Development and Validation of an Evidence-Based Breathing Exercise Intervention Protocol for Chronic Pain Management in Breast Cancer Survivors.
Breathing exercise has been utilized as a promising approach to pain management in cancer survivors. However, the development process of the breathing exercise intervention protocol was rarely reported. To develop an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors and to provide a detailed account of the intervention development process. The study design was guided by the Medical Research Council Framework for Developing and Evaluating Complex Intervention. The breathing exercise intervention development process adopted phase one of the Medical Research Council Framework for Developing and Evaluating Complex Intervention framework. The content validity index was applied to determine the consensus of the appropriateness of the breathing exercise intervention protocol among the panel experts. The preliminary breathing exercise intervention protocol was developed based on fight-or-flight theory and vagus nerve theory, and the best available research evidence identified from seven systematic reviews, three clinical trials, and four practice recommendations. The breathing exercise intervention was designed as slow deep pursed-lip breathing with a time ratio of inspiration to expiration 1:2-3. The intensity of the breathing exercise was determined as 3 to 5 sessions a day, 5 minutes per session, for 4 weeks. The content validity of the breathing exercise intervention protocol was excellent as consensus was achieved among all panel experts with both the item-level and scale-level CVIs reaching 1.0. This study developed an evidence-based breathing exercise intervention protocol for chronic pain management in breast cancer survivors. The protocol is well-supported by the relevant theories, research evidence, practice recommendations, and experts' consensus.


Protein oligomerization through domain swapping: role of inter-molecular interactions and protein concentration.
Domain swapping has been shown to be an important mechanism controlling multiprotein assembly and has been suggested recently as a possible mechanism underlying protein aggregation. Understanding oligomerization via domain swapping is therefore of theoretical and practical importance. By using a symmetrized structure-based (Gō) model, we demonstrate that in the free-energy landscape of domain swapping, a large free-energy barrier separates monomeric and domain-swapped dimeric configurations. We investigate the effect of finite monomer concentration, by implementing a new semi-analytical method, which involves computing the second virial coefficient, a thermodynamic indicator of inter-molecular interactions. This method, together with the symmetrized structure-based (Gō) model, minimizes the need for expensive many-protein simulations, providing a convenient framework to investigate concentration effect. Finally, we perform direct simulations of domain-swapped trimer formation, showing that this modeling approach can be used for higher-order oligomers.


Computational identification and analysis of immune-associated nucleotide gene family in Arabidopsis thaliana.
GTP-binding proteins represent a ubiquitous regulatory mechanism in controlling growth and development in eukaryotes under normal and stress conditions. The IAN/GIMAP proteins belong to a novel family of functionally uncharacterized GTP-binding proteins expressed in both plant and vertebrate cells during anti-pathogenic responses. To gain novel insights into their roles in plants, we did genome-wide analysis of the IAN/GIMAP gene family. We identified 13 Arabidopsis IAN/GIMAP genes, which share similar gene structures and mostly reside in a tandem cluster on chromosomes. Sequence comparison reveals that these genes encode 26-52 kDa proteins with one GTP-binding domain and a conserved box unique to the family. Phylogenetic analysis suggests that the IAN/GIMAP genes of angiosperms and vertebrates may have evolved by independent gene duplication events. GENEVESTIGATOR sources were mined for comprehensive and comparative Arabidopsis IAN/GIMAP gene family expression analysis. These data reveal that IAN/GIMAPs exhibit diverse expression patterns during development and in response to external stimuli, indicating that these paralogous genes are likely involved in complex biological processes in Arabidopsis. Our present findings provide a basis for elucidating the novel GTPase family protein-mediated regulatory mechanisms in the future.


[AEC syndrome: ankyloblepharon, ectodermal defect, cleft lip and palate (Hay-Wells syndrome)].
A 12 month-old female is described, with clinical features of AEC syndrome. This case is a novo mutation. Clinical diagnosis at an early age is emphasised to get a better management and genetic counseling. Also we review the literature.


Molecular evolution and diversity of dimeric alpha-amylase inhibitor gene in Kengyilia species (Triticeae: Poaceae).
Kengyilia Yen et J. L. Yang is a group of allohexaploid species with StYP genomic constitutions in the wheat tribe. To investigate the evolution and diversity of dimeric alpha-amylase inhibitor genes in the Kengyilia, forty-five homoeologous DAAI gene sequences were isolated from sampled Kengyilia species and analyzed together with those of its close relatives. These results suggested that (1) Kengyilia species from Central Asia and the Qinghai-Tibetan Plateau had different origins from those of the geographically differentiated P genome; (2) the St and P genomes of Kengyilia were donated by Pseudoroegneria and Agropyron, respectively, and the Y genome had an independent origin and showed an affinity with the St genome; (3) purifying selection dominated the DAAI gene members and the St-DAAI gene was evolving at faster rate than the P- and Y-DAAI genes in Kengyilia; and (4) natural selection was the main factor on the codon usage pattern of the DAAI gene in Kengyilia.


A multidisciplinary course to teach staff to conduct psychodynamic group psychotherapy for assaultive men.
A course in leading psychodynamic psychotherapy groups for assaultive men. To teach multidisciplinary staff members to lead these groups, using both didactic and experiential learning. The author's own experience. Multidisciplinary staff members learned about the process of leading psychotherapy groups for assaultive men by attending lectures and observing the author lead a group over a 6-month period. The author's openness about her own thoughts, feelings, fantasies, and countertransference allowed students to explore their own reactions and to empathize with the patients, observing that they were not so different from them.


A hybrid algorithm for speckle noise reduction of ultrasound images.
Medical images are contaminated by multiplicative speckle noise which significantly reduce the contrast of ultrasound images and creates a negative effect on various image interpretation tasks. In this paper, we proposed a hybrid denoising approach which collaborate the both local and nonlocal information in an efficient manner. The proposed hybrid algorithm consist of three stages in which at first stage the use of local statistics in the form of guided filter is used to reduce the effect of speckle noise initially. Then, an improved speckle reducing bilateral filter (SRBF) is developed to further reduce the speckle noise from the medical images. Finally, to reconstruct the diffused edges we have used the efficient post-processing technique which jointly considered the advantages of both bilateral and nonlocal mean (NLM) filter for the attenuation of speckle noise efficiently. The performance of proposed hybrid algorithm is evaluated on synthetic, simulated and real ultrasound images. The experiments conducted on various test images demonstrate that our proposed hybrid approach outperforms the various traditional speckle reduction approaches included recently proposed NLM and optimized Bayesian-based NLM. The results of various quantitative, qualitative measures and by visual inspection of denoise synthetic and real ultrasound images demonstrate that the proposed hybrid algorithm have strong denoising capability and able to preserve the fine image details such as edge of a lesion better than previously developed methods for speckle noise reduction. The denoising and edge preserving capability of hybrid algorithm is far better than existing traditional and recently proposed speckle reduction (SR) filters. The success of proposed algorithm would help in building the lay foundation for inventing the hybrid algorithms for denoising of ultrasound images.


Low temperature in the golden hamster accelerates the gonadal atrophy induced by short photoperiod but does not affect the daily pattern of melatonin secretion.
Male golden hamsters were exposed to short photoperiod at either 20 degrees C or 5 degrees C. After 4 weeks a complete gonadal inhibition was observed in animals kept at 5 degrees C while in animals kept at 20 degrees C such an inhibition was much less. No significant difference in the pattern of pineal and plasma melatonin concentrations was observed between hamsters kept at 20 degrees C and 5 degrees C. If in the golden hamster pineal melatonin secretion is implicated in the transduction of the photoperiodic information, it is probably not implicated in the transduction of thermal information.


Development of a photoinduced fragmentation ion trap for infrared multiple photon dissociation spectroscopy.
Methods for isomer discrimination by mass spectroscopy are of increasing interest. Here we describe the development of a three-dimensional ion trap for infrared multiple photon dissociation (IRMPD) spectroscopy that enables the acquisition of the infrared spectrum of selected ions in the gas phase. This system is suitable for the study of a myriad of chemical systems, including isomer mixtures. A modified three-dimensional ion trap was coupled to a CO2 laser and an optical parametric oscillator/optical parametric amplifier (OPO/OPA) system operating in the range 2300 to 4000 cm-1 . Density functional theory vibrational frequency calculations were carried out to support spectral assignments. Detailed descriptions of the interface between the laser and the mass spectrometer, the hardware to control the laser systems, the automated system for IRMPD spectrum acquisition and data management are presented. The optimization of the crystal position of the OPO/OPA system to maximize the spectroscopic response under low-power laser radiation is also discussed. OPO/OPA and CO2 laser-assisted dissociation of gas-phase ions was successfully achieved. The system was validated by acquiring the IRMPD spectra of model species and comparing with literature data. Two isomeric alkaloids of high economic importance were characterized to demonstrate the potential of this technique, which is now available as an open IRMPD spectroscopy facility in Brazil.


Nonlinear canonical correspondence analysis and its application.
The canonical correspondence analysis (CCA) is a multivariate direct gradient analysis method performing well in many fields, however, when it comes to approximating the unimodal response of species to an environmental gradient, which still assumes that the relationship between the environment and the weighted species score is linear. In this work, we propose a nonlinear canonical correspondence analysis method (NCCA), which first determines the most appropriate nonlinear explanatory factor through two screenings by correlation and LASSO regression, and successively uses the linear regression method and the improved heuristic optimal quadratic approximation method to fit the chi-square transformation values of the response variables. Thus, our method effectively reflects the nonlinear relationship between the species and the environment factors, and a biplot is employed to visualize the effects of the later on the distribution of species. The results from applying this method over a real dataset show that the NCCA method not only maintains the advantages of the polynomial canonical correspondence analysis (PCCA) proposed by Makarenkov (2002), but also outperforms Makarenkov's method in explaining the variance of response variables.


Effects of caffeinated alcoholic beverages with low alcohol and high caffeine content on cognitive and motor functions.
In Taiwan, caffeinated alcoholic beverages (CABs), with high caffeine but low alcohol concentrations compared to those sold in Western countries, are commonly consumed at work and have been associated with work-related injuries. However, the effects on cognitive and motor functions and self-perception have not been examined. Twenty-eight healthy male volunteers (mean age: 32.6 ± 2.7) participated in the study. Each participant visited our laboratory 4 times at intervals of at least 1 week and was assigned to one of 4 trials in a counterbalanced order at each visit: placebo, alcohol, caffeinated energy drink, and CAB. They completed the subjective perception ratings, go/no-go tasks, Stroop color-word tests, Purdue pegboard tests, and the standardized field sobriety test. We used analysis of variance to examine the intraindividual differences in the performance. Consuming alcohol of 0.23 g/kg typically consumed by Taiwanese CAB drinkers caused significant impairments in fine and crude motor functions; caffeine (1.5 mg/kg) did not antagonize these effects but led to an improvement in response speed in the go/no-go task. The subjective perceptions produced by alcohol were not masked by caffeine. CABs that contains a higher ratio of caffeine to alcohol did not counteract the motor function impairments induced by alcohol.


Intrauterine creation and repair of pulmonary artery stenosis in the fetal lamb. Weight and ultrastructural changes of the ventricles.
Fetal lamb experimental models were employed for intrauterine creation and repair of pulmonary artery stenosis. The study group was composed of 51 fetal lambs including 29 models of pulmonary artery stenosis and 22 control lambs. Gestational age was 89 days at creation of pulmonary artery stenosis. Fourteen fetal lambs (Group A) were studied after creation of the stenosis at 131 days of gestation and compared to normal age-matched control lambs. The systolic right ventricular pressure was significantly higher after creation of pulmonary artery stenosis (76.6 +/- 17.8 versus 50.3 +/- 23.5 mm Hg), but the systolic pulmonary artery pressure was unchanged. The mean right ventricular weight and the mean right ventricular/left ventricular weight ratio were significantly greater after pulmonary artery stenosis than in normal control animals. The transverse myocyte diameter was not modified by pulmonary artery stenosis, but on electron microscopic study the myocytes appeared mature. Ten lambs (Group B) underwent intrauterine repair of pulmonary artery stenosis at 131 days of gestation without cardiopulmonary bypass. The pulmonary artery was clamped and patched. Immediately after repair the right ventricular pressure fell significantly from 85.8 +/- 18.9 to 62.2 +/- 14.6 mm Hg. At birth, 7 +/- 6 days after repair, Group B was compared to Group C (unrepaired pulmonary artery stenosis, five fetuses) and to normal control lambs. The mean right ventricular weight and the mean right ventricular/left ventricular weight ratio were not statistically different in Group B and in the control group. There were no ultrastructural changes after intrauterine repair. We conclude that intrauterine creation of pulmonary artery stenosis causes right ventricular hypertrophy with more mature myocytes. Intrauterine repair of pulmonary artery stenosis is feasible without cardiopulmonary bypass and rapidly abolishes the preponderance of right ventricular weight over left ventricular weight.


Cell lines producing human T-cell lymphoma virus show altered HLA expression.
Human T-cell leukaemia/lymphoma virus (HTLV) can be identified in fresh and cultured T-lymphocytes from patients with adult T-cell malignancies. HLA typing of the peripheral blood lymphocytes and cultured cell lines from the patient from which the virus was originally isolated suggested the expression of additional HLA-A and -B locus antigens on the HTLV positive cultured T-cells that were not present on the EBV transformed B-cell line or on the peripheral blood lymphocytes. Peripheral blood lymphocytes (PBLs) and T-cell lines established from patients and cord blood lymphocytes, infected with virus by co-culture with T-cell lines, were typed for HLA antigens with alloantisera and in addition tested for reactivity with a monoclonal antibody (4D12) which recognizes a polymorphic HLA class-I antigen. In all HTLV positive cells, with demonstrable provirus replication, altered HLA alloantigen expression was observed. This may be explained by the observations reported in the accompanying paper which shows homology between the envelope gene region of HTLV and the region of an HLA-B locus gene which codes for the extracellular portion of a class I histocompatibility antigen.


Exploration of GPs' views and use of the fit note: a qualitative study in primary care.
Sickness certification constitutes daily clinical practice for GPs. In April 2010, the UK sickness certification system changed to reflect the evidence that work is generally good for health and a new Statement of Fitness for Work - the 'fit note' - was introduced. Sickness certification is a contentious topic among GPs and the proposed fit note generated mixed reviews. To explore GPs' views and use of the fit note during its first year of operation. Qualitative interview study of GPs based in different geographical locations across the UK. GPs (n = 15), who were recruited from a national sample, participated in semi-structured telephone interviews which were subject to constant comparative analysis. Overall, the fit note was well received. GPs recognised that work is generally good for health and felt the fit note facilitated using an earlier return to work as a negotiation tool. GPs perceive employers as the major obstacle to early return to work. There were reports of scepticism towards the system that negatively impacted on some GPs' operation of sickness certification. Feedback over the fit note's impact on employer behaviour and the return of a mechanism that enables GPs to request early independent assessments would be welcomed. A revised approach is needed to address the scepticism towards the sickness certification system that persists among some GPs. New strategies need to be designed to engage employers in facilitating an early return to work and to enable the objectives of the medical statement reforms to be achieved.


New measures improved the reporting of heterogeneity in diagnostic test accuracy reviews: a metaepidemiological study.
To describe the methods used to quantify heterogeneity and to propose alternative measures to improve reporting of heterogeneity in Cochrane diagnostic test accuracy (DTA) reviews. Our metaepidemiological study included all DTA reviews in the Cochrane Library up to October 6th, 2019. We summarized reviews' characteristics focusing on heterogeneity analysis. We selected reviews with a bivariate model and ≥4 studies for reanalysis. In this group, we fitted bivariate random effects models and we quantified heterogeneity by means of logit variances of sensitivity and specificity, bivariate I2, median odds ratio (OR), and the area of the 95% prediction ellipse. We provided a narrative interpretation of these measures in different scenarios. There were 124 Cochrane DTA reviews of which 91 (73%) included meta-analysis. Only in 5 meta-analyses, variances of the logit sensitivity and specificity were reported, and in 21 meta-analyses (23%), the 95% prediction ellipse was reported without any calculation of its area. We selected 60 of these 91 reviews to explore the behavior of all measures of heterogeneity. We found that most reviews described the subjective heterogeneity as moderate or extreme (n = 31/60, 52%), whereas the area of the 95% prediction ellipse and the median OR for sensitivity and specificity showed high variability; the area ranged from 5% to 97%, the median OR of sensitivity ranged from 1.13 to 10.7, and the median OROR of specificity ranged from 1.18 to 19.68. Cochrane DTA reviews show a poor reporting of between-study heterogeneity. Using median OR and the area of the 95% prediction ellipse will improve reporting and interpretation of this crucial aspect of DTA meta-analysis.


Molecular basis for the properties of the thyroxine-binding globulin-slow variant in American blacks.
Thyroxine-binding globulin-slow (TBG-S), a variant found in 4-12% of Black and Pacific Island populations, is inherited as an X-chromosome linked trait. This variant is detected on isoelectric focusing by the characteristic cathodal shift of all its isoforms, suggesting that the difference resides in the core protein. In addition, TBG-S is slightly more thermolabile, which explains why subjects expressing TBG-S have on the average lower serum TBG, and thus reduced T4, concentrations. We now report the molecular basis for this TBG variant, deduced from sequencing the TBG-S gene of an American Black man. Sequencing of the four coding regions and all intron/exon junctions revealed a single nucleotide substitution in the codon for amino acid 171 of the mature protein. The resulting change of the codon GAC to AAC results in replacement of the normal aspartic acid by asparagine. Since the negative charge provided by the aspartic acid is lost when replaced by the neutral asparagine, this substitution seems responsible for the cathodal shift on isoelectric focusing and slower electrophoretic mobility of TBG-S. An identical nucleotide substitution was identified in an unrelated American Black man expressing TBG-S. Whether the TBG-S phenotype observed in populations from the Pacific Islands is caused by the same mutation remains to be determined.


Validation in colorectal procedures of a useful novel approach for the use of C-reactive protein in postoperative infectious complications.
Our aim was to validate a novel use of C-reactive protein (CRP) measurement to identify postoperative infectious complications in patients undergoing colorectal surgery, and to compare the predictive value in this setting against white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR). This was a retrospective study of CRP, NLR and WBC measurements in patients undergoing colorectal surgery. CRP, NLR and WBC were recorded on the second postoperative day and on the day of infectious complication (patients who developed infectious complications) or within 3 days prior to discharge (subjects with no complications). The test for detecting infectious complications consisted of comparing the value of the inflammatory marker on the day on which a complication was suspected against the value recorded on the second postoperative day. The test was considered positive if a given value was higher than the registered peak at postoperative day 2. Factors influencing the postoperative peak CRP were also studied. A total of 254 patients were retrospectively studied. Patients whose CRP value was higher than on the second postoperative day had a diagnostic accuracy for infectious complications of up to 94.4% and sensitivity, specificity, positive predictive value and negative predictive value of up to 97.4%, 93.4%, 85.7% and 99.1%, respectively. Poorer results were observed when WBC count and NLR were used rather than CRP measurement. Multiple linear regression analysis showed that surgical procedure and approach, as well as additional resections, were independent factors for 48 h peak CRP. C-reactive protein is a better parameter than WBC count and NLR for detecting infectious complications. Our proposed methodology presents good diagnostic accuracy and performance and could potentially be used for any surgical procedure.


Employee mindfulness and proactive coping for technostress in the COVID-19 outbreak: The roles of regulatory foci, technostress, and job insecurity.
The transition to digital platforms during the COVID-19 pandemic has created technostress to several workers. Our study aims to investigate whether employee mindfulness contributes to their proactive coping for technostress. We built the dataset from 714 employees from service industries during the pandemic. The findings lent credence to the role of prevention focus in mediating the positive link between dispositional mindfulness and proactive coping for technostress as well as the role of promotion focus in mediating the positive relationship between interpersonal mindfulness and proactive coping for technostress. Technostress was found to strengthen the negative association between prevention focus and proactive coping for technostress while job insecurity represented an attenuating effect on such a link. The results further confirmed the attenuating effect of job insecurity on the positive link between promotion focus and proactive coping for technostress. This study adds dispositional and interpersonal mindfulness as crucial personal antecedents to proactive coping for technostress as well as offers insights into mechanisms underlying such relationships.


The role of calcium in amrinone action on intestinal smooth muscle.
In the guinea-pig isolated ileum amrinone (3 microM to 0.3 M) induced transient, dose-dependent contractions which were followed by pronounced relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). The contractile effect was potentiated by eserine and abolished by scopolamine. Verapamil, at concentrations (0.1-1 microM) that did not affect basal tension of the preparations or the contractile response to exogenous acetylcholine, selectively reduced amrinone-evoked contraction, while the relaxing component was abolished by verapamil concentrations (5-10 microM) that per se reduced muscle tension as well as acetylcholine-induced contraction. Similarly, when external Ca2+ concentration was reduced from 2.5 to 1.25 and 0.5 mM, the contractile component of amrinone effect was markedly reduced, while relaxation was not significantly altered. Any further decrease of Ca2+ content in the superfusion medium (0.25 to 0 mM) also reduced the relaxing effect of amrinone and the response of the ileum to exogenous acetylcholine. The present results indicate that in guinea-pig ileum amrinone-induced contractions are sustained by acetylcholine release as well as by Ca2+ entry into smooth muscle cells through verapamil-sensitive channels, while other Ca2+ pools may play a role in the relaxing effect of the drug.


Analysis of the vitamin D system in cutaneous malignancies.
1,25-dihydroxyvitamin D3, the biological active metabolite of vitamin D, has great impact on keratinocyte growth and differentiation, and consequently has already been successfully used in the therapy of hyperproliferative skin disorders. We have now characterized the key components of the vitamin D system (VDR, 1alpha-OHase, 24-OHase and 25-OHase) in cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), using immunohistochemical and quantitative real-time PCR techniques. Additionally, proliferative activity (Ki-67 expression), differentiation status (cytokeratin 10 and transglutaminase K expression), rate of apoptosis (TUNEL assay) and the abundance of the main heterodimerization partners of VDR (RXRs) was determined for these tumours and correlated with the components of the Vitamin D system. Our findings indicate that the Vitamin D system may be of high importance for the growth behaviour of BCCs and SCCs and that new vitamin D analogues that exert less calcaemic side effects may be effective in the prevention or treatment of these tumours.


Influence of sildenafil on copulatory behaviour in sluggish or normal ejaculator male rats: a central dopamine mediated effect?
The present study investigates the effects induced by sildenafil (1 mg/kg, p.o.) and the dopamine agonist, SND 919 (0.1 mg/kg, i.p.) on copulatory behaviour of male rats, categorized, on the basis of seven consecutive mating pre-tests, as sluggish and normal ejaculators (SE and NE, respectively). The data obtained show that sildenafil modifies both sexual arousal and ejaculatory mechanisms of copulation. It appears that, although it induced a facilitatory effect on ejaculation of all rats, similarly to SND 919, the lowering of ejaculatory threshold was achieved by means of a reduction of mount frequency and intromission frequency in SE and NE groups, respectively. Differently from SND 919, sildenafil increased sexual arousal, diminishing post ejaculatory interval in SE animals and inter-intromission interval in both SE and NE rats. As the dopamine antagonist, (-)eticlopride (0.02 mg/kg, s.c.), significantly inhibited sildenafil-induced enhancement of sexual arousal in SE rats, it is suggested that the drug acts both peripherally and centrally.


[Geriatric syndromes in intermediate care resources: Screening, prevalence and inpatient mortality. Multicenter prospective study].
To determine the prevalence of geriatric syndromes (GS) in the geriatric population of the different intermediate care resources, as well as its relationship with intrahospital mortality. A prospective observational descriptive study, carried out in intermediate care resources in the Vic area (Barcelona) between July 2018 and September 2019. All people aged ≥65 years and/or criteria of complex chronic patient and/or advanced chronic disease, who were assessed for the presence of GS using the trigger questions of the Frail VIG-Index (IF-VIG), administered at baseline, on admission, on discharge and 30 days after discharge. Four hundred and forty-two participants were included, of which 55.4% were women, with a mean age of 83.48 years. There are significant differences (P<.05) between frailty, age and number of GS in relation to the intermediate care resource at the time of admission. There were significant differences in the prevalence of GS between the group of patients who died during the hospitalization (24.7% of the sample) in relation to the survivors: both in a situation baseline (malnutrition, dysphagia, delirium, loss of autonomy, pressure ulcers, and insomnia), as well as in the admission assessment (falls, malnutrition, dysphagia, cognitive impairment, delirium, loss of autonomy, and insomnia). There is a close relationship between the prevalence of GS and in-hospital mortality in intermediate care resources. In the absence of more studies, the use of the IF-VIG as a screening checklist for GS could be useful for its detection.


Synthesis and subcellular localization of the murine coronavirus nucleocapsid protein.
The synthesis and processing of the nucleocapsid protein (pp60) of the JHM strain of murine coronaviruses were examined. Pulse-chase experiments showed that pp60 was synthesized initially as a protein of approximately 57,000 in molecular weight (p57). Immunoprecipitation using mouse anti-JHMV antiserum indicated that p57 was virus specific. Immunoprecipitation with monoclonal antibodies specific for pp60 showed that p57 was antigenically related to pp60 and was not phosphorylated, while the intracellular protein that comigrated with the virion nucleocapsid protein, pp60, was phosphorylated. The p57 was found exclusively in the cytosol while the majority of pp60 was associated with the membrane fraction but pp60 was not an integral membrane protein.


Home range ecology of Indian rock pythons (Python molurus) in Sathyamangalam and Mudumalai Tiger Reserves, Tamil Nadu, Southern India.
The Indian rock pythons (Python molurus) are classified as a near-threatened snake species by the International Union for the Conservation of Nature and Natural Resources (IUCN); they are native to the Indian subcontinent and have experienced population declines caused primarily by poaching and habitat loss. We hand-captured the 14 rock pythons from villages, agricultural lands, and core forests to examine the species' home ranges. We later released/translocated them in different kilometer ranges at the Tiger Reserves. From December 2018 to December 2020, we obtained 401 radio-telemetry locations, with an average tracking duration of (444 ± 212 days), and a mean of 29 ± SD 16 data points per individual. We quantified home ranges and measured morphometric and ecological factors (sex, body size, and location) associated with intraspecific differences in home range size. We analyzed the home ranges of rock pythons using Auto correlated Kernel Density Estimates (AKDE). AKDEs can account for the auto-correlated nature of animal movement data and mitigate against biases stemming from inconsistent tracking time lags. Home range size varied from 1.4 ha to 8.1 km2 and averaged 4.2 km2. Differences in home range sizes could not be connected to body mass. Initial indications suggest that rock python home ranges are larger than other pythons.


Utilization of Km for phenytoin dosage after folate addition to patient regimen.
Phenytoin decreases serum and red blood cell folates in 50% of the patients on the anticonvulsant. The supplementation of folic acid changes the disposition of phenytoin, a drug that exhibits Michaelis-Menten kinetics. In a retrospective study at the Veterans Administration Medical Center, seven adult male folate-deficient epileptic patients on phenytoin alone and compliant with the anticonvulsant were supplemented with 1 mg oral folic acid. Before and after the addition of the vitamin, Vmax and Km were calculated for phenytoin. With folic acid, the total serum phenytoin concentration decreased significantly by an average of 22.6 +/- 13.0%. The Km decreased significantly from 6.7 +/- 1.1 to 4.1 +/- 1.5 micrograms/ml. The Vmax remained unchanged. It is hypothesized that folic acid is a cofactor in the metabolism of phenytoin. A cofactor would be expected to alter the affinity (Km) of the enzymes for phenytoin with no change in the liver's total capacity (Vmax) to metabolize phenytoin. This retrospective study in seven male epileptic patients is a convincing argument for the hypothesis.


Multi-contact functional electrical stimulation for hand opening: electrophysiologically driven identification of the optimal stimulation site.
Functional Electrical Stimulation (FES) is increasingly applied in neurorehabilitation. Particularly, the use of electrode arrays may allow for selective muscle recruitment. However, detecting the best electrode configuration constitutes still a challenge. A multi-contact set-up with thirty electrodes was applied for combined FES and electromyography (EMG) recording of the forearm. A search procedure scanned all electrode configurations by applying single, sub-threshold stimulation pulses while recording M-waves of the extensor digitorum communis (EDC), extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) muscles. The electrode contacts with the best electrophysiological response were then selected for stimulation with FES bursts while capturing finger/wrist extension and radial/ulnar deviation with a kinematic glove. The stimulation electrodes chosen on the basis of M-waves of the EDC/ECR/ECU muscles were able to effectively elicit the respective finger/wrist movements for the targeted extension and/or deviation with high specificity in two different hand postures. A subset of functionally relevant stimulation electrodes could be selected fast, automatic and non-painful from a multi-contact array on the basis of muscle responses to subthreshold stimulation pulses. The selectivity of muscle recruitment predicted the kinematic pattern. This electrophysiologically driven approach would thus allow for an operator-independent positioning of the electrode array in neurorehabilitation.


Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine.
The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitrile, rather than a carboxamide. Although this modification typically was detrimental to antimicrobial activity, hydrophobic vancomycin aglycon analogues that lack a lipid anchor as well as the disaccharide are detailed that exhibit unusual potency against VanB, but not VanA, resistant bacteria.


[Secreted tumor markers and breast cancer].
The tumor secretion markers used most in the daily practice are reviewed, emphasizing the physiological aspects having great practical usefulness. Likewise, the possible value of other recently described substances which could be introduced into the daily practice in the near future is explained.


Mg2+ release coupled to Ca2+ uptake: a novel Ca 2+ accumulation mechanism in rat liver.
Isolated hepatocytes release 2-3 nmol Mg2+/mg protein or approximately 10% of the total cellular Mg2+ content within 2 minutes from the addition of agonists that increase cellular cAMP, for example, isoproterenol (ISO). During Mg2+ release, a quantitatively similar amount of Ca2+ enters the hepatocyte, thus suggesting a stoichiometric exchange ratio of 1 Mg2+:1Ca2+. Calcium induced Mg2+ extrusion is also observed in apical liver plasma membranes (aLPM), in which the process presents the same 1 Mg2+:1Ca2+ exchange ratio. The uptake of Ca2+ for the release of Mg2+ occurs in the absence of significant changes in Deltapsi as evidenced by electroneutral exchange measurements with a tetraphenylphosphonium (TPP+) electrode or 3H-TPP+. Collapsing the Deltapsi by high concentrations of TPP+ or protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) does not inhibit the Ca2+-induced Mg2+ extrusion in cells or aLPM. Further, the process is strictly unidirectional, serving only in Ca2+ uptake and Mg2+ release. These data demonstrate the operation of an electroneutral Ca2+/Mg2+ exchanger which represents a novel pathway for Ca2+ accumulation in liver cells following adrenergic receptor stimulation.


Transglutaminase-mediated cross-linking in mammalian epidermis.
The epsilon-(gamma-glutamyl)lysine isopeptide bond has been identified in certain structural proteins of the hair fibre and the epidermis. The major cross-linked proteins are not keratins and generally have little or no cysteine, but have a high glutamic acid/glutamine residue content. In the hair fibre the cross-link appears in the citrulline-containing proteins of the medulla and the inner root sheath of the follicle. In the epidermis the cross-linked proteins are involved in the formation of the cornified envelope of the stratum corneum cells. In both cases, the cross-linked proteins contribute the characteristic property of chemical resistance to their biological structures.


Lineage-dependent mating-type transposition in fission and budding yeast.
The basis of cellular differentiation is perhaps best understood in the yeast mating-type switching system. The yeast cell produces daughter cells that differ from each other or from their parent cell via developmentally regulated genomic rearrangements. Recent experiments on cell-type determination in fission yeast have revealed that this process is determined by the inheritance of specific parental chromosome strands by the progeny cells.


Overlap between VACTERL and hemifacial microsomia illustrating a spectrum of malformations seen in axial mesodermal dysplasia complex (AMDC).
We describe a male infant born to consanguineous healthy parents with multiple congenital anomalies of the skeleton and internal organs. His phenotype displays an overlap between VACTERL and hemifacial microsomia (oculo-auriculo-vertebral spectrum/OAV). In addition, striking asymmetry of the malformations further supports the classification as part of the "axial mesodermal dysplasia complex" (AMDC) which is supposed to arise from disturbed mesodermal cell migration during early blastogenesis. The present case was instructive to review the continuous spectrum of AMDC related anomalies.


Immunological risk and complement genetic evaluations in early onset de novo thrombotic microangiopathy after living donor kidney transplantation: A Japanese multicenter registry.
Thrombotic microangiopathy (TMA) after kidney transplantation (KTx), particularly early onset de novo (dn) TMA, requires immediate interventions to prevent irreversible organ damage. This multicenter study was performed to investigate the allogeneic clinical factors and complement genetic background of dnTMA after KTx. Perioperative dnTMA after KTx within 1 week after KTx were diagnosed based on pathological or/and hematological criteria at each center, and their immunological backgrounds were researched. Twelve aHUS-related gene variants were examined in dnTMA cases. Seventeen recipients (15 donors) were enrolled, and all dnTMA cases were onset within 72-h of KTx, and 16 of 17 cases were ABO incompatible. The implementation rate of pre-transplant plasmaphereses therapies were low, including cases with high titers of anti-A/anti-B antibodies. Examination of aHUS-related gene variants revealed some deletions and variants with minor allele frequency (MAF) in Japan or East Asian genome databases in genes encoding alternative pathways and complement regulatory factors. These variants was positive in 8 cases, 6 of which were positive in both recipient and donor, but only in one graft loss case. Although some immunological risks were found for dnTMA after KTx, only a few cases developed into TMA. The characteristic variations revealed in the present study may be novel candidates related to dnTMA in Japanese or Asian patients, but not pathogenic variants of aHUS. Future studies on genetic and antigenic factors are needed to identify factors contributing to dnTMA after KTx.


Transplacental transfer of oseltamivir and its metabolite using the human perfused placental cotyledon model.
Given the lack of data regarding the use of oseltamivir (Tamiflu) during pregnancy, we aimed to evaluate the placental transfer of oseltamivir phosphate and its active metabolite oseltamivir carboxylate, using the perfused placental cotyledon model. Cotyledons were coperfused with oseltamivir phosphate and oseltamivir carboxylate using the maximal concentrations described with a 75 mg, twice-daily oral dose. Main transfer parameters such as fetal transfer rate (FTR) and clearance index (CI) were assessed. Five placentas were coperfused with oseltamivir phosphate and oseltamivir carboxylate. The median FTR of oseltamivir phosphate was 8.5% (range, 5.0-11.6%) and the median CI was 0.3 (range, 0.2-0.6). Regarding oseltamivir carboxylate transplacental transfer, the median FTR was 6.6% (range, 3.9-9.7%), whereas the median CI was 0.2 (range, 0.2-0.5). A transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate was detected and might have clinical relevance. Clinicians should be encouraged to report oseltamivir treatment outcomes during pregnancy.


Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis.
Circulation levels of estrone sulfate (E1S) and dehydroepiandrosterone sulfate (DHAS) have been measured in plasma using a radioimmunoassay for estrone and dehydroepiandrosterone following extraction and hydrolysis of the sulfate. The mean +/- SE concentrations of E1S and DHAS in normal men were 458 +/- 25 pg/ml and 1.45 +/- 0.19 micrograms/ml, respectively. In normal women the values for days 5-7 of the cycle were 880 +/- 117 pg/ml and 1.25 +/- 0.12 micrograms/ml which were not different than the values for days 20-22 of 1195 +/- 176 pg/ml and 1.58 +/- 0.29 micrograms/ml. The mean values in post-menopausal women were 250 +/- 33 pg/ml and 0.47 +/- 0.07 micrograms/ml, both lower than the values in young women. In a group of cirrhotic men the mean values were 325 +/- 55 pg/ml and 0.38 +/- 0.12 micrograms/ml, both significantly lower than the normal values. This suggests a defect in sulfurylation in men with hepatic cirrhosis.


Corresponding risk factors between cognitive impairment and type 1 diabetes mellitus: A narrative review.
Type 1 diabetes mellitus (T1DM) is a type of diabetes caused by the destruction of pancreatic β cells and the absolute lack of insulin secretion. T1DM usually starts in adolescence or develops directly as a severe disease state of ketoacidosis. T1DM and its complications make many people suffer and have psychological problems, which make us have to pay more attention to the prevention and early control of T1DM. Cognitive impairment (CI) is one of the major complications of T1DM. It can further develop into Alzheimer's disease, which can seriously affect the quality of life of the elderly. Furthermore, the relationship between T1DM and CI is unclear. Hence, we conducted a narrative review of the existing literature through a PubMed search. We summarized some risk factors that may be associated with the cognitive changes in T1DM patients, including onset age and duration, education and gender, glycemic states, microvascular complications, glycemic control, neuropsychology and emotion, intestinal flora, dyslipidemia, sleep quality. We aimed to provide some content related to CI in T1DM, and hoped that it could play a role in early prediction and treatment to reduce the prevalence.


Congenital infections and the nervous system.
Despite vaccines, new antimicrobials, and improved hygienic practices, congenital infections remain an important cause of death and long-term neurologic morbidity among infants world-wide. Important agents include Toxoplasma gondii, cytomegalovirus, Treponema pallidum, herpes simplex virus types 1 and 2, and rubella virus. In addition, several other agents, such as the varicella zoster virus, human parvovirus B19, and Borrelia burgdorferi, can potentially infect the fetus and cause adverse fetal outcomes. This article provides an overview of these infectious disorders and outlines current strategies for acute treatment and long-term management.


Past smoking and current dopamine agonist use show an independent and dose-dependent association with impulse control disorders in Parkinson's disease.
Previous studies have described the association between dopamine replacement therapy in Parkinson's disease and impulse control disorders. A case-control study was performed to establish the prevalence of four of these behaviors in Brazilian patients with Parkinson's disease on stable dopamine replacement therapy and the possible associated risk factors. We investigated 152 patients and 212 healthy controls for pathological gambling, compulsive sexual behavior and compulsive buying and eating. Overall, patients had more impulsive control disorders than controls (18.4% vs. 4.2%, P < 0.001). Impulse control disorders were more common in younger patients (P = 0.008) and in those taking dopamine agonist (P < 0.001) and levodopa (P = 0.02). Higher Unified Parkinson's Disease Rating Scale motor score (P = 0.03) and past smoking (P = 0.02) were also associated in the univariate analysis. Variables independently associated with impulse control disorders were history of smoking (odds ratio = 1.059 for each year of smoking, P = 0.010) and current use of pramipexole (odds ratio = 2.551 for each increase in 1 mg, P < 0.001). Dopaminergic stimulation and previous exposure to smoking are independently associated with impulse control disorders in a dose-dependent manner.


Prolonged apneas and hypoxia mediated by nicotine and endotoxin in piglets.
Infections and maternal smoking are risk factors for SIDS, and toxins from common bacteria have been proposed as a causative link between infections and SIDS. Nicotine can be transferred in significant amounts postnatally to the infant through environmental tobacco smoke or maternal smoking before nursing. We investigated the acute effects of nicotine and endotoxin on repeated apnea by laryngeal reflex stimulation and the following autoresuscitation. Thirty-four 1-week-old (+/- 1 day) piglets were sedated and randomized to 1 of 4 pretreatment groups: (1) 1 microg endotoxin i.v./kg; (2) 5 microg nicotine i.v./kg; (3) 1 microg endotoxin i.v./kg and 5 microg nicotine i.v./kg, and (4) placebo. Apnea was induced by insufflation of 0.1 ml of acidified saline (pH 2) in the subglottic space of the trachea three times with intervals of 2 min. Pretreatment with endotoxin caused a significant increase in plasma TNF-alpha in the endotoxin groups (mean value +/- SEM 953 +/- 246 and 980 +/- 226 pg/ml, respectively) but no significant change in plasma IL-1 beta. Blood pressure, respiratory rate or S(a)O(2) was not significantly affected before induced apnea. Both pretreatment with nicotine and endotoxin caused prolonged apneas by 35-45%, a complete loss of normal hyperventilation during autoresuscitation, and prolonged hypoxia after apnea. Nicotine and endotoxin interferes with autoresuscitation after apnea. This experimental model on piglets may shed light over important mechanisms involved in the causation of SIDS.


miRNA-29 aggravates myocardial infarction via inhibiting the PI3K/mTOR/HIF1α/VEGF pathway.
MI is defined by the presence of myocardial necrosis, which is caused by acute and persistent ischemia and hypoxia of the coronary artery. In recent years, its incidence rate has been on the rise in China. GSE34198, GSE97320 and GSE141512 datasets were download for DEG analysis. KEGG pathway analysis, GO analysis, GSEA and PPI network construction were performed. Later, target genes of candidate miRNAs were predicted. Next, echocardiography was conducted to detect the effects of miR-29 on left ventricular structure and cardiac function in vivo, and H&E staining was adopted to study the effects of miR-29 on angiogenesis and fibrosis in vivo. Furthermore, Western blotting was employed to investigate the effects of miR-29 inhibition on the expressions of proteins related to the PI3K\mTOR\ HIF-1α\VEGF pathway. There were 162 DEGs involved in MI. GO analysis revealed that inflammatory responses, negative regulation of apoptosis and innate immune response were the main enriched biological processes. KEGG analysis manifested that DEGs were mainly enriched in the PI3K/Akt signaling pathway, and GSEA demonstrated that they were mainly enriched in the PI3K/Akt/mTOR, HIF and VEGF pathways. Moreover, target gene prediction showed that miR-29 was lowly expressed in MI. According to Masson's trichrome staining, miR-29 inhibition promoted angiogenesis, reduced fibrosis, and increased the protein expressions of p-PI3K, p-mTOR, HIF-1α, and VEGF. MiR-29 may play an important role in the growth and development of MI. After inhibition of miR-29, the PI3K/mTOR/HIF-1α/VEGF pathway is activated to alleviate MI.


An evaluation of reported cases of median mandibular cysts.
All English-language reports of median mandibular cysts and one German article were carefully studied. All but three of 20 such cases were readily interpreted as being various forms of odontogenic cysts. Tissue sections of two of the three others were obtained, and it was eventually concluded that all three probably also represented odontogenic cysts. The median mandibular cyst does not appear to exist as an entity. All cysts reported as such are probably odontogenic. In previous reports on median mandibular cysts, undue emphasis has been placed on the "vitality" of adjacent teeth, as determined by thermal or electrical pulp testing. These tests are not completely reliable. Mucous cells and cilia can be found in odontogenic cysts, and consequently their presence in lesions reported as median mandibular cysts does not preclude these cysts from being odontogenic.


Late-onset post-lesional paroxysmal hypothermia: a case series and literature review.
Paroxysmal hypothermia (PH) is a rare condition characterized by recurrent episodes of spontaneous hypothermia, bradycardia, disorders of consciousness and, in some cases, hyperhidrosis. When associated with a detectable hypothalamic lesion, PH episodes usually occur shortly after the brain insult. We performed a retrospective study to identify patients who had demonstrated at least one episode of symptomatic spontaneous PH as defined by (i) tympanic temperature < 35 °C; (ii) drowsiness and/or confusion state and/or coma; (iii) duration of the episode ≥ 24 h; (iv) absence of other condition resulting in hypothermia RESULTS: Among 8824 patients, we identified four patients with recurrent late-onset PH episodes of 1-26-day duration that occurred 6-46 years after the brain insult. The lesion always involved the diencephalon. All patients suffered from epilepsy and three of hypopituitarism. PH episode typically included severe hypothermia, bradycardia, drowsiness, thrombocytopenia and in some patients central hypoventilation and narcolepsy-like hypersomnia. In ¼ of episodes, confusion was mistaken as non-convulsive epileptic manifestation resulting in benzodiazepine administration which aggravated symptoms. In the two patients with nocturnal hypoventilation, chronic non-invasive ventilation with bi-level positive airway pressure allowed cessation of symptomatic episodes. Late-onset post-lesional PH is exceptional with only a single case hitherto reported in the literature. Distinguishing hypothermia-related disturbances of consciousness from epileptic seizures or post-ictal phenomena is crucial since treatment with benzodiazepines may worsen hypothermia through their action on GABAa receptors. Lastly, PH may be associated with sleep disorders and hypoventilation, for which investigations and treatment should be considered.


Using iPSC-Based Models to Understand the Signaling and Cellular Phenotypes in Idiopathic Autism and 16p11.2 Derived Neurons.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is remarkably heterogeneous at the clinical, neurobiological, and genetic levels. ASD can also affect language, a uniquely human capability, and is caused by abnormalities in brain development. Traditionally obtaining biologically relevant human cells to study ASD has been extremely difficult, but new technologies including iPSC-derived neurons and high-throughput omic techniques now provide new, exciting tools to uncover the cellular and signaling basis of ASD etiology.


Reducing O2 sensitivity in electrochemical nitric oxide releasing catheters: An O2-tolerant copper(II)-ligand nitrite reduction catalyst and a glucose oxidase catheter coating.
Electrocatalytic nitric oxide (NO) generation from nitrite (NO2-) within a single lumen of a dual-lumen catheter using CuII-ligand (CuII-L) mediators have been successful at demonstrating NO's potent antimicrobial and antithrombotic properties to reduce bacterial counts and mitigate clotting under low oxygen conditions (e.g., venous blood). Under more aerobic conditions, the O2 sensitivity of the Cu(II)-ligand catalysts and the reaction of O2 (highly soluble in the catheter material) with the NO diffusing through the outer walls of the catheters results in a large decreases in NO fluxes from the surfaces of the catheters, reducing the utility of this approach. Herein, we describe a new more O2-tolerant CuII-L catalyst, [Cu(BEPA-EtSO3)(OTf)], as well as a potentially useful immobilized glucose oxidase enzyme-coating approach that greatly reduces the NO reactivity with oxygen as the NO partitions and diffuses through the catheter material. Results from this work demonstrate that very effective NO fluxes (>1*10-10 mol min-1 cm-2) from a single-lumen silicone rubber catheter can be achieved in the presence of up to 10% O2 saturated solutions.


A Reliability Generalization Meta-analysis of the Padua Inventory-Revised (PI-R).
Background/Objective: The Padua Inventory-Revised (PI-R) is a widely applied instrument to measure obsessive-compulsive symptoms in clinical and nonclinical samples. We conducted a reliability generalization meta-analysis on the PI-R. Method: An exhaustive literature search yielded 118 empirical studies that had applied the PI-R, from which 30 studies (33 samples) reported an original reliability estimate. Results: Assuming a random-effects model, the average internal consistency reliability (Cronbach's alpha) was .92 (95% CI [.91, .93]) for the total scores, and ranged from .74 to .89 for the subscales. Assuming mixed-effects models, moderator analyses showed a positive statistically significant association between the standard deviation of the total scores and the reliability coefficients (p = .002; R2 = .38). Conclusions: In terms of reliability, the PI-R scale was found to be adequate for both research and clinical purposes, although exhibiting large heterogeneity across studies. Future empirical studies using the PI-R should be required to provide at least one reliability estimate based on their own data.


Expression of HSP70 family mRNAs in albino northern snakehead, Channa argus: Response to extreme temperature stress and bacterial infection.
The wild albino northern snakehead, Channa argus, has only been found in Jialing Rivers System of China so far. It is easy to be affected by the environmental factors such as temperature changes and bacterial infection, thus causing a huge economic loss. Therefore, this study cloned a 2,213 bp cDNA that encodes a protein of heat shock protein 70 (CaHSP70), which has an open reading frame (ORF) that encodes 639 amino acids and the corresponding polypeptides of 70.50 kDa. And the oretical isoelectric point (pI) of CaHSP70 is 5.79. Additionally, we also cloned a cDNA for heat shock cognate protein 70 (CaHSC70) with a total length of 2,300 bp. And the ORF of CaHSC70 encodes 648 amino acids and 71.18 kDa peptides. The pI of CaHSC70 is 5.22. Moreover, the cDNA length of stress-70 protein mitochondrial (CaHSPA9) is 2,944 bp with an ORF that encodes 679 amino acids, polypeptides of 73.74 kDa, and a pI of 6.68. The quantitative real-time PCR (qRT-PCR) analysis showed that the mRNA expression levels of CaHSP70, CaHSC70, and CaHSPA9 genes were tissue-specific in the control groups. After the heat shock at 37 °C, the mRNA expression levels of CaHSP70 were extremely significantly upregulated in the kidney, liver, spleen, and brain tissues, while fewer mRNA expression levels of CaHSC70 and CaHSPA9 showed a relatively induction in these tissues. In contrast, after the cold shock at 8.5 °C, fewer mRNA expression levels of CaHSP70, CaHSC70, and CaHSPA9 showed the changes of expression in all the tissues, compared to heat shock. In addition, CaHSP70, CaHSC70, and CaHSPA9 mRNA expression levels showed an overall trend of first upregulating and then falling after Edwardsiella tarda (strain No. DL1,476) challenge. In conclusion, this study demonstrated that temperature had a great effect on the mRNA expression levels of CaHSP70, CaHSC70, and CaHSPA9, and the mRNA expression levels of these three genes were also sensitive to pathogen infection, especially CaHSP70 in the albino C. argus.


The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro.
The polymorphic cytochrome P450 enzyme 2C9 (CYP2C9) catalyses the metabolism of many drugs including S-warfarin, acenocoumarol, phenytoin, tolbutamide, losartan and most of the non-steroidal anti-inflammatory drugs. Diclofenac is metabolised to 4'-hydroxy (OH), the major diclofenac metabolite, 3'-OH and 3'-OH-4'-methoxy metabolites by CYP2C9. The aim of the present study was to clarify the impact of the CYP2C9 polymorphism on the metabolism of diclofenac both in vivo and in vitro. Twenty healthy volunteers with different CYP2C9 genotypes [i.e. CYP2C9*1/ *1 (n = 6), *1/*2 (n = 3), *1,/*3 (n = 5), *2/*3 (n = 4), *21*2 (n = 1), *31*3 (n = 1)] received a single 50-mg oral dose of diclofenac. Plasma pharmacokinetics [peak plasma concentration (Cmax), half-life (t 1/2) and area under the plasma concentration-time curve (AUCtotal)] and urinary recovery of diclofenac and its metabolites were compared between the genotypes. Diclofenac 4'-hydroxylation was also analysed in vitro in 16 different samples of genotyped [i.e. CYP2C9*1/*1 (n = 7), *1/*2 (n=2), *1/*3 (n = 2), *2/*3 (n = 2), *2/*2 (n = 2), *31/*3 (n = 1)] human liver microsomes. Within each genotype group, a high variability was observed in kinetic parameters for diclofenac and 4'-OH-diclofenac (6- and 20-fold, respectively). No significant differences were found between the different genotypes either in vivo or in human liver microsomes. No correlation was found between the plasma AUC ratio of diclofenac/4'-OH-diclofenac and that of losartan/ E-3174, previously determined in the same subjects. No relationship was found between the CYP2C9 genotype and the 4'-hydroxylation of diclofenac either in vivo or in vitro. This, together with the lack of correlation between losartan oxidation and diclofenac hydroxylation in vivo raises the question about the usefulness of diclofenac as a CYP2C9 probe.


Resident and Fellow Participation in Breast Surgery: An American College of Surgeons NSQIP Clinical Outcomes Analysis.
In our present health and medical education system, participation of residents and fellows is under increasing scrutiny regarding their role in surgery and the outcomes of the procedure. Our goal was to perform a clinical outcomes analysis investigating resident and fellow participation in breast surgery. Early postoperative complication rates and total operation times for partial and simple mastectomy cases were gathered from the ACS-NSQIP database. The cases were divided based on the training level of the participating resident surgeon: junior (post-graduate year [PGY] 1 to 2), senior (PGY 3 to 5), fellow (PGY > 5), as well as an attending only group (no resident present). We compared the clinical outcomes of each group with the attending only group. Statistical analysis included odds ratios and regression analysis that analyzed the correlation between years in training vs complication rate, and years in training vs total operation time. A total of 13,254 cases were identified, and residents participated in 64% of them. There was no statistically significant difference in rate of complications between any of the trainee groups when compared with the attending only group. However, total operative times were correlated with training year levels and found to be significantly lower with each year of training (R(2) = 0.53, p = 0.025 for partial mastectomy; R(2) = 0.45, p = 0.046 for complete mastectomy). Resident/fellow participation does not negatively affect early postoperative breast surgery outcomes, and complication rates are unrelated to the training level of the participating resident/fellow surgeon.


Management of oral Graft versus Host Disease with topical agents: A systematic review.
Oral Graft-versus-Host Disease (oGvHD) is a common complication of haematopoietic stem cell transplantation. Choosing the right topical application to be used intra orally can be a challenge. Consequently, the aim of this work is to review the effectiveness and safety of topical agents currently used in the management of the inflammatory mucosal lesions encountered in oGVHD. We carried out electronic searches of publications up to May 2015 of the databases Pubmed, National Library of Medicine's Medline, Embase and the Cochrane Central Register of Controlled Clinical trials to identify potentially relevant studies (keywords: "oral", "graft", "versus", "host", "disease" and "treatment"). The main inclusion criterion was the reported use of a topical agent which was not intentionally swallowed when used for the treatment of oGVHD. A 3-point grading system, described by the Swedish Council on Technology Assessment in Health Care and the Centre for Reviews and Dissemination, University of York, was used to rate the methodological quality of the papers. From the 902 entries identified in the search, 7 studies qualifying for inclusion were analysed. Overall, there is limited evidence with regards to the effectiveness of topical steroids for oGVHD. However, the studies showed some effect of Budesonide alone and when combined with dexamethasone. Topical tacrolimus also appears to have some effect and clobetasol propionate mouthwash had a significantly better clinical response than dexamethasone mouthwash in treating oGVHD. As the number of clinical trials conducted is limited, there is little evidence to support the use of topical therapies to treat the inflammatory mucosal lesions found in oGVHD. High quality randomised control trials are needed in order to measure the effectiveness of any topical application for the treatment of the inflammatory mucosal lesions found in oGVHD.


Direct experimental observation of the molecular J eff = 3/2 ground state in the lacunar spinel GaTa4Se8.
Strong spin-orbit coupling lifts the degeneracy of t 2g orbitals in 5d transition-metal systems, leaving a Kramers doublet and quartet with effective angular momentum of J eff = 1/2 and 3/2, respectively. These spin-orbit entangled states can host exotic quantum phases such as topological Mott state, unconventional superconductivity, and quantum spin liquid. The lacunar spinel GaTa4Se8 was theoretically predicted to form the molecular J eff = 3/2 ground state. Experimental verification of its existence is an important first step to exploring the consequences of the J eff = 3/2 state. Here, we report direct experimental evidence of the J eff = 3/2 state in GaTa4Se8 by means of excitation spectra of resonant inelastic X-ray scattering at the Ta L3 and L2 edges. We find that the excitations involving the J eff = 1/2 molecular orbital are absent only at the Ta L2 edge, manifesting the realization of the molecular J eff = 3/2 ground state in GaTa4Se8.The strong interaction between electron spin and orbital degrees of freedom in 5d oxides can lead to exotic electronic ground states. Here the authors use resonant inelastic X-ray scattering to demonstrate that the theoretically proposed J eff = 3/2 state is realised in GaTa4Se8.


CNT-Strung LiMn2 O4 for Lithium Extraction with High Selectivity and Stability.
LiMn2 O4 is of great potential for selectively extracting Li+ from brines and seawater, yet its application is hindered by its poor cycle stability and conductivity. Herein a two-step strategy to fabricate highly conductive and stable CNT-strung LiMn2 O4 (CNT-s-LMO) is reported, by first stringing Mn3 O4 particles with multiwalled carbon nanotube (CNT), then converting the hybrids into CNT-s-LMO through hydrothermal lithiation. The as-synthesized CNT-s-LMO materials have a net-like structure with CNTs threading through LMO particles. This unique structure has endowed the CNT-s-LMO electrode with excellent conductivity, high specific capacitance, and enhanced rate performance. Because of this, the CNT-s-LMO electrode in the hybrid capacitive deionization cell (HCDI) can deliver a high Li+ extraction percentage (≈84%) in brine and an outstanding lithium selectivity with a separation factor of ≈181 at the Mg2+ /Li+ molar ratio of 60. Significantly, the CNT-s-LMO-based HCDI cell has a high stability, evidenced by 90% capacity retention and negligible Mn loss in 100 cycles. This method has paved a new way to fabricate carbon-enabled LMO-based absorbents with tuned structure and superior capacity for electrochemical lithium extraction with high Li+ selectivity and exceptional cycling stability, which may help to tackle the shortage in supply of Li-ion batteries in industry in the future.


Prediction of proliferative vitreoretinopathy after retinal detachment surgery: potential of biomarker profiling.
To investigate the potential of a combined assessment of clinical risk factors and biomarker profiling in the prediction of proliferative vitreoretinopathy (PVR) after retinal detachment surgery. Retrospective case-control study. Multiplex bead-based immunoassays were used for the simultaneous measurement of 50 biomarkers in subretinal fluid samples obtained from patients who underwent scleral buckling surgery for primary rhegmatogenous retinal detachment (RRD). Of 306 samples that were collected and stored in our BioBank, we selected 21 samples from patients in whom a redetachment developed as a result of PVR within 3 months after reattachment surgery for primary RRD (PVR group). These were compared with age-, sex-, and storage time-matched RRD samples from 54 patients with an uncomplicated postoperative course after primary RRD repair (RRD group). Preoperative PVR was the only clinical variable that was an independent predictor of postoperative PVR development (P = .035) and resulted in an area under the receiver operating characteristic curve of 0.67 (95% confidence interval, 0.51 to 0.83). The addition of the biomarkers chemokine (C-C motif) ligand 22, interleukin-3, and macrophage migration inhibitory factor improved the model significantly (P < .001) and resulted in an area under the receiver operating characteristic curve of 0.93 (95% confidence interval, 0.82 to 1.04). A sensitivity of 94.1% and a specificity of 94.2% were reached, using a cutoff value of 5%. In combination with preoperative PVR grade, the measurement of a single biomarker or a small multibiomarker panel shows great potential and may predict postoperative PVR development after primary RRD in a highly sensitive and specific manner.


Techno-economic evaluation of stillage treatment with anaerobic digestion in a softwood-to-ethanol process.
Replacing the energy-intensive evaporation of stillage by anaerobic digestion is one way of decreasing the energy demand of the lignocellulosic biomass to the ethanol process. The biogas can be upgraded and sold as transportation fuel, injected directly into the gas grid or be incinerated on-site for combined heat and power generation. A techno-economic evaluation of the spruce-to-ethanol process, based on SO2-catalysed steam pretreatment followed by simultaneous saccharification and fermentation, has been performed using the commercial flow-sheeting program Aspen Plus™. Various process configurations of anaerobic digestion of the stillage, with different combinations of co-products, have been evaluated in terms of energy efficiency and ethanol production cost versus the reference case of evaporation. Anaerobic digestion of the stillage showed a significantly higher overall energy efficiency (87-92%), based on the lower heating values, than the reference case (81%). Although the amount of ethanol produced was the same in all scenarios, the production cost varied between 4.00 and 5.27 Swedish kronor per litre (0.38-0.50 euro/L), including the reference case. Higher energy efficiency options did not necessarily result in lower ethanol production costs. Anaerobic digestion of the stillage with biogas upgrading was demonstrated to be a favourable option for both energy efficiency and ethanol production cost. The difference in the production cost of ethanol between using the whole stillage or only the liquid fraction in anaerobic digestion was negligible for the combination of co-products including upgraded biogas, electricity and district heat.


Resistance, Motor Control, and Mindfulness-Based Exercises Are Effective for Treating Chronic Nonspecific Neck Pain: A Systematic Review With Meta-Analysis and Dose-Response Meta-Regression.
OBJECTIVE: We aimed to analyze the effects and dose-response relationship of the most effective exercises for improving pain and disability in people with chronic nonspecific neck pain. DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched the PubMed, PEDro, and CENTRAL databases from their inception to September 30, 2022. STUDY SELECTION CRITERIA: We included randomized controlled trials that involved people with chronic neck pain adopting a longitudinal exercise intervention and assessed one pain and/or disability outcome. DATA SYNTHESIS: Restricted maximum-likelihood random-effects meta-analyses were modeled separately for resistance, mindfulness-based, and motor control exercises; standardized mean differences (Hedge's g, standardized mean difference [SMD]) were effect estimators. Meta-regressions (dependent variable: effect sizes of the interventions; independent variables: training dose and control group effects) were conducted to explore the dose-response relationship for therapy success of any exercise type. RESULTS: We included 68 trials. Compared to true control, effects on pain and disability were significantly larger for resistance exercise (pain: SMD, -1.27; 95% confidence interval [CI]: -2.26, -0.28; |2 = 96%; disability: SMD, -1.76; 95% CI: -3.16, -0.37; |2 = 98%), motor control exercise (pain: SMD, -2.29; 95% CI: -3.82, -0.75; |2 = 98%; disability: SMD, -2.42; 95% CI: -3.38, -1.47; |2 = 94%), and Yoga/Pilates/Tai Chi/Qui Gong exercise (pain: SMD, 1.91; 95% CI:-3.28, -0.55; |2 = 96%; disability: SMD, -0.62; 95% CI: -0.85, -0.38; |2 = 0%). Yoga/Pilates/Tai Chi/Qui Gong exercise was more effective than other exercises (SMD, -0.84; 95% CI: -1.553, -0.13; |2 = 86%) for reducing pain. For disability, motor control exercise was superior to other exercises (SMD, -0.70; 95% CI: -1.23, -0.17; |2 = 98%). There was no dose-response relationship for resistance exercise (R2 = 0.32). Higher frequencies (estimate = -0.10) and longer durations (estimate = -0.11) of motor control exercise had larger effects on pain (R2 = 0.72). Longer sessions (estimate = -0.13) of motor control exercise had larger effects on disability (R2 = 0.61). CONCLUSION: Resistance, mindfulness-based, and motor control exercises were effective for reducing neck pain (very low- to moderate-certainty evidence). Higher frequencies and longer duration of sessions had a significant effect on pain for motor control exercise. J Orthop Sports Phys Ther 2023;53(8):1-41. Epub: 20 June 2023. doi:10.2519/jospt.2023.11820.


Imaging soft samples with the atomic force microscope: gelatin in water and propanol.
We have imaged mica coated with thin gelatin films in water, propanol, and mixtures of these two liquids by atomic force microscopy (AFM). The elastic modulus (Young's modulus) can be tuned from 20 kPa to more than 0.1 GPa depending on the ratio of propanol to water. The resolution is best in pure propanol, on the order of 20 nm, and becomes worse for the softer samples. The degradation in resolution can be understood by considering the elastic indentation of the gelatin caused by the AFM tip. This indentation becomes larger and thus the contact area becomes larger the softer the sample is. Therefore this study may be used to estimate the resolution to be expected with an AFM on other soft samples, such as cells. Nondestructive imaging was possible only by imaging at forces < 1 nN. This was difficult to achieve in contact mode because of drift in the zero load deflection of the cantilever, supposedly caused by temperature drift, but straightforward in tapping mode.


What matters when doctors die: A qualitative study of family perspectives.
The challenges of supporting the end-of-life preferences of patients and their families have often been attributed to poor understanding of the patient's condition. Understanding how physicians, as patients, communicate their end-of-life care preferences to their families may inform shared decision making at end of life. The purpose of this study was to understand what matters to families of physicians when decision making with and for a physician who is approaching the end of life. Cross-sectional qualitative design. We conducted interviews with family members of deceased physicians. We analyzed the data using the constant comparison method to identify themes. Family members (N = 26) rarely were unclear about the treatment preferences of physicians who died. Three overarching themes emerged about what matters most to physicians' families: (1) honoring preferences for the context of end-of-life care; (2) supporting the patient's control and dignity in care; and, (3) developing a shared understanding of preferences. Families struggled to make decisions and provide the care needed by the physicians at the end of life, often encountering significant challenges from the healthcare system. Even when disease and prognosis are well understood as in this group of physicians, families still experienced difficulties in end-of-life decision making. These findings highlight the need to specifically address preferences for caregiver, care setting and symptom management in shared end-of-life decision making conversations with patients and families.


The influence of prenatal or neonatal administration of 2-bromo-alpha-ergocryptine on pituitary prolactin secretion and normal and neoplastic mammary growth in adult mice.
In view of the clinical use of 2-bromo-alpha-ergocryptine (CB-154) during pregnancy, longterm effects of perinatal exposure to this drug on pituitary prolactin secretion and mammary tumorigenesis were studied experimentally using a high mammary tumor strain of SHN female mice. Pregnant mice were given daily subcutaneous injections of 0.3 mg CB-154 for 4 days from day 12 to day 15 of pregnancy (prenatal treatment). Another group of mice received daily dose of 0.06 mg CB-154 for the first 5 days of postnatal life (neonatal treatment). Either prenatal or neonatal treatment with CB-154 resulted in little alteration of the pattern of estrous cycle, ovarian structure and pituitary and plasma levels of prolactin. There was no difference between the control and mice treated neonatally with CB-154 in mammary tumorigenesis. On the other hand, somewhat delayed mammary tumor appearance was observed in mice treated prenatally with CB-154. These findings postulate that there is little deleterious influence of perinatal exposure to CB-154 on pituitary-ovary-mammary gland systems at advanced ages.


Nausea, Vomiting, and Weight Loss in a Young Adult Patient With a History of a Gunshot Wound.
Assessing victims of gunshot wounds with retained bullets/bullet fragments for lead toxicity is not always considered until the patient develops signs and symptoms of toxicity. We discuss the case of a 19-year-old young man who received a diagnosis of chronic lead toxicity (serum lead concentration 51 μg/dL) 5 weeks after a hunting accident. Extensive wound debridement occurred following the accident; however, lead toxicity was not diagnosed until after his fourth emergency department visit. Oral chelation therapy was required for the management of his lead toxicity.


Aortic dissection: review of value and limitations of two-dimensional echocardiography in a six-year experience.
The utility of transthoracic two-dimensional echocardiography in patients with aortic dissection was assessed by retrospective analysis in 67 patients: 31 patients with DeBakey type I, 21 patients with type II, 10 patients with type III, and five patients with false-positive diagnoses. Aortic dissection was correctly identified by two-dimensional echocardiography in 49 patients; 13 had false-negative diagnoses. Therefore the sensitivity was 79%, and the positive predictive accuracy was 91%. Transthoracic two-dimensional echocardiography is a reasonable screening technique for diagnosis of aortic dissection.


Metabolic differences and the development of obesity.
Studies, such as those on Pima Indians, have shown that metabolic factors are involved in the development of obesity and that being overweight is not simply a result of "sloth and gluttony." However, the environment also affects the development of obesity. Among individuals in a given environment, the variability in body size is influenced by genetically determined responses to that environment. People with a low metabolic rate (adjusted for body size and composition) are prone to weight gain, whereas those with a high level of spontaneous physical activity are less likely to become obese. Similarly, individuals with a high 24-hour respiratory quotient (RQ) are more likely to gain weight than those with a low RQ. Insulin sensitivity (not insulin resistance) is another metabolic predictor of obesity. Genetic linkage studies suggest a number of genes are linked to the development of obesity. By sibling-pair linkage analysis, tumor necrosis factor-alpha (TNF-alpha) was found to be linked to the percentage of body fat, and other studies have shown that fat cell production of TNF-alpha is greater in obese individuals.


Ascending and intrinsic projections of the superior olivary complex in the cat.
The ascending and intrinsic projections of the superior olivary complex (SO) in the cat were investigated by injection of 3H-leucine and horseradish peroxidase (HRP) in SO and the inferior colliculus (IC), respectively. A topically arranged projection was demonstrated from the nucleus of the trapezoid body (NTB) to the ipsilateral lateral superior olivary nucleus (LSO) wiht a lesser connection in the opposite direction. The medial superior olivary nucleus (MSO) has a strictly ipsilateral projection, whilst LSO projects symmetrically through the lateral lemniscus (LL) of both sides, to end with topically arranged terminals in the ventrolateral part of the central nucleus of the inferior colliculus (CNIC). Terminal labelling found in the ventral and dorsal nuclei of LL (VNLL and DNLL) probably represents collaterals from bypassing fibres originating in MSO and LSO, respectively. These results were demonstrated by both techniques, whilst in addition the HRP method revealed an ipsilateral and contralateral projection to IC from VNLL and DNLL, respectively.


Helical tomotherapy as a new treatment technique for whole abdominal irradiation.
To describe a new intensity-modulated radiotherapy (IMRT) technique using helical tomotherapy for whole abdominal irradiation (WAI) in patients with advanced ovarian cancer. A patient with radically operated ovarian cancer FIGO stage IIIc was treated in a prospective clinical trial with WAI to a total dose of 30 Gy in 1.5-Gy fractions as an additional therapy after adjuvant platinum-based chemotherapy. The planning target volume (PTV) included the entire peritoneal cavity. PTV was adapted according to breathing motion as detected in a four-dimensional respiratory-triggered computed tomography (4D-CT). Inverse treatment planning was done with the Hi-Art tomotherapy planning station. Organs at risk (OARs) were kidneys, liver, bone marrow, spinal cord, thoracic and lumbosacral vertebral bodies, and pelvic bones. Daily control of positioning accuracy was performed with megavoltage computed tomography (MV-CT). Helical tomotherapy enabled a very homogeneous dose distribution with excellent sparing of OARs and coverage of the PTV (V90 of 93.1%, V95 of 86.9%, V105 of 1.9%, and V110 of 0.01%). Mean liver dose was 21.57 Gy and mean kidney doses were 9.75 Gy and 9.14 Gy, respectively. Treatment could be performed in 18.1 min daily and no severe side effects occurred. Helical tomotherapy is feasible and fast for WAI. Tomotherapy enabled excellent coverage of the PTV and effective sparing of liver, kidneys and bone marrow.


Facile synthesis of fluorescent Au@SiO2 nanocomposites for application in cellular imaging.
A novel fluorescent Au@SiO(2) nanocomposite, with average size of ca. 30 nm in the diameter, was prepared via a simple microemulsion method. Additionally, transmission electron microscopy (TEM), UV-Vis absorption spectra, Fourier transform infrared (FT-IR) spectra and fluorescence spectra were used to characterize this nanocomposite. This newly synthesized, silica-wrapped, gold nanocluster has the following advantages: good water solubility, exceptional biocompatibility, favorable surface properties and excellent fluorescence properties. Because of these advantages, a Au@SiO(2) nanocomposite is exceptionally suitable for biological applications. In this study, cellular imaging, as a form of biological application, has been fully investigated, and it was discovered, after covalent conjugation of folic acid (FA), that the nanocomposite effectively recognized over expressed folic acid receptors (FARs) on the HeLa cell's surface. Therefore, this fluorescent Au@SiO(2) nanocomposite could be used as a new fluorescent probe for selective biological imaging.


Experiences of Advanced Practitioners with Inserting the Copper Intrauterine Device as Emergency Contraception.
The copper intrauterine device (IUD) is the most effective method of emergency contraception (EC) available for use after unprotected intercourse. Family planning clinics, commonly staffed by advanced practice clinicians, fulfill a significant role in health care and contraceptive service delivery for women in the United States. There are limited data assessing the perspectives and experiences of these providers in using the copper IUD as EC in these settings. Semistructured individual interviews were conducted with 12 advanced practice clinicians with experience inserting the copper IUD. A phenomenological approach was used to frame the study and analysis. A modified version of the Van Kaam method of analysis was used to analyze the data from interview transcripts. Participants reported feelings of responsibility to support long-acting and highly effective methods of contraception. Patients' abilities to provide an accurate history of the last instance of unprotected intercourse in relation to their menstrual cycles and fear of painful insertions influenced participants' willingness to offer the copper IUD. This included provider concerns about causing uterine perforation prompting discontinuation of IUD insertion attempts. The participants perceived patients as having little knowledge about the copper IUD in general and as not being committed to using the copper IUD long term. Numerous factors influenced advanced practice clinicians' decisions to present the copper IUD as a method of EC. Promoting support and sharing practitioner experiences with inserting the copper IUD as EC may increase practitioner comfort with the copper IUD as EC.


Anti-apoptotic effect of HeidihuangWan in renal tubular epithelial cells via PI3K/Akt/mTOR signaling pathway.
Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.


A phagosome of one's own: a microbial guide to life in the macrophage.
Macrophages protect their host by engulfing foreign bodies within phagosomes that rapidly develop into microbicidal organelles. Numerous pathogens, such as species of Toxoplasma, Leishmania, Mycobacterium, Salmonella and Legionella, thrive in human macrophages, sometimes with disastrous effects. Defining the survival tactics of intracellular parasites is one approach to understanding macrophage function. Here, we briefly review phagosome maturation, then discuss how particular microbes may target particular host factors to short-circuit membrane traffic in macrophages. Recent studies support a new paradigm in which pathogens evade lysosomal degradation by entering macrophages within specialized lipid microdomains of the plasma membrane.


Probiotics as additives on therapy in allergic airway diseases: a systematic review of benefits and risks.
We conducted a systematic review to find out the role of probiotics in treatment of allergic airway diseases. A comprehensive search of the major electronic databases was done till March 2013. Trials comparing the effect of probiotics versus placebo were included. A predefined set of outcome measures were assessed. Continuous data were expressed as standardized mean difference with 95% CI. Dichotomous data were expressed as odds ratio with 95% CI. P value < 0.05 was considered as significant. A total of 12 studies were included. Probiotic intake was associated with a significantly improved quality of life score in patients with allergic rhinitis (SMD -1.9 (95% CI -3.62, -0.19); P = 0.03), though there was a high degree of heterogeneity. No improvement in quality of life score was noted in asthmatics. Probiotic intake also improved the following parameters: longer time free from episodes of asthma and rhinitis and decrease in the number of episodes of rhinitis per year. Adverse events were not significant. As the current evidence was generated from few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy in subjects with allergic airway diseases cannot be recommended.


The successful treatment of flat warts with auricular acupuncture.
Flat warts are a common presenting complaint in adolescents and adults and may be a cosmetic problem as well. Patients suffering from flat warts are often unsatisfied with conventional medical care because of adverse effects such as intolerable pain, hyperpigmentation, hypopigmentation, or occasionally allergic contact dermatitis. To offset the possibilities of hyperpigmentation, hypopigmentation, and scar formation, the method of auricular acupuncture was used. Single-blind method adopted, 60 subjects with flat warts were all outpatients and randomly allocated to a treatment group or a control group, with 30 patients in each group. Thirty subjects in the treatment group were treated with weekly auricular acupuncture for 10 weeks while the other subjects in the control group were treated with 0.1% of tretinoin ointment topically for 10 weeks. Sixteen subjects in the treatment group (53.33%) recovered fully from flat warts without recurrence during the ensuing six months' follow-up after 10 weeks' surgery compared with only one subject in the control group (3.33%). The therapeutic effect of the treatment group was statistically better than that of the control group by Mann-Whitney U-test with SPSS software (P < 0.01). During the treatment period and the ensuing six months' follow-up, no adverse effects were observed by the investigators or reported by patients. Our findings suggest that auricular acupuncture may be a viable alternative for the treatment of flat warts. Larger randomized studies are needed to fully evaluate auricular acupuncture against more conventional treatments, and these are planned.


Knowledge, Attitude of Sikkim Primary School Teachers About Paediatric Hearing Loss.
Our purpose of the study was to assess the knowledge and any gaps of early educators regarding hearing impairment, and to attempt to delineate the attitudes and perceptions of the educators regarding the outcomes of their students with hearing disabilities and their views on inclusive teaching, using a questionnaire based study. Only 71 respondents completed the questionnaire. The present questionnaire based study was conducted on 100 primary school teachers, undertaken on randomly selected schools from Gangtok, East Sikkim. Their knowledge and attitudes regarding hearing impairment in children in the areas of cause, diagnosis, investigations, treatment, prevention, special care and inclusion into mainstream schools were assessed. Our study showed that the knowledge of causes, investigation and treatment of hearing impairement [HI] among respondents/teachers was poor. The data was shown statistically significant with P < 0.001. However, responses testing behavior and attitudes towards HI was encouraging. 52.9% respondents disagreed that HI was a social handicap and 88.2% felt that teachers need special training before a HI child is admitted to the school. The results were statistically significant with P < 0.001. The biggest obstacle found for inclusive education of HI children was a lack of proper training to teachers (40.8%) and attitude of other students (29.5%).


An in vitro study of the influence of plasma protease inhibitors and aprotinin on trypsin-induced C3 cleavage in human serum.
Cleavage of native C3 in human serum following the addition of increasing amounts of human cationic trypsin was studied using an in vitro model. The cleavage was correlated with the degree of saturation of the plasma protease inhibitors alpha 2-macroglobulin and alpha 1-antitrypsin, and also with varying amounts of aprotinin (Trasylol). When alpha 2-macroglobulin reached 70% saturation, there was a prompt cleavage of most of the native C3 in spite of 90% free alpha 1-antitrypsin. The consumption of alpha 2-macroglobulin, and especially of alpha 1-antitrypsin, decreased with increasing concentrations of aprotinin. Aprotinin was needed in a concentration of 60 microM to block trypsin-induced C3 cleavage almost completely. This concentration is about 20 times higher than ever used clinically. One possible explanation of the poor clinical effect of aprotinin to date in human pancreatitis is the need for this high concentration.


[Change in the level of available lysine under the action of moisture and different types of carbohydrates in the thermal processing of casein and sunflower protein products].
Casein, notfat seed meal and extract of the sunflower notfat seed meal were exposed to the effects of moisture, glucose, lactose and saccharose under different thermal conditions to study the degree to which the level of the available lysine falls in all of the study products under the effect of the mentioned factors. Differences in the action of the factors and conditions of technological treatment revealed by the present investigations on the biological value of the protein products justify emphasizing the importance of choosing adequate parameters for each product, together with the need for considering the complexity of physico-chemical and conformable characteristics of the product.


Corneoscleral abscess resulting from a broken suture after cataract surgery.
An 82-year-old man had pain and decreased vision in his right eye 15 months after uncomplicated cataract surgery. Examination revealed a large corneoscleral abscess with a 2 mm x 1 mm area of fluorescein staining at the base of a broken protruding 10-0 nylon suture. Streptococcus pneumoniae was isolated from both the suture and base of the ulcer. Despite intensive topical, subconjunctival, and systemic antibiotics, a large corneal perforation developed, necessitating a 10 mm tectonic penetrating keratoplasty. Long-term follow-up of patients after cataract surgery is important and should include an inspection of the limbal wound and removal of loose or broken exposed sutures. Suture-related complications will be eliminated if clinical studies prove the safety and efficacy of sutureless cataract surgery.


Angioleiomyoma of the Extremities: Findings on Ultrasonography and Magnetic Resonance Imaging.
The purpose of this study was to describe the features of angioleiomyomas of the extremities on ultrasonography (US) and magnetic resonance imaging (MRI). We retrospectively reviewed the US and MRI findings of 29 pathologically confirmed cases of angioleiomyomas of the extremities in 29 patients. Twenty patients underwent only US; 7 patients underwent only MRI; and 2 patients underwent US and MRI. Clinical data and histopathologic specimens were reviewed. There were 19 women and 10 men. The mean patient age was 48.9 years (range, 23-80 years). On US, angioleiomyomas were located primarily in the subcutaneous fat layer (n = 20 [91%]), were oval (n = 17 [77%]), had well-circumscribed margins (n = 22 [100%]), had hypoechoic protrusions on one or both ends (n = 9 [41%]), had a homogeneous echo texture (n = 17 [ 77%]), had posterior acoustic enhancement (n = 20 [91%]), and had color Doppler flow (n = 20 [91%]). On MRI, the masses showed heterogeneous enhancement (n = 7 [88%]) and enhancing structures on one or both ends (n = 4 [50%]) on contrast-enhanced T1-weighted images. Angioleiomyoma of the extremities is usually a well-circumscribed oval mass with a homogeneous echo texture and occasionally hypoechoic protrusions on US and shows heterogeneous enhancement with occasionally enhancing structures on one or both ends of the mass on MRI. Therefore, it should be included in the differential diagnosis of a soft tissue mass that has protruding structures from one or both ends.


Attenuation of nonenzymatic glycation, hyperglycemia, and hyperlipidemia in streptozotocin-induced diabetic rats by chloroform leaf extract of Azadirachta indica.
The hypoglycemic effects of hexane, chloroform and methanol extracts of leaves of Azadirachta indica (AI) were evaluated by oral administration in streptozotocin-induced severe diabetic rats (SD). The effect of chronic oral administration of the extract for 28 days was evaluated in streptozotozin diabetic rats. Lipid peroxidation, glycogen content of liver and skeletal muscles, insulin, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), oxidized glutathione (GSSG) levels were determined. In addition, advanced glycation end product formation (AGEs) was evaluated. The most active extracts were obtained with chloroform. Chloroform extract from AI shows increased levels of SOD, GSH, GSSG and CAT, hepatic glycogen content, glucose-6-phosphatase and insulin plasma levels, which also decreased the glucokinase (GK), lipid peroxidation and insulin resistance. The chloroform extract exhibited significant inhibitory activity against advanced glycation end product formation with an IC(50) average range of 79.1 mg/ml. Azadirachta indica can improve hyperlipidemia and hyperinsulinema in streptozocin-induced diabetic rats and, therefore, AI can be potentially considered to be an antidiabetic-safe agent.