Clinical effects of interspace between the popliteal artery and capsule of the posterior knee block with multimodal analgesia for total knee arthroplasty: a systematic review and meta-analysis.
Combination of regional anaesthesia technique that is most effective in analgesia and postoperative functional outcome with the fewest complications needs investigation. Interspace between the popliteal artery and the capsule of the posterior knee block (IPACK) has been introduced clinically. We evaluated the efficacy of IPACK in combination with other nerve blocks after total knee arthroplasty. Data were obtained from PubMed, Cochrane Library, Web of Science, and Sciencedirect. Studies that compared outcomes using IPACK combined with other regional nerve blocks after total knee arthroplasty with other analgesic modalities and those which used pain scores or opioid consumption as primary or secondary outcomes were included. Seventeen articles (20 trials, 1652 patients) were included. IPACK supplementation significantly reduced rest pain scores after total knee arthroplasty at postoperative hours 8-12(95%CI - 0.85 [- 1.36, - 0.34], I2 = 94%, p = 0.001), postoperative day 1 (95% CI - 0.49 [- 0.85, - 0.14], I2 = 87%, p = 0.006), and postoperative day 2 (95% CI - 0.28 [- 0.51, -0.05], I2 = 72%, p = 0.02); there was no significant difference at postoperative day 3 or discharge (95% CI - 0.14 [- 0.33, 0.05], I2 = 0%, p = 0.14). Combination treatment resulted in reduced dynamic pain scores at postoperative hours 8-12 (95%CI - 0.52 [- 0.92, - 0.12], I2 = 86%, p = 0.01) and postoperative day 1(95% CI - 0.49 [- 0.87, - 0.11], I2 = 88%, p = 0.01). There was no difference between postoperative day 2(95% CI - 0.29 [- 0.63, 0.05], I2 = 80%, p = 0.09), postoperative day 3 or discharge (95% CI - 0.45 [- 0.92, 0.02], I2 = 83%, p = 0.06). In addition, it strongly reduced postoperative opioid consumption within 24 H (95% CI - 0.76 [- 1.13, - 0.39], I2 = 85%, p < 0.00001), 24-48 H (95% CI - 0.43 [- 0.85, - 0.01], I2 = 83%, p = 0.04), and total opioid use (95% CI - 0.64 [- 1.07, - 0.22], I2 = 86%, p = 0.003). Although IPACK supplementation improved timed up and go test and walking distance at postoperative day 2, there was no statistically significant difference at other time periods or obvious improvement in knee range of motion and quadriceps strength. IPACK block supplementation could shorten the length of stay (LOS) (95% CI - 0.40 [- 0.64, - 0.15], I2 = 70%, p = 0.001) and improve patient satisfaction (95% CI 0.43 [0.01, 0.84], I2 = 87%, p = 0.04). Based on these results, IPACK supplementation, in addition to standard postoperative analgesia, can be used effectively and safely to relieve early postoperative pain after total knee arthroplasty.


In the midst of every crisis, lies great opportunity? Analysing environmental attitudes in the face of the Covid-19 pandemic.
A widely used media narrative suggests that the environment benefitted from the Covid-19 lockdowns. Numerous publications which came out following the lockdowns only reinforced this view by seeing Covid-19 as an opportunity to think more about the environment. However, these narratives are largely anecdotal, assumptive and pay little attention to the question of what people actually think about the lockdowns in environmental terms. To fill this gap, this study provides the empirical basis needed to either support or reject the aforementioned dominant narrative on Covid-19 and environment. Survey data (eighty questionnaires per country) were collected from participants in Cameroon (Buea), Egypt (Cairo), Italy (several major cities) India (Mumbai and New Delhi), and The Netherlands (mainly Amsterdam). The findings of this study reveal that generally, Covid-19 has not changed the way most people think about the environment. This is either because people were already pro-environmental before Covid-19, or people see Covid-19 and the visible environmental changes as temporal phenomenon. One other major observation in this study is the regional differences in environmental attitudes in relation to Covid-19. The least change in environmental attitudes was observed in high-income countries and the most change in low-middle-income countries. Therefore, the paper concludes that the importance of Covid-19 on a more sustainable future should not be overplayed or overemphasised. It will take more than a two-year break from normal living to mitigate environmental degradation. Accordingly, pro-environmentalism should focus on other intervention points.


Fetomaternal hemorrhage assessment in Rh-negative patients undergoing dilation and evacuation between 20 and 24 weeks' gestational age: A retrospective cohort study.
To estimate the rate of requiring more than one 300-mcg Rh D immune globulin dose for fetomaternal hemorrhage (FMH) at the time of second-trimester dilation and evacuation (D + E). We performed a retrospective cohort analysis of patients at greater than 20 weeks' gestation who underwent D + E, had Rh D-negative blood type, and received FMH quantification testing. Of 25 eligible patients, 24 had negative quantification of FMH; one had positive quantification that did not meet the clinical threshold for additional dosing. The absolute risk of requiring additional Rh D immune globulin after D+E for pregnancies greater than 20 weeks' gestation was 0%.


Whole-body MRI: detecting bone metastases from prostate cancer.
Whole-body magnetic resonance imaging (WB-MRI) is currently used worldwide for detecting bone metastases from prostate cancer. The 5-year survival rate for prostate cancer is > 95%. However, an increase in survival time may increase the incidence of bone metastasis. Therefore, detecting bone metastases is of great clinical interest. Bone metastases are commonly located in the spine, pelvis, shoulder, and distal femur. Bone metastases from prostate cancer are well-known representatives of osteoblastic metastases. However, other types of bone metastases, such as mixed or inter-trabecular type, have also been detected using MRI. MRI does not involve radiation exposure and has good sensitivity and specificity for detecting bone metastases. WB-MRI has undergone gradual developments since the last century, and in 2004, Takahara et al., developed diffusion-weighted Imaging (DWI) with background body signal suppression (DWIBS). Since then, WB-MRI, including DWI, has continued to play an important role in detecting bone metastases and monitoring therapeutic effects. An imaging protocol that allows complete examination within approximately 30 min has been established. This review focuses on WB-MRI standardization and the automatic calculation of tumor total diffusion volume (tDV) and mean apparent diffusion coefficient (ADC) value. In the future, artificial intelligence (AI) will enable shorter imaging times and easier automatic segmentation.


Author Correction: Formation and purification of tailored liposomes for drug delivery using a module-based micro continuous-flow system.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Spontaneous and action potential-evoked Ca2+ release from endoplasmic reticulum in neocortical synaptic boutons.
Although the endoplasmic reticulum (ER) is present throughout axons, and IP3 and ryanodine receptors are widely expressed in nerve terminals, whether Ca2+ release from presynaptic stores contributes to action potential (AP)-evoked Ca2+ transients remains controversial. We investigated the release of Ca2+ from ER stores in boutons en passant of neocortical layer 5 pyramidal neurons. A hallmark of these stores is that they spontaneously release Ca2+ at a low frequency. Using a high-affinity Ca2+ indicator, we documented and characterised such spontaneous Ca2+ transients (sCaTs), which occurred at a rate of ~0.2 per min and raised the intracellular Ca2+ concentration ([Ca2+]i) by ~2 µM in the absence of exogenous buffers. Caffeine increased the average frequency of sCaTs by 90%, without affecting their amplitude and decay kinetics. Therefore, presynaptic ryanodine receptors were likely involved. To determine if presynaptic ER stores contribute to intracellular Ca2+ accumulation during repetitive stimulation, we measured [Ca2+]i during 2 s long trains of APs evoked at 10-50 Hz. We found that for frequencies <20 Hz, [Ca2+]i reached a steady state within ~500 ms after stimulation onset. However, for higher frequencies, [Ca2+]i continued to increase with AP number, suggesting that the rate of Ca2+ entry exceeded the rate of clearance. Comparison between measured and predicted values indicates supralinear summation of Ca2+. Block of the sarco/endoplasmic reticulum Ca2+-ATPase reduced the supralinearity of summation, without reducing the amplitude of a single AP-evoked Ca2+ transient. Together, our results implicate presynaptic ER stores as a source of Ca2+ during repetitive stimulation.


The Experience of Moral Distress in an Academic Family Medicine Clinic.
Primary care providers (PCPs) report decreased job satisfaction and high levels of burnout, yet little is known about their experience of moral distress. The aim of this study was to gain insight into the experiences of PCPs regarding moral distress including causative factors and proposed mitigation strategies. This qualitative pilot study used semi-structured interviews to identify causes of moral distress in PCPs in an academic family medicine department. Interviews were analyzed using conventional content analysis. Of 35 eligible participants, 12 completed the study (34% participation rate). Most were white, female, and had practiced for less than 10 years. Four PCPs had considered leaving their position due to moral distress. Participants identified five causes of moral distress: policies and procedures that conflict with patient needs, the unpredictable nature of primary care, need to "bend the rules," lack of accountability, and lack of support staff. Six internal conflicts made resolving morally distressing situations difficult: perceived powerlessness, sense of responsibility, socialization to follow orders, emotional toll of the job, competing obligations, and fear of mistakes. These findings matched themes in the current literature and identified an unbending infrastructure. This, coupled with the chaotic nature of primary care, resulted in frequent moral distress. Participants offered solutions to reduce and mitigate moral distress (also similar with current literature) and suggested moral distress and burnout are closely linked.


Tobacco use among American Indian adolescents: protective and risk factors.
To determine the prevalence of, and identify protective and risk factors for, current tobacco use among American Indian adolescents. Data from the Voices of Indian Teens Project were used to determine the prevalence of cigarette and smokeless tobacco (ST) use among a sample of 2390 American Indian adolescents, aged 13 to 20 years. Approximately 49% of the sample were female. Data were collected in Fall 1993 among participants from 10 high schools located in five western American Indian communities. The instrument consisted of scales that assessed psychosocial beliefs, attitudes, and behaviors as well as tobacco use. Logistic regression was used to identify protective and risk factors for tobacco use. A replication subsample was used to test the final models. Approximately 50% of American Indian adolescents in this sample reported some type of cigarette use, and approximately 21% reported using smokeless tobacco. Academic orientation was the only protective factor for cigarette use that replicated in both subsamples. Death/loss and other stressful life events were the risk factors for cigarette and/or ST use that replicated in both subsamples. The prevalence of tobacco use was high in this sample of American Indian adolescents. Several risk and protective factors were identified, the knowledge of which may inform preventive interventions in this population.


Transcriptomic profiling of sesame during waterlogging and recovery.
Sesame is naturally adapted to arid environments but highly susceptible to waterlogging stress. A few hours of waterlogging (lasting over 36 h) are detrimental to the crop growth, yield and survival. To better understand the molecular mechanisms underlying sesame responses to waterlogging and recovery, it is essential to design a high-resolution time-series experiment. In this study, we reported the RNA-seq profiling of two contrasting genotypes under waterlogging and recovery. The plants were grown in pots and subjected to waterlogging treatment at the flowering stage for 36 h and subsequently, 12 h drainage. Root samples were collected in triplicate at 22 time points under waterlogging/drainage treatments and at 10 time points in the control condition. This represents a total of 195 biological samples and the RNA-seq yielded over eight billion reads. Basic data analyses demonstrated a clear separation of transcriptomes from control, waterlogging and drainage treatments. Overall, the generated high-quality and comprehensive RNA-seq resources will undoubtedly advance our understanding of waterlogging/drainage responses in a non-model sensitive crop.


Semi-synthetic analogs of pinitol as potential inhibitors of TNF-alpha cytokine expression in human neutrophils.
Semi-synthetic analogs of pinitol were subjected to screening by determining TNF-alpha expression in human neutrophils using flowcytometry. Among the tested compounds, three derivatives displayed more than 50% inhibition of TNF-alpha cytokine secretion in LPS induced stimulated neutrophils and can be considered as potent anti-inflammatory moieties.


Rat plasma fibronectin contains two distinct chemotactic domains for fibroblastic cells.
Mechanism of fibronectin (FN)-induced chemotaxis of fibroblastic cells has not been fully understood. The present study was performed to establish a molecular nature of the chemotactic region of rat plasma FN. The chemotactic dose-response pattern of intact FN for mouse embryo fibroblastic cells, NIH-L13 cells, which was represented as a "bell-shape" curve with a maximum activity at around 50 nM, changed to a "biphasic" mode through a proteolysis with thermolysin. Two distinct chemotactic components were isolated from the thermolytic fragments. One component, a fragment with a molecular mass of 110-150 kDa, was estimated to contain the central cell-binding domain and the carboxyl-terminal heparin-binding domain of the intact FN molecule. Cell migration stimulated by the 110-150-kDa fragment increased successively in a dose-dependent manner, and the capability to promote the migration was much higher than that of the intact FN (over 2-fold). The second chemotactic component, a fragment with a molecular mass of 21 kDa, was shown to reside in the carboxyl-terminal fibrin-binding domain. The 21-kDa fragment produced a bell-shape dose-response pattern, being consistent with the intact FN, whereas a maximum response occurred at a 100-fold lower concentration (0.5 nM) than that of the intact FN molecule. At higher concentrations, this fragment revealed an inhibitory activity for the cell migration in response to the 110-150-kDa fragment. No significant molecular interaction between these two active components was observed by polyacrylamide gel electrophoresis under nondenaturing conditions, suggesting that the 21-kDa fragment may act directly on the cell to inhibit the cell migration. These results suggest that rat plasma FN contains at least two chemotactically active components that regulate cooperatively chemotactic migration of fibroblastic cells.


Interaction of isolated Lp(a) lipoprotein with calcium ions and glycosaminoglycans in vitro.
The interaction between the lipoprotein carrying the Lp(a) antigen, i.e. the Lp(a) lipoprotein, and agarose gels substituted with glycosaminoglycans, as well as the precipitation of the Lp(a) lipoprotein by Ca++ were studied. Comparisons between Lp(a) lipoprotein and other serum lipoproteins were conducted. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) were bound to the tested glycosaminoglycans at low ionic strength of sodium chloride, but no binding was found with the Lp(a) lipoprotein. However, Ca++ as a divalent buffer cation gave a precipitating Ca++-Lp(a) lipoprotein complex even at a physiological Ca++ concentration. VLDL and LDL were not precipitated under these conditions. These findings may be of interest in relation to the previously reported higher frequency of the phenotype Lp(a+) in subjects with coronary heart disease.


Spinal cord localization of the motoneurons innervating the sacrococcygeus dorsi lateralis muscle and their noradrenergic nerve terminals in rats.
We examined in the present study the spinal cord localization of motoneurons innervating the caudal portion of the sacrococcygeus dorsi lateralis (SCDL) muscle and their noradrenergic nerve terminals in Sprague-Dawley rats, using horseradish peroxidase (HRP) and dopamine-beta-hydroxylase (DBH) double-labeling techniques. Retrogradely HRP-labeled motoneurons innervating the caudal part of the SCDL muscle were located ipsilaterally in the ventromedial aspect of the ventral horn (lamina IX) in spinal segments of S2-S4. These cells were polygonal in shape, with an average soma diameter of 37.0 +/- 1.1 microns (mean +/- S.E.M., n = 95) and amounted to 33.6 +/- 5.7 (n = 7) in the horizontal plane. Of note was the presence of abundant DBH-positive nerve terminals arborizing on the soma and dendrites of HRP-labeled motoneurons. These results provided anatomical evidence to further support our previous findings that the coerulospinal noradrenergic neurotransmission is involved in the mediation of fentanyl-induced muscular rigidity.


Association of T cell acute lymphoblastic leukemia and histiocytic medullary reticulosis.
Seventeen reported cases of acute lymphoblastic leukemia that terminated in a clinical picture of histiocytic medullary reticulosis were reviewed. Using the presence of T cell markers, mediastinal mass, or very high initial white blood cell count as suggestive of T cell acute lymphoblastic leukemia, nine of 13 evaluable cases fulfilled such criteria. This review raises the possibility that the histiocytic medullary reticulosis appearing in the course of T cell acute lymphoblastic leukemia is the result of lymphokine production by the leukemic cells.


Apron strings of working mothers: Maternal employment and housework in cross-national perspective.
This paper asks whether maternal employment has a lasting influence on the division of household labor for married women and men. Employing multi-level models with 2002 ISSP survey data for 31 countries, we test the lagged accommodation hypothesis that a long societal history of maternal employment contributes to more egalitarian household arrangements. Our results find that living in a country with a legacy of high maternal employment is positively associated with housework task-sharing, even controlling for the personal socialization experience of growing up with a mother who worked for pay. In formerly socialist countries, however, there is less gender parity in housework than predicted by the high historical level of maternal employment.


Stimulus-related difference in the formation of leukotrienes and PGD2 after immunological and non-immunological challenge of human lung parenchyma "in vitro".
The stimulation of human lung parenchymal fragments with A-23187 induces formation of leukotrienes as well as of PGD2: LTE4 is the compound found in larger amount and independently of the intensity of the stimulus the % of metabolized precursor which is converted to leukotrienes or PGD2 is remarkably similar. However, under conditions of IgE-Anti IgE challenge the predominant conversion of arachidonic acid occurs to PGD2, LTB4 is almost negligible and LTD4 and E4 together represent less than 30% of the oxidative products of arachidonic acid. Whether PGD2 and leukotrienes derive from the same or different subset of cells is unresolved.


Behavioral effects after intrathecal administration of cholinergic receptor agonists in the rat.
Behavioral effects of nicotine and cytisine, and the cholinesterase inhibitors physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (THA), administered intrathecally (IT) at the lumbar level in the rat have been evaluated. Antinociceptive dose relationships were established using the tail immersion test. Total activity, locomotion and rearing were also measured in computerized test boxes. The nicotinic receptor antagonist, mecamylamine, and the muscarinic receptor antagonist, atropine, were used to study the selectivity of the effects. Physostigmine and THA significantly decreased total activity, locomotion and rearing as compared to control animals. The motor effects of physostigmine were completely antagonized only partly. Mecamylamine had no antagonistic effect. Nicotine did not affect any activity parameter. Cytisin reduced total activity and locomotion 1-6 min after dose. IT physostigmine, 15 micrograms, increased tail immersion latency for 30 min. No significant increase in response latency in this test was observed after the IT administration of nicotine or THA, whereas cytisine elicited a small increase. The IT administration of THA, nicotine and cytisine was also associated with gnawing, vocalization and hyperactivity and in the case of THA, diarrhoea. These effects were blocked by mecamylamine. Physostigmine antinociception as well as the behavioral effects including total activity, locomotion and rearing caused by physostigmine and by THA are most probably due to an action on spinal muscarinic receptors. Nicotinic receptors do not seem to be involved in spinal antinociception. Some aversive behavioral effects caused by the IT administration of nicotinic receptor agonists could, however, be attenuated by the spinal administration of the antagonist mecamylamine, which may indicate the involvement of nicotinic receptors in afferent sensory transmission.


Short-term effect of foot-and-mouth disease (FMD) vaccination on the milk yield in the Deoni and crossbred cows.
Biannual vaccination of the cattle with inactivated foot-and-mouth disease (FMD) vaccine is the control strategy in endemic countries. Reduction in the milk yield is one of the main reasons for poor compliance of the cattle owners to FMD vaccination. As it can adversely affect the herd immunity, the present study aimed to quantify the losses in the milk yield post-FMD vaccination. Retrospective data on the milk yield (kg) recordings, days in milk, parity, and age at vaccination of the Deoni and crossbred cows were collected from 10 days before (-10) to 10 days after (+10) FMD vaccination (dpv). Days in milk were categorized into three stages of lactation for Deoni and crossbred cows. Age (month) was categorized into four classes. Least squares means of the milk yield were generated after adjusting for year, age, parity, and stage of lactation. Based on exploratory data analysis, the corrected milk yield records from -2 to +2 dpv for 5 years comprising 614 data points on Deoni cows (n=54) and 488 data points on crossbred cows (n=55) were used for the final analysis. Because of the correlated errors on the corrected milk yield, linear mixed model ANOVA was done by fitting dpv as fixed effect and cow as random effect, and the results revealed the effect of dpv was non-significant (P>0.05) in either breed. With respect to dpv 0, a marginal reduction of 90 g in the corrected milk yield in the Deoni cow was recorded on dpv 1, while the reduction was about 360 g on dpv 0 as compared dpv -1 in the crossbred cow. It was concluded that FMD vaccination caused a transient non-significant reduction in the milk yield in the Deoni and crossbred cows.


Simple and rapid radiosynthesis of N-18F-labeled glutamic acid as a hepatocellular carcinoma PET tracer.
We have reported that N-(2-18F-fluoropropionyl)-L-glutamate (18F-FPGLU) showed good tumor-to-background contrast and 18F-FPGLU was prepared via complex multi-step reaction sequence; here, it is synthesized by a facile two-step reaction sequence. The objectives of this study are to synthesize 18F-FPGLU via a two-step reaction sequence and to evaluate the value of 18F-FPGLU in nude mice bearing human hepatocellular carcinoma SMCC-7721 (HCC SMCC-7721). 18F-FPGLU was synthetized from the precursor (2S)-dimethyl 2-(2-bromopropanamido)pentanedioate via the two-step on-column hydrolysis using a modified commercial FDG synthesizer. To investigate the transport mechanism of 18F-FPGLU, we conducted a series of competitive inhibition experiments on HCC SMCC-7721 cells in the absence or presence of Na+ and various types of inhibitors. Small-animal PET-CT imaging was performed on tumor-bearing nude mice using 18F-FPGLU and 2-18F-2-deoxy-D-glucose (18F-FDG). The radiochemical yield of 18F-FPGLU was up to 15±5% (EOS, n=10) in 35min with the two-step procedure and the radiochemical purity was higher than 95% with a specific activity of 30-40GBq/μmol. In vitro cell experiments show that 18F-FPGLU is primarily transported through the Na+-dependent system XAG- and Na+-independent system XC-. PET imaging in a tumor model indicates that 18F-FPGLU may be superior to 18F-FDG for hepatocellular carcinoma (HCC) imaging. An optimized route to prepare 18F-FPGLU was developed and 18F-FPGLU was synthetized from the precursor ((2S)-dimethyl 2-(2-bromopropanamido)pentanedioate) via the two-step on-column hydrolysis. 18F-FPGLU was a potential novel PET tracer for HCC imaging.


Nanostructured AgBr loaded TiO2: An efficient sunlight active photocatalyst for degradation of Reactive Red 120.
The AgBr loaded TiO2 catalyst was prepared by a feasible approach with AgBr and tetraisopropyl orthotitanate and characterized by BET surface area measurement, diffuse reflectance spectra (DRS), scanning electron microscope (SEM), energy dispersive spectra (EDS), X-ray diffraction (XRD), transmission electron microscope (TEM) and atomic force microscope (AFM) analysis. The results of characterization reveal that AgBr loaded TiO2 has a nanostructure. Formation of the nanostructure in AgBr loaded TiO2 results in substantial shifting of the absorption edge of TiO2 to red and enhancement of visible light absorption. Electrochemical impedance spectroscopy measurements reveal that AgBr loaded TiO2 has a higher photoconductivity than prepared TiO2 due to higher separation efficiency of electron-hole pairs. Cyclic voltammetric studies reveal enhanced conductivity in AgBr loaded TiO2, which causes an increase in its photocatalytic activity. AgBr loaded TiO2 exhibited a higher photocatalytic activity than TiO2-P25 and prepared TiO2 in the photodegradation of Reactive Red 120 (RR 120).


Bioaugmentation on humification during co-composting of corn straw and biogas slurry.
In order to increase the nutrients and humic acid (HA) contents of corn straw (CS) derived organic fertilizer and recover resources from biogas slurry (BS) simultaneously, the co-composting of CS and BS was carried out with the addition of biochar and microbial agents including lignocellulose degrading and ammonia assimilating bacteria. The results showed that 1 kg straw could treat 2.5 L BS by recovering nutrients and bio-heat introduced evaporation. The bioaugmentation strengthened both the polyphenol and Maillard humification pathways by promoting the polycondensation of precursors (reducing sugars, polyphenols, and amino acids). HA obtained in the microbial-enhanced group (20.83 g/kg), biochar-enhanced group (19.34 g/kg), and combined-enhanced group (21.66 g/kg) were significantly higher than that in the control group (16.26 g/kg). The bioaugmentation achieved directional humification and reduced the loss of C and N by promoting the CN formation of HA. The humified co-compost had nutrient slow-release effect in agricultural production.


The binding of tyrosine hydroxylase to negatively charged lipid bilayers involves the N-terminal region of the enzyme.
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of catecholamines. We have studied the association of recombinant human TH with model membranes by using either liposomes or silica gel beads coated with single phospholipid bilayers (TRANSIL). The use of TRANSIL beads has allowed the determination of apparent dissociation constants (Kd) for the binding of the enzyme to negatively charged bilayers (Kd=230-380 microM, at pH 6.0-7.0). Binding to the bilayers is accompanied by a decrease in enzyme activity. Proteolysed forms of the enzyme show decreased binding affinity and two putative amphipathic N-terminal alpha-helices are proposed to be involved in membrane binding. As seen by circular dichroism, binding to the bilayer does not seem to induce significant changes on the secondary structure content of the enzyme, but alpha-helical structures appear to be stabilized against thermal denaturation in the membrane-bound state. Thus, amphitropism, a mechanism that regulates the function of peripheral proteins by weak binding to membrane lipids, may add to the factors that regulate both the activity and the stability of TH.


Magnetic properties of terrestrial moss (Hylocomium splendens) along a north-south profile crossing the city of Oslo, Norway.
Magnetic measurements are routinely used in geophysics and environmental sciences to obtain detailed information about concentrations and quality of iron minerals. Here, magnetic properties of 38 terrestrial moss samples (Hylocomium splendens) from a ~120km south-north transect through Oslo are studied to gain better insight into the nature and origin of their Fe fraction. The concentration-dependent quantities, magnetic susceptibility k, and isothermal remanent magnetization IRM(700mT) after weight normalization have significantly higher values in urban regions, and parallel the previously found concentration signals of 16 out of 29 chemical elements (Ag, Al, Au, Bi, Cd, Co, Cr, Cu, Fe, Mo, Ni, Pb, Pt, Sb, Ti, and Zn). Because there is no evidence that Hylocomium splendens produces biogenic magnetic remanence carriers, the increase in IRM is attributed to adsorption of dust containing iron oxide minerals. This agrees with previous observations that Ti concentrations, related to local mineral dust, have a peak in Oslo, and at sites close to known dust sources. Scanning electron microscopy images also showed an increased density of minerogenic particles on the moss surfaces in the urban samples, which qualitatively supports the dust based interpretation. The concentration-independent ratios k/Fe and IRM(700mT)/Fe also have extreme values in the urban parts of the transect. This indicates that more of the total iron occurs in magnetically ordered form and in remanence carriers, interpreted as adsorbed dust. In addition, purely magnetic ratios displayed differences in urban and rural areas, indicating that their magnetic dust particles are inherently of different types. Therefore, it is likely that anthropogenic dust sources contribute considerably to the magnetic signal. Urban dust enhancement is not exclusively due to increased erosion, leading to higher loads of geogenic dust in the atmosphere, but also to specific anthropogenic sources from combustion, corrosion, or other synthetic emitters.


Effects of Partial Replacement of Conventional with Alternative Feeds on Nutrient Intake, Digestibility, Milk Yield and Composition of Awassi Ewes and Lambs.
Two experiments were done to assess the effects of alternative feeds (AF; dried distillers grains with solubles, carob pods, olive cake, and bread by-product) on lactating performance of ewes and digestibility and nitrogen (N) retention of lambs. Diets were: no AF (CON); 200 g/kg AF (AF200); and 400 g/kg AF (AF400). In Experiment 1, 27 Awassi ewes were randomly distributed into three groups, and each was fed one of the diets described before (9 ewes/diet). Evaluation of milk composition and yield was performed at the beginning of the experiment and on days 18, 36, and 54. In Experiment 2, 18 Awassi lambs were allocated to the same diets (6 ewe lambs/diet) during a 21-day trial (14 days housed individually in shaded pens and 7 days in metabolic cages). In Experiment 1, no differences in body weight (BW) of the ewes and their lambs were detected. With the exception of neutral detergent fiber intake, which was lower in the AF-containing diets compared with CON, dry matter, crude protein, and acid detergent fiber intake were not affected by dietary treatment. Milk yield and composition was comparable among diets, and the cost of milk production was lower in AF compared to CON diet. In Experiment 2, nutrient digestibility and N retention were not affected by the diet. Results showed the possibility of including different AF in ewe and lamb diets to mitigate production cost without negatively affecting intake, milk yield, and composition, digestibility, and animal welfare and health.


Monomer leakage from polymerizing acrylic bone cement. An in vitro study on the influence of speed and duration of mixing, cement volume and surface area.
An in vitro study was dthesigned to measure the effects of variable cement volumes and modified mixing techniques on the monomer leakage after simulated implantation. The cement volume as such was found to be an irrelevant parameter for calculations of the monomer loss from bone cement. The leakage was directly related to the surface area of the cement. Variations in the thickness of the cement mantle from 1 to 5 mm did not affect the leakage. Late cement insertion should reduce the total monomer leakage into the tissues. It is doubtful whether an increased stirring speed during mixing reduces the monomer leakage after implantation.


Use of concept map as a reinforcement tool in undergraduate curriculum: An analytical study.
Ever-expanding medical literature demands successful amalgamation of huge information and clinical practice for budding doctors. This study aimed to find the effectiveness of the concept map, a novel method of teaching to improve performance among undergraduate pharmacology students. The undergraduate medical students pursuing pharmacology in 2017-18 in our institute was divided into two groups after stratified randomization based on the last semester grades. After a session of didactic lecture on 'Drugs affecting Calcium Metabolism' and a pre-test, one group was taught using traditional tutorial methods and another group using the concept map method. Finally, a post-test was taken and feedback received from the intervention group. A significant improvement of student performance was found in both groups using validated questionnaire from pre-test to post-test. There was no significant difference in the percentage of improvement between the groups. This finding was consistent in both Low scorers and High scorers of the previous semester examination. Students found the new method better in terms of understanding the concept and interactivity. Concept mapping encourages the students to actively participate and get a comprehensive and accurate overview of the topic, but the improvement in performance in the test was not evident.


Verifynow P2Y12 PRU-Guided Modification of Clopidogrel for Prevention of Recurrent Ischemic Stroke: A Real-World Prospective Cohort Study.
Clopidogrel resistance causes recurrent stroke. However, outcomes of modified antiplatelet medications to prevent recurrent ischemic stroke are not well known. Patients who received clopidogrel with and without modification as initial treatment for stroke were recruited and compared. The primary outcome was ischemic stroke and myocardial infarction at the 1-year follow-up. The secondary outcome was bleeding complications. Overall, 206 patients treated with clopidogrel were enrolled and were divided into the modification (n = 39) and no modification (n = 167) groups. There was a significant difference in the incidence of severe cerebral arterial stenosis between the two groups (modification group, 16/39, 41.03%; no modification group, 36/167, 21.56%, P = 0.012) at baseline. The loss to follow-up rate was 12.14% (25/206). After adjustment for severe cerebral artery stenosis, antiplatelet modification based on the platelet reactivity unit (PRU) value significantly improved in the per protocol set (odds ratio 0.142, 95% confidential interval 0.022-0.898, P = 0.038). The area under the curve of the different PRU cutoff values were 0.630, 0.605, and 0.591 (P = 0.016, 0.051, and 0.092) for PRU 190, 208, and 235, respectively. Verifynow P2Y12 PRU-guided modification of clopidogrel for ischemic stroke significantly improved or prevented recurrence at the 1-year follow-up. Our findings suggest that clopidogrel therapy based on the PRU cutoff value of 190 should be considered to improve outcomes. ClinicalTrials.gov NCT02618265 (December 1, 2015).


The perspectives of adolescents conceived using surrogacy, egg or sperm donation.
What are the perspectives of adolescents conceived using surrogacy, egg or sperm donation regarding their conception and the third party involved? The majority of adolescents described feeling indifferent about their conception, and yet simultaneously reported an interest in the third party involved, or were in contact with them. There is an assumption that children conceived through reproductive donation will feel negatively about their origins in adolescence. However, little is known about the views of adolescents who have been conceived through different types of reproductive donation. Forty-four adolescents, all of whom had been told about their conception in childhood, participated in a semi-structured interview as part of the sixth phase of a longitudinal, multi-method, multi-informant study of assisted reproduction families in the UK. All adolescents were aged 14 years, had been conceived using surrogacy (n = 22), egg donation (n = 13) or sperm donation (n = 9) to heterosexual couples, and varied in terms of their information about, and contact with, the third party involved in their conception. Semi-structured interviews were conducted in participants' homes. Interviews were analysed qualitatively to determine adolescents' perceptions of their conception, and their thoughts and feelings about the surrogate or donor involved. Adolescents were found to feel positive (n = 7), indifferent (n = 32) or ambivalent (n = 5) about their conception. Amongst adolescents not in contact with the surrogate or donor, most were interested (n = 16) in the surrogate or donor, and others were ambivalent (n = 4), or not interested (n = 6) in them. Adolescents in contact with the surrogate or donor expressed positive (n = 14), ambivalent (n = 1) or negative (n = 1) feelings about them. Of 56 adolescents invited to take part in the study, 47 consented to take part, giving a response rate of 84%. It was not possible to obtain information from adolescents who do not know about their conception. The findings contradict the assumption that children conceived through reproductive donation will feel negatively about their origins in adolescence and suggest that it may be helpful to draw a distinction between adolescents' feelings about their conception in general, and their feelings about the surrogate or donor in particular. This study was funded by the Wellcome Trust [097857/Z/11/Z]. The authors have no conflicts of interest to declare.


On the edge: ward-rounds in a South African psychiatric emergency department.
Psychiatry, like other institutions in South Africa, is affected by issues of race. An examination of ward-rounds in a South African psychiatric emergency department, however, revealed that as important to an understanding of this unit is the recognition of the place of psychiatry in biomedicine. A key feature affecting staff in the unit was the fact of psychiatry's marginality relative to general medicine. Race was seldom and obliquely discussed, but played an important contributory role. Work towards the transformation of psychiatric care in a democratic South Africa must consider the institutional level as well as the more obvious question of racial inequality.


Comparison of Generic Drug Reviews for Marketing Authorization between Japan and Canada.
Generic drugs are assuming an increasingly important role in sustaining modern healthcare systems, as the cost of healthcare, including drug usage, is gradually expanding around the world. To date, published articles comparing generic drug reviews between different countries are scarce. The objective of this study was to examine generic drug reviews in Japan and Canada. We surveyed generic drug reviews from Japan and Canada and compared the following points: general matter (application types, type of partial change or Supplement to an Abbreviated New Drug Submission, application and approval numbers, review period, application format, review report, responsibility for review), bioequivalence studies for solid oral dosage forms, and bioequivalence guidelines, guidance, or basic principles regarding various dosage forms. This survey described the many similarities and differences in generic drug reviews between the two countries and points that should be improved to promote better generic drug reviews. In particular, regulations for the definition of the same or different active pharmaceutical ingredients (APIs) are similar for both authorities. The results clarified the future challenges of generic drug reviews, and the differences highlighted by this survey will be important considerations for the future. This is the first article to present and discuss the details of generic drug reviews between Japan and Canada.


[Experimental polymyositis induced by the injection of acetylcholine receptors. Study of the lesions in rats and guinea pigs].
The injection of acetylcholine receptors, from the Electrophorus electricus induces in Guinea Pigs and Rats an experimental disease, which is characterized by the appearance of antibodies to sarcolemma and by massive histological alterations of the degenerative type, similar to those observed in clinical polymyositis.


Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital.
Intravenous immunoglobulin G (IVIG) is a blood product from polyvalent and polyclonal immunoglobulin G. It covers a broad range of indications as immunomodulator or replacement therapy. In addition, although it is considered a safe therapy, the incidence of adverse reactions reported in the bibliography ranges from 1 % to 81 %. The objective of this study was to assess IVIG use and describe related adverse events in a tertiary care children's hospital. This was a pharmacoepidemiological, observational, and prospective study. Patients receiving IVIG for 7 months in 6 areas of a tertiary care children's hospital in the Autonomous City of Buenos Aires were assessed. The analysis unit was each IVIG infusion, and the main variable was the presence of adverse reactions. A total of 305 infusions in 111 patients were analyzed. In 81.6 % of cases, the indication was for replacement. The maximum dose was 1 g/kg. In 99.6 % of infusions, some type of premedication was indicated; diphenhydramine was the most common drug, with varying dosages. A total of 12 adverse reactions (3.9 % of infusions) were recorded; 3 were severe: aseptic meningitis (2 cases) and seizures (1 case). All resolved to normal. The rate of IVIG adverse reactions in our setting was low; most reactions were mild and immediate and resolved favorably in all patients.


Maintained activity of cells in the three shrew's optic tract.
The maintained activity of different types of ganglion cells in the tree shrew's retina has been investigated in darkness and different adaptation luminances, with particular reference to on-centre sustained and transient cells. The firing rate of on-centre sustained cells rises with increasing luminance up to 5.10(-2) W/m2 (human photopic equivalent 5.10(4) cd/m2) whereas, for on-centre transient cells no simple relationship between luminance and activity could be found. The ratio of mean and standard deviation (regularity) of the interval length of sustained cells increases with light intensity, while in most transient cells a constant ratio is observed. Various kinds of interval histograms are observed for sustained units: exponential, gamma, bimodal and other types. Transient cells tend to fire in bursts with correspondent biomodal interval histograms. The first order serial correlation coefficient is positive for the majority of sustained cells and negative for most transient cells. It is argued that the final statistical properties of the maintained activity of retinal ganglion cells are mainly determined by the retinal circuitry between photoreceptors and ganglion cells.


Chromosomal-level genome assembly of the semi-dwarf rice Taichung Native 1, an initiator of Green Revolution.
Here we report the 409.5 Mb chromosome-level assembly of the first bred semi-dwarf rice, the Taichung Native 1 (TN1), which served as the template for the development of the Green Revolution (GR) cultivar IR8 "miracle rice". We sequenced the TN1 genome utilizing multiple platforms and produced PacBio long reads, Illumina paired-end reads, Illumina mate-pair reads and 10x Genomics linked reads. We used a hybrid approach to assemble the 226× coverage of sequences by a combination of de novo and reference-guided approaches. The assembled TN1 genome has an N50 scaffold size of 33.1 Mb with the longest measuring 45.5 Mb. We annotated 37,526 genes, in which 24,102 (64.23%) were assigned Blast2GO annotations. The genome has 4672 or 95.4% complete BUSCOs and a repeat content of 51.52%. We developed our own method of creating a GR pangenome using the orthologous relationships of the proteins of TN1, IR8, MH63 and IR64, identifying 16,999 core orthologue groups of Green Revolution. From the pangenome, we identified a set of shared and unique gene ontology terms for the accessory clusters, characterizing TN1, IR8, MH63 and IR64. This TN1 genome assembly and GR pangenome will be a resource for new genomic discoveries about Green Revolution, and for improving the disease and insect resistances and the yield of rice.


The Personal Nutrition Planner: a 5-week, computer-tailored intervention for women.
To conduct a dietary intervention using the Personal Nutrition Planner (PNP), an on-line nutrition intervention tool. Randomized controlled trial with pretest, posttest, and 2-month follow-up self-report assessments. Web/on-line. Female university staff (n = 307; 59.1% Caucasian) recruited via e-mail. Retention rate was 85.0% (118 treatment; 143 comparison). PNP on-line produces individualized nutrition feedback based on initial on-line assessment. Intervention lasted 5 weeks and included weekly e-mail reminders. Dietary intake frequencies, weight loss, opinions regarding intervention. Repeated-measures analysis of variance to determine intervention effects on dietary intake and weight loss (P < .05). Relative to the comparison group who received no program, the treatment group increased dairy intake frequency across the 3 assessments (F(2,304) = 3.15; P < .05). Among participants who wanted to lose weight, weight loss in the treatment group was significantly higher than that of the comparison group from pretest to posttest (F(1,92) = 4.50; P < .05). On a scale of 1-5, mean ratings of the PNP program characteristics ranged from 3-4. PNP produced significant increases in dairy intake and decreases in weight. Further revisions will tailor PNP to better fit individuals' dietary goals and increase motivation.


Abscisic acid in soil facilitates community succession in three forests in China.
Plants release secondary metabolites into the soil that change the chemical environment around them. Exogenous abscisic acid (ABA) is an important allelochemical whose role in successional trajectories has not been examined. We hypothesized that ABA can accumulate in the soil through successional processes and have an influence on forest dynamics. To this end, we investigated the distribution of ABA in forest communities from early to late successional stages and the response of dominant species to the gradient of ABA concentrations in three types of forests from northern to southern China. Concentrations of ABA in the soils of three forest types increased from early to late successional stages. Pioneer species' litters had the lowest ABA content, and their seed germination and seedling early growth were the most sensitive to the inhibitory effect of ABA. Mid- and late-successional species had a much higher ABA content in fallen leaves than pioneer species, and their seed germination and seedling early growth were inhibited by higher concentrations of ABA than pioneers. Late-successional species showed little response to the highest ABA concentration, possibly due to their large seed size. The results suggest that ABA accumulates in the soil as community succession proceeds. Sensitivity to ABA in the early stages, associated with other characteristics, may result in pioneer species losing their advantage in competition with late-successional species in an increasingly high ABA concentration environment, and being replaced by ABA-tolerant, late-successional species.


NAPG mutation in family members with hereditary hemorrhagic telangiectasia in China.
Hereditary hemorrhagic telangiectasia (HHT) is a disease characterized by arteriovenous malformations in the skin and mucous membranes. We enrolled a large pedigree comprising 32 living members, and screened for mutations responsible for HHT. We performed whole-exome sequencing to identify novel mutations in the pedigree after excluding three previously reported HHT-related genes using Sanger sequencing. We then performed in silico functional analysis of candidate mutations that were obtained using a variant filtering strategy to identify mutations responsible for HHT. After screening the HHT-related genes, activin A receptor-like type 1 (ACVRL1), endoglin (ENG), and SMAD family member 4 (SMAD4), we did not detect any co-segregated mutations in this pedigree. Whole-exome sequencing analysis of 7 members and Sanger sequencing analysis of 16 additional members identified a mutation (c.784A > G) in the NSF attachment protein gamma (NAPG) gene that co-segregated with the disease. Functional prediction showed that the mutation was deleterious and might change the conformational stability of the NAPG protein. NAPG c.784A > G may potentially lead to HHT. These results expand the current understanding of the genetic contributions to HHT pathogenesis.


Degradation of chloramphenicol by Ti/PbO2-La anodes and alteration in bacterial community and antibiotics resistance genes.
Antibiotics accumulation in the environment has given rise to multi-drug resistant 'superbugs' and antibiotics resistence genes (ARGs). Chloramphenicol (CAP), a kind of widely used antibiotics, was chosen as the model compound to investigate its degradation during electrochemical treatment process. The prepared Ti/PbO2-La electrodes had a denser surface and a more complete PbO2 crystal structure than Ti/PbO2 electrode. The doping of La increased the onset potential and the overpotential, increased the current value of the oxidation peak and the reduction peak, reduced the impedance, and increased the lifetime. The reactions CAP degradation and TOC removal on Ti/PbO2-La electrode was both primary kinetic reactions. CAP degradation rate increased with current density, and TOC obtained the highest removal at current density of 25 mA cm-2. The electrolyte concentration had a small effect in the range of 0.050-0.150 mol L-1. The effects under acidic and neutral conditions were better than under alkaline conditions. CAP was mainly directly oxidized at the electrode surface and indirect oxidation also took place via generated ·OH and SO4·-. 15 intermediates and 2 degradation pathways have been postulated. The entry of CAP and CAP intermediates into the environment caused the alteration in bacterial community and ARGs, while complete degradation products had little effect on them. Redundancy analysis showed that intI1 was the dominant factor affecting ARGs, and Actinobacteria and Patescibacteria were the main factors affecting the abundances of ARGs in the microbial community.


Preparation of molecularly imprinted polymers for the selective recognition of the bioactive polyphenol, (E)-resveratrol.
(E)-Resveratrol imprinted polymers have been rationally designed with the aid of molecular modelling and NMR spectroscopic titration techniques to determine the optimal ratio of the template to functional monomer for polymer formation. Based on this approach, (E)-resveratrol imprinted polymers were prepared via non-covalent self-assembly with the functional monomer 4-vinylpyridine (4VP) in a 1:3 molar ratio. Polymerisation in the presence of a cross-linker resulted in rigid block copolymers that had selective capacities towards (E)-resveratrol (e.g. 14 μmol/g) when compared to the non-imprinted reference polymer. The selectivity of these MIPs was also examined using several structurally related polyphenolic compounds to determine the influence of polyphenolic hydroxyl number and position on binding and molecular recognition.


Patients with genital HPV lesion, as well as partners, usually present higher psychological stress, than the actual medical consequences of the lesion. Follow-up of these patients should be based on education and counseling. HPV molecular tests are not recommended as a follow-up test, or for screening partners. Development and implementation of protocols, by the centers or units, that follow these patients, are recommended.


The Relationship Between Organizational Stress Levels and Patient Safety Attitudes in Operating Room Staff.
The aim of this study was to determine the relationship between organizational stress levels and patient safety attitudes in operating room (OR) staff. The study was conducted using a descriptive correlational research method. The study sample was made up of 164 OR staff (38 surgeons, 32 anesthetists, 46 nurses, and 48 anesthetic technicians/OR support staff) at a university hospital. The data were collected with a Personal Information Form, the Organizational Stress Scale, and the Safety Attitudes Questionnaire-Operating Room (SAQ-OR) version. The most important factor affecting organizational stress was sources of stress related to financial means, whereas the most important factor affecting patient safety attitudes was teamwork climate. Sources of stress related to the nature of the work performed and to management were higher in surgeons; mean scores in the subdimension of stress sources related to financial means were higher in nurses; whereas, total scores in the SAQ-OR version and mean scores in the subdimensions of perceptions of management, working conditions, and stress recognition were higher in anesthetic technicians/OR support staff. A statistically significant weak negative correlation was found between the Organizational Stress Scale and the SAQ-OR version. In this study, as organizational stress levels of OR staff increased, patient safety attitudes were negatively affected. To improve patient safety attitudes of OR staff, it is recommended that work environments that reduce organizational stress are created.


High Throughput Identification of the Potential Antioxidant Peptides in Ophiocordyceps sinensis.
Ophiocordyceps sinensis, an ascomycete caterpillar fungus, has been used as a Traditional Chinese Medicine owing to its bioactive properties. However, until now the bio-active peptides have not been identified in this fungus. Here, the raw RNA sequences of three crucial growth stages of the artificially cultivated O. sinensis and the wild-grown mature fruit-body were aligned to the genome of O. sinensis. Both homology-based prediction and de novo-based prediction methods were used to identify 8541 putative antioxidant peptides (pAOPs). The expression profiles of the cultivated mature fruiting body were similar to those found in the wild specimens. The differential expression of 1008 pAOPs matched genes had the highest difference between ST and MF, suggesting that the pAOPs were primarily induced and play important roles in the process of the fruit-body maturation. Gene ontology analysis showed that most of pAOPs matched genes were enriched in terms of 'cell redox homeostasis', 'response to oxidative stresses', 'catalase activity', and ' integral component of cell membrane'. A total of 1655 pAOPs was identified in our protein-seqs, and some crucial pAOPs were selected, including catalase, peroxiredoxin, and SOD [Cu-Zn]. Our findings offer the first identification of the active peptide ingredients in O. sinensis, facilitating the discovery of anti-infectious bio-activity and the understanding of the roles of AOPs in fungal pathogenicity and the high-altitude adaptation in this medicinal fungus.


Introduction: Sea changes in reproductive physiology.
Advances in medically assisted reproduction led to new understanding of many key facets of reproductive physiology often upending prior dogma. This series of reviews covers unexpected and thought-provoking advances in the hypothalamus and pituitary, folliculogenesis, ovulatory triggering, what triggering misses physiologically, control of follicular growth and in vitro activation, and the relationship between male genitourinary birth defects and male infertility.


The (in)dependency of blood and sweat sodium, chloride, potassium, ammonia, lactate and glucose concentrations during submaximal exercise.
To reduce the need for invasive and expensive measures of human biomarkers, sweat is becoming increasingly popular in use as an alternative to blood. Therefore, the (in)dependency of blood and sweat composition has to be explored. In an environmental chamber (33 °C, 65% relative humidity; RH), 12 participants completed three subsequent 20-min cycling stages to elicit three different local sweat rates (LSR) while aiming to limit changes in blood composition: at 60% of their maximum heart rate (HRmax), 70% HRmax and 80% HRmax, with 5 min of seated-rest in between. Sweat was collected from the arm and back during each stage and post-exercise. Blood was drawn from a superficial antecubital vein in the middle of each stage. Concentrations of sodium, chloride, potassium, ammonia, lactate and glucose were determined in blood plasma and sweat. With increasing exercise intensity, LSR, sweat sodium, chloride and glucose concentrations increased (P ≤ 0.026), while simultaneously limited changes in blood composition were elicited for these components (P ≥ 0.093). Sweat potassium, lactate and ammonia concentrations decreased (P ≤ 0.006), while blood potassium decreased (P = 0.003), and blood ammonia and lactate concentrations increased with higher exercise intensities (P = 0.005; P = 0.007, respectively). The vast majority of correlations between blood and sweat parameters were non-significant (P > 0.05), with few exceptions. The data suggest that sweat composition is at least partly independent of blood composition. This has important consequences when targeting sweat as non-invasive alternative for blood measurements.


Low body mass is associated with reduced left ventricular mass in Chinese elderly with severe COPD.
There is limited information on the association of body mass index (BMI) with left ventricular (LV) remodeling corresponding to severity of reduced lung function in patients with chronic obstructive pulmonary disease (COPD). Therefore, we investigated whether BMI is associated with cardiac atrial and ventricular dimensions according to severity of lung functional impairment in Chinese COPD elderly. A total of 563 hospitalized COPD patients with lung function impairment and 184 patients with non-COPD (aged 65-92 years) were collected retrospectively in a cross-sectional study in a university affiliated tertiary hospital in China. BMI and cardiac echocardiographic parameters were compared according to severity of lung functional impairment in COPD patients. BMI was 22.9 ± 3.9 kg/m2 in COPD patients, 24.0 ± 4.1 kg/m2 in non-COPD patients respectively. Reduced BMI, LV mass index, LV wall thickness and left atrial diameter, and dilated right ventricle (RV) existed in COPD patients with severe lung dysfunction as compared the COPD patients with mild to moderate lung functional reduction and non-COPD patients (P < 0.05), while there were no differences in BMI and echocardiographic parameters between the COPD patients with mild to moderate lung functional decline and non-COPD patients (P > 0.05). Logistic regression analysis showed that low BMI (BMI < 18.5 kg/m2) was correlated with reduced LV mass and wall thickness, dilated RV and reduced lung function in the COPD patients with severe lung dysfunction. In conclusion, this study demonstrates that lower BMI is associated not only with dilated RV and impaired pulmonary function, but also it is related to reduced LV mass in Asian COPD elderly with severe lung dysfunction.


Development of subsequent bloodstream infection in patients with positive Hickman catheter blood cultures and negative peripheral blood cultures.
There are limited data on the incidence of subsequent bloodstream infection (BSI) and the effect of systemic antibiotics in patients who had positive catheter-drawn blood cultures (CBC) and negative peripheral blood cultures (PBC). We retrospectively reviewed all paired blood cultures from patients with Hickman catheter in the hematology-oncology ward between January 1997 and December 2008. There were 112 episodes with positive CBC and negative PBC. Nine episodes (8.0%; 95% CI, 3.0-13.1%) led to subsequent BSI within 28 days. Subsequent BSI developed in 6 of 31 episodes (19%) where empiric antibiotics were inappropriate but in 3 of 81 episodes (4%) where empiric antibiotics were appropriate (P = 0.01). Subsequent candidemia (50%, 2 of 4) was more common than subsequent bacteremia (6%, 7 of 108) (P = 0.03). In conclusion, for patients with positive CBC and negative PBC, the overall incidence of subsequent BSI was 8.0%, and inappropriate empiric antibiotics was associated with subsequent BSI.


Effectiveness of two intramuscular combined vaccines for the control of Mycoplasma hyopneumoniae and porcine circovirus type 2 in growing pigs: a randomized field trial.
Mycoplasma hyopneumoniae and Porcine circovirus type 2 are two economically important pathogens affecting growing pigs. Control and prevention of both diseases can be accomplished by vaccination, together with biosecurity and good management practices. Many commercial vaccines are available. The aim of this study was to assess the efficacy of Hyogen® and Circovac® administered mixed at weaning and to compare this protocol with a competitor ready-to-use (RTU) vaccine. A randomised field trial was designed in a commercial farrow-to-finish farm located in France. A total of 641 pigs born from 54 different sows were included in this study. Piglets at weaning were allocated into three groups: the first one vaccinated with Hyogen® and Circovac® combined (group A), the second one vaccinated with a competitor RTU vaccine (group B) and the last one unvaccinated. Only minor local reactions for both vaccination groups could be observed which revealed a good safety of both protocols. Both vaccination schemes in this trial didn't improve wean-to-slaughter growth performances but significantly reduced lung lesions, lung fissures and pleurisy at slaughter, produced a seroconversion for both M. hyopneumoniae and PCV-2 and significantly reduced the PCV-2 viral load in blood. When we compared groups A and B, we observed no significant differences in growth performances, mortality, clinical signs, percentages of affected lungs at slaughter, lung fissures and pleurisy, and no difference in pathogens detection. However, two statistical differences were observed between both vaccines: the mean lung lesion score and the percentage of extensive lung lesions were lower in group A. This is consistent with lower M. hyopneumoniae loads in the lower respiratory tract in pigs from group A but this difference was not statistically significant. Results reported in this case study must be considered with caution since it was done in only one farm. In this trial, Hyogen® and Circovac® mixed together under field conditions offered a successful protection of growing pigs and significantly decreased the extension of lung lesions during a natural field challenge when compared with a competitor RTU vaccine.


Human A beta-amyloid and amyloid precursor protein accumulates in rat brain cells after cultured human leptomeningeal fibroblast implants.
Cultured human leptomeningeal fibroblasts grafted into rat frontal cortex were localized to the implant pocket and to adjacent host leptomeninges. Immunohistochemical studies using a panel of human-specific and domain-specific APP antibodies revealed that all grafted cells expressed both APP and A beta in situ. Remarkably, these antibodies also labeled rat pial and ependymal cells as well as reactive astrocytes adjacent to vessels. In addition, apical projections and cell bodies of many cortical pyramidal neurons contained human-specific APP immunoreactive material. Groups of subcortical neurons, particularly those of the amygdala, hippocampal formation and suprachiasmatic nuclei, were similarly labeled. The presence of human APP in host brains was confirmed by immunoblotting. Birefringent Congo Red staining was observed in the cortical neuropil and in leptomeningeal vessels. These data indicate that grafted leptomeningeal fibroblasts hyperexpress APP and A beta which can diffuse into parenchyma and be taken up by specific rat cells.


Production of Antigens for ELISA.
Immunologic assays such as ELISA allow detection of either virus antigens or the host's immune response to antigens associated with prior infections and offer a powerful means to approach understanding the epidemiology and epizootiology of these agents. However, the success of these assays is highly dependent on the production of high-quality materials both to establish the assays (i.e., antigen target for antibody) and to serve as controls for establishing assay parameters and sensitivity. Here we describe methods for preparing ebolavirus antigens suitable for use as either reagents or controls in a variety of ELISA formats. Considering work with filoviruses is typically restricted to maximum containment laboratories; thus, we also provide methods for inactivating and safety testing of these antigens for safe use in properly established field laboratories.


Context shapes: Efficient complementary shape matching for protein-protein docking.
We describe an efficient method for partial complementary shape matching for use in rigid protein-protein docking. The local shape features of a protein are represented using boolean data structures called Context Shapes. The relative orientations of the receptor and ligand surfaces are searched using precalculated lookup tables. Energetic quantities are derived from shape complementarity and buried surface area computations, using efficient boolean operations. Preliminary results indicate that our context shapes approach outperforms state-of-the-art geometric shape-based rigid-docking algorithms.


Implications of the World Health Organization definition of atypia on surgically treated functional and non-functional pituitary adenomas.
The World Health Organization (WHO) defines atypical pituitary adenomas as tumours with a MIB-1 labelling index ≥3%, p53 positivity and increased mitotic activity. Although a few reports have described the clinical and radiological correlates of atypia in pituitary adenomas, its impact on postoperative outcomes is not clearly defined. We reviewed preoperative and postoperative records of patients undergoing surgery for pituitary adenomas. Postoperative outcomes for functional adenomas (FPAs) were assessed according to contemporary definitions of remission and recurrence. For non-functional pituitary adenomas (NFPAs), extent of resection and disease progression were defined on the basis of postoperative magnetic resonance imaging. Of 394 patients included for analysis, 29 cases (7.4%) fulfilled criteria for atypia. Patients with atypical tumours were significantly younger than those with typical adenomas. Remission was possible in 47.4% of FPAs, and was unrelated to the presence of atypia. In NFPAs, local invasiveness was negatively associated with extent of resection (OR, 0.255; 95% CI, 0.086-0.753; p < 0.001). In 93 NFPAs followed postoperatively with serial imaging over a mean duration of 37.5 months, disease progression/recurrence was significantly associated with the presence of atypia (OR, 5.058; 95% CI, 1.273-20.098; p = 0.021) on multivariate analysis. Patients with atypical non-functional pituitary adenomas are at risk for postoperative recurrence and disease progression, suggesting a need for adjuvant therapy. However, only a small fraction of pituitary tumours demonstrate atypia, as defined by the WHO, limiting its clinical utility.


An inhibitory role for noradrenaline in the mouse vas deferens.
1 Noradrenaline (0.1-3.0 muM) inhibited the twitch responses to single pulse field stimulation of the isolated vas deferens of the mouse. The higher concentrations of noradrenaline (ca. 0.3-3.0 muM) were required to make the tissue contract.2 Phentolamine (10 muM) abolished the contractor response to higher concentrations of noradrenaline and antagonized the inhibitory effect of lower concentrations on the twitch response.3 Propranolol (10 muM) potentiated both the contractor and the inhibitory effect of noradrenaline on the twitch response.4 Isoprenaline (0.1-3.0 muM) and salbutamol (1.0-3.0 muM) both inhibited the twitch response. Their effects were antagonized by propranolol (10 muM), but not by practolol (10 muM).5 The effects of uptake(1) and uptake(2) blocking agents were determined. Cocaine (10 muM) reduced the size of the twitch response in 2 out of 4 experiments. Imipramine (0.18 muM) also reduced the size of the twitch, as did oestradiol (3.7 muM) and a combination of cocaine and oestradiol.6 Contractor responses to exogenous noradrenaline showed tachyphylaxis, but when this was not very marked, the response could be shown to be potentiated by uptake blocking agents.7 The inhibitory effect of noradrenaline on the twitch response was greatly potentiated by cocaine (10 muM) and much less so by oestradiol (3.7 muM).8 It is concluded that the transmitter responsible for the twitch response is either an unknown substance released from the sympathetic neurone, or noradrenaline acting upon a receptor with none of the characteristics of known alpha- or beta-adrenoceptors. In either case, noradrenaline can inhibit the output, probably by stimulation of presynaptic alpha-adrenoceptors.


Complement deficiencies.
Complement system plays a crucial role in innate imunity. Complement deficiencies are often associated with severe infections, usually meningoccocal, pneumococcal or caused by Haemophilus influenzae, or with autoimmune diseases, especially systemic lupus erythematodes. Inherited complement deficiencies are very rare although their prevalence in population may be underestimated due to lower availability of adequate laboratory testing. Acquired complement deficiencies accompany other underlying diseases and often are caused by increased consumption and only partial.


Assessment of the burden on caregivers of patients with mental disorders in Jeddah, Saudi Arabia.
Mental disorders are considered important public health problems not only to people with mental illness but also their caregivers. As is the case in many countries, the deinstitutionalization of mental health services in Saudi Arabia, has meant that informal caregivers are shouldering responsibilities for which they are not usually prepared; therefore, the current study was aimed at assessment of the burden on caregivers of people with mental illness. Through a cross-sectional design, a sample of the caregivers of people with mental illness (n = 377) was selected randomly from a psychiatric hospital in Jeddah. An Arabic version of the Involvement Evaluation Questionnaire (IEQ) was used for collection of data. The data were analyzed on the subscale scores and the 27 items in two ways. First, we used the summed scores for the subscales based on the Likert scale (0-4) for univariate and multivariate statistical analyses, as recommended. We also used parametric statistics (t-tests, one-way ANOVA) because the IEQ subscale scores were fairly normally distributed. Males constituted more than one-half of the participating caregivers (55%), with a mean age of 36.6, SD = 11.4 years. As reported by the caregivers, most of the patients were males (62.7%) with a mean age of 33.8, SD = 13.7 years and a range of 17-90 years old. The total mean IEQ burden score of the caregivers was 38.4, SD = 17.5. "Tension" was significantly prominent among younger caregivers aged ≤30 years. "Worrying" was significantly higher among caregivers living with their spouse and children and those living in families with relatively fewer members (<6 members). "Urging" was significantly higher among caregivers who are living with the patient in the same household and those who had been in close contact with the patient for 28 days in the four weeks prior to the study (13.4, SD = 6.8) p < 0.05. Meanwhile, "Urging" was also significantly higher among caregivers caring for mentally ill females (13.5, SD = 6.6) and those not receiving any kind of professional support (12.8, SD = 6.7). The overall burden and the subscale scores were highest among caregivers caring for a close relative such as a parent (44.1, SD = 17.6), son/daughter (39.1, SD = 12.9), sibling (37.1, SD = 18.6), or spouse (37.1, SD = 18.6) p < 0.05. Care for people with mental illness is burdensome for their caregivers, the magnitude of burden is potentially augmented by factors related to the patients and households. These factors should be considered when planning for preparing caregivers to cope with people with mental illness in Saudi Arabia.


Antioxidant activity of Nigella sativa Seeds Aqueous Extract and its use for cryopreservation of buffalo spermatozoa.
The free radical scavenging activity (RSA) of Nigella sativa extract and its efficiency for cryopreservation of buffalo spermatozoa was investigated. In experiment 1, Nigella sativa extract was prepared and evaluated for RSA using 2,2-diphenyl-1-picrylhydrazyl assay. The results showed increased pattern of RSA at 1%-5% of Nigella sativa extract. In experiment 2, buffalo semen from three bulls (24 ejaculates) was incubated at 0%, 0.1%, 0.3%, 0.5%, 1%, 1.5%, 2%, 3%, 4%, 5% and 6% extract to assess in vitro tolerability to Nigella sativa in terms of progressive motility (PM). Buffalo spermatozoa showed tolerance to all levels; rather, sperm PM was increased at 1%-4% extract. In experiment 3, semen from three bulls (24 ejaculates) was cryopreserved with 0%, 1%, 2%, 3%, 4% and 5% of Nigella sativa extract. Sperm PM and plasma membrane integrity (PMI) were evaluated after dilution and cooling, while PM, PMI, viability and DNA integrity were evaluated after thawing. Nigella sativa extract at 4% in extender improved (p < .05) post-dilution, post-cooling and post-thaw sperm quality. In conclusion, Nigella sativa extract at all concentrations (1%-6%) showed antioxidant activity and its supplementation at 4% in extender improved buffalo sperm quality at all stages of cryopreservation.


Major depressive disorder in a family study of obsessive-compulsive disorder with pediatric probands.
This study examined the comorbidity of obsessive-compulsive disorder (OCD) with major depressive disorder (MDD) in a family study of OCD with pediatric probands. This study assessed the lifetime prevalence of MDD in 141 first-degree relatives (FDR) and 452 second-degree relatives (SDR) of pediatric probands with OCD and healthy controls, and identified variables associated with MDD in case FDR. All available FDR were directly interviewed blind to proband status; parents were also interviewed to assess the family psychiatric history of FDR and SDR. Best-estimate diagnoses were made using all sources of information. Data were analyzed with logistic regression and robust Cox regression models. Lifetime MDD prevalence was significantly higher in case than in control FDR (30.4 versus 15.4%). Lifetime MDD prevalence was significantly higher in FDR of case probands with MDD than in FDR of case probands without MDD or control FDR (46.3 versus 19.7 versus 15.4%, respectively). MDD in case FDR was significantly associated with MDD in case probands and with age and OCD in those relatives. Lifetime MDD prevalence was similar in case and control SDR. However, lifetime MDD prevalence was significantly higher in SDR of case probands with MDD than in SDR of case probands without MDD or control SDR (31.9 versus 16.8 versus 15.4%, respectively). MDD prevalence was significantly higher in both FDR and SDR of case probands with MDD than in relatives of case probands without MDD or control relatives, suggesting that pediatric OCD comorbid with MDD is a complex familial syndrome.


Maternal protein restriction early in rat pregnancy alters brain development in the progeny.
We assessed the effects of a dietary protein restriction (5% vs. 20% casein in diet) initiated at conception and imposed during the first 2 weeks of rat gestation on postnatal brain development. At the end of the malnutrition period, protein-restricted animals exhibited significantly smaller fetal body weight and brain cortical thickness than controls. At birth and thereafter, body weight was normalized in the progeny. Similarly, brain weight and cytoarchitecture were normal in postnatal animals. In contrast, we observed, during the first 2 postnatal weeks, several abnormalities of brain development which affected all the studied areas for most of the studied parameters: (i) delayed astrocytogenesis as shown by a reduced GFAP staining; (ii) delayed production of hyaluronan in the extracellular matrix studied with binding of biotinylated hyaluronectin; (iii) abnormal neuronal differentiation as shown by reduced expression of MAP-5 and increased expression of MAP-1; (iv) abnormal synaptogenesis as shown by the increased expression of synaptophysin in the basal ganglia; (v) decreased programmed cell death. In adult prenatally protein-restricted animals, all the above parameters were normalized excepted MAP-1 labeling which remained high. In addition, we observed slight alterations of the ventilatory response to hypoxia in adult animals. The present study demonstrates that early protein malnutrition during embryonic development induces multiple, transient alterations of brain development. However, the almost complete normalization in adults of brain architecture and differentiation as well as our physiological data strongly suggest a remarkable plasticity of the developing brain following an early aggression.


High prevalence of multi-drug resistances and diversity of mobile genetic elements in Escherichia coli isolates from captive giant pandas.
The purpose of this study was to characterize the antimicrobial resistance produced by mobile genetic elements and integron gene cassettes in Escherichia coli isolated from the feces of captive giant pandas. We performed a standard disk diffusion antimicrobial susceptibility test with 84 E. coli isolates and further evaluated the mobile genetic elements and integron gene cassettes. The antimicrobial susceptibility test demonstrated that 43.37% (36/84) of the isolates showed multiple drug resistances. The E. coli isolates mainly showed resistance to aztreonam (86.90%, 73/84) and amoxicillin/clavulanic acid (80.95%, 68/84). The most frequently observed resistance patterns were ampicillin/amoxicillin-clavulanic acid (13.10%, n = 11), and doxycycline/amoxicillin-clavulanic acid (4.76%, n = 4). Further analyses detected 11 mobile genetic elements, of which merA (54/84, 64.30%) had the highest frequency. All isolates were negative for intI3, traA, tnpU, traF, tnp513, tnsA, ISkpn7, ISpa7, ISkpn6, and ISCR1. We further analyzed antimicrobial resistance-related integrons among 30 E. coli isolates (the 27 intI1-positive isolates and the 3 intI2-positive isolates); six gene cassette profiles (dfrA17+aadA5, aadA2, dfrA12+aadA2, dfrA1+aadA1, dfrA1, and aadA1) were identified in the 27 intI1-positive isolates, but not in the three intI2-positive ones. Our study sheds light on the prevalence of multiple drug resistances and the diversity of mobile genetic elements in E. coli isolates, and highlights the necessity to monitor antibiotic resistance in more E. coli strains from captive giant pandas.


The Arg64 allele of the beta 3-adrenoceptor gene but not the -3826G allele of the uncoupling protein 1 gene is associated with increased leptin levels in the Spanish population.
To determine whether there are variations in leptin levels according to the beta(3)-adrenoceptor (beta(3)-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826A-->G polymorphisms, given the regulatory role of catecholamines through the beta(3)-AR in leptin production and the previously reported association of the UCP1 -3826A-->G variant with obesity. A total of 160 men and 172 women randomly chosen from a nationwide population-based obesity cross-sectional survey in Spain were studied. Body mass index (BMI), waist-to-hip ratio (WHR), leptin, insulin, fasting and 2-hour post-glucose load glycemia, high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)-, and total cholesterol, and triglyceride plasma levels were measured. beta(3)-AR Trp64Arg and UCP1 -3826A-->G genotypes were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). UCP1 -3826G allele frequency was higher in men than in women (0.31 v 0.22, P = .015) and in obese women than in non-obese women (0.31 v 0.17, P = .008). Women carriers of the Arg64 or the alleles also showed higher leptin levels than noncarriers. Multiple linear regression analysis showed that the Arg64 allele is associated with higher leptin levels after the adjustment for gender, age, WHR, and the degree of glucose tolerance. In conclusion, the beta(3)-AR Trp64Arg polymorphism might have an impact on the mechanisms involved in leptin release from adipose tissue. Furthermore, our results agree with the previously reported association between UCP1 -3826G allele and obesity and point to a gender-related effect.


Burden of migraine and unmet needs from the patients' perspective: a survey across 11 specialized headache clinics in Korea.
Migraine is a neurological, primary headache disorder affecting more than 1 billion people worldwide, with a multi-faceted burden that can significantly impact the everyday life of a patient, both during and between attacks. However, studies on patient awareness, burden, and clinical management of migraine in Korea are limited and outdated. The aim of this study was to comprehensively investigate the current difficulties and unmet needs that Korean patients with migraine encounter from their perspective. A total of 207 patients with episodic or chronic migraine aged between 15 and 76 years, completed a survey designed to cover the following topics: diagnosis, understanding of the disease, treatment experience, disability, and quality of life. Patients were recruited by their neurologists from 11 specialized headache clinics in Korea and completed the survey between 22 July and 19 August 2019. Validated scales such as the Migraine Disability Assessment (MIDAS) questionnaire and Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQv2.1) were used to assess levels of disability and quality of life, respectively, in patients. On average, it took 10.1 years from onset of symptoms to diagnosis and a mean of 3.9 hospitals were visited for treatment prior to the patient's current hospital. There was a lack of understanding among respondents about migraine, with 55.6% believing that unilateral headache is a unique feature of migraine compared with other headache disorders. On average, high levels of disability and poor quality of life were reported by patients, as assessed by MIDAS and MSQv2.1, respectively, but only 23.7% had regularly taken preventive medication in the past. Overall satisfaction with previous doctor-patient relationships was reported by 29.5% of respondents, and satisfaction with preventive and acute medications by only 40.8% and 27.1% of the respondents, respectively. Korean patients with migraine experience significant disability and reduced quality of life as a result of the disease and have clear unmet needs in terms of diagnosis, understanding of the disease, and disease management including treatment.


Liquid chromatography-dielectric barrier discharge ionization mass spectrometry for the analysis of neutral lipids of archaeological interest.
Dielectric barrier discharge ionization has gained attention in the last few years due to its versatility and the vast array of molecules that can be ionized. In this study, we report on the assessment of liquid chromatography coupled to dielectric barrier discharge ionization with mass spectrometry for neutral lipid analysis. A set of different neutral lipid subclasses (triacylglycerides, diacylglycerides, and sterols) were selected for the study. The main species detected from our ionization source were [M-H2 O+H]+ , [M+H]+ or [M-R-H2 O+H]+ , attributed to sterol dehydration, protonation or the fragmentation of an acyl chain accompanied by a water loss of the glycerolipids, respectively. In terms of sensitivity, the dielectric barrier discharge displayed overall improved abundances and comparable or better limits of quantitation than atmospheric pressure chemical ionization for both acylglycerols and sterols. As a case study, different archaeological samples with variable content in neutral lipids, particularly triacylglycerides, were studied. The identification was carried out by combining accurate mass and the tentative formula associated with the exact mass, retention time matching with standards, and additional structural information from in-source fragmentation. The high degree of unsaturation and the presence of sterols revealed the potential vegetal origin of the material stored in the analyzed samples.


Correlation between power Doppler ultrasonography and clinical severity in Achilles tendinopathy.
Twenty-five patients with chronic Achilles tendinopathy were clinically and ultrasonographically evaluated. A positive correlation existed between power Doppler ultrasonography (PDU) and tendon thickness (r=0.63, p<0.001) and patient's age (r=0.40, p<0.05). A negative correlation existed between PDU and a functional test (number of toe raises to pain) (r=-0.57, p<0.005) and one recorded item of the Victorian Institute of Sport Assessment Achilles score (VISA-A questionnaire, item 6: jumping capability) (r=-0.46, p<0.05). Three patients had no detectable blood flow on PDU. PDU of Achilles tendons does not seem to be strictly related to symptoms but rather to functionality and chronicity of tendinopathy as indicated by toe-raises testing, jumping capability, patient age and tendon thickening.


Effect of property gradients on enamel fracture in human molar teeth.
A model for the fracture of tooth enamel with graded elastic modulus and toughness is constructed using an extended finite element modeling (XFEM) package. The property gradients are taken from literature data on human molars, with maximum in modulus at the outer enamel surface and in toughness at the inner surface. The tooth is modeled as a brittle shell (enamel) and a compliant interior (dentin), with occlusal loading from a hard, flat contact at the cusp. Longitudinal radial (R) and margin (M) cracks are allowed to extend piecewise along the enamel walls under the action of an incrementally increasing applied load. A simple stratagem is deployed in which fictitious temperature profiles generate the requisite property gradients. The resulting XFEM simulations demonstrate that the crack fronts become more segmented as the property gradients become more pronounced, with enhanced propagation at the outer surface and inhibited propagation at the inner. Whereas the growth history of the cracks is profoundly influenced by the gradients, the ultimate critical loads required to attain full fractures are relatively unaffected. Some implications concerning dentistry are considered.


Immunology of leprosy and diagnostic challenges.
Leprosy, caused by noncultivable Mycobacterium leprae (ML), has varied manifestations, which are associated with the host immune responses. The dermal involvement is accompanied by peripheral nerve damage, which leads to sensory motor loss and deformities. Both innate and acquired immune responses are involved. The main cell to be compromised is the CD4 + T helper cell, which shows antigen specific unresponsiveness to only ML and not to other common antigens in the bacilliferous generalized lepromatous form of the disease. In contrast, the paucibacillary localized tuberculoid form shows appropriate T cell functions and poor antibody response. The dichotomy between T cell functions and antibodies are discussed against the current information on cytokines, Th subsets, and regulatory T cells. During lepromatous reactions, there is a temporary, heightened T cell immunity, even in lepromatous subjects. The dermal lesions confirm many features observed with peripheral blood mononuclear cells and give additional information on local immune responses. Nerve damage involves both immune and nonimmune mechanisms. Leprosy is a model disease for understanding host immune responses to intracellular bacilli. There are challenges in diagnosing early leprosy. In spite of intensive efforts by many groups, consensus on a universal test suitable for endemic areas is awaited.


Current status and trends in subspecialty certification in physical medicine and rehabilitation.
There is a need to better understand the overall state of sub-specialization in physical medicine and rehabilitation (PM&R). To examine the status and trends in subspecialty certification for each of the seven subspecialties approved for American Board of Physical Medicine and Rehabilitation (ABPMR) diplomates. Retrospective analysis of deidentified information from the ABPMR database. Physicians certified by ABPMR through 2019. Not applicable. For each subspecialty, we examined: (1) the number of certificates issued to ABPMR diplomates; (2) the recertification rate; (3) the yearly trends for total active, new, and expired certificates; and (4) for ABPMR-administered subspecialties, recertification rates for those entering the subspecialty through fellowship completion versus a "grandfathered" practice pathway. Of 11,421 ABPMR diplomates in the United States in 2019, a total of 3560 (31.2%) had 3985 active subspecialty certificates. Pain Medicine (PM) was the most common subspecialty certification (15.5% of all ABPMR diplomates) followed by Sports Medicine (SM, 6.6%), Brain Injury Medicine (BIM, 4.8%), Spinal Cord Injury Medicine (SCIM, 4.2%), Pediatric Rehabilitation Medicine (PRM, 2.5%), Neuromuscular Medicine (NMM, 0.7%), and Hospice and Palliative Medicine (HPM, 0.5%). For diplomates with more than one subspecialty certification, PM and SM was the most frequent combination. Both the recertification rate and the end of practice track eligibility influenced certification trends differently for individual subspecialties. The average number of new certificates added annually for every subspecialty was higher before than after the temporary practice track-based eligibility ended; the difference was statistically significant (p < .05) for SCIM, PM, SM, and NMM. The recertification rate for all subspecialties combined was 73.4%. For the subspecialties (SCIM, PRM) for which these data were available, fellowship candidates had higher recertification rates than those grandfathered through a practice track. This report informs stakeholders about the state and evolution of subspecialty certification in PM&R over time.


Human gallbladder morphology after gallstone dissolution with methyl tert-butyl ether.
The effects of methyl tert-butyl ether exposure on the human gallbladder in five patients who were treated for gallstones by contact dissolution is described. Two patients underwent cholecystectomy within 1 week of methyl tert-butyl ether treatment, one patient 2 weeks after, another 10 weeks after, and one 12 weeks after. Indications for cholecystectomy were bilirubinate stones (resistant to methyl tert-butyl ether), catheter dislodgement, bile leakage, and gallstone recurrence (2 patients). Gallstones were dissolved completely in three patients, there was approximately 50% stone reduction in one patient, and no dissolution occurred in the fifth patient. Each gallbladder was examined grossly and histologically. Electron microscopic evaluation was performed in one cases. Typical inflammatory findings of chronic cholecystitis were observed in each gallbladder and were most conspicuous in the submucosa; the mucosal and serosal surfaces were intact. Mild acute inflammatory changes were noted in the submucosa in the two patients with the shortest interval between methyl tert-butyl ether administration and cholecystectomy. There were no ulcerations in the mucosa and no unusual wall thickening or fibrosis in any patient. These observations support the safety of methyl tert-butyl ether perfusion in the human gallbladder; the mild acute changes may be a transient and reversible phenomenon.


Ultrasonographic differentiation between Kikuchi's disease and lymphoma in patients with cervical lymphadenopathy.
Kikuchi's disease, or histiocytic necrotizing lymphadenitis, is a self-limited necrotizing lymphadenitis. Clinically, it resembles lymphoma. We want to compare the sonographic features between Kikuchi's disease and lymphoma in patients with cervical lymphadenopathy. The study protocol was approved by the institutional review board. Two hundred and twenty six cervical lymph nodes (137 nodes from 21 Kikuchi's disease patients and 89 nodes from 20 malignant lymphoma patients) were examined. The demographic and ultrasonographic characteristics of lymph nodes were collected and analyzed. The Kikuchi's disease patients (mean age, 24.2 years; range, 8-57 years) were younger than those with lymphoma (mean age, 54 years; range, 13-81 years). There was no difference in laterality of nodes (p=0.19). The nodal distribution demonstrated most enlarged neck lymph nodes located at level II, III and V. The ranges of short-axis and long-axis length were 6.5±2.3mm (mean±SD) versus 13.4±5.1mm and 13.4±5.0mm versus 21.2±9.2mm for Kikuchi's disease versus lymphoma (p<0.01), respectively. The S/R ratio of Kikuchi's disease nodes was 0.5±0.2 compared to 0.7±0.2 in lymphoma nodes (p<0.01). Eighty-seven of 137 nodes (63.5%) of Kikuchi's disease, and eight of 89 nodes (9%) of malignant lymphoma had signs of cortical widening (p<0.01). Seventy-six nodes (55.5%) of Kikuchi's disease and twenty-eight nodes (31.5%) of malignant lymphoma were matted (p<0.01). Forty-five of 89 nodes among lymphoma and twenty-four among 137 of Kikuchi's disease had features of micronodular reticular echotexture (p<0.01). All nodes exhibited hypoechogenicity except one lymphomatous node demonstrated isoechogenicity, and there was no difference in sharpness of border and presence of echogenic hilum between the two diseases (p>0.05). Analysis of basic ultrasonographic characteristics (size, shape, rims, matting and echotexture) helps differentiate cervical lymph nodes in patients with Kikuchi's disease and lymphoma. Cervical lymphadenopathies in patients with Kikuchi's disease have smaller size, less round, less micronodular reticular echotexture, and more signs of matting and cortical widening than those with lymphoma examined under ultrasound.


Palladin is a novel binding partner of ILKAP in eukaryotic cells.
Palladin was a novel binding partner of ILKAP in eukaryotic cells. Palladin's C-terminal fragment including only its last three Ig domains (residues 710-1106) and the PP2C domain of ILKAP (residues 108-392) were necessary and sufficient for their interaction. The biological significance of the interaction between palladin and ILKAP was that palladin recruited the cytoplasmic ILKAP to initiate ILKAP-induced apoptosis. Our results suggested that palladin played a specific role in modulating the subcellular localization of the cytoplasmic ILKAP and promoting the ILKAP-induced apoptosis.


Normal findings in vulvar examination and vulvoscopy.
To determine the normal vulvar findings by naked eye examination and by vulvoscopy in healthy women without vulvar complaints. Observational study. Forty healthy volunteers without vulvar complaints recruited via a newspaper advertisement. Vulvar examination, human papillomavirus (HPV) polymerase chain reaction of vulvar and cervical swabs, saline and KOH smears and vulvoscopy before and after the application of 5% acetic acid. Prevalence of vestibular erythema, vestibular papillomatosis, HPV infection on the vulva and in the cervix and vulvoscopic findings. The mean age of the women was 37.8 years (median 38.0, range 21-56). Nine women were current smokers and 21 had previously smoked. Naked eye vulvar examination showed vestibular papillomatosis in 13 women (33%) and vestibular erythema in 17 women (43%). The touch test was positive in 9 of the 17 women (53%) with vestibular erythema. Vulvoscopy after the application of acetic acid 5% showed an acetowhite vestibule in all women. Twelve women (30%) had acetowhite lesions outside the vestibule. Six women (15%) were positive for HPV DNA. The presence of HPV DNA did not correlate with vestibular erythema or vestibular papillomatosis. There was a weak association between HPV DNA and acetowhite lesions outside the vestibule (P = 0.055, Fisher's exact test). In this group the younger women significantly more often had vestibular papillomatosis (t-statistic = 3.07; P = 0.003) and women who smoke more often had a genital HPV infection (P = 0.016, Fisher's exact test). Vestibular erythema, vestibular papillomatosis, and acetowhite lesions are common in this group of healthy women without vulvar complaints.