptor obsidiansis revealed that the cellulolytic biofilm needs to generate more hydrolysate than it consumes to establish a higher than bulk solution intra-biofilm substrate concentration to support its growth. This produces a hydrolysate surplus that diffuses through the thin biofilm structure into the bulk solution, which gives rise to a uniform growth rate and hence the homogeneous morphology of the cellulolytic biofilm. Model predictions were tested against experimental data from a cellulose-fermenting bioreactor and the results were consistent with the model prediction and indicated that only a small fraction (10-12%) of the soluble hydrolysis products are utilized by the biofilm. The factors determining the rate-limiting step of cellulolytic biofilm growth are also analyzed and discussed.


Imprinting. A study of cholinergic receptor sites in parts of the chick brain.
The distribution of cholinergic receptor binding sites was studied in certain areas of the chick brain, especially that part (IMHV) of hyperstriatum ventrale which has previously been implicated in the imprinting process. There was relatively little binding of [125I]-alpha-bungarotoxin in this region, as shown using an autoradiographic technique. In contrast muscarinic receptor sites, with an affinity for [3H]-quinuclidinyl benzilate (QNB), are present in relatively high concentration in a medial forebrain sample containing IMHV and also in a visual projection area, the hyperstriatum accessorium (HA). To assess the effects of imprinting on the concentration of QNB binding sites 26 young chicks were exposed to an imprinting stimulus (a pulsing red light) for 20 min. Thirteen of the chicks were returned to the dark and the other 13 were trained for a further 100 min. There was no effect of further training on specific QNB binding in HA or in the medial forebrain sample. In undertrained chicks there was a positive correlation between QNB binding in the medial forebrain sample of the left hemisphere and that in the right; there was no such relationship in overtrained birds. Mean QNB binding in the right medial forebrain sample was greater than in the left by 21%. There was no such hemispheric asymmetry in HA.


Epithelial Stem Cells: Making, Shaping and Breaking the Niche.
Epithelial stem cells maintain tissues throughout adult life and are tightly regulated by their microenvironmental niche to balance cell production and loss. These stem cells have been studied extensively as signal-receiving cells, responding to cues from other cell types and mechanical stimuli that comprise the niche. However, studies from a wide range of systems have identified epithelial stem cells as major contributors to their own microenvironment either through producing niche cells, acting directly as niche cells or regulating niche cells. The importance of stem cell contributions to the niche is particularly clear in cancer, where tumour cells extensively remodel their microenvironment to promote their survival and proliferation.


High affinity IgE receptor (Fc epsilon RI) expression on eosinophils infiltrating the lesions and mite patch tested sites in atopic dermatitis.
Expression of the high affinity IgE receptor (Fc epsilon RI) on eosinophils has recently been reported. This led us to evaluate Fc epsilon RI expression on eosinophils in atopic dermatitis (AD). Double immunofluorescence stainings with an anti-Fc epsilon RI monoclonal antibody (mAb) and a polyclonal antieosinophil cationic protein (ECP) antibody were performed on lesional biopsy specimens from patients with AD and from patients with bullous pemphigoid (BP) as controls. In AD and BP lesions, 77% and 70% of eosinophils expressed Fc epsilon RI, respectively. However, the intensity of Fc epsilon RI staining in AD was much stronger than in BP, suggesting upregulation of Fc epsilon RI expression on eosinophils in AD. In addition, the eosinophils infiltrating AD lesions were stained strongly with anti-CD23 mAb and anti-IgE antibody. At the sites of mite patch testing in AD, Fc epsilon RI-, CD23- and IgE-positive eosinophils were observed to the same degree as in the lesions, and a considerable number of mite antigen-bearing eosinophils were detected. Fc epsilon RI and CD23 were both upregulated on the skin-infiltrating eosinophils in AD and bound IgE molecules.


Clinical limitations of acetylcholinesterase antagonists.
Administration of a nondepolarizing neuromuscular blocking drug (muscle relaxant) is a standard practice in many anesthetic scenarios. These muscle relaxants work by competitive antagonism of the neurotransmitter acetylcholine at nicotinic cholinergic receptors within the neuromuscular junction of skeletal muscle (Martyn et al; Neuromuscular physiology and pharmacology, anesthesia. Edited by RD Miller, Philadelphia, Churchill Livingstone, 2000). At the conclusion of the procedure for which the muscle relaxant was administrated, there will be a greater or lesser degree of residual muscle weakness. It is usually necessary to pharmacologically reverse this residual weakness to restore full function to the patient's muscles. Indeed, failure to reverse neuromuscular block is associated with increased perioperative morbidity and mortality (Arbous et al; Impact of anesthesia management characteristics on severe morbidity and mortality. Anesthesiology 2005;102:257-268; quiz 491-2). Pharmacologic reversal currently relies on the administration of an anticholinesterase drug, which decreases the metabolism of acetylcholine at the neuromuscular junction and allows its concentration to increase and hopefully overcome the effect of the muscle relaxant. This approach to reversal has significant limitations; the mechanism of reversal is indirect, the efficacy is limited and unpredictable, and undesirable autonomic responses occur. This review will address these limitations.


Cytotoxic and antimicrobial potential of benzimidazole derivatives.
New benzimidazole derivatives were synthesized and their structures were characterized by spectroscopic and microanalysis techniques. The cytotoxic properties of ten benzimidazole derivatives, five of which were synthesized in our previous studies, were determined against the lung cancer cell line, A549, and the healthy lung epithelial cell line, BEAS-2B. Among the ten compounds tested, based on the 72-h incubation results, compound 12 was the most cytotoxic against the A549 cell line, whereas against the BEAS-2B cell line, it was as cytotoxic as cisplatin. The IC50 values of compound 12 were 3.98 and 2.94 µg/ml for A549 and BEAS-2B cells, respectively. The cisplatin values were 6.75 and 2.75 µg/ml for A549 and BEAS-2B cells, respectively. Compounds 10, 8, 7, and 13 showed toxic effects against A549 cells, but were less toxic against BEAS-2B cells than cisplatin. The antimicrobial activity of these compounds against pathogenic bacteria and yeasts was also evaluated based on their minimum inhibitory concentration (MIC) values. The compounds, except 12 and 13, generally showed higher antimicrobial activity against yeasts, compared with bacteria. Compound 12 showed better activity against Pseudomonas aeruginosa and Staphylococcus aureus than against Escherichia coli. Compounds 7, 8, and 11 were the most effective ones against the microorganisms, and yeasts were highly sensitive to these compounds with MIC values of 25-100 µg/ml.


Reply to Böning et al. Comment on "Ceruti et al. Temporal Changes in the Oxyhemoglobin Dissociation Curve of Critically Ill COVID-19 Patients. J. Clin. Med. 2022, 11, 788".
We would like to thank Böning et al. for all the important issues raised in the present commentary [...].


The fall of the postural-structural-biomechanical model in manual and physical therapies: exemplified by lower back pain.
Manual and physical therapists often use a postural-structural-biomechanical (PSB) model to ascertain the causes of various musculoskeletal conditions. It is believed that postural deviations, body asymmetries and pathomechanics are the predisposing/maintaining factors for many musculoskeletal conditions. The PSB model also plays an important role in clinical assessment and management, including the choice of manual techniques and the exercise prescribed. However, the most important question is consistently being ignored--can a person's physical shape/posture/structure/biomechanics be the cause of their lower back pain?


Identification of a novel HLA-A allele, A*29:28, in an East African population.
The new allele is identical to A*29:01:01:01 in exons 2 and 3, except for a single-nucleotide substitution (TTG to TGG) at codon 156.


Directed embryonic stem cell differentiation with small molecules.
Embryonic stem cells (ESCs) are a promising cell source for regenerative medicine and transplantation therapy.ESCs are able to self-renew indefinitely in culture; however, the ability to differentiate ESCs into specific cell lineages is key to exploiting their therapeutic potential. Cell-based phenotypic and reporter-based screens have been used to identify small molecules that selectively promote ESC differentiation into a variety of cell lineages. Not only will such molecules facilitate the clinical applications of stem cells, the detailed study of their mechanism is providing new insights into the biology that regulates ESC self-renewal and differentiation. In this article we discuss key issues, challenges and opportunities in the application of this chemical approach to stem cell biology.


Cardiac amyloidosis characterization by kinetic model fitting on [18F]florbetaben PET images.
To evaluate the feasibility of kinetic modeling-based approaches from [18F]-Flobetaben dynamic PET images as a non-invasive diagnostic method for cardiac amyloidosis (CA) and to identify the two AL- and ATTR-subtypes. Twenty-one patients with diagnoses of CA (11 patients with AL-subtype and 10 patients with ATTR-subtype of CA) and 15 Control patients with no-CA conditions underwent PET/CT imaging after [18F]Florbetaben bolus injection. A two-tissue-compartment (2TC) kinetic model was fitted to time-activity curves (TAC) obtained from left ventricle wall and left atrium cavity ROIs to estimate kinetic micro- and macro-parameters. Combinations of kinetic parameters were evaluated with the purpose of distinguishing Control subjects and CA patients, and to correctly label the last ones as AL- or ATTR-subtype. Resulting sensitivity, specificity, and accuracy for Control subjects were: 0.87, 0.9, 0.89; as far as CA patients, the sensitivity, specificity, and accuracy were respectively 0.9, 1, and 0.97 for AL-CA patients and 0.9, 0.92, 0.97 for ATTR-CA patients. Pharmacokinetic analysis based on a 2TC model allows cardiac amyloidosis characterization from dynamic [18F]Florbetaben PET images. Estimated model parameters allows to not only distinguish between Control subjects and patients, but also between AL- and ATTR-amyloid patients.


Strategies to reduce and prevent polypharmacy in older patients.
Deprescribing can be accomplished by using tested tools, good judgment, and a team approach.


Degree of Frugivory Predicts Rates of Food-Related Agonism and Intragroup Proximity in Wild Gray Woolly Monkeys (Lagothrix lagotricha cana).
The main factors influencing feeding competition among members of diurnal primate groups are the distribution, availability, and quality of food resources. Socioecological models predict that temporal availability of preferred resources, such as fruit, can influence intragroup feeding competition, which is expected to affect rates of agonism and intragroup spatial patterns. We evaluated the effects of temporal variation in fruit availability on the degree of frugivory (i.e., the proportion of time spent feeding on fruit in relation to total food consumption) and the effects of fruit availability and degree of frugivory on rates of agonistic interactions, and intragroup proximity in two wild groups of gray woolly monkeys (Lagothrix lagotricha cana) in southwestern Brazilian Amazonia. We recorded 227 agonistic interactions via the all occurrences method and 3549 records of spacing via scan sampling during an 8-mo field study from March to October 2017. We found that fruit availability showed a positive relationship with the woolly monkeys' degree of frugivory, which in turn showed a positive relationship with the rates of agonism. We also found that degree of frugivory positively affected intragroup proximity in periods of lower fruit availability, and that agonistic interactions and proximity covaried positively. Conversely, as the degree of frugivory increased, monkeys exhibited greater interindividual distances and, consequently, lower rates of agonism, consistent with lower levels of feeding competition in periods of higher fruit availability. Therefore, we suggest that intragroup contest competition for fruits is an important cost of group living even for generalized, opportunistic frugivorous primates, such as woolly monkeys.


Prediction of temperature profiles in the human skin and subcutaneous tissues.
Exact mathematical solutions in terms of confluent hypergeometric and Airy's functions are obtained to study the steady state temperature distributions in human skin and subcutaneous tissues (SST). It is assumed that the skin is exposed to an air environment and heat transfer from the skin occurs by convection, radiation and evaporation. A mathematical model of the SST, accounting for heat conduction, perfusion of the capillary beds and metabolic heat productions of the dermis and subcutaneous tissues, has been solved to obtain interface temperatures for a wide range of environmental temperatures, rates of evaporation of sweat, wind speeds and relative humidities. The solutions provide inter-relationships between interface temperatures, thermal conductivities, metabolic heat production, blood perfusion, thicknesses of various layers of SST and ambient temperature.


Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by oxidized and reduced lipoic acid.
Peroxynitrite, formed by combination of superoxide radical with nitric oxide, is a reactive tissue-damaging species apparently involved in the pathology of several human diseases. Peroxynitrite nitrates tyrosine residues and inactivates alpha 1-antiproteinase. We show that both lipoic acid and dihydrolipoic acid efficiently protect against damage by peroxynitrite. By contrast, other disulphides tested did not. The biological antioxidant effects of lipoate/dihydrolipoate may involve scavenging of reactive nitrogen species as well as reactive oxygen species.


Academic general pediatric fellowships: curriculum design and educational goals and objectives.
Academic generalists are unique and important members of the pediatric landscape.(1) Academic general pediatrics (AGP) is not considered a subspecialty, because it adheres to generalist values and embraces a wide range of clinical activities. Nonetheless, academic generalists engage in important scholarly efforts, contribute extensively to the education of new pediatricians, and must be prepared to survive in academia. Academic general pediatric faculty positions are subject to the same appointment and promotion requirements as those of subspecialist faculty.


Association between prenatal and postnatal tobacco smoke exposure and allergies in young children.
Many studies have shown a positive association between environmental tobacco smoke (ETS) exposure and allergic disorders, whereas epidemiological evidence of the effect of maternal smoking during pregnancy on allergic diseases is inconsistent. We investigated the independent and joint effects of in utero exposure to maternal smoking and postnatal ETS exposure at home on allergic disorders among Japanese children. Study subjects were 1951 children aged 3 years. Data on maternal smoking during pregnancy and postnatal exposure to ETS at home, allergic symptoms, and potential confounders were collected through the use of a questionnaire. Outcomes were defined according to the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). The prevalence values of symptoms of wheeze, asthma, and eczema in the previous 12 months were 22.0%, 8.8%, and 17.2%, respectively. We found that postnatal ETS exposure at home in the absence of in utero exposure to maternal smoking was associated with a higher prevalence of wheeze (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.67). In contrast, in utero exposure without subsequent postnatal ETS exposure at home or exposure to postnatal ETS at home in addition to in utero exposure to maternal smoking was not associated with the prevalence of wheeze. No measurable associations were observed between fetal, postnatal, or joint exposure and the prevalence of asthma or eczema. Data from this study indicate that ETS at home may be associated with a higher prevalence of wheeze among young Japanese children.


The antioxidant defense protein heme oxygenase 1 is a novel target for statins in endothelial cells.
Cholesterol-independent, pleiotropic actions of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert anti-inflammatory and antioxidant action by as yet unidentified mechanisms. This study explores the role of heme oxygenase 1 (HO-1) as a target and mediator of statins. In cultured endothelial cells derived from human umbilical vein, simvastatin and lovastatin increased HO-1 mRNA levels in a concentration- and time-dependent fashion. HO-1 induction by statins remained unaffected by mevalonate and N-nitro-l-arginine methyl ester, precluding the involvement of isoprenoid- and NO-dependent pathways. HO-1 mRNA induction was abrogated in the presence of actinomycin D and cycloheximide. In cells transfected with a reporter gene construct containing the proximal 4 kB of the HO-1 gene promoter 5'-flanking region, significant upregulation of promoter activity was detected, indicating that regulatory elements binding to this region were involved in transcriptional HO-1 induction by statins. Increased transcriptional expression of HO-1 was associated with elevated HO-1 protein levels and reduction of free radical formation. Our results show that the antioxidant defense protein HO-1 is a target site of statins in endothelial cells. Statins lead to HO-1 promoter activation, transcript and protein accumulation. This novel pathway may contribute to and explain the pleiotropic antioxidant, anti-inflammatory, and antiatherogenic actions of statins.


Acute thoracic epidural hematoma following spinal manipulative therapy: case report and review of the literature.
Spinal epidural hematoma is a rare complication of chiropractic manipulation. This study reports a case of thoracic spinal epidural hematoma following spinal manipulative therapy in the absence of predisposing factors. The effectiveness and safety of chiropractic treatment in chronic spinal pain and a literature review are also presented.


Decision-making criteria for damage control surgery in Japan.
Controversy still remains regarding the optimal criteria for selecting damage control surgery (DCS). Our objective was to propose an indication for implementing DCS for abdominal trauma requiring emergency laparotomy. This was a multicenter, retrospective, observational study that used data from the Japan Trauma Data Bank. Patients who underwent emergency laparotomy were included. We compared the patients regarding the performance of DCS. Of the 4447 patients included in the study, 532 patients were in the DCS group and 3915 patients were in the non-DCS group. Logistic regression analysis revealed that body temperature, level of consciousness (Glasgow Coma Scale), and type of injury (blunt or penetrating) were independent predictors of DCS. Using these predictors, we created the Damage Control Indication Detecting score. The score showed a positive correlation with mortality. The score was obtained as 5 of 9 points in total, revealing mortality of 30.8%, sensitivity of 64.8%, and specificity of 70.0%. The area under the curve for the receiver operating characteristic curve was 0.715. This score can help surgeons determine when to perform DCS. However, more than 95% of trauma cases in Japan involve blunt injuries, suggesting that the results of our study may not be applicable internationally.


Modulation of salt appetite by lateral ventricular infusions of angiotensin II and carbachol during sodium depletion.
Infusions of angiotensin II (AII) or carbachol (CBC) into the lateral ventricles of rats which had been depleted of sodium 4 h previously with either furosemide or polyethylene glycol produced significant changes in salt appetite and sodium and water balances relative to rats infused with saline vehicle. Infusions of AII enhanced the salt appetite and led to rapid retention of both sodium and water. Infusions of CBC abolished the salt appetite and consequently did not produce any increase in sodium balance. Water intake was greater in both AII- and CBC-infused than in vehicle-infused rats and water balances increased during CBC infusion, causing severe dilution of plasma osmolality, sodium and potassium concentrations. Carbachol thus suppressed salt appetite, despite a considerable worsening of the condition of body sodium in these hypovolemic animals. Angiotensin II facilitated the appetite and this enhancement was not secondary to any natriuresis produced by AII infusions.


Creating "boots on the ground": addressing the shortage of field epidemiologists in the Philippines through intermediate-level training programmes.
As of 2022, only 49 graduates of the Philippines' Field Epidemiology Training Programme (FETP) were employed by the Philippine Government, emphasizing the urgent need to increase the number of practicing field epidemiologists to better equip the country for public health emergencies. The FETP-Intermediate Course (IC) curriculum is based mainly on the module of the United States Centers for Disease Control and Prevention that was incorporated into the Philippine context. It consists of five 1-2-week lecture series that provide participants with the knowledge and tools necessary to conduct job-relevant field projects. Individual projects are the centrepiece of the FETP-IC, requiring trainees to investigate outbreaks, design and develop protocols, conduct field data collection, manage data, analyse data, interpret data, write reports and deliver oral presentations. To address the shortage of practicing field epidemiologists in the Philippines, a subnational initiative in Northern Luzon was implemented. Within 3 years, the two FETP-IC subnational training programmes have produced 42 applied epidemiologists who will strengthen epidemiology and surveillance in their respective localities. As of February 2023, 92 studies have been conducted, including 39 outbreak investigations, 37 data quality analysis/process improvement projects, 10 epidemiological studies and six surveillance evaluations. By training and deploying skilled epidemiologists to local health offices and hospitals, the programme is helping to improve the capacity of the health system to respond to public health threats and protect the health of the population. The programme's emphasis on practical training and real-world experience is an effective way to build a strong and sustainable epidemiological workforce.


Clinical variability in keratometry, ultrasound biometry measurements, and emmetropic intraocular lens power calculation.
We calculated inter-examiner and intra-examiner variability in keratometry and ultrasound biometry when performed by two different examiners. The potential effect on intraocular lens power calculation was also considered. Intra-examiner variability was statistically and clinically significant for axial measurements, particularly in eyes with axial length greater than 24 mm. Thus, variability in biometric examination affected the emmetropic intraocular lens power, especially in myopic eyes.


Protective action of phenytoin in cerebral ischemia.
Thirty-six rabbits were subjected to 15-minute periods of stagnant cerebral hypoxia while blood flow to the rest of the body was preserved. After this ischemic interval the animals, divided into three groups, received either saline, phenytoin, 15 mg/kg IV, or thiopental 10 mg/kg IV and 10 mg/kg IM. Histologic examination of tissue sections of the brains, 72 hours after ischemia, indicated that phenytoin afforded significant protection (p less than 0.001) of neurons in the hippocampus and in the dentate nucleus when compared to saline, while the findings noted after thiopental were not statistically significant when compared to placebo. No statistically significant difference was noted between the two drugs. Neuron destruction was seen only in rabbits receiving either saline (92%) or thiopental (50%).


Physalis alkekengi L. var. franchetii combined with hormone therapy for atopic dermatitis.
Atopic dermatitis (AD) is a common, chronic, and recurring inflammatory skin disease. Physalis alkekengi L. var. franchetii (Mast) Makino (PAF), a traditional Chinese medicine, is primarily used for the clinical treatment of AD. In this study, a 2,4-dinitrochlorobenzene-induced AD BALB/c mouse model was established, and a comprehensive pharmacological method was used to determine the pharmacological effects and molecular mechanisms of PAF in the treatment of AD. The results indicated that both PAF gel (PAFG) and PAFG+MF (mometasone furoate) attenuated the severity of AD and reduced the infiltration of eosinophils and mast cells in the skin. Serum metabolomics showed that PAFG combined with MF administration exerted a synergistic effect by remodeling metabolic disorders in mice. In addition, PAFG also alleviated the side effects of thymic atrophy and growth inhibition induced by MF. Network pharmacology predicted that the active ingredients of PAF were flavonoids and exerted therapeutic effects through anti-inflammatory effects. Finally, immunohistochemical analysis confirmed that PAFG inhibited the inflammatory response through the ERβ/HIF-1α/VEGF signaling pathway. Our results revealed that PAF can be used as a natural-source drug with good development prospects for the clinical treatment of AD.


Repigmentation of segmental vitiligo by autologous minigrafting.
Segmental vitiligo (SV) shows distinct clinical, physiologic, and therapeutic characteristics as opposed to those seen in generalized vitiligo (GV). Three patients affected with SV, a relatively unresponsive dermatosis, were successfully repigmented by autologous minigrafting. The achieved results demonstrate a new therapeutic approach for SV.


Noncontraceptive benefits of modern low-dose oral contraceptives.
Most oral contraceptive formulations in current use contain 50 micrograms or less of ethinyl estradiol and 1 mg or less of the various progestins: norethindrone (0.5-1 mg), norgestrel (0.3-0.5 mg), or levonorgestrel (0.05-0.25 mg) [1]. The new generation of progestins--norgestimate, desogestrel and gestodene--are derived from levonorgestrel, the biologically active enantiomer of norgestrel. These steroids have specific metabolic and pharmacologic activity that allow oral contraception at lower doses than previous progestins. Desogestrel and norgestimate are both prodrugs and must undergo hepatic and gastrointestinal metabolism to become biologically active compounds. Gestodene is immediately and completely bioavailable [2]. For the new formulations containing less than 50 micrograms of ethinyl estradiol, the incidence of complications has decreased. With most of the early medical problems identified, current research can now focus on other aspects of oral contraception such as compliance and OC use failure. Prominent noncontraceptive health benefits have been observed in OC users and represent new directions for future research. When the risk-benefit ratio of OC use is evaluated in healthy women today, it clearly favors the benefits. However, these will not be fully realized without an increase in method compliance.


Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study.
Hypospadias is one of the most common urogenital congenital anomalies affecting baby boys. Prevalence estimates in Europe range from 4 to 24 per 10,000 births, depending on definition, with higher rates reported from the United States. Relatively little is known about potential risk factors, but a role for endocrine-disrupting chemicals (EDCs) has been proposed. Our goal was to elucidate the risk of hypospadias associated with occupational exposure of the mother to endocrine-disruptor chemicals, use of folate supplementation during pregnancy, and vegetarianism. We designed a case-control study of 471 hypospadias cases referred to surgeons and 490 randomly selected birth controls, born 1 January 1997-30 September 1998 in southeast England. Telephone interviews of mothers elicited information on folate supplementation during pregnancy and vegetarianism. We used a job exposure matrix to classify occupational exposure. In multiple logistic regression analysis, there were increased risks for self-reported occupational exposure to hair spray [exposed vs. nonexposed, odds ratio (OR) = 2.39; 95% confidence interval (CI), 1.40-4.17] and phthalate exposure obtained by a job exposure matrix (OR = 3.12; 95% CI, 1.04-11.46). There was a significantly reduced risk of hypospadias associated with of folate use during the first 3 months of pregnancy (OR = 0.64; 95% CI, 0.44-0.93). Vegetarianism was not associated with hypospadias risk. Excess risks of hypospadias associated with occupational exposures to phthalates and hair spray suggest that antiandrogenic EDCs may play a role in hypospadias. Folate supplementation in early pregnancy may be protective.


Recent achievements of bioluminescence imaging based on firefly luciferin-luciferase system.
Bioluminescence imaging (BLI) is a newly developed noninvasive visual approach which facilitates the understanding of a plethora of biological processes in vitro and in vivo due to the high sensitivity, resolution and selectivity, low background signal, and the lack of external light excitation. BLI based on firefly luciferin-luciferase system has been widely used for the activity evaluation of tumor-specific enzymes, for the detection of diseases-related bioactive small molecules and metal ions, and for the diagnosis and therapy of diseases including the studies of drug transport, the research of immune response, and the evaluation of drug potency and tissue distribution. In this review, we highlight the recent achievements in luciferin derivatives with red-shifted emission spectra, mutant luciferase-luciferin pairs, and the diagnostic and therapeutic application of BLI based on firefly luciferin-luciferase system. The development and application of BLI will expand our knowledge of the occurrence and development of diseases and shed light on the diagnosis and treatment of various diseases.


The impact of music on the PACU patient's perception of discomfort.
Pain is a normal finding in the postoperative patient, and noise can accentuate one's perception of discomfort. In this study, physiological measurements, intravenous (IV) opioid administration, length of stay, and satisfaction for postoperative patients who listened to music were compared with patients not provided music during their PACU stay. Of the 213 subjects enrolled, 163 experienced postoperative pain. The mean change in experimental subjects' respiratory rate was significantly lower than the controls. Decreases in heart rate and blood pressure from admission to discharge were similar between the two groups. On average, peripheral oxygen saturation and opioid pain control were not significantly different between control and experimental subjects. Subjects provided with music reported acceptable noise levels and increased satisfaction with their PACU experience. Music intervention is therefore a viable, minimal cost, and alternative therapy that PACU nurses can use to assist patients coping with postoperative pain.


Occurrence of histone H10-related protein fraction in trout liver.
The lysine-rich histones of trout liver were studied in order to see whether a protein similar to mammalian histone H1(0) exists in this lower vertebrate. The biochemical methods used involved SDS and acid-urea polyacrylamide gel electrophoresis, gel exclusion and ion-exchange chromatography. Specific rabbit antibodies were elicited against chromatographically-purified mouse liver H1(0) and applied for further characterization of the presumptive trout-liver H1(0) fraction. The results from the indirect immunofluorescence on nitrocellulose-immobilized crude H1 subfractions and from the complement fixation test supplied additional evidence for the existence of an H1(0)-like protein in trout liver.


FT-IR spectroscopy for rapid differentiation of Aspergillus flavus, Aspergillus fumigatus, Aspergillus parasiticus and characterization of aflatoxigenic isolates collected from agricultural environments.
In agricultural areas, Aspergillus flavus, Aspergillus fumigatus and Aspergillus parasiticus are commonly identified in various feedstuffs and bioaerosols originated from feed handling. Some isolates belonging to these fungal species could produce mycotoxins and constitute a risk factor for human and animal health. In this study, Fourier-transform infrared spectroscopy was used for a rapid detection and characterization of 99 isolates collected from agricultural areas. The results showed a first cluster corresponding to strains previously attributed to the A. fumigatus group according to current taxonomic concepts, and a second cluster divided in 2 groups around reference strains of A. flavus and A. parasiticus species. The toxigenic capacity of isolates was evaluated by high performance liquid chromatography coupled to mass spectrometry. In the A. flavus group, only 6 strains of A. parasiticus and 4 strains of A. flavus were able to produce aflatoxins on culture media. FT-IR spectroscopy, respectively, allowed the differentiation of non-toxigenic and toxigenic A. flavus and A. parasiticus isolates at 75 and 100%. Discrimination between toxigenic and non-toxigenic A. fumigatus was not possible because all of the isolates produced at least one mycotoxin.


Two pediatric cases with occlusions of the ipsilateral internal carotid and posterior cerebral arteries associated with moyamoya vessels: "unilateral" moyamoya disease.
Two pediatric cases of unilateral Moyamoya disease are reported. The clinical symptoms and the findings of electroencephalography, angiography, and positron emission tomography in these cases were quite the same as those in the cases with bilateral involvement, which is typical of this disease. In both cases angiography demonstrated unilateral occlusion not only of the internal carotid artery but also of the posterior cerebral artery together with so-called Moyamoya vessels on the same side. Although infectious diseases were mentioned in the patients' histories, no obvious basic diseases related to the cerebrovascular occlusion were detected. We consider that these cases with unilateral involvement suggest the presence of unilateral Moyamoya disease without progression onto the opposite side.


Diagnostic application of the exponentially modified Gaussian model for peak quality and quantitation in high-throughput liquid chromatography-tandem mass spectrometry.
Typical area calculation for a chromatographic peak assumes the observed signal strength at every measurement is an exactly accurate count of the signal. We compared that approach to one using the exponentially modified Gaussian (EMG) in an automated, clinical production setting. Peak areas in a 47 analyte high throughput clinical production liquid chromatography-tandem mass spectrometry assay were compared across four months of production data to determine trends over the lifespan of a chromatographic column. The EMG parameters were superior to traditional quality control methods for monitoring data reproducibility, accuracy and precision. Because the EMG calculations are performed for every peak in the system, a constant monitor of system health is integrated into the operational workflow. Parameter trends confirmed the need for column replacement, and indicated the opportunity for a reduced schedule of preventive and routine maintenance.


A Report of 61 Cases of Retroperitoneal Laparoscopic Nephron-Sparing Surgery and Factors Affecting Postoperative Renal Function.
To explore the situation of 61 patients with renal tumors who underwent retroperitoneal laparoscopic nephron-sparing surgery (RLNSS) and the factors affecting postoperative renal function. A total of 61 patients with renal tumors who underwent RLNSS in our hospital from January 2018 to January 2021 were included in this study. All patients were treated with RLNSS. The clinical data of patients were recorded. Before operation and 3 months after operation, the change value of glomerular filtration rate (ΔGFR) was measured by the Gates method. Multivariate linear regression was used to analyze the related factors affecting postoperative renal function. All 61 patients successfully completed the operation. The mean operative time was 60-150 min' average (98.75 ± 14.38) min. The estimated intraoperative blood loss was 20-310 ml' average (107.93 ± 68.55) ml. Intraoperative warm ischemia time (WIT) was 0-39 min, with an average of (21.16 ± 6.47) min. All patients' pathological margins were negative after operation. In all patients, there were 5 postoperative complications, including 2 cases of renal wound bleeding (3.28%), 1 case of hematuria (1.64%), 1 case of urinary fistula (1.64%), and 1 case of subcutaneous emphysema (1.64%). There were significant differences in tumor diameter, preoperative GFR, operation time and WIT (P < 0.05). Multivariate analysis showed that tumor diameter, preoperative GFR, and WIT were all factors affecting the postoperative renal function of patients with RLNSS (P < 0.05). RLNSS has a good curative effect on patients with renal tumor, and tumor diameter, preoperative GFR, and WIT were all factors affecting the postoperative renal function of patients with RLNSS.