Shifts in soil bacterial community after eight years of land-use change.
The interaction between plants, soil and microorganisms is considered to be the major driver of ecosystem functions and any modification of plant cover and/or soil properties might affect the microbial structure, which, in turn, will influence ecological processes. Assuming that soil properties are the major drivers of soil bacterial diversity and structure within the same soil type, it can be postulated whether plant cover causes significant shifts in soil bacterial community composition. To address this question, this study used 16S rRNA pyrosequencing to detect differences in diversity, composition and/or relative abundance of bacterial taxa from an area covered by pristine forest, as well as eight-year-old grassland surrounded by the same forest. It was shown that a total of 69% of the operational taxonomic units (OTUs) were shared between environments. Overall, forest and grassland samples presented the same diversity and the clustering analysis did not show the occurrence of very distinctive bacterial communities between environments. However, 11 OTUs were detected in statistically significant higher abundance in the forest samples but in lower abundance in the grassland samples, whereas 12 OTUs occurred in statistically significant higher abundance in the grassland samples but in lower abundance in the forest samples. The results suggested the prevalence of a resilient core microbial community that did not suffer any change related to land use, soil type or edaphic conditions. The results illustrated that the history of land use might influence present-day community structure.


Alkaline chemical burn to the face requiring full-thickness skin grafting.
A case of a patient with an alkaline chemical burn to the face from the misuse of the aerosol form of an oven cleaner is presented. The low concentration of sodium hydroxide and lack of early pain delayed the patient's presentation to the emergency department for two hours. After this delay in seeking treatment, continuous irrigation in the ED did little to modify the pH of the patient's injured skin. Thus, she developed a full-thickness alkaline burn that eventually required skin grafting.


Rapid detection of Mycobacterium bovis in bovine cytological smears and tissue sections by peptide nucleic acid fluorescence in-situ hybridization.
Bovine tuberculosis is the leading cause of death in cattle and other species worldwide. Quick and precise identification of mycobacteria is critical to control the occurrence of tuberculosis in cattle. We developed a fluorescent peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) approach to detect Mycobacterium bovis and Mycobacterium avium in cytological smears and tissue sections of bovines suspected of having tuberculosis. PNA-FISH was conducted on smears of lung and lymph node tissues. Standard bovine mycobacterial cultures were used to standardize the probes using 50 % formamide for M. bovis and 30 % formamide for M. avium. M. bovis probe (MTBCcy3), which was standardized at hybridization conditions of (55 °C and 40 % formamide) concentrations, was positive in all cytological smears. Four out of twenty five samples tested positive in tissue sections observed as a bright red fluorescence with a cy3 filter (MTBC probe). No results were observed with (MAVTAMRA) probe for M. avium which was standardized at hybridization conditions of (55 °C and 30 % formamide). No fluorescence was observed in the control tissue sections. Additionally, the results were juxtaposed with those of other commonly used detection methods such as immunohistochemistry and Polymerase Chain Reaction (PCR) by targeting the esxA gene. None of the samples tested positive for M. avium infection. PNA-FISH can be used to obtain cytological impression smears and tissue sections. When compared to PCR it consumes less time in the diagnosis of bovine tuberculosis in post mortem cases.


Prenatal exposure to phthalates and phenols and preclinical vascular health during early adolescence.
Exposure to endocrine-disrupting chemicals may increase cardiovascular risk from early life, but studies in children have shown inconsistent results, most focused on analysis of single chemicals, and none included measures of micro-vascularization as early preclinical markers. This study aimed to evaluate the association between prenatal exposure to phthalates and phenols and macro- and microvascular health during early adolescence. Using data from a Spanish birth cohort (n = 416), prenatal exposure to eight phthalate metabolites and seven phenols (bisphenol A, four parabens, benzophenone-3, triclosan) were assessed using first and/or third trimester spot-urine concentrations. Macrovascular health (systolic and diastolic blood pressure (SBP and DBP, mmHg), pulse wave velocity (PWV, m/s)) and microvascular health (central retinal artery/vein equivalent (CRAE/CRVE, μm)), were measured at 11 years old. Linear regression models assessed associations for individual chemicals and Bayesian weighted quantile sum regression (BWQS) evaluated the overall association of the phthalate and phenol mixture with cardiovascular health. In single exposure models, bisphenol-A was associated with decreased PWV (β per doubling of exposure = -0.06; 95% CI: -0.10, -0.01). Mono-iso-butyl phthalate was associated with an increase in CRAE (β = 1.89; 95% CI: 0.34, 3.44). Methyl- and butyl-parabens were associated with a decrease in CRVE (β = -0.71; 95% CI: -1.41, -0.01) and (β = -0.96; 95% CI: -1.57, -0.35), respectively. No statistically significant associations were observed between any of the exposures and SBP or DBP. BWQS models showed no evidence of associations between the phthalate and phenol mixture and any of the outcomes. Our results provide little evidence to suggest that prenatal exposure to phthalates and phenols is associated with macro- or microvascular health during early adolescence, except a few associations with certain compounds. Errors in exposure measurement and reduced variability in cardiovascular measures at this early age limit our ability to draw strong conclusions.


Systems pharmacology approach to investigate the mechanism of Artemisia argyi in treating rheumatic diseases.
Artemisia argyi (AA) has been proven to be effective in the adjuvant treatment of rheumatism (RA), but the mechanism of its action in RA is not clear. This study aims to clarify the molecular mechanism of AA as a potential therapy for RA by using network pharmacology. The TCM systems pharmacology (TCMSP) was used to screen the active components of AA, and identification of the potential target genes of active compounds and rheumatism was performed with PharmMapper and GeneCards, respectively. Construction of complex target networks and protein-protein interaction networks was based on the Cytoscape software. The biological functions and pathway analysis of targets and effective targets were analyzed using DAVID. Our study demonstrated that 105 target genes were associated with these active compounds and RA. ALB, AKT1, and MAPK1 were the first three hub genes, and the metabolic and signaling pathways related to these hub genes were remarkably abundant. Results showed that AA might play a role in RA by affecting multiple targets and multiple ways, reflecting that TCM was characterized by multicomponents and multitargets. AA has the potential to be a promising new candidate for the treatment of RA and has value for further research and development.


Efficacy in size and symptom reduction of radiofrequency ablation of benign non-functioning thyroid nodules.
Radiofrequency ablation (RFA) plays an increasing role in the management of thyroid nodules. The purpose of this study was to evaluate the safety and efficacy of RFA of benign thyroid nodules in terms of volume reduction and symptom relief. We reviewed the medical records of patients with a solitary thyroid nodule who received RFA at our centre from April 2016 to January 2020. Ultrasound-guided RFA was performed by the moving-shot technique. Patients were followed up with ultrasound examinations and thyroid function tests. We evaluated changes in volume and in compressive (0-10 scale) and cosmetic (4-point scale) symptoms to analyse efficacy and complications, and in thyroid function to evaluate safety. A total of 72 patients were included in the study. The mean follow-up was 11.1±0.7 months. There was a statistically significant reduction in size of the nodules at Month 1, 3, 6 and 12 after RFA (expressed as volume reduction rate: 34%±2.1, 50.8%±2.2, 60.3%±2.6, 58.87%±3.5, p<0.0001). We found statistically significant improvement in compressive symptoms (from 7.1±0.26 to 1.76±0.33, p<0.0001) and in cosmetic alteration (from 3.66±0.09 to 2.14±0.14, p<0.0001). No major complications were observed. RFA achieved significant volume reduction and improved compressive symptoms as well as cosmetic complaints, with minimum side effects. Our results are in line with recent available evidence and further support the use of RFA as a safe and effective therapeutic option in the management of benign thyroid nodules.


Cytokines and other important inflammatory mediators in gestation and bacterial intraamniotic infections.
Intraamniotic infections caused by viruses, bacteria or mycoplasmas are frequently followed by damage of fetus or increased perinatal morbidity and mortality. Cytokines are key substances regulating a number of biological processes including reproductive and inflammatory processes. An association between intraamniotic infections, rising concentrations of inflammatory cytokines in amniotic fluid and preterm labor is suggested. A great effort is made to find reliable markers typical for intraamniotic infections with high predictive value that make possible prompt identification of patients with intraamniotic infection. This review concerns inflammatory mediators, especially IL-1, IL-6, IL-8, TNF-alpha, and other important biologically active substances as prostaglandins and NO metabolites and their roles in intraamniotic infections. Finally, we discuss their relevance for diagnosis of intraamniotic infections.


The effect of AY-9944 on yeast sterol and sterol ester metabolism.
The effects of the hypocholesterolemic drug AY-9944 (trans-1,4-bis(2-chlorobenzylaminoethyl)cyclohexane dihydrochloride) at two concentrations (10(-4) M and 5 X 10(-4) M) on the synthesis of sterols and sterol esters by Saccharomyces cerevisiae were investigated. Although growth was not markedly affected by the drug, there was a decrease in the free sterol to sterol ester ratio with increased drug concentration. A concomitant increase in the saturated fatty acids esterified to sterol relative to the unsaturated fatty acids was also noted in response to increased drug concentration. Ergosterol accounted for 94.7% of the free sterol in the control culture and for 87.8% of the 5 X 10(-4) M drug-treated culture, respectively. However, in the sterol ester fraction, the ergosterol content decreased from a value of 45.1% in the control culture to 2.4% in the 5 X 10(-4) M AY-9944 treated culture. The sterol ester fraction simultaneously showed increased levels of the delta 8 sterol, fecosterol, in response to increased drug concentration from a 7.4% control value to 57.4% in the 5 X 10(-4) M drug-treated culture. The accumulation of the delta 8 sterol suggests that the site of action of the drug is probably at the delta 8 to delta 7 isomerase step in the biosynthesis of ergosterol. The fact that ergosterol is retained as the major free sterol suggests a biological advantage to the retention of this particular sterol. In addition, the near normal growth in the presence of the drug, in spite of the occurrence of an altered sterol ester profile, indicates that the composition of the sterol ester fraction is not as critical as the free sterol fraction.


Toolkits and Libraries for Deep Learning.
Deep learning is an important new area of machine learning which encompasses a wide range of neural network architectures designed to complete various tasks. In the medical imaging domain, example tasks include organ segmentation, lesion detection, and tumor classification. The most popular network architecture for deep learning for images is the convolutional neural network (CNN). Whereas traditional machine learning requires determination and calculation of features from which the algorithm learns, deep learning approaches learn the important features as well as the proper weighting of those features to make predictions for new data. In this paper, we will describe some of the libraries and tools that are available to aid in the construction and efficient execution of deep learning as applied to medical images.


Different Effects of Metformin on the Hypothalamic-Pituitary-Thyroid Axis in Bromocriptine- and Cabergoline-treated Patients with Hashimoto's Thyroiditis and Glucose Metabolism Abnormalities.
Metformin was found to reduce serum thyrotropin levels in patients with hypothyroidism. This effect was less pronounced if patients were additionally treated with bromocriptine. The study included 39 premenopausal women with autoimmune thyroiditis and thyrotropin levels exceeding 3.0 mU/L. All patients had been treated for at least 6 months with bromocriptine (5.0-7.5 mg daily) or cabergoline (0.5-1.0 mg weekly). Because of coexisting type 2 diabetes or impaired glucose tolerance, they were then given metformin (1.7-2.55 g daily). Glucose homeostasis markers, thyroid antibody titers, as well as serum levels of thyrotropin, total and free thyroid hormones and prolactin were determined before and after 6 months of metformin treatment. At baseline, cabergoline-treated patients were less insulin resistant as well as tended to have lower levels of prolactin than bromocriptine-treated patients. Although in both treatment groups, metformin decreased plasma levels of fasting and post-challenge plasma glucose and improved insulin receptor sensitivity, this effect was more prominent in patients receiving cabergoline. However, only in bromocriptine-treated patients, metformin decreased serum thyrotropin and this effect reached the level of significance in a subgroup of patients with subclinical hypothyroidism. Neither in cabergoline- nor in bromocriptine-treated patients, metformin affected thyroid hormone levels and thyroid antibody titers. Our results indicate that the effect of metformin on hypothalamic-pituitary-adrenal axis activity is partially determined by endogenous dopaminergic tone, thyrotrope activity and insulin sensitivity.


[How do general practitioners deal with patients they do not consider to be depressed but who are classified as such according the PHQ-9?].
OBJECTIVES How GPs describe their patients who they did not identify as suffering from depression but who were classified as such by PHQ-9? What conclusions can be drawn with regard to how depression is dealt with and the illness model in use? METHOD GPs who took part in a screening study were asked in interviews to talk about some of their patients - not being informed that these were those not identified as depressive by them. This study comprises 21 narrative interviews from 18 GPs. Analysis by Framework method by Lewis and Ritchie. RESULTS The low identification rate of depression is not the result of failed recognition of "psychological problems" but of other factors centring on GPs' particular way of working and their concepts about mental illness: making a diagnosis only in a contextual way of interpreting symptoms; using the time passing as a help for diagnosing; emphasis on the impairment rather the diagnosis; considering the therapeutic consequences before making a diagnosis; a tolerance concerning "deviation" respectively wider view on "normality". CONCLUSION Understanding the different ways of conceptionalizing mental illness by psychiatrists and general practitioners is basic for their cooperation.


The effects of N-methyl-D-aspartate antagonists on the development of vestibular compensation in the guinea pig.
In order to investigate the possible role of the N-methyl-D-aspartate (NMDA) receptor in the development of the behavioural recovery which occurs following unilateral labyrinthectomy (vestibular compensation) in the guinea pig, we administered systemically the specific NMDA receptor/channel antagonists MK801 and CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) during the compensation process. MK801 disrupted the development of ocular motor compensation when administered at 18-22 h post-op (1.0 mg/kg i.p.). CPP had a smaller but still significant disruptive effect when injected at this time (1.0 or 5.0 mg/kg i.p.). We conclude that NMDA receptors may contribute to the development of ocular motor compensation in the guinea pig.


Effects of naloxone on the breathing pattern of a newborn exposed to maternal opiates.
To give new insights into how an infant responded to naloxone, given after acquiring a maternal opiate by recording the breathing pattern directly after birth. A respiratory recording is presented of an infant during resuscitation in the delivery room after receiving naloxone for respiratory depression, resulting from maternal remifentanyl use. The infant was born apneic and bradycardic. Normal resuscitation manoeuvres had no effect on the respiratory drive. Directly after administration of naloxone, a tachypneic breathing pattern with sporadic expiratory breaking manoeuvres was observed. The immediate tachypnoea is most likely a direct effect of the naloxone causing an immediate 'rebound response' after the release of the opiate-induced inhibition of the respiratory drive.


Failure of Emperion modular femoral stem with implant analysis.
Modularity in total hip arthroplasty provides multiple benefits to the surgeon in restoring the appropriate alignment and position to a previously damaged hip joint. The vast majority of modern implants incorporate modularity into their design with some implants having multiple modular interfaces. There is the potential for failure at modular junctions because of fretting and crevice corrosion in combination with mechanical loading. This case report details the failure of an Emperion (Smith and Nephew, Memphis, TN) femoral stem in a 67-year-old male patient 6 years after total hip replacement. Analysis of the implant revealed mechanically assisted crevice corrosion that likely accelerated fatigue crack initiation in the hip stem. The benefits of modularity come with the potential drawback of a combination of fretting and crevice corrosion at the modular junction, which may accelerate fatigue, crack initiation and ultimately reduce the hip longevity.


Corrigendum: Southern African guidelines on the safe, easy and effective use of pre-exposure prophylaxis: 2020.
[This corrects the article DOI: 10.4102/sajhivmed.v21i1.1152.].


Perfusion imaging of parotid gland tumours: usefulness of arterial spin labeling for differentiating Warthin's tumours.
To assess prospectively the efficacy of arterial spin labelling (ASL) against conventional and diffusion-weighted (DW) MR imaging for differentiating parotid gland tumours. We included 10 pleomorphic adenomas, 12 Warthin's tumours, and nine malignant tumours of the parotid glands. Only tumours larger than 10 mm were included in this study. All parotid gland tumours underwent T1-weighted, T2-weighted, DW, and ASL imaging. Tumour-to-parotid gland signal intensity ratios (SIRs) and apparent diffusion coefficients (ADCs) of solid components were correlated with these pathologies. SIRs on T2-weighted images and ADCs were higher in pleomorphic adenomas than in Warthin's tumours (p < .01) and malignant tumours (p < .01). SIRs on ASL were higher in Warthin's tumours than in pleomorphic adenomas (p < .01) and malignant tumours (p < .05). Az value of SIRs on ASL for differentiating Warthin's tumours from the other pathologies was 0.982. The sensitivity, specificity, and accuracy of SIRs on ASL for the diagnosis of Warthin's tumours at an optimal SIR threshold of over 8.70 were 91.7%, 94.7%, and 93.5%, respectively. ASL with SIR measurements could non-invasively evaluate tumour blood flow of parotid gland tumours and differentiate Warthin's tumours from pleomorphic adenomas and malignant tumours. • ASL non-invasively evaluates tumour blood flow of parotid gland tumours • ASL differentiates Warthin's tumours from pleomorphic adenomas and malignant tumours • ASL cannot differentiate between pleomorphic adenomas and malignant tumours.


The design of today's operating rooms.
With the exception of radiation therapy, the surgical suite is still the most costly area in a health care facility to renovate or construct. It is also the most needs intensive, as far as staff, equipment, material, and building system. Health care providers need an environmentally sensitive area that meets the needs of today, as well as the future. It is equally important to create a working environment that promotes staff comfort, while streamlining time and cost.


Examination of physical and regulatory variables leading to small dam removal in Wisconsin.
The decision to remove or repair a dam depends on multiple variables, many of which encompass both physical and social factors. In Wisconsin, the Department of Natural Resources is mandated to inspect small dams every ten years. A safety inspection often acts as a trigger event to a dam removal or repair decision. Although the issues surrounding a dam removal decision are often couched as ecological, these decisions are influenced by their social and regulatory context. In this work, we examine descriptive variables of Wisconsin dams that were inspected and consequently removed or maintained between 1985 and 1990. We hypothesize that geographic location, height of dam, size of impoundment, age of dam, and type of ownership determine the likelihood of a safety inspection, and the subsequent likelihood of removal. Using a logistic model, we find that publicly owned dams had the greatest probability of inspection after 1985. Of these dams, older dams and those with smaller impoundments were most likely to be removed. We were unable to build a strong predictive model for dam removal with our suite of variables, suggesting that a community's decision to remove or maintain a dam is complex and heterogeneous.


Metagenomic assembled plasmids of the human microbiome vary across disease cohorts.
We compiled a human metagenome assembled plasmid (MAP) database and interrogated differences across multiple studies that were originally designed to investigate the composition of the human microbiome across various lifestyles, life stages and events. This was performed as plasmids enable bacteria to rapidly expand their functional capacity through mobilisation, yet their contribution to human health and disease is poorly understood. We observed that inter-sample β-diversity differences of plasmid content (plasmidome) could distinguish cohorts across a multitude of conditions. We also show that reduced intra-sample plasmidome α-diversity is consistent amongst patients with inflammatory bowel disease (IBD) and Clostridioides difficile infections. We also show that faecal microbiota transplants can restore plasmidome diversity. Overall plasmidome diversity, specific plasmids, and plasmid-encoded functions can all potentially act as biomarkers of IBD or its severity. The human plasmidome is an overlooked facet of the microbiome and should be integrated into investigations regarding the role of the microbiome in promoting health or disease. Including MAP databases in analyses will enable a greater understanding of the roles of plasmid-encoded functions within the gut microbiome and will inform future human metagenome analyses.


Heat exposure during outdoor activities in the US varies significantly by city, demography, and activity.
Environmental heat is a growing public health concern in cities. Urbanization and global climate change threaten to exacerbate heat as an already significant environmental cause of human morbidity and mortality. Despite increasing risk, very little is known regarding determinants of outdoor urban heat exposure. To provide additional evidence for building community and national-scale resilience to extreme heat, we assess how US outdoor urban heat exposure varies by city, demography, and activity. We estimate outdoor urban heat exposure by pairing individual-level data from the American Time Use Survey (2004-2015) with corresponding meteorological data for 50 of the largest metropolitan statistical areas in the US. We also assess the intersection of activity intensity and heat exposure by pairing metabolic intensities with individual-level time-use data. We model an empirical relationship between demographic indicators and daily heat exposure with controls for spatiotemporal factors. We find higher outdoor heat exposure among the elderly and low-income individuals, and lower outdoor heat exposure in females, young adults, and those identifying as Black race. Traveling, lawn and garden care, and recreation are the most common outdoor activities to contribute to heat exposure. We also find individuals in cities with the most extreme temperatures do not necessarily have the highest outdoor heat exposure. The findings reveal large contrasts in outdoor heat exposure between different cities, demographic groups, and activities. Resolving the interplay between exposure, sensitivity, adaptive capacity, and behavior as determinants of heat-health risk will require advances in observational and modeling tools, especially at the individual scale.


A novel immuno-molecular strategy for the detection of Streptococcus pneumoniae serotypes in human cerebrospinal and middle ear fluids.
Streptococcus pneumoniae is one of the most common microorganisms causing acute otitis media (AOM) in children. While bacterial culture of middle ear fluid (MEF) is the gold standard to detect the etiological organisms, several host and pathogen factors impact the survival of the organisms resulting in false negatives. To overcome this limitation, we have developed and validated an innovative multiplex immuno-molecular assay to screen and detect the S. pneumoniae 15-valent pneumococcal conjugate vaccine (PCV15; STs 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) vaccine serotypes in MEF. This novel in vitro approach involves two-step testing. First, the MEF specimens were tested for highly conserved pneumococcal genes, autolysin, lytA, and pneumolysin, ply using direct PCR to identify pneumococcus positive specimens. The pneumococcus positive specimens were screened for the presence of vaccine serotype specific pneumococcal polysaccharides using a 15-plex Pneumococcal Antigen Detection (PAD) assay, with specific capture and detection monoclonal antibodies. Due to the lack of availability of MEF samples, cerebrospinal fluid (CSF) was used as the surrogate matrix for the development and validation of the PCR-PAD assays. The PCR and PAD assays were separately evaluated for sensitivity and specificity. Subsequently, the PCR-PAD assays were cross-validated with human MEF samples (n = 39) which were culture confirmed to contain relevant bacterial strains. The combined PCR-PAD assays demonstrated high rate of agreement 94.9% (95% CI; 82.7, 99.4%) with historical Quellung serotype data of these MEF samples. This novel PCR-PAD assay demonstrates the feasibility of combining molecular and immunological assays to screen and identify PCV15 pneumococcal vaccine serotypes in AOM clinical samples.


[Our experience in the use of anterolateral thigh flap for reconstruction of the head and neck neoplasms].
Free flaps with vascular anastomosis have been widely used in clinical practice for more than 30 years. They are standard in reconstructive surgery following extensive resections caused by neoplasms of the head and neck. The anterolateral thigh flap (ALT) constitutes very good reconstructive material due to the long vascular pedicle, the appropriate diameter of vessels, the large skin island plane, and thickness depending on requirements. The own material comprises 5 patients who have had extensive neoplastic infiltrations removed at different anatomic locations within the area of healthy tissue. Reconstructions have been conducted using a microvascular thigh flap (ALT). All of the operated patients are under constant supervision. The observation period ranges from 2 to 3 months. No recurrence of the neoplastic process or graft rejection has been observed in any of the patients.


Near-Infrared-Induced Contractile Proteinosome Microreactor with a Fast Control on Enzymatic Reactions.
Inspired by the compartmentalized structure of cells, self-regulating responsive hollow microcapsules are highly desirable for the modulation of enzymatic reactions. Here, we report a strategy to fabricate gold nanorod embedded proteinosomes by covalently grafting gold nanorods onto the surface of proteinosomes. The excellent photothermal conversion efficiency of the embedded gold nanorod and the thermal phase transition of the grafted PNIPAAm allow the constructed hybrid proteinosomes to show reversible contraction behaviors triggered by near-infrared light with the molecular weight cutoff of the membrane decreased to ca. 50 kDa, and importantly, the contraction frequency of the constructed proteinosomes could be as fast as 1 min and last for at least 15 cycles. Subsequently, the effective encapsulation of three cascade enzymes into the proteinosomes realizes the construction of a near-infrared responsive microreactor that allows control of the cascade reaction by near-infrared illumination, thereby enabling reversible on and off of the enzymatic reaction. Such microcapsule-based reactors demonstrate the potential to alter the membrane molecular weight cutoff, and it is believed that the development of such responsive microcapsules will have great potential for studying cellular responses and provide a platform for future applications in biosensing and drug delivery.


Echocardiography performed by emergency physicians: impact on diagnosis and therapy.
Echocardiography is the "gold standard" for diagnosing many cardiac and pericardial abnormalities. It is noninvasive and accurate, but in most emergency departments is only as available as the technician or the cardiologist. We describe our experience in training emergency physicians to perform cardiac ultrasound, and clinical situations in which we have found echocardiography to be useful.


Comparison of laryngeal mask airway (LMA) insertion with and without muscle relaxant in pediatric anesthesia; a randomized clinical trial.
This study aimed to evaluate the effectiveness of using muscle relaxant on the ease of laryngeal mask airway (LMA) insertion and possibility of its related complications. This double-blind, randomized clinical trial was performed on 60 children aged 1-4 years with ASA (American Society of Anesthesiology) I or II with upper limb injuries who were candidates for surgery. The patients were randomly allocated to the two groups receiving atracurium group as muscle relaxant (MR) or saline group (S). Regarding ease of placement, the LMA was inserted in 66.7% and 63.3% of patients straightforwardly in the MR and S groups, respectively. While it was performed with one maneuver in 23.3% and 26.7% of cases in the MR and S groups, respectively (p = 0.955). Moreover, LMA dislodgment in the two groups was 36.7% in the MR group and 20.0% in the S group without a meaningful difference (P = 0.152). The only complication observed in the two groups was laryngospasm, which occurred in 0.10% and 13.3% in the MR and S groups, respectively (p = 0.688). In some pediatric anesthesia, the use of atracurium, as a muscle relaxant had no significant effect on capability of LMA insertion, maintaining airway patency, LMA seal pressure and oxygenation variations. Moreover, it did not have a preventive effect on the occurrence of complications such as laryngospasm.


Potentials induced by applied electrical fields in and around particles comprised of four dielectric layers.
Knowledge of the electrical potentials within different compartments of a biological cell induced by applied alternating fields is needed for assessing the effects of electromagnetic radiation on cells, understanding electroporation and other electric field-induced effects, and deriving expressions for the complex permittivity of suspensions of cells. In the work presented in this paper, closed-form analytical expressions have been derived for the electrical potentials within different layers of an inhomogeneous particle consisting of four different dielectric layers and suspended in a homogeneous medium. Those expressions have been used to derive, for the case of a realistic model of a cell containing a large concentric organelle, expressions for the transmembrane potentials (at cell and organelle level) and electric fields within the cell compartments induced by applied fields. The results of the present theoretical model indicate points of departure between the present and previous theoretical models. The present theory also confirms the validity of the equivalence approach introduced by Irimajiri and co-workers for computing the complex permittivity for suspensions of multi-shelled particles. In addition, it shows that the electric field is amplified at the level of the cell and organelle membranes, but not within other cell compartments.


Fetal nasal bone length and Down syndrome during the second trimester in a Chinese population.
The purpose of the present study was to build a database of reference ranges of fetal nasal bone length (NBL) in a Chinese population. The accuracy rate of detecting Down syndrome was also analyzed using fetal NBL as a marker. The control group of fetuses included 342 normal singleton pregnancies with no chromosomal or congenital anomalies. The present study was a cross-section study and the control group was used to construct percentile values of NBL from 13 to 29 gestational weeks of age. Two-dimensional ultrasonography was used for the nasal bone studies. Measurements of NBL were collected and each fetus contributed a single value to the reference sample. During the study period, 14 fetuses with Down syndrome were examined. Measurement of fetal NBL was made during amniocentesis, with gestational age ranging from 13 to 19 weeks. From 342 normal fetuses with gestational age ranging from 13 to 29 weeks, reference ranges of NBL were constructed. The reference ranges were constructed from the 100(1 - p)% reference range: Y +/- Zp x square root sigma 2, where Y = 25 - exp(3.58 - 0.044 x t + 0.0006 x t2), with Y being the fitted mean of regression model and t being gestational age (weeks). Using fetal NBL, the regression model was Pr(Down syndrome) = exp(W)/ [1 + exp(W)], where W = 0.62-4.80 x NBL (multiples of the median) in predicting Down syndrome. Fetal NBL was found to have a sensitivity and specificity of 0.78 and 0.78, respectively, in predicting Down syndrome in the second trimester of pregnancy. Fetal NBL measurement can provide a simple and useful algorithm to predict Down syndrome during the second trimester of pregnancy.


Hydrolysis of cis and trans isomers of retinyl palmitate by retinyl ester hydrolase of pig liver.
Relative retinyl ester hydrolase activities of pig liver homogenates (n = 4) toward 9,13-cis-, 13-cis-, 9-cis-, and all-trans-retinyl palmitate were 6.8 +/- 0.5 (SE), 5.7 +/- 0.5, 2.4 +/- 0.1, and 1, respectively. The range of apparent Km values for the four isomers was 142 to 268 microM, and the pH optima were 8-9 in all cases. Peak activities of retinyl ester hydrolase activities in pig liver cytosol toward 13-cis- and all-trans-retinyl palmitate were found in the 20 to 40% and in the 60 to 80% saturated ammonium sulfate (AS) fractions, respectively. By use of size-exclusion chromatography in 2 M KCl, hydrolase activity eluted at volumes corresponding to greater than 2000, 180, and 15 kDa from the 20-40% AS fraction, and at 180 kDa from the 60-80% AS fraction. On the basis of molecular size, different substrate specificities, detergent effects, and susceptibilities to inhibition by phenylmethylsulfonyl fluoride, we conclude that at least three distinct retinyl ester hydrolases are present in pig liver cytosol.


Dopamine and acetylcholine elevation on lever-press acquisition in rat prefrontal cortex.
To determine whether the rat medial prefrontal cortex (PFC) is involved in acquiring operant learning, we observed changes in extracellular concentration of dopamine (DA) and acetylcholine (ACh) in the rat medial PFC during lever-press acquisition (acquisition group) or retrieval (retention group) using in vivo microdialysis. We found that DA or ACh elevation related to acquisition occurred. DA elevation was observed in the acquisition group only. These results indicate that the medical PFC is related to acquisition, and suggest that interaction between DA and ACh may be involved in learning acquisition.


Subtle effects of environmental stress observed in the early life stages of the Common frog, Rana temporaria.
Worldwide amphibian populations are declining due to habitat loss, disease and pollution. Vulnerability to environmental contaminants such as pesticides will be dependent on the species, the sensitivity of the ontogenic life stage and hence the timing of exposure and the exposure pathway. Herein we investigated the biochemical tissue 'fingerprint' in spawn and early-stage tadpoles of the Common frog, Rana temporaria, using attenuated total reflection-Fourier-transform infrared (ATR-FTIR) spectroscopy with the objective of observing differences in the biochemical constituents of the respective amphibian tissues due to varying water quality in urban and agricultural ponds. Our results demonstrate that levels of stress (marked by biochemical constituents such as glycogen that are involved in compensatory metabolic mechanisms) can be observed in tadpoles present in the pond most impacted by pollution (nutrients and pesticides), but large annual variability masked any inter-site differences in the frog spawn. ATR-FTIR spectroscopy is capable of detecting differences in tadpoles that are present in selected ponds with different levels of environmental perturbation and thus serves as a rapid and cost effective tool in assessing stress-related effects of pollution in a vulnerable class of organism.


Amino acid analysis by high-performance liquid chromatography of a single stained protein band from a polyacrylamide gel.
A single stained band containing approximately 5 micrograms of protein was cut out of a polyacrylamide gel and subjected to hydrolysis together with the gel. The hydrolysate was subsequently analyzed for its amino acid content by high-performance liquid chromatography and postlabeling with o-phthalaldehyde. Bovine serum albumin, ribonuclease B, ovalbumin, pepsin, and chymotrypsinogen A were analyzed by this method, and their amino acid compositions were found to be in good agreement with the reported values. By this method, it is possible to quantitate 16 amino acids: Asx, Thr, Ser, Glx, Pro, Cys, Gly, Ala, Val, Ile, Leu, Tyr, Phe, His, Lys, and Arg. Thioglycolic acid is effective protection against the decomposition of Tyr, Cys, and Met; however, the recovery of Met is inconsistent. This method might be very helpful for the amino acid analysis of proteins of multicomponent systems, especially, those which can be resolved only by polyacrylamide gel electrophoresis.


A 22 year follow-up study on lymphatic filariasis in Tanzania: analysis of immunological responsiveness in relation to long-term infection pattern.
Seventy-one individuals who had been examined for Wuchereria bancrofti microfilaraemia in 1975, some of whom had been offered mass treatment with diethylcarbamazine (DEC) in subsequent years, were re-identified in 1996 and examined for microfilaraemia, circulating filarial antigenemia and cellular and humoral immunoresponsiveness to crude antigen homogenates prepared from Brugia pahangi parasite material. 85.9% of the study individuals had the same infection status in 1975 and 1996, suggesting strong predisposition to infection over extended periods of time. IL-4, IL-5 and IFNγ responses were associated with being infection negative in 1996 whereas IL-10 responses were associated with being infection positive. Similarly, specific IgG3 and IgE were strongly associated with being infection negative in 1996 whereas specific IgG4, and thus high IgG4/IgE ratios, were strongly associated with being infection positive. Intermediary levels of mainly IL-5, IFNγ and PBMC stimulation indices were observed for study individuals who changed from being infection positive in 1975 to infection negative in 1996, or vice versa, suggesting a transition in cellular immunoresponsiveness associated with changing infection status. The findings suggest that some people are more disposed to infection with bancroftian filariasis than others and that this is largely unaffected by treatment with DEC. The findings also suggest that specific cellular and antibody responses are more related to current than past infection status, and that IL-4, IL-5, IFNγ, specific IgG3 and IgE are associated with parasite clearance, whereas IL-10 and specific IgG4 are associated with parasite protection.


Coenzyme Q systems in ascomycetous black yeasts.
72 Strains belonging to 44 species of ascomycetous black yeasts were analyzed for their coenzyme Q systems. Prevalent were Q-10 and dihydrogenated Q-10 systems. Members of the Dothidealean suborder Dothideineae have Q-10(H2), while those belonging to the suborder Pseudosphaeriineae mostly have Q-10. The anamorph genus Exophiala Carmichael and the teleomorph genus Capronia Sacc. seem to be heterogeneous.


Single-nucleotide-polymorphism mapping of the Pseudomonas aeruginosa type III secretion toxins for development of a diagnostic multiplex PCR system.
We mapped the coding single nucleotide polymorphisms in four toxin genes-exoS, exoT, exoU, and exoY-of the Pseudomonas aeruginosa type III secretion system among several clinical isolates. We then used this information to design a multiplex PCR assay based on the simultaneous amplification of fragments of these genes. Eight strains of known genotype were used to test our multiplex PCR method, which showed 100% sensitivity and specificity in this small sample size. This assay appears to be promising for the rapid and accurate genotyping of the presence of these genes in clinical strains of P. aeruginosa.


The mechanisms, functions and clinical applications of miR-542-3p in human cancers.
MicroRNAs, as a major type of noncoding RNAs, have crucial roles in various functions during development. Available data have shown that miR-542-3p decreased in various types of cancers. MiR-542-3p is engaged in various cancer-related behaviors like glycolysis, metastasis, epithelial-to-mesenchymal transition (EMT), cell cycle, apoptosis, and proliferation via targeting at least 18 genes and some important signaling pathways like Wnt/β-catenin, Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Janus kinase 2 (JAK2) signaling, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling. Current studies have proposed that the level of miR-542-3p could be modulated by several upstream regulators like transcription factors, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). In addition, the level of miR-542-3p or its related lncRNAs/circRNAs are correlated with poor prognosis and clinicopathological features of cancer-affected patients. Here, we have discussed the biogenesis, function, and regulation of miR-542-3p as well as its aberrant expression in various types of neoplastic cells. Moreover, we have discussed the prognostic value of miR-542-3p in cancer. Finally, we have added the underlying molecular mechanism of miR-542-3p in cancer pathogenesis.


Efficacy of Praziquantel for the Treatment of Human Schistosomiasis in Ethiopia: A Systematic Review and Meta-Analysis.
Schistosomiasis is one of the neglected tropical diseases causing a serious human health problem in Ethiopia. Praziquantel is the only drug that has been used for the treatment of human schistosomiasis in the country. In line with this, the efficacy of praziquantel has been evaluated in a few interventional studies in the country, but there is a lack in systematically gathered and analyzed information for policymakers. The aim of this systematic review and meta-analysis was to provide a summary of the efficacy of praziquantel for the treatment of human schistosomiasis in Ethiopia. We conducted a literature search from ScienceDirect, PubMed/Medlin, and Google Scholar databases. A total of 140 articles published in English from 1980 to June 2021 were accessed and 15 of them were eligible for this meta-analysis. The meta-analysis was conducted using Stata 14 software, "metan command." The heterogeneities among studies were evaluated using I 2 test. A total of 140 articles were reviewed, but only 15 of them fulfilled the inclusion criteria. The polled cure rate of 40 mg/kg praziquantel was 89.2% (95% CI: 85.4-93.1) and 93.6% (95% CI: 80.6-106) among Schistosoma mansoni and S. haematobium, respectively. Similarly, the mean egg reduction rates of 40 mg/kg praziquantel were 90.2% and 85% among S. mansoni and S. haematobium infected subjects, respectively. The common adverse events observed after receiving praziquantel include abdominal pain, vomiting, headache, diarrhea, and bloody stool. This systematic review and meta-analysis has indicated that praziquantel is still an appropriate drug for the treatment of human schistosomiasis in Ethiopia.


Epidemiology of psoriatic arthritis in the population of the United States.
Estimates of the prevalence of psoriatic arthritis vary widely and are usually not determined by population-based studies. We sought to determine the prevalence of psoriatic arthritis and the impact of the disease on quality of life in the US population. Patients were selected randomly from the US population and were interviewed by telephone. Cases were defined as patients who reported a physician diagnosis of psoriasis and psoriatic arthritis. Interviews of 27,220 persons were conducted; 601 of the interviewees had psoriasis and 71 had psoriasis and psoriatic arthritis. The prevalence of psoriatic arthritis was 0.25% (95% confidence interval [CI]: 0.18%, 0.31%). The prevalence of psoriatic arthritis among patients with psoriasis was 11% (95% CI: 9%, 14%) and varied substantially based on self-reporting of the extent of skin involvement with psoriasis. Thirty-nine percent of patients with psoriatic arthritis indicated that it was a large problem in everyday life. Psoriatic arthritis was classified on the basis of the patient's self-report. Psoriatic arthritis affects an estimated 520,000 patients in the US population, and many rate it as a large problem in everyday life. The prevalence varies widely based on the extent of skin involvement, which demonstrates the importance of performing broadly representative studies to measure the prevalence of psoriatic arthritis.


Enantioseparation of 1-phenyl-1-propanol by supercritical fluid-simulated moving bed chromatography.
The enantioseparation of 1-phenyl-1-propanol through the supercritical fluid-simulated moving bed (SF-SMB) process is studied. Non-linear isotherms were measured on an analytical column, and used together with the triangle theory for SMB design to select operating conditions for the SF-SMB. Experiments were carried out on a pilot-scale SF-SMB plant at conditions that corresponded to the non-linear range of the isotherm. Under conditions of low feed concentration, complete separation (extract purity = 99.5%; raffinate purity = 98.4%) was achieved. Under conditions of larger feed concentration, the best separation corresponded to an extract purity of 98.0% and a raffinate purity of 94.0%, and yielded a productivity of 110 g of racemate per kg stationary phase per day.


"Emerging Topics in Pain Medicine": Advancing Research and Patient-Centered Health Strategies.
Pain, in all its various forms and manifestations, impacts the lives of millions worldwide [...].


Nuclear roundness factor: a quantitative approach to grading in prostatic carcinoma, reliability of needle biopsy tissue, and the effect of tumor stage on usefulness.
Morphometric analysis and histologic grading were performed on case material from 26 patients. Relative nuclear roundness factor (RNRF) was calculated and correlated with clinical course in 14 patients undergoing prostatectomy for stage A or B prostatic carcinoma. The only patients with progression of disease were two with RNRF of 1.10. RNRF in cases without progression ranged from 0.98 to 1.07. Histologic grading by the methods of Gleason or the M.D. Anderson system failed to discriminate between the progressing and nonprogressing groups. However, when RNRF was measured in tumors initially diagnosed as stage C or D, four of eight were below 1.10, within the range of the nonprogressing low-stage cases. Thus, the usefulness of morphometry and RNRF may be limited to low-stage disease. It was additionally found that RNRF could not be reliably measured in needle biopsy specimens.


Pilot testing of nurse led multimodal intervention for falls prevention.
Patient fall-risk awareness, self-efficacy, and engagement in fall-prevention activities are important aspects of fall-prevention. The current pilot study examined the effect of a nurse-led multimodal intervention on hospitalized adults' levels of fall risk awareness, self-efficacy, and engagement in fall prevention. Sixty hospitalized older adults in an acute care setting in Florida participated in the study. There were significant differences [pre-test (M = 19.02, SD=1.152) and post-test (M = 21.71, SD=0.527); t (17.355) = 58, p≤.001] on level of fall risk awareness in fall prevention. There were no significant findings for fall self-efficacy and engagement. Study findings suggested that the higher the fall self-efficacy, the higher the engagement. Future research is needed to examine self-efficacy and engagement for fall prevention in larger diverse cohorts of hospitalized older adults.


Psychosocial factors associated with j-pouch surgery for patients with IBD: a scoping review.
Ulcerative colitis and Crohn's disease are subtypes of inflammatory bowel disease: a chronic condition of unclear etiology characterized by inflammation of the small and large intestine. Inflammatory bowel disease is managed with diet, medications, and surgeries, with the most common surgery, recommended to ulcerative colitis patients being j-pouch surgery. To assess the current literature concerning psychosocial factors associated with j-pouch surgery for patients with inflammatory bowel disease. A systematic scoping review of the empirical and grey literature was conducted for original research on j-pouch surgery and psychosocial variables. Eight databases were searched: Medline, PsychInfo, CINAHL, EBM Reviews, ProQuest Dissertations and Theses Global, ResearchGate, Prospero, and PrePubMed. Thirty-nine articles were identified. Many studies (n = 18) adopted a case-series design, and none examined psychosocial interventions. The most popular psychosocial variables assessed were quality of life (n = 34) and those associated with sexual health and functioning (n = 9). Despite being an established surgical procedure, little research has examined the psychosocial implications of j-pouch surgery. As such, clinicians lack a robust understanding of how this procedure affects patients' psychiatric and social status and adaptive abilities. There is a need for high-quality research utilizing validated measures and rigorous design methodologies with control populations.


[Place of internal medicine specialists in inpatient unprogrammed care of adult patients in France: A survey of in training and senior internal medicine specialists].
French internal medicine specialists are trained in clinical immunology and rare diseases as well as frequent ones. The latest activity is rarely highlighted by practitioners themselves and their representative authorities. Frequent diseases care in French hospitals are also the tasks of physicians without internal medicine specialty, mostly trained in general medicine, who practice in departments carrying various names. We conducted a survey to estimate the part of frequent diseases' care and unplanned hospital medicine in the practice of specialists and residents in internal medicine in France, and its designation, through two surveys released by the "Collège National Professionnel de Médecine Interne" (for the internal medicine specialists), and the "Amicale des Jeunes Internists" (for the internal medicine residents). A total of 180 and 247 responses were obtained among the residents and the specialists, respectively, representing 31.3% and 24.8% of the internal medicine specialist's workforce. The most suitable qualifier for frequent diseases' care and unplanned hospital medicine, primarily post-emergency, was "general hospital medicine" for 48.9% of the residents and "general internal medicine" for 35.6% of the specialists. Unplanned hospital medicine was considered to represent a large part of the internal medicine activity by 66.7% and 64.7% of residents and specialists, respectively. A 50% and more hourly part of the activity devoted to it was reported by 71.4% of the residents and 76.1% of the specialists. General hospital medicine was reported to be distinct from internal medicine-clinical immunology by 46.1% of the residents and 47.4% of the specialists. French internists devote a large part of their activities to frequent diseases' care and unscheduled medicine, the name of which was not consensual. However, their work could not be summarized to it, often involving a specific activity named internal medicine - clinical immunology.


Role of Gardnerella vaginalis as an etiological agent of bacterial vaginosis.
Bacterial vaginosis is a risk factor for obstetric infections, various adverse outcomes of pregnancy and pelvic inflammatory disease. The objectives of this study were to assess the prevalence of bacterial vaginosis in women attending Gynaecology Outpatient Department (O.P.D) and sexually transmitted disease (S.T.D.) clinic and to assess the role of Gardnerella vaginalis as an etiological agent of bacterial vaginosis. Two hundred women attending Gynaecology O.P.D and S.T.D. clinic with symptoms suggesting lower genital tract infection were included in the study. pH of the vaginal discharge was measured and three high vaginal swabs were collected. Bacterial vaginosis was diagnosed using Amsel's criteria and Nugent's method. Gardnerella vaginalis was isolated and identified by standard methods. Prevalence of bacterial vaginosis using Amsel's criteria and Gram stain scoring method was found to be 51.5% and 49% respectively. Gardnerella vaginalis was isolated in only 8.7% cases of bacterial vaginosis. Our study showed a relatively high prevalence of bacterial vaginosis in the population under study. Women attending various healthcare facilities should be screened and treated properly to prevent recurrence. Low isolation rate of Gardnerella vaginalis may be attributed to factors like poor viability and fastidiousness of the organism to grow in various media.


Investigating effects of sodium beta-hydroxybutyrate on metabolism in placebo-controlled, bilaterally infused human leg with focus on skeletal muscle protein dynamics.
Systemic administration of beta-hydroxybutyrate (BHB) decreases whole-body protein oxidation and muscle protein breakdown in humans. We aimed to determine any direct effect of BHB on skeletal muscle protein turnover when administered locally in the femoral artery. Paired design with each subject being investigated on one single occasion with one leg being infused with BHB and the opposing leg acting as a control. We studied 10 healthy male volunteers once with bilateral femoral vein and artery catheters. One artery was perfused with saline (Placebo) and one with sodium-BHB. Labelled phenylalanine and palmitate were used to assess local leg fluxes. Femoral vein concentrations of BHB were significantly higher in the intervention leg (3.4 (3.2, 3.6) mM) compared with the placebo-controlled leg (1.9 (1.8, 2.1) mM) with a peak difference of 1.4 (1.1, 1.7) mM, p < 0.0005. Net loss of phenylalanine for BHB vs Placebo -6.7(-10.8, -2.7) nmol/min vs -8.7(-13.8, -3.7) nmol/min, p = 0.52. Palmitate flux and arterio-venous difference of glucose did not differ between legs. Under these experimental conditions, we failed to observe the direct effects of BHB on skeletal muscle protein turnover. This may relate to a combination of high concentrations of BHB (close to 2 mM) imposed systemically by spillover leading to high BHB concentrations in the saline-infused leg and a lack of major differences in concentration gradients between the two sides-implying that observations were made on the upper part of the dose-response curve for BHB and the relatively small number of subjects studied.


Chitosan-grafted tetrapolymer using two monomers: pH-responsive high-performance removals of Cu(II), Cd(II), Pb(II), dichromate, and biphosphate and analyses of adsorbed microstructures.
For circumventing the cumbersome and expensive multifunctional and multipolymer adsorbents for high-performance removals of hazardous water-contaminant(s), chitosan-g-[2-acrylamido-2-methyl-1-propanoic acid (AMPS)-co-2-(3-acrylamidopropanamido)-2-methylpropane-1-sulfonic acid (APAMPS)-co-2-(N-(3-amino-3-oxopropyl)acrylamido)-2-methylpropane-1-sulfonic acid (NAOPAMPS)-co-acrylamide (AM)] (i.e., chitosan-g-tetrapolymer), a multifunctional scalable and reusable hydrogel, was synthesized by grafting of chitosan and in situ attachments of N-H functionalized NAOPAMPS and APAMPS hydrophilic acrylamido-monomers during free-radical solution-polymerization of the two ex situ added AMPS and AM monomers in water. The response surface methodology was employed to synthesize one hydrogel envisaging the optimum balance between swelling and stability for the superadsorption of Cu(II), Cd(II), Pb(II), Cr2O72-, and HPO42-. The in situ attachments of NAOPAMPS and APAMPS, grafting of chitosan into tetrapolymer, structures and properties, pH-responsive abilities, superadsorption mechanism, and reusability were understood via in depth microstructural analyses of adsorbed and/or unadsorbed chitosan-g-tetrapolymer(s) through 1H/13C NMR, FTIR, XPS, TGA, XRD, DLS, and pHPZC. The maximum adsorption capacities of Cd(II), Cu(II), Pb(II), Cr2O72-, and HPO42- were 1374.41, 1521.08, 1554.08, 47.76, and 32.76 mg g-1, respectively.


Extracting continuum electron dynamics from high harmonic emission from molecules.
We show that high harmonic generation is the most sensitive probe of rotational wave packet revivals, revealing very high-order rotational revivals for the first time using any probe. By fitting high-quality experimental data to an exact theory of high harmonic generation from aligned molecules, we can extract the underlying electronic dipole elements for high harmonic emission and uncover that the electron gains angular momentum from the photon field.


Determinants of self-monitoring of blood glucose in patients with Type 1 diabetes: a multi-centre study in Brazil.
The aim of this study was to determine the relationship between the daily frequency of self-monitoring of blood glucose and glycaemic control, demographic and socio-economic status in patients with Type 1 diabetes under routine clinical care in Brazil. This was a cross-sectional, multi-centre study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The data were obtained from 3176 patients, aged 22 ± 11.8 years, of whom 56.3% were female and 57.4% were Caucasian. The mean time since diabetes diagnosis was 11.7 ± 8.1 years. The prevalence of self-monitoring of blood glucose was 88.5%. There was a significant increase in self-monitoring frequency associated with female gender, lower ages, more intensive diabetes management and higher socio-economic status. A correlation between HbA(1c) levels and the daily frequency of self-monitoring was observed (r(s) = -0.13; P = 0.001). The mean HbA1c levels were related to the daily frequency of self-monitoring (P < 0.001) without additional benefit to patients who performed self-monitoring more than four times daily (9.2, 11.2, 10.2,15.2 and 15% for one, two, three, four, five or more self-monitoring tests daily, respectively; P < 0.0001). The majority of our patients (88.5%) performed three or more self-monitoring tests daily, with more frequent testing reported by females, younger patients, those on intensive insulin regimens and of higher socio-economic status. No additional benefit was found in patients who performed self-monitoring more than four times daily. The diabetes care team must improve patients' education regarding self-monitoring of blood glucose and its benefits.


Circadian Clocks: Mosquitoes Master the Dark Side of the Room.
Aedes aegypti and Anopheles coluzzii mosquitoes exhibit diurnal and nocturnal behaviors, respectively. Baik et al. reveal the clock network architecture underlying each species' light preferences.


Intralesional interferon-alpha therapy in advanced malignant melanoma.
Fifty-one evaluable patients with histologically proven metastatic melanoma and at least one skin metastasis were treated intralesionally with interferon-alpha (IFN-alpha). Twenty-six of the patients were given highly purified natural IFN-alpha 6 Mio. IU three times per week. Twenty-five patients were given 10 Mio. IU three times per week of a recombinant IFN-alpha 2b (rIFN-alpha 2b). All patients were examined for systemic and local responses to this treatment. The systemic responses consisted of nine objective remissions, each of which lasted from 2 to 18 or more months. There were 24 complete or partial local responses. Forty-two of the 51 patients had at least two skin metastases so that IFN-injected and noninjected tumor sites could be compared. The difference between systemic and local efficacy was highly significant statistically (P = 0.0004). The results show that IFN-alpha has clinically observable antitumor activity in malignant melanoma.


Measurement of adherence to brimonidine therapy for glaucoma using electronic monitoring.
To assess the patient adherence and behavior with brimonidine twice daily (bid) or 3 times daily (tid) in patients used to topical glaucoma medication. Seventy-five patients with glaucoma or ocular hypertension were enrolled in a prospective, observational cohort study. Consenting patients were randomly assigned to brimonidine bid or tid and received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks. Patients were not explicitly informed on the compliance monitoring. The study was completed by 67 patients (89%). In 65 patients (97%), at least 1 dosing interval exceeded 24 hours. The mean adherence rates were better in the brimonidine bid group (72 ± 19% vs. 62 ± 16%, P=0.04), although dosing frequency was higher in the tid group (1.9 ± 0.5 vs. 1.4 ± 0.4 per day; P<0.001). On average medication coverage was 70% for the bid group and 67% for the tid group; 19 patients (28%) had a coverage rate above 75%, 42 patients (63%) 50% to 75%, and 6 (9%) below 50%. Patients with normal-tension glaucoma had lower coverage rates than patients with primary open-angle glaucoma and ocular hypertension (P<0.05). Data also showed that on average 20% of the glaucoma medication was wasted owing to inefficient drug delivery by using more than 1 drop per dosing. Individual adherence with brimonidine was highly variable and pharmacologically insufficient for more than two-third of the patients. Special attention should be paid to compliance of patients with normal-tension glaucoma. Our findings underline the need to improve individual adherence and drug delivery in topical glaucoma therapy.


T-cell receptor gene rearrangement and its expression in human myeloid leukemia cell lines.
ML cell lines (ML-1, -2, and -3) were derived from the cells of a patient with acute myelocytic leukemia preceded by a T-cell malignant lymphoma. A deletion of chromosome 11 (11q-) was common to the affected cells in both neoplastic phases. We report here that the three ML cell lines have DNA rearrangements of the T-cell receptor (TcR)-beta and gamma-chain genes in addition to immunoglobulin heavy-chain gene rearrangement, though they do not have TcR gene messages. The findings presented here indicate that ML cell lines could be used as models for the elucidation of the bilineal nature of hematopoietic neoplastic cells, though they have a biphenotypic (myelomonocytic/T-cell) marker expression.


Crossover from 'mesoscopic' to 'universal' phase for electron transmission in quantum dots.
The measurement of phase in coherent electron systems--that is, 'mesoscopic' systems such as quantum dots--can yield information about fundamental transport properties that is not readily apparent from conductance measurements. Phase measurements on relatively large quantum dots recently revealed that the phase evolution for electrons traversing the dots exhibits a 'universal' behaviour, independent of dot size, shape, and electron occupancy. Specifically, for quantum dots in the Coulomb blockade regime, the transmission phase increases monotonically by pi throughout each conductance peak; in the conductance valleys, the phase returns sharply to its starting value. The expected mesoscopic features in the phase evolution--related to the dot's shape, spin degeneracy or to exchange effects--have not been observed, and there is at present no satisfactory explanation for the observed universality in phase behaviour. Here we report the results of phase measurements on a series of small quantum dots, having occupancies of between only 1-20 electrons, where the phase behaviour for electron transmission should in principle be easier to interpret. In contrast to the universal behaviour observed thus far only in the larger dots, we see clear mesoscopic features in the phase measurements when the dot occupancy is less than approximately 10 electrons. As the occupancy increases, the manner of phase evolution changes and universal behaviour is recovered for some 14 electrons or more. The identification of a transition from the expected mesoscopic behaviour to universal phase evolution should help to direct and constrain theoretical models for the latter.


Effect of application mode (capping and amendment) on the control of cadmium release from sediment by apatite/calcite mixture and its phosphorus release risk.
In this research, the influence of application mode (capping and amendment) on the control of cadmium (Cd) liberation from sediment by apatite/calcite mixture and its phosphorus release risk were investigated. The results showed that calcite addition had a limited effect on the speciation of Cd in sediment, but apatite addition had a significant impact on the fractionation of Cd in sediment. Apatite amendment could effectively immobilize the most readily mobilized Cd by transferring the acid-soluble fraction to the reducible and residual fractions. Apatite addition also could effectively reduce the concentration of toxicity characteristic leaching procedure (TCLP)-leachable Cd in sediment, and apatite had a much higher reduction efficiency of TCLP-leachable Cd than calcite. Apatite/calcite mixture capping could reduce the risk of Cd liberation from sediment into the overlying water, and the controlling efficiency of apatite/calcite mixture capping was higher than that of apatite/calcite mixture amendment. The effect of apatite/calcite mixture addition on the concentration of reactive soluble phosphorus (SRP) in the overlying water was limited. The introduction of calcite into the apatite capping layer could lower the risk of phosphorus release from apatite to the overlying water as compared to single apatite capping. However, the apatite/calcite mixture capping layer still had a relatively high risk of phosphorus liberation into the overlying water. Results of this work suggest that apatite/calcite mixture has a high potential to be used as a capping material to control Cd release from sediment from the perspective of controlling efficiency and application convenience.


Developing Committed Resident Leaders: A Survey of the Administrative Chief Resident Experience in Surgical Fields.
Administrative chief residents (ACRs) are integral to residency programs, however little research has been done on the experiences, training, and support of ACRs in surgical fields. The objective of this study was to define the challenges and experiences of surgical ACRs and identify support needed to make them successful. A Qualtrics survey was electronically distributed to participants. Response styles included multiple choice questions, yes/no, Likert scales, and short answers. Question topics included demographics, ACR duties, support, and experiences. Obstetrics & Gynecology and General Surgery residency programs in the United States. Current and past administrative chief residents (2019-2020; 2018-2019) and program directors from Obstetrics & Gynecology and General Surgery residency programs. Seventy-nine surveys were completed by 48 (61%) ACRs and 31 (39%) program directors. The majority (52%) were from academic programs with a median of 6 residents and 2 ACRs per year. On a 10-point Likert scale, mean perceived support from faculty, program director, administration, and other residents was 7.0, 8.8, 6.7, and 7.7 respectively; however, mean stress level was also perceived to be high. Regarding preparation for the role, 56% of administrative chief residents do not receive a job description, 41% do not have a formal handoff process, 42% do not have formal leadership training, and only 61% agreed or strongly agreed that the administrative chief role was clear prior to starting. Common challenges reported by ACR's are limited preparation and training, conflict resolution, and workload management. Many ACRs felt they would benefit from formal leadership training and protected time. These results summarize the experiences of ACRs in surgical residencies. Best practices and formal training in identified challenge areas should be added to residency curriculum and used to develop toolkits to support ACRs nationwide.


Antihyperglycemic, antihyperlipidemic and antioxidant activities of polysaccharides from Catathelasma ventricosum in streptozotocin-induced diabetic mice.
It is the first time to extract polysaccharides (CVPs) from Catathelasma ventricosum. The antihyperglycemic and antioxidant activity of CVPs in streptozotocin-induced diabetic mice were examined. Compared with untreated diabetic mice, the administration of CVPs for 30 days caused a significant decrease in the concentrations of blood glucose, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein-cholesterol (LDL-C) and maleic dialdehyde (MDA), and a significant increase in the concentrations of high density lipoprotein-cholesterol (HDL-C) and the activities of antioxidant enzymes. Specially, when normal mice were treated with CVPs, all detection indexes and pathologic morphologies of liver, kidney and pancreas are similar to untreated normal mice, which indicated CVPs are safe for normal mice. In addition, the average molecular weight of CVPs was estimated to be from 3.7 × 10(3) to 1.7 × 10(7)Da and they were mainly composed of glucose (93.5%) with the conformation of α-d-Glucopyranose.


Treatment of proteoglycan aggregates with physeal enzymes reduces their ability to inhibit hydroxyapatite proliferation in a gelatin gel.
In vitro, cartilage proteoglycans (PGs) are effective inhibitors of hydroxyapatite formation and growth. Their inhibitory ability decreases with decreasing PG size and charge density. It has been suggested that the enzyme-mediated alteration in the size and conformation of PGs in the growth plate may similarly facilitate the calcification process. In this study, a gelatin gel system was used to monitor hydroxyapatite formation and growth in the presence of proteoglycan aggregates, before and after enzyme treatment. To reproduce the physeal degradation cascade, an enzyme preparation was used that contained all of the growth plate enzymes. At a concentration of 500 micrograms/ml, the untreated proteoglycan aggregates reduced the amount of mineral formed by 30%. When the aggregates were treated with the heat-inactivated enzyme, the same extent of inhibition was found. In contrast, treating the aggregates with the crude growth plate enzyme preparation removed all the inhibitory ability, such that 500 micrograms/ml of proteoglycan preparation yielded 10% more mineral than the controls. Treatment of the aggregates with chondroitinase ABC and trypsin, similarly removed all the inhibitory ability. These data, suggest that enzymatic degradation of proteoglycans may contribute to the regulation of growth plate calcification.


[Diabetes mellitus in old age].
In the treatment of diabetes in old age cognitive, functional and constitutional resources of the individual must be taken into account. Purely glycated hemoglobin (HbA1c)-oriented treatment goals are less relevant. The primary focus should be freedom from symptoms while avoiding hypoglycemia and maintaining the quality of life. The geriatric assessment helps to clarify the current functional, psychological and cognitive status as well as the need for support in multimorbid older people and to define appropriate treatment strategies. With drug treatment of diabetes in old age, particular attention must be paid to renal insufficiency and dehydration as well as slow dose adjustments. According to the Robert Koch Institute (RKI), diabetes patients belong to the risk group for a severe course of the coronavirus disease 2019 (COVID-19); further risk factors are high blood pressure, underlying oncological diseases, cerebrovascular and coronary heart diseases.


Directional coronary atherectomy for the treatment of Palmaz-Schatz in-stent restenosis.
Management of in-stent restenosis has become a significant challenge in interventional cardiology. The results of balloon angioplasty have been disappointing due to the high recurrence of restenosis at follow-up. Debulking of the restenotic tissue within the stents using directional coronary atherectomy (DCA) may offer a therapeutic advantage. We report the immediate clinical and angiographic outcomes and long-term clinical follow-up results of 45 patients (46 lesions), mean age 63+/-12 years, 73% men, with a mean reference diameter of 2.9+/-0.6 mm, treated with DCA for symptomatic Palmaz-Schatz in-stent restenosis. DCA was performed successfully in all 46 lesions and resulted in a postprocedural minimal luminal diameter of 2.7+/-0.7 mm and a residual diameter stenosis of 17+/-10%. There were no in-hospital deaths, Q-wave myocardial infarctions, or emergency coronary artery bypass surgeries. Four patients (9%) suffered a non-Q-wave myocardial infarction. Target lesion revascularization was 28.3% at a mean follow-up of 10+/-4.6 months. Kaplan-Meier event-free survival (freedom from death, myocardial infarction, and repeat target lesion revascularization) was 71.2% and 64.7% at 6 and 12 months after DCA, respectively. Thus, DCA is safe and efficacious for the treatment of Palmaz-Schatz in-stent restenosis. It results in a large postprocedural minimal luminal diameter and a low rate of both target lesion revascularization and combined major clinical events at follow-up.


A modified immunoperoxidase method for the detection of ABH tissue isoantigens in patients with bladder carcinoma.
Detectable ABH blood group antigens (BGAg) on tumor cells from transitional carcinoma of the urinary bladder, used for diagnosis and prognosis may be evidenced with the existing immunoperoxidase methods. In this study, a modification of the immunoperoxidase method was shown to enable the detection of BGAg in deparaffinized tissue section of normal and malignant human urothelium. To detect antigens A and B a peroxidase-conjugated rabbit anti-human IgM was used and antigen H was visualized by biotinylated lectin.


Prospective Evaluation of Acupuncture as Treatment for Glaucoma.
To evaluate acupuncture as treatment for glaucoma. Prospective double-masked randomized crossover study. setting: Clinical practice. One eye per patient with primary open-angle glaucoma and stable intraocular pressure (IOP). Patients were randomized to receive 1 acupuncture series (12 sessions with either eye-related [eye-points] or non-eye-related [non-eye-points] acupoints) and then crossed over to receive the other series. IOP, blood pressure (BP), heart rate (HR), best-corrected visual acuity (BCVA), visual field (VF), optic disc and peripapillary retinal nerve fiber layer (RNFL) measurements, compliance, and adverse reactions. Probability to detect 3 mm Hg IOP difference between series was 90%. Twenty-two patients volunteered and 11 (50.0%) completed the study; 8 (36.4%) did not complete treatment owing to changes of health, moving away, lack of transportation, or family crisis; and 3(13.6%) were withdrawn owing to needle sensitivity or IOP elevation (8 mm Hg) in the contralateral eye. After an acupuncture session, mean IOP increased slightly with both eye-points (from 12.9 ± 1.8 mm Hg to 13.6 ± 2.0 mm Hg, P = .019) and non-eye-points (from 13.0 ± 1.5 mm Hg to 13.5 ± 1.7 mm Hg, P = .073) series. HR, diurnal IOP, and BCVA showed no statistically significant changes after 12 sessions of either series. Systolic and diastolic BP were reduced after 12 sessions of non-eye-points series (P = .040, P = .002, respectively). Optic disc, RNFL, and VF showed no statistically significant changes. Acupuncture has no overall effect on diurnal IOP or BCVA but may temporally increase the IOP immediately after a treatment session. BP is lowered by acupuncture with non-eye-points, but not with eye-points. Compliance and adverse event rates were low.


Treatment of hospita-acquired infections with amikacin.
Amikacin was used in the treatment of 56 serious gram-negative infections in 54 patients of whom 47 survived. In six of the seven nonsurvivors, the infections were under control at the time of death. The clinical isolates were multiple drug-resistant gram-negative organisms, with Proteus rettgeri being most common. Forty-five (80%) of these infections were nosocomial in origin, and the genitourinary tract was the source in 39 (70%). Complications directly related to amikacin therapy were few and suggested renal or otologic toxicity. In this series of patients, amikacin appeared to be of therapeutic benefit in the treatment of serious gram-negative infections.


[A successful biventricular repair in an adult case with "common ventricle" and isomeric atrial appendages previously undergoing the conventional Glenn procedure].
We describe herein a successful biventricular repair in a 21-year-old male who had severe hypoplasia of isomeric right appendages. He had previously undergone the conventional Glenn procedure at the age of one and a half years. Although he had grown uneventfully until adolescence, cyanosis as well as fatigue than gradually became worse. When referred to us for further treatment, we deemed a Fontan type procedure to be contraindicated, because of the hypoplastic nature of the right pulmonary artery, and the presence of abundant collateral arteries supplying the right lung. In terms of ventricular morphology, however, because both apical components were present, separated by the hypoplastic septum, biventricular repair seemed feasible. Initially, the Glenn anastomosis was taken down, and systemic-to-pulmonary shunts were constructed via a median sternotomy to both the right and left pulmonary arteries. This was followed by surgical division of the developed collaterals to the right lung via the right thoracotomy. Definitive biventricular repair was then carried out by reconstructing the pulmonary arteries and right ventricular outflow tact, separating and rerouting within the ventricles using a EPTFE patch, and achieving redirection of blood within the atriums using bovine pericardium. Such staged surgical approaches, although extensive, can provide useful options when seeking definitive repair in grown-up patients with complicated malformations.


Are cup-like blasts specific to AML patients with FLT3 ITD and a normal karyotype? An ALL case report and review of the literature.
Cup-like morphology is defined as cup-like nuclear invagination spanning ≥25% of the nuclear diameter in >10% of blasts. Studies have shown that FLT3 ITD and normal cytology are strongly associated with cup-like morphology in acute myeloid leukemia (AML) patients. Herein we describe a patient with cup-like blasts that was diagnosed and treated for common acute lymphoblastic leukemia (ALL). In contrast to the literature, the presented case was Philadelphia chromosome positive and FLT3 ITD negative.


Comparison of the use of aqueous and nonaqueous buffers in association with cyclodextrin for the chiral separation of 3,4-methylenedioxymethamphetamine and related compounds.
A comparison of the use of aqueous and nonaqueous buffers in association with beta-CD for the chiral separation of (R)- and (S)-3,4-methylenedioxymethamphetamine and related compounds is described. The (R)- and (S)-isomers of 3,4-methylenedioxymethamphetamine (MDMA) and its major metabolite 3,4-methylenedioxyamphetamine (MDA) were prepared. Under aqueous and nonaqueous buffer conditions and based on the CZE and MEKC modes, the order of migration of (R)-MDA, (S)-MDA, (R)-MDMA, and the (S)-MDMA enantioisomers were determined. Several electrophoretic parameters, including the concentration of beta-CD (aqueous, 25-60 mM; nonaqueous, 20-150 mM) used in the electrophoretic separation and the amount of organic solvents required for the separation, were optimized.


Phillyrin lowers body weight in obese mice via the modulation of PPAR<beta>/<delta>-ANGPTL 4 pathway.
Previous investigations have shown that the peroxisome proliferator activated receptor beta/delta (PPAR<beta>/<delta>)-angiopoietin-like protein 4 (ANGPTL4) pathways may be a new pharmacologic target for treatment of obesity. The present study was conducted to test the effect of phillyrin, a glucoside, on obesity in mice. Fifty mice were randomly divided into 5 groups (n=10): control group (C57BL/6J mice), obese mice group, two groups of obese mice treated with phillyrin (15 or 45mg/kg/day), one group of obese mice treated with PPAR<beta>/<delta> agonist GW0742 (3mg/kg/day). Twelve weeks after treatment, body weight, liver weight, fat weight, lipid levels in the liver, serum levels of tumour necrosis factor-<alpha>(TNF-<alpha>), leptin, and insulin, expression of PPAR<beta>/<delta>, ANGPTL4, and AMP-activated protein kinase (AMPK) were determined. Treatment with phillyrin (15 or 45mg/kg) significantly decreased body weight, liver weight, fat weight, hepatic total cholesterol, free fatty acid, and triglyceride concentrations, serum levels of TNF-<alpha>, leptin, and insulin concomitantly with up-regulated expression of PPAR<beta>/<delta>, ANGPTL4, and p-AMPK-<alpha>. In addition, GW0742 has similar effect of phillyrin. The present results suggest that phillyrin could regulate the PPAR<beta>/<delta>-ANGPTL 4 pathway to lower body weight in obese C57BL/6J mice.


Structural sequencing and anti-inflammatory, anti-lung cancer activities of 1,4-α/β-sulfomalonoglucan in Antrodia cinnamomea.
Antrodia cinnamomea is a precious Polyporaceous fungus with various bioactivities. This study reports the chemical identification and biological activities of sulfomalonoglucan, a sulfated polysaccharide (SPS), from the sodium sulfate enriched medium of the title fungus. The SPS-containing fraction was separated by gel filtration chromatography (GFC) to give the title SPS (denoted as Na10_SPS-F3). By analyzing the evidence for key inter-glycosidic linkages in the 1D and 2D NMR spectroscopic data, one possible repeat unit was proposed as: Na10_SPS-F3 inhibited the secretion of tumor necrosis factor (TNF-α) and interleukin (IL)-6 after lipopolysaccharide (LPS) stimulation in RAW264.7 macrophages. Mechanistically, Na10_SPS-F3 downregulated TGFRII also attenuated the LPS-induced IκB-α degradation. Moreover, Na10_SPS-F3 inhibited lung cancer cell H1975 EGFR/ERK signaling. This is the first paper reporting a 3-O-sulfomalonyl glucan (Na10_SPS-F3) with eight 1,4-β-Glc moieties connected with ten 1,4-α-Glc moieties from Antrodia cinnamomea and its anti-inflammatory and anti-cancer activities.


Influence of linseed and antioxidant-rich diets in pig nutrition on lipid oxidation during cooking and in vitro digestion of pork.
Enrichment of pig diets with polyunsaturated fatty acids (PUFA) is considered an emerging strategy to increase their intake in the human diet. However, PUFA are particularly vulnerable to oxidative reactions leading to the generation of toxic compounds. The aim of this study was to evaluate the effect of supplementation of pig diets with extruded linseed (L), either or not in combination with synthetic antioxidants (E, tocopheryl-acetate and selenium) or natural extracts (P, grape-skin and oregano), and basal diet (C, without linseed) on the oxidative stability in raw, grilled and in vitro digested pork. The diet supplementation with antioxidant-rich ingredients resulted in the accumulation of specific metabolites in meat. Actually, 11 different phenolic- and 6 tocopherol-derived metabolites were identified by UHPLC/HR-MS. These metabolites were potentially correlated with the reduction in the oxidative phenomena occurring during meat cooking and digestion. Specifically, 16% and 35% reduction in the amounts of lipid hydroperoxides and TBA-RS were assessed after cooking of meat from P diet, respect to the L diet. Diet supplementations with α-tocopheryl acetate and selenium reduced the oxidative reactions only during meat cooking. A significant reduction was attended at the end of in vitro digestion, showing about 24% and 34% hydroperoxides and TBA-RS concentration reductions, respectively, in P diet samples respect to the L ones. Thus, our study suggests that the appearance of phenolic metabolites in meat could be associated to a reduction in the oxidative phenomena during meat cooking and digestion.


Axotomy increases glycogen phosphorylase activity in motoneurones.
The relative distribution of glycogen phosphorylase a and b in the lumbar spinal cord of the adult rat following either transection or crush of the sciatic nerve has been studied. The activity of the glycogen phosphorylase was measured histochemically by its capacity to convert glucose-1-phosphate to glycogen which was then stained with iodine. Prior to any treatment, the enzyme was largely in its inactive b form. Sciatic section and crush produced a transient (24 h) decrease in the amount of the active glycogen phosphorylase a in the sciatic motoneurone pool. Fourteen days post-transection, but not crush, a marked increase in the level of the active glycogen phosphorylase a form of the enzyme could be detected in the axotomised motoneurones which persisted for up to 6 weeks. No equivalent changes occurred in the axotomized dorsal root ganglion cells. Glycogen phosphorylase although normally present in neurones in its inactive b form can be converted to the active a form by calcium or adenosine 3':5'-phosphate. The substantial increase in the level of glycogen phosphorylase a in axotomized motoneurones may be a reflection of an increased calcium influx into these cells due to the development of abnormally hyperexcitable membranes and the appearance of dendritic spikes that is known to occur in these motoneurones.


Circadian misalignment increases 24-hour acylated ghrelin in chronic shift workers: a randomized crossover trial.
Shift workers typically experience misalignment between their circadian system and behavioral/environmental cycles and have an increased risk for obesity. Experimental studies in non-shift workers have suggested that circadian misalignment can disrupt energy balance regulation. This study examined the impact of circadian misalignment in the most relevant population, i.e., chronic shift workers. Seven healthy chronic night shift workers underwent a randomized crossover study with two 3-day laboratory protocols: a night work protocol including 12-hour inverted behavioral/environmental cycles (circadian misalignment) and a day work protocol (circadian alignment). Circadian misalignment led to a ~17% increase in 24-hour acylated ghrelin levels in the chronic shift workers (p = 0.009). Consistently, circadian misalignment resulted in ~14% higher hunger at breakfast in the night shift (p = 0.04). Circadian misalignment did not significantly change fasting and postprandial energy expenditure or respiratory exchange ratio (all p > 0.32). Unexpectedly, 24-hour behavioral activity levels were ~38% higher (p < 0.0001) during circadian misalignment, despite a concurrent increase in sleepiness (p = 0.03). These results reveal that circadian misalignment, while carefully controlling for dietary intake, increases acylated ghrelin in chronic shift workers. Further studies should test whether the observed acute effects of circadian misalignment in chronic shift workers contribute to their increased obesity risk in the long term.


Diversity patterns and conservation gaps of Magnoliaceae species in China.
Magnoliaceae, a primitive group of angiosperms and distinguished ornamental plants with more than 100 species in China, is one of the most threatened plant family in the wild due to logging, habitat loss, over-collection and climate change. To provide a scientific guide of its conservation for policymakers, we explore the diversity patterns of 114 Magnoliaceae species in China using three diversity indices (species richness, weighted endemism, β-diversity) with a spatial resolution of 10 km by 10 km. Two methods, the top 5% richness algorithm and complementary algorithm, are used to identify diversity hotspots. Conservation gaps are recognized by overlapping the diversity hotspots with Chinese nature reserves. Our results indicate that Magnoliaceae species richness and weighted endemism are high in tropical to subtropical low montane forests in southern China, exceptionally high in southernmost Yunnan and boundary of Guizhou, Guangxi and Hunan. The β-diversity are scattered in southern China, suggesting a different species composition among grid cells. We identify 2524 grids as diversity hotspots for Magnoliaceae species in China, with 24 grids covered by three diversity indices (first-level diversity hotspots), 561 grids covered by two indices (second-level diversity hotspots) simultaneously and 1939 grids (76.8%) covered by only one index (third-level diversity hotspots). The first-level diversity hotspots include over 70% of the critically endangered Magnoliaceae species and are the priority areas for Magnoliaceae conservation. However, only 24% of the diversity hotspots fall in nature reserves and only ten grids are from the first-level diversity hotspots. Zhejiang, Guizhou and Fujian have less than 20% of diversity hotspots covered by nature reserves and need attention in future Magnoliaceae conservation. Using multiple diversity indices and algorithms, our study identifies diversity hotspots and conservation gaps and provides scientific basis for Magnoliaceae conservation in future.


Antibody Drug Conjugates in Lung Cancer.
An antibody-drug conjugate (ADC) comprises a monoclonal antibody that is specific to a tumor cell protein, bound to a cytotoxic agent, known as the payload. The use of ADCs is already common practice in several cancers, thanks to their efficacy and potentially more manageable toxicity profile, resulting from the release of the cytostatic payload directly in the tumors. Currently, early-phase trials of ADCs in non-small cell lung cancer are rapidly gaining ground, with promising results targeting HER2 (human epidermal growth factor 2), HER3, TROP2 (trophoblast cell surface antigen 2), MET, CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5), and PTK7 (tyrosine protein kinase-like 7). Unfortunately, in small cell lung cancer, trials targeting the ubiquitous DLL3 (delta-like ligand 3) protein have failed to show clinically relevant results, despite significant toxicity.


Reduction of benzyl halides by liver microsomes. Formation of 478 NM-absorbing sigma-alkyl-ferric cytochrome P-450 complexes.
The benzyl halides benzyl bromide and 4-nitrobenzyl chloride are reduced anaerobically by NADPH and rat liver microsomes to yield toluene and 4-nitrotoluene, respectively. These reductions and cytochrome P-450-dependent since they are inhibited by CO and metyrapone, and are increased after pretreatment of rats by phenobarbital and 3-methylcholanthrene. During benzyl halide reduction, cytochrome P-450 complexes, which are very unstable to O2 and characterized by a Soret peak at 478 nm, are formed in steady-state concentrations. These concentrations are very dependent on pretreatment of rats and on the nature of the reducing agent (NADPH or dithionite) and the benzyl halide:4-methylbenzyl bromide and benzyl bromide lead to 478 nm absorbing complexes in the presence of NADPH whereas 4-nitrobenzyl chloride and benzyl chloride lead to such completes only in the presence of dithionite. Microsomal reductions of 4-nitrobenzyl chloride and benzyl bromide in D2O lead to partially deuterated 4-nitrotoluene and toluene. From these results, we propose a mechanism for anaerobic microsomal reduction of benzyl halides involving the intermediate formation of sigma-alkyl cytochrome P-450-Fe(III)-CH2Ar complexes which exhibit red-shifted Soret peaks around 478 nm. Toluenes, ArCH3, are formed either by protonation of the sigma-alkyl complexes or by hydrogen abstraction by the intermediate free radical ArCH2.


The prognostic value of tumor mitotic rate in children and adolescents with cutaneous melanoma: A retrospective cohort study.
Mitotic rate is a strong predictor of outcome in adult patients with primary cutaneous melanoma, but for children and adolescent patients this is unknown. We sought to assess the prognostic value of primary tumor mitotic rate in children and adolescents with primary melanoma. This was a cohort study of 156 patients who were <20 years of age and who had clinically localized cutaneous melanoma. Patients <12 years of age were classified as children and those 12 to 19 years of age as adolescents. Clinicopathologic and outcome data were collected. Recurrence-free and melanoma-specific survival were calculated. Univariable and multivariable analyses were performed using Cox proportional hazard models. Thirteen of 156 patients (8%) were children. The mitotic rate was ≥1/mm2 in 104 patients (67%) and correlated with increasing Breslow thickness. A positive sentinel node was found in 23 of 61 patients (38%) in whom a sentinel lymph node biopsy specimen was obtained. The median follow-up was 61 months. Five-year melanoma-specific and recurrence-free survival rates were 91% and 84%, respectively. Mitotic rate was a stronger predictor of outcome than tumor thickness and was the only factor independently associated with recurrence-free survival. This research was conducted at a single institution and the sample size was small. Mitotic rate is an independent predictor of recurrence-free survival in children and adolescents with clinically localized melanoma.


Association between oral contraceptive use and markers of iron deficiency in a cross-sectional study of Tanzanian women.
To analyze the associations between oral contraceptive (OC) use and markers of iron deficiency, objectively measured using hemoglobin and soluble transferrin receptor. A secondary data analysis was performed of a population-based cross-sectional study using data from the 2010 Tanzania Demographic and Health Survey. Weighted percentages were calculated. Multivariable logistic regression was used to examine the associations between OC use and iron deficiency, anemia, and iron deficiency anemia. Of the 4336 participants, only 7.3% reported a history of OC use. The prevalence rates of iron deficiency, anemia, and iron deficiency anemia were 30.3%, 40.9%, and 15.1%, respectively. Use of OCs was negatively associated with anemia and iron deficiency anemia, independent of potential confounders. Compared with OC nonusers, the multivariable-adjusted odds ratio among OC users was 0.44 (95% confidence interval 0.32-0.59; P<0.001) for anemia and 0.43 (95% confidence interval 0.27-0.68; P<0.001) for iron deficiency anemia. A longer duration of OC use was negatively associated with iron deficiency (P=0.003 for trend), anemia (P<0.001 for trend), and iron deficiency anemia (P<0.001 for trend). The significant association between OC use and iron status has important implications for educating healthcare providers and women about additional nutritional benefits of the use of OCs.


Biomechanical outcomes after bioenhanced anterior cruciate ligament repair and anterior cruciate ligament reconstruction are equal in a porcine model.
The objective of this study was to compare the biomechanical outcomes of a new method of anterior cruciate ligament (ACL) treatment, bioenhanced ACL repair, with ACL reconstruction in a large animal model. Twenty-four skeletally immature pigs underwent unilateral ACL transection and were randomly allocated to receive bioenhanced ACL repair with a collagen-platelet composite, allograft (bone-patellar tendon-bone) reconstruction, or no further treatment (n = 8 for each group). The structural properties and anteroposterior laxity of the experimental and contralateral ACL-intact knees were measured 15 weeks postoperatively. All dependent variables were normalized to those of the contralateral knee and compared by use of generalized linear mixed models. After 15 weeks, bioenhanced ACL repair and ACL reconstruction produced superior biomechanical outcomes to ACL transection. However, there were no significant differences between bioenhanced ACL repair and ACL reconstruction for maximum load (P = .4745), maximum displacement (P = .4217), or linear stiffness (P = .6327). There were no significant differences between the 2 surgical techniques in anteroposterior laxity at 30° (P = .7947), 60° (P = .6270), or 90° (P = .9008). Bioenhanced ACL repair produced biomechanical results that were not different from ACL reconstruction in a skeletally immature, large animal model, although the variability associated with both procedures was large. Both procedures produced significantly improved results over ACL transection, showing that both were effective treatments in this model. Bioenhanced ACL repair may one day provide an alternative treatment option for ACL injury.