Psychometric assessment of the Edinburgh Postnatal Depression Scale in an obstetric population.
The prevalence and negative effects of perinatal depression are well known. The Edinburgh Postnatal Depression Scale (EPDS) is a common screening tool for perinatal depression and it is recommended for use by several professional organizations. The current study tested competing EPDS factor structures and assessed EPDS change from intake to 6-week follow-up, and identified demographic correlates in an outpatient obstetric sample. Using a retrospective observational study design, medical records were coded for demographic, mental health, and EPDS patient data (n = 524). Confirmatory factor analysis, t-tests, and ANOVA were utilized. Findings included: (1) a 3-factor model (i.e. anxiety, depression, anhedonia) of the EPDS displayed the best fit to the current data; (2) small declines in all 3 subscales of the EPDS from intake to 6-week follow-up appointments and; (3) demographic correlates of EPDS subscales included history of depression, history of anxiety, race, and pregnancy status (i.e. first child or not). The 3-factor structure can be used in clinical practice to assess perinatal depression in a nuanced fashion. Given that history of depression and anxiety are risk factors for perinatal depression, a thorough assessment of these items in clinical practice is needed.


Prognostic Value of Post-PCI Angiography-Derived Fractional Flow Reserve: A Systematic Review and Meta-Analysis of Cohort Studies.
The post-percutaneous coronary intervention (post-PCI) fractional flow reserve (FFR) can detect suboptimal PCI or residual ischemia and potentially lead to fewer adverse clinical outcomes. We sought to investigate the predictive value of the angiography-derived FFR for adverse cardiovascular events in patients after PCI. We conducted a comprehensive search of electronic databases, MEDLINE, EMBASE, and the Cochrane Library, for studies published until March 2023 that investigated the prognostic role of angiography-derived fractional flow reserve values after PCI. We investigated the best predictive ability of the post-PCI angiography-derived FFR and relative risk (RR) estimates with 95% confidence intervals (CIs) between post-PCI angiography-derived FFR values and adverse events. Thirteen cohort studies involving 6961 patients (9719 vascular lesions; mean follow-up: 2.2 years) were included in this meta-analysis. The pooled HR of the studies using specific cut-off points for post-PCI angiography-derived FFR was 4.13 (95% CI, 2.92-5.82) for total cardiovascular events, while the pooled HRs for target vessel revascularization, cardiac death, target vessel myocardial infarction, and target lesion revascularization were 6.87 (95% CI, 4.93-9.56), 6.17 (95% CI, 3.52-10.80), 3.98 (95% CI, 2.37-6.66) and 6.27 (95% CI, 3.08-12.79), respectively. In a sensitivity analysis of three studies with 1789 patients assessing the predictive role of the post-PCI angiography-derived FFR as a continuous variable, we found a 58% risk reduction for future adverse events per 0.1 increase in the post-PCI angiography-derived FFR value. In conclusion, post-PCI angiography-derived FFR is an effective tool for predicting adverse cardiovascular events and could be potentially used in decision making, both during PCI and in the long-term follow-up.


Free hand proprioception is well calibrated to verbal estimates of slanted surfaces.
We investigate the relationship between verbal and hand proprioception of slant. In Experiment 1 we demonstrate that verbally estimating free hand orientation produces overestimates by a factor of 1.67. These values are similar to those seen for verbal overestimates of slanted surfaces. In Experiment 2, participants positioned their hand to a ramp at 1 of 4 different orientations, and then verbally estimated the orientation of either their hand or the ramp. We show that verbal estimates of the ramp are a product of the orientation of their hand and the perception of the orientation of their hand. We discuss how this work is consistent with the proprioception calibration hypothesis that proposes that similar biases exist in both verbal estimates of visually perceived slant and proprioceptively perceived hand orientation and how this may explain free hand estimates to outdoor hills that are greater than actual hill orientation by a factor of ~2, but are still less than verbal (over)estimates.


Inferior Dislocation of Shoulder Complicated with Undisplaced Greater Tuberosity Fracture, Rupture of the Supraspinatus Tendon, and Brachial Plexus Injury in the Elderly: Case Report and Literature Review.
Inferior dislocation of the shoulder, also called luxatio erecta, is a rare form of the otherwise common shoulder dislocation. It appears in less than 0.5% of all shoulder dislocations. An awareness of associated potential axillary artery injury, brachial plexus complications, and rotator cuff tears is important in this rare entity and should be excluded with a high index of suspicion. In our case report, we have an 83-year-old female who inferiorly dislocated her dominant shoulder with brachial plexus injury and musculotendinous injury, which was caused by an accidental fall. The dislocation was manually reduced at the emergency department. After 18 months of conservative treatment with physical therapy, the range of motion and muscle strength of the shoulder recovered to a satisfactory mobile level according to the patient's demands.


[The clinical presentation and gene mutation of probands in Chinese patients with Charcot-Marie-Tooth disease].
To identify the gene mutation of Chinese Charcot-Marie-Tooth (CMT) pedigrees and investigate the association of gene mutation to the clinical manifestations and electrophysiology, and the underlying mechanisms. A total of 105 pedigrees with CMT in our hospital were enrolled from January, 2007 to December 2013. The clinical features, CMT neuropathy score (CMTNS) and electrophysiological data were collected. Gene mutations were analyzed using multiplex ligation-dependent probe amplification (MLPA) and Sanger gene sequencing. We found 31(29.5%) PMP22 duplication pedigrees, 8(7.6%) GJB1 mutation pedigrees, 4(3.8%) MFN2 mutation pedigrees, 4(3.8%) HSPB1 mutation pedigrees, 3(2.9%) MPZ mutation pedigrees and 1(1.0%) PMP22 mutation pedigree. In Chinese Han population, the proportion of PMP22 duplication was relatively lower than that in western countries and manifested with classical clinical characteristics of CMT. Subjects with axonal CMT often presented with isolated lower extremity injury and with central nervous system involvement. Hereditary motor neuropathy might be underestimated in clinical setting and should be differentiated from motor neuron disease. The gene frequency distribution in patients with CMT in Chinese Han population is different from that in patients from western countries. We should establish our own epidemiological data of CMT in Chinese Han population.


Tailoring a fluorophosphate as a novel 4 V cathode for lithium-ion batteries.
Lithium-ion batteries, which have been widely used to power portable electronic devices, are on the verge of being applied to new automobile applications. To expand this emerging market, however, an electrode that combines fast charging capability, long-term cycle stability, and high energy density is needed. Herein, we report a novel layered lithium vanadium fluorophosphate, Li(1.1)Na(0.4)VPO(4.8)F(0.7), as a promising positive electrode contender. This new material has two-dimensional lithium pathways and is capable of reversibly releasing and reinserting ~1.1 Li(+) ions at an ideal 4 V (versus Li(+)/Li) to give a capacity of ~156 mAh g(-1) (energy density of 624 Wh kg(-1)). Moreover, outstanding capacity retentions of 98% and 96% after 100 cycles were achieved at 60°C and room temperature, respectively. Unexpectedly high rate capability was delivered for both charge and discharge despite the large particle size (a few microns), which promises further enhancement of power density with proper nano-engineering.


Administration of perilla oil coated with Calshell increases glucagon-like peptide secretion.
Recently, we found that unsaturated long-chain fatty acids (such as alpha-linolenic acid) promote the secretion of glucagon-like peptide-1 (GLP-1) via G protein-coupled receptor GPR120, which is expressed predominantly in the colon. In order to ensure that the triglycerides or free fatty acids, such as alpha-linolenic acid, reach the distal intestinal tract effectively, we developed a Calshell technique. Following single treatment of Calshell perilla oil powder, the GLP-1 secretion level was significantly higher than following vehicle treatment, 120 min after treatment. Next, we examined the effects of long-term Calshell perilla oil powder treatment on GLP-1 secretion. Plasma GLP-1 level of Calshell perilla oil powder treatment was significantly higher than of vehicle treatment for 1, 14, 28 and 56 d. We thereby demonstrated for the first time the utility of Calshell oil powder treatment for effective and sustainable GLP-1 secretion. The Calshell technique is apparently useful as a drug delivery system, since Calshell unsaturated oil powder is protected from gastric acid, reaches enteroendocrine cells in the gastrointestinal tract, and then induces effective incretin secretion.


A case report of severe systemic herpes simplex virus-1 (HSV-1) infection with multi-organ involvement after a course of oral corticosteroid treatment.
Herpes simplex virus (HSV) rarely causes organ-invasive infection. Diagnosis and treatment for such infections are often delayed, and mortality is high. We present the first reported case of disseminated HSV-1 infection in an adult causing liver failure, myocarditis, and encephalitis in a patient who recovered after receiving parenteral acyclovir treatment. A 46-year-old female presented with fever, chills, and malaise after 2 weeks of oral corticosteroid treatment for uveitis. She was diagnosed with disseminated HSV-1 infection with multi-organ involvement causing hepatitis, encephalitis, and myocarditis. Diagnosis was made timely using serum polymerase chain reaction (PCR) for HSV DNA and the patient was given intravenous acyclovir treatment promptly, which led to her survival without significant morbidity. Clinicians should have a low threshold for suspecting HSV infection and ordering HSV PCR to decrease morbidity and mortality when there is a high clinical suspicion of systemic HSV infection with multi-organ involvement. Serum PCR for HSV DNA is an excellent modality for an initial diagnostic approach. Further research is warranted to elucidate causality between a course of corticosteroid therapy and systemic HSV-1 infection without major immunosuppressive comorbidities or treatments.


Muscle histological changes in a large cohort of patients affected with Becker muscular dystrophy.
Becker muscular dystrophy (BMD) is a severe X-linked muscle disease. Age of onset, clinical variability, speed of progression and affected tissues display wide variability, making a clinical trial design for drug development very complex. The histopathological changes in skeletal muscle tissue are central to the pathogenesis, but they have not been thoroughly elucidated yet. Here we analysed muscle biopsies from a large cohort of BMD patients, focusing our attention on the histopathological muscle parameters, as fibrosis, fatty replacement, fibre cross sectional area, necrosis, regenerating fibres, splitting fibres, internalized nuclei and dystrophy evaluation. We correlated histological parameters with both demographic features and clinical functional evaluations. The most interesting results of our study are the accurate quantification of fibroadipose tissue replacement and the identification of some histopathological aspects that well correlate with clinical performances. Through correlation analysis, we divided our patients into three clusters with well-defined histological and clinical features. In conclusion, this is the first study that analyses in detail the histological characteristics of muscle biopsies in a large cohort of BMD patients, correlating them to a functional impairment. The collection of these data help to better understand the histopathological progression of the disease and can be useful to validate any pharmacological trial in which the modification of muscle biopsy is utilized as outcome measure.


Optimal model for 4-band biorthogonal wavelets bases for fast calculation.
A class of 4-band symmetric biorthogonal wavelet bases has been constructed, in which any wavelet system the high-pass filters can be determined by exchanging position and changing the sign of the two low-pass filters. Thus, the least restrictive conditions are needed for forming a wavelet so that the free degrees can be reversed for application requirement. Some concrete examples with high vanishing moments are also given, the properties of the transformation matrix are studied and the optimal model is constructed. These wavelets can process the boundary conveniently, and they lead to highly efficient computations in applications.


Interaction of m-nitrophenylfluorone-Mo(VI) complex as a probe with human serum albumin: a fluorescence quenching study.
In this paper, the binding characteristics of human serum albumin (HSA) and m-nitrophenylfluorone (m-NPF)-molybdenum (Mo(VI)) complex have been studied by fluorophotometry. The binding constants are measured at different temperature. Based on the theory of Forster energy transfer, the binding distance and the energy transfer efficiency between m-nitrophenylfluorone-Mo(VI) complex and protein are obtained. According to the thermodynamic parameters, the main sort of binding force can be judged. The results indicate that HSA and m-NPF-Mo(VI) complex have strong interactions. The mechanism of quenching belongs to static quenching and the main sort of binding force is electrostatic gravitation.


Activation of GSDMD contributes to acute kidney injury induced by cisplatin.
Cisplatin is one of the most effective antitumor agents, but its clinical use is highly limited by its severe side effects, especially nephrotoxicity. Recently, the active form of gasdermin D (GSDMD), termed GSDMD-N, was identified to mediate pyroptotic inflammatory cell death in several diseases. However, the role of the GSDMD-N fragment in cisplatin-induced acute kidney injury (AKI) remains unclear. In the present study, we found that pyroptosis was induced by cisplatin in both mouse kidney tissues and renal tubular epithelial cells, accompanied by increased expression of the GSDMD-N fragment. In GSDMD knockout mice with cisplatin-induced AKI, we found that cisplatin-induced loss of renal function, renal tubular injury, and inflammation was significantly attenuated compared with wild-type mice. Furthermore, the GSDMD-N fragment was overexpressed by an established rapid plasmid tail vein injection approach to evaluate the role of this cleaved form of GSDMD in AKI. As expected, mice with GSDMD-N fragment overexpression in the kidney were more susceptible to cisplatin-induced AKI than control mice, as evidenced by further elevated serum levels of blood urea nitrogen and creatinine, aggravated renal pathology, increased expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, and enhanced renal inflammatory cytokine secretion, which indicates a pathogenic role of GSDMD-N in cisplatin-induced AKI by triggering cell pyroptosis. Similar results were also observed in renal tubular epithelial cells overexpressing the GSDMD-N fragment. Thus these findings suggested that the activation of GSDMD contributes to cisplatin-induced AKI, possibly through triggering pyroptosis.


A method for the refinement of data arising from electrophoresis of biological fluids.
Gingival crevicular fluid (GCF) is being analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) in our laboratory. We wish to characterize the major protein species in GCF and to investigate their association with the progression of disease. Laser densitometry of SDS/PAGE provides estimates of log molecular weight (LMW) and relative abundance for each band in each sample. Our aim was to develop a method for the refinement of these data into clusters which could be treated as distinct protein species, whose relation to disease progression could be assessed. A reproducibility study showed that the estimated LMW would fall within 3% of the true LMW 95% of the time. The method clusters the estimated LMWs of each band in each sample so that clusters form at LMWs which occurred frequently. The data from each band in each sample are thus refined into cluster number and relative abundance. Application of the technique to data from the reproducibility study showed that clusters formed around the individual components in the mixture, with little misclassification. The technique was then applied to two data sets: from SDS/PAGE of 104 GCF samples from 74 adolescents without progressive periodontal disease, and from 2 patients suffering from advanced progressive disease. The clusters appeared accurately to reflect the appearance of the gels, and clear differences were observed between the two data sets. The method will enable changes in the composition of biological fluids to be associated with external factors such as disease status and should be widely applicable.


Germination initiation and outgrowth of spores of Bacillus brevis strain Nagano and its gramicidin S-negative mutant.
Bacillus brevis strain Nagano and its gramicidin S-negative mutant, BI-7, were compared with respect to germination of their spores produced in several media. Germination initiation occurred in the presence of nutrient broth or L-alanine but not with inosine, glucose, glycerol or fructose; the process was activated by heat. Parental and mutant spores behaved similarly in these experiments. During outgrowth, parental spores remained in this phase of germination much longer than did mutant spores, but only when the parental spores had been harvested from a sporulation medium where significant gramicidin S synthesis had occurred. When parental spores were extracted or treated with an enzyme that hydrolyzes gramicidin S, rapid outgrowth occurred. Adding exogenous gramicidin S or the extract from parental spores to mutant spores lengthened the outgrowth in a dose-dependent manner. The uptake of labeled L-alanine by parental spores was delayed compared to mutant spores in the presence or absence of chloramphenicol. These data suggest a mechanism of action for gramicidin S whereby it interferes in membrane function, such as transport or energy metabolism, in outgrowing spores.


Three Separate Clinical Entities of Infective Endocarditis-A Population-Based Study From Southern Finland 2013-2017.
Health care-associated infective endocarditis (HAIE) and intravenous drug use-related IE (IDUIE) have emerged as major groups in infective endocarditis (IE). We studied their role and clinical picture in a population-based survey. A population-based retrospective study including all adult patients diagnosed with definite or possible IE in Southern Finland in 2013-2017. IE episodes were classified according to the mode of acquisition into 3 groups: community-acquired IE (CAIE), HAIE, and IDUIE. Total of 313 episodes arising from 291 patients were included. Incidence of IE was 6.48/100 000 person-years. CAIE accounted for 38%, HAIE 31%, and IDUIE 31% of IE episodes. Patients in the IDUIE group were younger, and they more frequently had right-sided IE (56.7% vs 5.0%; P < .001) and S. aureus as etiology (74.2% vs 17.6%; P < .001) compared with the CAIE group. In-hospital (15.1% vs 9.3%; P = .200) and cumulative 1-year case fatality rates (18.5% vs 17.5%; P = .855) were similar in CAIE and IDUIE. Patients with HAIE had more comorbidities, prosthetic valve involvement (29.9% vs 10.9%; P = .001), enterococcal etiology (20.6% vs 5.9%; P = .002), and higher in-hospital (27.8% vs 15.1%; P = .024) and cumulative 1-year case fatality rates (43.3% vs 18.5%; P < .001) than patients with CAIE. Staphylococcus aureus caused one-fifth of IE episodes in both groups. Our study indicates that in areas where injection drug use is common IDUIE should be regarded as a major risk group for IE, along with HAIE, and not seen as part of CAIE. Three different risk groups, CAIE, HAIE, and IDUIE, with variable characteristics and outcome should be recognized in IE.


Ambiguities and conflicting results: the limitations of the kappa statistic in establishing the interrater reliability of the Irish nursing minimum data set for mental health: a discussion paper.
In a study to establish the interrater reliability of the Irish Nursing Minimum Data Set (I-NMDS) for mental health difficulties relating to the choice of reliability test statistic were encountered. The objective of this paper is to highlight the difficulties associated with testing interrater reliability for an ordinal scale using a relatively homogenous sample and the recommended kw statistic. One pair of mental health nurses completed the I-NMDS for mental health for a total of 30 clients attending a mental health day centre over a two-week period. Data was analysed using the kw and percentage agreement statistics. A total of 34 of the 38 I-NMDS for mental health variables with lower than acceptable levels of kw reliability scores achieved acceptable levels of reliability according to their percentage agreement scores. The study findings implied that, due to the homogeneity of the sample, low variability within the data resulted in the 'base rate problem' associated with the use of kw statistic. Conclusions point to the interpretation of kw in tandem with percentage agreement scores. Suggestions that kw scores were low due to chance agreement and that one should strive to use a study sample with known variability are queried.


Data on farmers' determinants of manure and inorganic fertiliser use in the semi-arid Ethiopian Rift Valley.
This article contains the data on farmers' determinants of binary choices for manure use (i.e., manure is used or unused) and fertiliser use (i.e., fertiliser is used or unused) at their fields in semi-arid northern Ethiopian Rift Valley. The data includes (i) a schematic diagram that represents local farmers' distinctions of the crop field types in terms of the distance from their houses and soil fertility and (ii) a table that describes a representative farmer's crop sequences and soil fertilisation methods in two consecutive years. Details about the literature review of the previous case studies on farmers' determinants of manure application technique adoption conducted in some parts of sub-Saharan Africa where cattle dung is used for manure are also summarized in a table. A table shows descriptive statistics of the independent variables used in the empirical analyses. Summary statistics of 4 binomial logit models and 4 multinomial logit models are indicated in a table, which represent model fit. Last two tables exhibited in this article show the logit analyses.


Screening of kinase substrates using kinase knockout mutants.
Protein kinases are widely known to be major regulators of various signaling processes, particularly in eukaryotes, including plants. To understand their role in signal transduction pathways, it is necessary to determine which proteins are phosphorylated by these enzymes. Recent studies have applied a comparative phosphoproteomic approach to identify protein kinase substrates in plants. The results demonstrated that kinase knockout mutants are useful for screening protein kinase substrates via such a comparative analysis. Here some technical points are described for the experimental design and comparative analysis using kinase knockout mutants.


Adenosine diphosphate moiety does not participate in structural changes for the signaling state in the sensor of blue-light using FAD domain of AppA.
A sensor of blue light using FAD (BLUF) protein is a flavin adenine dinucleotide (FAD) based new class blue-light sensory flavoprotein. The BLUF domain of AppA was reconstituted in vitro from apoprotein and flavin adenine dinucleotide, flavin adenine mononucleotide or riboflavin. The light-induced FTIR spectra of the domain reconstituted from various flavins and the 13C-labeled apoprotein showed that identical light-induced structural changes occur in both the flavin chromophore and protein for the signaling state in all of the reconstituted holoproteins. The results showed that an adenosine 5'-dinucleotide moiety is not required for signaling-state formation in a BLUF domain.


Magnetic resonance imaging of embolism from intracranial aneurysms.
Two patients with embolism from unruptured intracranial aneurysms are reported. These patients experienced cerebral ischemic attacks at the ages of 10 and 64 years, respectively. Angiography revealed normal extracranial vessels and middle cerebral artery aneurysms. Preoperative magnetic resonance imaging showed intraaneurysmal clots and cerebral infarcts distal to the aneurysms. Aneurysmal neck clipping was carried out on the young patient. In the other case, the aneurysmal sac was excised, the intraluminal clot was removed, and the neck was closed with nylon sutures. These are the first cases of embolism from unruptured aneurysms in which magnetic resonance imaging revealed intraaneurysmal clots and cerebral infarcts distal to the aneurysms.


Blood Pressure and Cardiovascular Disease in Older Patients With Diabetes: Retrospective Cohort Study.
Background Blood pressure (BP) targets in elderly patients with diabetes remain unclear. We evaluated the association between BP and cardiovascular disease in elderly patients with diabetes without cardiovascular disease or heart failure. Methods and Results We performed a retrospective cohort study of 225 563 elderly (aged ≥65 years) patients with diabetes without cardiovascular disease or heart failure from 2009 to 2017 using the National Health Information Database. We divided the participants by systolic BP (SBP) and diastolic BP. Primary composite outcomes were stroke, myocardial infarction, heart failure, and all-cause death analyzed by Cox proportional hazards regression analysis adjusted for baseline covariates. During a median follow-up of 7.76 years, the incidence rate of primary composite outcomes was 26.62 per 1000 person-years. In multivariable Cox proportional hazard modeling, the risk of the primary outcome had a U-curved association with SBP/diastolic blood pressure with a nadir between 120 and 129 mm Hg/65 and 69 mm Hg, respectively. Hypertension medication was associated with lower risk of primary composite outcomes in SBP ≥140 mm Hg (P for interaction for SBP <0.001) and diastolic blood pressure ≥90 mm Hg (P for interaction for diastolic blood pressure=0.018). In participants aged ≥80 years, SBP ≥160 mm Hg was only a marginally higher risk for primary composite outcomes (hazard ratio=1.11; 95% CI, 0.98-1.24). Conclusions In this large sample of older Korean patients with diabetes, cardiovascular events were more common in people with resting SBP or diastolic BP ≥140 or 95 mm Hg, respectively, and also more common in people with resting SBP or diastolic BP <120 or 65 mm Hg, respectively.


Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics.
Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.


Impact of Mitral Regurgitation Severity and Cause on Effort Tolerance-Integrated Stress Myocardial Perfusion Imaging and Echocardiographic Assessment of Patients With Known or Suspected Coronary Artery Disease Undergoing Exercise Treadmill Testing.
Background Mitral regurgitation ( MR ) has the potential to impede exercise capacity; it is uncertain whether this is because of regurgitation itself or the underlying cause of valvular insufficiency. Methods and Results The population comprised 3267 patients who underwent exercise treadmill myocardial perfusion imaging and transthoracic echocardiography within 6±8 days. MR was present in 28%, including 176 patients (5%) with moderate or greater MR . Left ventricular systolic function significantly decreased and chamber size increased in relation to MR , paralleling increments in stress and rest myocardial perfusion deficits (all P<0.001). Exercise tolerance (metabolic equivalents of task) decreased stepwise in relation to graded MR severity ( P<0.05). Workload was significantly lower with mild versus no MR (mean±SD, 9.8±3.0 versus 10.1±3.0; P=0.02); magnitude of workload reduction significantly increased among patients with advanced versus those with mild MR (mean±SD, 8.6±3.0 versus 9.8±3.0; P<0.001). MR -associated exercise impairment was accompanied by lower heart rate and blood pressure augmentation and greater dyspnea (all P<0.05). Both functional and nonfunctional MR subgroups demonstrated significantly decreased effort tolerance in relation to MR severity ( P≤0.01); impairment was greater with functional MR ( P=0.04) corresponding to more advanced left ventricular dysfunction and dilation (both P<0.001). Functional MR predicted reduced metabolic equivalent of task-based effort (B=-0.39 [95% CI, -0.62 to -0.17]; P=0.001) independent of MR severity. Among the overall cohort, advanced (moderate or greater) MR was associated with reduced effort tolerance (B=-1.36 [95% CI, -1.80 to -0.93]; P<0.001) and remained significant ( P=0.01) after controlling for age, clinical indexes, stress perfusion defects, and left ventricular dysfunction. Conclusions MR impairs exercise tolerance independent of left ventricular ischemia, dysfunction, and clinical indexes. Magnitude of exercise impairment parallels severity of MR .


Changes in Plasma and Ovarian Steroid Hormone Level in Wild Female Blue Tang Fish Paracanthurus hepatus during a Reproductive Cycle.
This study aimed to document the seasonal cycle of steroid levels in the plasma and ovary, including testosterone (T), estradiol-17β (E2) and 17α, 20β-dihydroxy-4-pregnen-3-one (DHP) in relation to ovarian development in wild populations of female blue tang fish. The gonadosomatic index (GSI%) maintained high values from April to July and increased from the II to IV ovarian stages and dropped in the V stage. Levels of plasma, ovary T and E2 and DHP were high from March to July. Plasma T and E2 levels were low in the II stage when most oocytes were previtellogenic, reaching a peak during spawning, and decreased in the V stages when fish were going to late spawning and termination. DHP was detected in all stages of the ovary with a higher level in spawning fish but decreased after spawning. These results revealed that T, E2 and DHP could be involved in ovarian development and DHP may play a significant role as a maturational inducing hormone in blue tang fish.


Voluntary muscle coactivation in quiet standing elicits reciprocal rather than coactive agonist-antagonist control of reactive balance.
Muscle coactivation increases in challenging balance conditions as well as with advanced age and mobility impairments. Increased muscle coactivation can occur both in anticipation of (feedforward) and in reaction to (feedback) perturbations, however, the causal relationship between feedforward and feedback muscle coactivation remains elusive. Here, we hypothesized that feedforward muscle coactivation would increase both the body's initial mechanical resistance due to muscle intrinsic properties and the later feedback-mediated muscle coactivation in response to postural perturbations. Young adults voluntarily increased leg muscle coactivation using visual biofeedback before support-surface perturbations. In contrast to our hypothesis, feedforward muscle coactivation did not increase the body's initial intrinsic resistance to perturbations, nor did it increase feedback muscle coactivation. Rather, perturbations with feedforward muscle coactivation elicited a medium- to long-latency increase of feedback-mediated agonist activity but a decrease of feedback-mediated antagonist activity. This reciprocal rather than coactivation effect on ankle agonist and antagonist muscles enabled faster reactive ankle torque generation, reduced ankle dorsiflexion, and reduced center of mass (CoM) motion. We conclude that in young adults, voluntary feedforward muscle coactivation can be independently modulated with respect to feedback-mediated muscle coactivation. Furthermore, our findings suggest feedforward muscle coactivation may be useful for enabling quicker joint torque generation through reciprocal, rather than coactivated, agonist-antagonist feedback muscle activity. As such our results suggest that behavioral context is critical to whether muscle coactivation functions to increase agility versus stability.NEW & NOTEWORTHY Feedforward and feedback muscle coactivation are commonly observed in older and mobility impaired adults and are considered strategies to improve stability by increasing body stiffness prior to and in response to perturbations. In young adults, voluntary feedforward coactivation does not necessarily increase feedback coactivation in response to perturbations. Instead, feedforward coactivation enabled faster ankle torques through reciprocal agonist-antagonist muscle activity. As such, coactivation may promote either agility or stability depending on the behavioral context.


Lithium attenuates lead induced toxicity on mouse non-adherent bone marrow cells.
Lead is a poisonous heavy metal that occurs in all parts of environment and causes serious health problems in humans. The aim of the present study was to investigate the possible protective effect of lithium against lead nitrate induced toxicity in non-adherent bone marrow stem cells. Trypan blue and MTT assays represented that exposure of the cells to different concentrations of lead nitrate decreased viability in a dose dependent manner, whereas, pretreatment of the cells with lithium protected the cells against lead toxicity. Lead reduced the number and differentiation status of bone marrow-derived precursors when cultured in the presence of colony stimulating factor (CSF), while the effect was attenuated by lithium. The cells treated with lead nitrate exhibited cell shrinkage, DNA fragmentation, anion superoxide production, but lithium prevented lead action. Moreover, apoptotic indexes such as PARP cleavage and release of HMGB1 induced by lead, were protected by lithium, suggesting anti-apoptotic effect of lithium. Immunoblot analysis of histone H3K9 acetylation indicated that lithium overcame lead effect on acetylation. In conclusion, lithium efficiently reduces lead toxicity suggesting new insight into lithium action which may contribute to increased cell survival. It also provides a potentially new therapeutic strategy for lithium and a cost-effective approach to minimize destructive effects of lead on bone marrow stem cells.


Supra-long chain surfactants with double or triple quaternary ammonium headgroups.
Novel supra-long chain surfactants with double or triple quaternary ammonium salts (C(n)-2Am, C(n)-3Am, in which n represents a hydrocarbon chain length of 18, 20, and 22) were synthesized, and electrical conductivity and surface tension were used to characterize their properties depending on both the hydrocarbon chain length and number of hydrophilic groups. The Krafft temperatures decreased remarkably with an increase in the quaternary ammonium headgroups, resulting in a high solubility in water. The critical micelle concentration (cmc) increased with an increase in the number of quaternary ammonium moieties in the hydrophilic group, and the difference in the cmc was smaller for C(n)-2Am and C(n)-3Am than for C(n)-2Am and C(n)-Am of alkyltrimethylammonium bromide. The surface tension at the cmc was approximately 45 and 48 mN m(-1) for C(n)-2Am and C(n)-3Am with n=18-22, respectively. This indicated that the supra-long chain surfactants could not efficiently adsorb at the air/water interface and orient by themselves, as is known for conventional surfactants.


Development and validation of an analytical protocol for the sampling and quantitative analysis of ions on the surface of unstable historic glass in museum collections using ion-exchange chromatography.
The early identification of unstable glass objects in museum collections is essential for their conservation, but as yet cannot be accomplished straightforwardly. Accordingly, this paper describes the development and validation of a simple protocol for quantitative determination of ions characteristic of the chemical decay of historic glass, using surface swabbing combined with ion-exchange chromatography. The establishment of a robust protocol is an important step in the development of an early warning system for the chemical deterioration of unstable glass. Using a model system, the protocol was validated for specificity, linearity, accuracy, precision, limits of detection, and limits of quantification for 10 anionic species (fluoride, acetate, formate, chloride, nitrite, bromide, nitrate, carbonate, sulfate and phosphate) and 6 cationic species (lithium, sodium, ammonium, potassium, magnesium and calcium). Good validation parameters (R2 > 0.995; RSD < 5%; Recovery 90-100%) were obtained for acetate, formate, nitrite, nitrate, phosphate, lithium, sodium, potassium, magnesium and calcium. Chloride (R2 = 0.934; RSD = 13.6%; recovery 71.4%) and carbonate (R2 = 0.993; RSD = 10.3%; recovery 120%) had poor validation parameters. Sulfate had low recovery (78.2%), but high reproducibility (RSD = 4.32%) with R2 = 0.997. Limits of quantification were below 1 mg/L for all analytes, which is satisfactory for the study of unstable glass in museum collections. The validated sampling protocol was trialled using artificially aged unstable glass fragments, which resulted in a high relative standard deviation (between 1 and 30%). The ability to achieve improved care of historic glass by application of the validated protocol in museum collections is discussed in the context of a pilot study undertaken at the Rijksmuseum, Amsterdam.


Aspergillus nidulans as a model system to characterize the DNA damage response in eukaryotes.
Interest in DNA repair in Aspergillus nidulans had mainly grown out of studies of three different biological processes, namely mitotic recombination, inducible responses to detrimental environmental changes, and genetic control of the cell cycle. Ron Morris started the investigation of the genetic control of the cell cycle by screening hundreds of cell cycle temperature sensitive Aspergillus mutants. The sequencing and innovative analysis of these genes revealed not only several components of the cell cycle machinery that are directly involved in checkpoint response, but also components required for DNA replication and DNA damage response machinery. Here, we will provide an overview about currently known aspects of the DNA damage response in A. nidulans. Emphasis is put on analyzed mutants that are available and review epistatic relationships and other interactions among them. Furthermore, a comprehensive list of A. nidulans genes involved in different processes of the DNA damage response, as identified by homology of genome sequences with well-characterized human and yeast DNA repair genes, is shown.


The role of growth hormone in determining birth size and early postnatal growth, using congenital growth hormone deficiency (GHD) as a model.
The role of GH in early human growth is unclear. Congenital GH deficiency (CGHD) provides a useful tool to explore this putative role. We have assessed the effects of CGHD on birth size and early postnatal growth, and the further impact of the presence of additional pituitary hormone deficiencies and midline brain defects on these parameters. Weight, length and BMI expressed as standard deviation scores (SDS), over the first two years of life, were retrospectively compared in 44 GH-deficient children (M:F 26 : 18). Thirty-eight of 44 patients underwent GH provocation testing and all patients had neuro-imaging of the brain. The patients were divided into three groups of increasing phenotypic complexity {group A [n = 12, isolated GHD, no midline defects], group B [n = 10, combined pituitary hormone deficiency (CPHD); no midline defects], group C (n = 22, CPHD with midline defects)}. Mean birth weight, length and BMI SDS were -0.4, -0.9 and +0.1 SDS, respectively. The differences were significant for weight (P = 0.03) and BMI (P = 0.003), but not length (P = 0.3) SDS, between groups A and C. Of the three groups, group A had a lower weight and BMI SDS than group C. The prevalence of postnatal complications (n = 25) was significantly different in the three groups [group A (8%), group B (80%), group C (73%); P < 0.001] and particularly between patients with isolated GH deficiency (IGHD) (group A) and CPHD (groups B and C; P < 0.0001). No patients in group A presented with neonatal hypoglycaemia as compared with 70% of those in group B and 59% in group C (P = 0.001). A reduced length SDS was observed in all patients within 6 months of birth and the reduction was greatest in group B (P = 0.03). Group C remained significantly (P < 0.05) heavier at 12, 18 and 24 months compared to group A. BMI SDS was significantly (P < 0.05) greater at all study points in CPHD patients (groups B and C) as compared with IGHD. Serum GH concentrations at testing did not correlate significantly with birth length (r = -0.08, P = 0.7), birth weight (r = -0.08, P = 0.6) or the age at induction of GH treatment (r = 0.12, P = 0.5). There were no significant differences between peak serum GH concentrations in patients in groups A (7.8 +/- 6.3 mU/l), B (3.9 +/- 4.8 mU/l) or C (8.7 +/- 5.4 mU/l). Length, weight and BMI data from our study groups suggest that GH per se has a minimal effect on intrauterine growth but a significant effect during the infancy period. Early growth may also be influenced by the complexity of the hypopituitary phenotype reflected by the presence of additional pituitary hormone deficiencies and midline forebrain defects.


Problems of undergraduate medical education in Saudi Arabia.
Throughout the world there are problems associated with undergraduate medical education, and likewise in Saudi Arabia. In this paper, some of these problems are discussed and solutions suggested, in the context of a survey conducted at the Faculty of Medicine of King Abdulaziz University with fourth-year medical students dealing with the language of medical instruction.


What Does Influence the Neonatal Microbiome?
This editorial aims to provide a concise summary of the factors involved in the dynamics of microbiome establishment and maturation. At the same time, it briefly updates the current knowledge and opens new questions in this regard. Many factors act as drivers of the microbiota's development at both pre- and post-natal levels (e.g., maternal factors, antibiotic usage, type of delivery, dietary pattern, post-natal feeding type, etc.). However, it is interesting to research into its real impact, the relationship between these external modulators, and how to modulate them. The are great opportunities for new research in the field.


Comparative evaluation of galactomannan test with bronchoalveolar lavage and serum for the diagnosis of invasive aspergillosis in patients with hematological malignancies.
Invasive pulmonary aspergillosis (IPA) is a major cause of morbidity and mortality in patients with hematological malignancies. In recent years, testing for values of galactomannan (GM) in serum and bronchoalveolar lavage (BAL) fluid has been investigated as a diagnostic test for IPA for such patients, but global experience and consensus on optical density (OD) cutoffs, especially for BAL galactomannan remains lacking. We performed a prospective case-control study to determine an optimal BAL GM OD cutoff for IPA in at-risk patients. Cases were subjects with hematological diagnoses who met established revised definitions for proven or probable IPA established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group (EORTC/MSG, 2008), without the use of BAL GM results. Exclusion criteria included the use of piperacillin/tazobactam and use of antifungals that were active against Aspergillus spp. before bronchoscopy. There were two control groups: patients with hematological diagnoses not meeting definitions for proven or probable IPA and patients with nonhematological diagnoses with no evidence of aspergillosis. Following bronchoscopy and BAL, GM testing was performed using the Platelia Aspergillus seroassay in accordance with the manufacturer's instructions. There were 51 cases and 20 controls. Cases had higher BAL fluid GM OD indices (ODIs) (mean: 1.27 and range: 0.4-3.78) compared with controls (mean: 0.26 and range: 0.09-0.35). Receiver operating characteristic analysis demonstrated an optimum ODI cutoff of 1.0, with high specificity (100%) and sensitivity (87.5%) for diagnosing IPA. Our results support BAL GM testing as a reasonably safe test with higher sensitivity compared to serum GM testing in at-risk patients with hematological diseases. A higher OD cutoff is necessary to avoid overdiagnosis of IPA.


A review of quality of life (QOL) assessments and indicators: Towards a "QOL-Climate" assessment framework.
Quality of life (QOL), although a complex and amorphous concept, is a term that warrants attention, especially in discussions on issues that touch on the impacts of climate change and variability. Based on the principles of RepOrting standards for Systematic Evidence Synthesis, we present a systematic review aimed at gaining insights into the conceptualization and methodological construct of previous studies regarding QOL and QOL-related indexes. We find that (i) QOL assessments vary in terms of conceptual foundations, dimensions, indicators, and units of analysis, (ii) social indicators are consistently used across assessments, (iii) most assessments consider indicators that pertain to the livability of the environment, and (iv) QOL can be based on objective indicators and/or subjective well-being, and on a composite index or unaggregated dimensions and indicators. However, we also find that QOL assessments remain poorly connected with climate-related issues, an important research gap. Our proposed "QOL-Climate" assessment framework, designed to capture the social-ecological impacts of climate change and variability, can potentially help fill this gap.


Primary stability of a cementless modular revision hip stem in relation with the femoral defect size: A biomechanical study.
Cementless modular fluted hip stems are commonly used in revision arthroplasty. Nevertheless, there is a wide spectrum of recommendations concerning the minimum bone stock required to enable osseous ingrowth and implant-bone micromotions <100 µm. This experimental study investigated the primary stability of a tapered cementless fluted revision stem depending on different types of bone defects. Implant-bone interface movements with a bimodular stem were examined under cyclic axial and torsional loading using composite femora. In four degrees of freedom, the implant subsidence and micromotions were captured with linear variable differential transformers for the intact femora and seven different defects ranging from Paprosky type I to type IIIB. With a 7-cm length of intact diaphysis proximal to the isthmus (Paprosky IIIA), mean implant-bone micromotions of 66 µm occurred. An implant-bone contact zone of only 5 cm (Paprosky IIIA) resulted in micromotions notably over 100 µm and significantly increased subsidence (p < 0.05). With a Paprosky IIIB defect (3 cm of intact diaphysis) rotational instability occurred in all specimens. Aside from critically increased interfacial micromotions (>100 µm), rotational instability emerged as a mechanism of fixation failure when the implant-bone contact zone was only 5 cm or less. Hence, future studies investigating the implant fixation in the case of femoral bone defects should consider both axial and torsional loading. With regard to the clinical application, our data suggest maintaining 7 cm of diaphyseal implant-bone contact for a safe anchorage of cementless fluted hip revision stems.


PaperClip DNA Assembly: Reduce, Reuse, Recycle.
Creating DNA constructs is a basic and fundamental step in molecular and synthetic biology. While prices for gene synthesis are decreasing, it is still more economical in most cases to assemble constructs from a library of components (Parts). Many methods for DNA assembly are available, but most require either a fixed and inflexible format for the construct, with all Parts first being cloned in specific donor plasmids, or remaking Parts with new homology ends for each specific assembly reaction, requiring large numbers of single-use oligonucleotides. PaperClip assembly allows Parts stored in any format (linear PCR products or synthetic DNA, or cloned in any plasmid) to be used in totally flexible assembly reactions; up to 11 parts can be assembled in a single reaction, in any order, to give a linear or circular construct, and the oligonucleotides required in the assembly process can be reused in any subsequent assembly. In addition to constructing plasmids for bacterial transformation, PaperClip is also well suited to generate linear products for direct transfection of yeast, mammalian, or cyanobacterial cell lines. Thus, PaperClip offers a simple, flexible, and economical route to multipart assembly of constructs for a wide variety of purposes.


Multimodal MR imaging signatures to identify brain diffuse midline gliomas with H3 K27M mutation.
Conventional MR imaging has limited value in identifying H3 K27M mutations. We aimed to investigate the capacity of quantitative MR imaging variables in identifying the H3 K27M mutation status of diffuse midline glioma. Twenty-three patients with H3 K27M mutation and thirty-two wild-type patients were recruited in this retrospective study, all of whom underwent multimodal MR imaging. Clinical data and quantitative MR imaging variables were explored by subgroup analysis stratified by age (juveniles and adults). Then, a logistic model for all patients was constructed to identify potential variables for predicting K27M mutation status. Besides, a retrospective validation set including 13 patients was recruited. The C-index and F1 score were used to evaluate the performance of the prediction model. It turned out that patients with H3 K27M mutation were younger in the adult subgroup. In the mutation group, some relative apparent diffusion coefficient (rADC) histogram parameters and myo-inositol/creatine plus phosphocreatine (Ins/tCr) ratio were lower than in the wild-type group of both juveniles and adults (p < 0.05). After nested cross-validation and LASSO algorithm, the age, Ins/tCr, and rADC_15th were selected as potential predictors for H3 K27M mutation in the model. The nomogram model showed good diagnostic power with a validated C-index of 0.884. In addition, the area under the curve (AUC) was 0.898 (0.976 in validation set) and the F1 score was 0.732. In conclusion, age, rADC_15th, and Ins/tCr values were helpful in identifying H3 K27M mutations in midline gliomas.


Mapping the functional domains of TCblR/CD320, the receptor for cellular uptake of transcobalamin-bound cobalamin.
The membrane receptor TCblR/CD320 binds transcobalamin (TC) saturated with vitamin B12 [cobalamin (Cbl)] and mediates cellular uptake of the vitamin. The specificity of TC for Cbl and of the receptor for TC-Cbl ensures efficient uptake of Cbl into cells. The high-affinity interaction of TCblR with TC-Cbl (Ka=10 nM(-1)) was investigated using deletions and mutations of amino acid sequences in TCblR. Only the extracellular region (aa 32-229) is needed for TC-Cbl binding, but the N-glycosylation sites (N126, N195, and N213) are of no importance for this function. Deleting the cysteine-rich region (aa 95-141) that separates the two low-density lipoprotein receptor type A (LDLR-A) domains does not affect TC-Cbl binding (Ka = 19-24 nM(-1)). The two LDLR-A domains (aa 54-89 and 132-167) with the negatively charged acidic residues involved in Ca(2+) binding are critical determinants of ligand binding. The cytoplasmic tail is apparently crucial for internalization of the ligand. Within this region, the RPLGLL motif and the PDZ binding motifs (QERL/KESL) appear to be involved in initiating and completing the process of ligand internalization. Mutations and deletions of these regions involved in binding and internalization of TC-Cbl are likely to produce the biochemical and clinical phenotype of Cbl deficiency.


Flow cytometric analysis of bacteria- and virus-like particles in lake sediments.
Flow cytometry (FCM) was successfully used to analyze freshwater bacteria and viruses in lake sediments after relatively simple sample treatment and optimization of dilution/fixation/staining procedures. Biological particles from Lakes Geneva and Bourget were first separated from the sediments by using both Sodium Pyrophosphate (0.01 M final concentration) and Polyoxyethylene-Sorbitan Monooleate (10% final concentration) and sonicating for 3 min in a water bath. The best results (based on FCM signature and the highest virus and bacterial yields from the sediments) were obtained by formaldehyde fixation carried out within less than one hour (2% final concentration, vs. no fixation or using glutaraldehyde at different concentrations), SYBR-Green II staining (x1/20,000 stock solution concentration, vs. use of SYBR-Gold and SYBR-Green I dyes at different concentrations). There was a considerable loss of particles after only a few days of storage at either 4 or -22 degrees C. For FCM analysis, the samples were diluted in Tris-EDTA buffer (pH 8) and heated for 10 min at 75 degrees C after incubating for 5 min in the dark. The bacterial and viral counts paralleled those obtained using epifluorescence microscopy (EFM), but EFM always gave lower counts than FCM. Analysis of the distribution of the viruses in the water column and in the sediments of Lakes Bourget revealed a marked gradient, with larger quantities in the top layer of the sediment than in the water above it. These results are discussed, as well as the possible novel application of flow cytometry in the study of aquatic viral ecology.


Structural fluctuations between two conformational states of a transmembrane helical peptide are related to its channel-forming properties in planar lipid membranes.
Putative transmembrane helices of membrane proteins in general and channel proteins in particular often contain proline residues which may induce a bend into an otherwise regular helical structure. Here we show by fluorescence-energy-transfer measurements and molecular-dynamics calculations that, in the case of synthetic bilayer-spanning helical polypeptides, a proline-induced bend in a helix acts as a flexible element mediating rigid body motions of the helical segments. Most important, such structural fluctuations in the transmembrane helices seem to play a functional role in the formation of ionic channels in planar lipid bilayers and biological membranes.


Bridging a DNA Break to Leave a Poly(ADP-Ribose) Mark on Chromatin.
Bilokapic at al. (2020) capture PARP2 and its accessory factor HPF1 bridging a DNA break between two nucleosomes, providing a captivating view of the context in which PARP2/HPF1 employ ADP-ribose protein modification to coordinate DNA repair and alter chromatin structure.


Medical views on the death by crucifixion of Jesus Christ.
The death of Jesus Christ remains a pivotal moment in world history and a symbol of love, mercy, and courage across the globe. Yet for centuries, the manner of Jesus' death has remained a subject of controversy in academic and medical circles. Forensic pathologists and clinicians have argued for several hypotheses concerning Jesus' death, including pulmonary embolism, cardiac rupture, suspension trauma, asphyxiation, fatal stab wound, and shock. This article surveys a broad range of medical and other specialist views regarding Jesus' experience on the cross, concluding that asphyxiation or asphyxiation-dominant theories have emerged as the consensus position regarding the cause of Jesus' death. Two features of this article are significant. First, it provides a rich resource of different medical opinions regarding the effects of Jesus' crucifixion. Second, and more importantly, the survey results show that, perhaps less similar to crucifixion in general, there is a growing consensus regarding Jesus' cause of death by medical professionals. A table maps these results, summarizing for those in the medical field as well as historians and theologians what medical professionals consider to be the cause of Jesus' death.


[Control of Respiratory Symptoms During Sleep in Patients with Stable Bronchial Asthma].
Awareness of respiratory symptoms during day- and night-time is important for asthma control. Acoustic long-term recording offers a possibility to monitor symptoms objectively. In this prospective observational study frequency of night-time cough and wheezing was evaluated in patients with stable asthma. Night-time cough and wheezing were monitored by LEOSound lung sound monitor in 40 patients with stable asthma. Patients did not complain of respiratory problems during day- and nighttime, asthma control test was 23 points on average. FEV1 was 84 ± 15 %; MEF 50 71 ± 27 % and Rtot 0,48 ± 0,18 kPas/l. The age of the patients was 35 ± 11 years. All patients had an antiobstructive and/or anti-inflammatory medication. The present study focuses on description of frequency, severity and characteristics of night-time symptoms like cough and wheezing in patients with stable asthma and tries to depict differences in patients who present cough or wheezing. Wheezing was monitored in 2 of the 40 patients. In the first patient duration of wheezing was 19 min, in the second 55 min. Lung function in patient 1 showed a moderate bronchial obstruction, he was still smoking. Patient 2 was a non-smoker with a significant bronchial obstruction (FEV1 49 %; MEF 50 27 % and Rtot 0,52 kPas/l). In 26 patients there was no coughing, 14 patients had 4 ± 3 (2 - 13) cough epochs during the night. By dividing the collective in two groups differentiated by the presence of cough/ no cough we found no significant differences regarding lung function and ACT-scores. Both patients with night-time wheezing presented low ACT- Scores (20 and 21 points). Nocturnal wheezing and cough episodes were detectable in 2 respectively 14 patients with stable asthma. Long-term recording of normal and adventitious breath sounds offers a practical opportunity to evaluate night-time cough and wheezing objectively.


Effect of trans-bullar gentamicin treatment on guinea pig angular and linear vestibulo-ocular reflexes.
This study provides the first systematic examination of the effects of intratympanic gentamicin instillation on vestibulo-ocular responses of guinea pigs during both Earth-vertical yaw axis and off-vertical axis rotation. A scleral search coil was sutured to the right eye of pigmented female guinea pigs prior to trans-bullar instillation of a 0.2-ml bolus of either 20 mg/ml or 40 mg/ml of gentamicin (1) into the right middle ear (unilateral treatment groups) or (2) into both ears (bilateral treatment groups). Two weeks later, eye movement responses were tested during yaw axis sinusoidal rotation at 7 frequencies (0.02, 0.05, 0.1, 0.2, 0.5, 1 and 2 Hz, 40 deg/s peak velocity) and during off-vertical axis rotation at five constant velocities (20, 40, 60, 80 and 100 deg/s), tilted 30 deg relative to the earth-vertical axis. The main result was that unilateral trans-bullar gentamicin instillation produced almost exclusively unidirectional deficits in horizontal angular vestibulocular reflex (HVOR) responses and modulation and bias responses to off-vertical axis rotation (OVAR). The HVOR gain was reduced during rotation toward the injected ear in a dose-dependent manner for frequencies of 1 Hz and lower, but there was no effect on responses during rotation toward the intact ear. Further, the modulation and bias responses to OVAR were reduced profoundly in a dose-dependent manner during rotation toward the treated ear. It is suggested that these effects indicate selective cytotoxic and/or physiologic effects of gentamicin intoxication in the inner ear or, possibly, the vestibular nerve and central nervous system.


[Psoriatic arthritis].
Psoriatic arthritis is a comorbidity frequently associated to psoriasis. A major problem is the absence of diagnostic criteria and the lack of consensus on the classification criteria of this arthritis. The clinical presentation is extremely variable, since axial, peripheric, and enthesopathic lesions can exist alone, successively or in association in a same patient. Peripheric lesions can be mono- or more often oligo- or polyarthritis. Onychopathies and dactylitis are frequently associated to arthritis. The dermatologist must recognize psoriatic arthritis at an early stage, in order to avoid the development of destructive lesions. The treatment includes symptomatic treatments (antalgics, non steroidal anti-inflammatory agents, corticosteroids), long-term treatments (sulfasalazine, methotrexate, azathioprine, ciclosporine, leflunomide), and TNF-alpha-inhibitors. Therapeutic strategies must be adapted to the clinical presentation.


Systemic-pulmonary shunts in infants and children. Early and late results.
From September, 1978, to January, 1983, 44 cyanotic infants and children underwent a systemic-pulmonary artery shunt for the treatment of reduced pulmonary blood flow. Age ranged from 18 hours to 4 years (mean age = 0.49 years). Weight ranged from 1.7 kg to 13.2 kg (mean weight = 4.9 kg). There were 12 classic Blalock-Taussig shunts, five central polytetrafluoroethylene shunts, six interposition modified Blalock-Taussig shunts, and 21 Great Ormond Street type of modified Blalock-Taussig shunts. No direct aorta-pulmonary artery anastomoses were performed. There was one postoperative death (1/44 = 2.3%) in a 1,700 gm neonate born with pulmonary atresia and intact ventricular septum (shunt patent). Four shunts required early revision: one thrombosed central shunt, a kinked patent interposition Blalock-Taussig shunt, a small but patent Blalock-Taussig shunt, and one excessive Great Ormond Street type of Blalock-Taussig shunt. Two late deaths were probably shunt-related: one Blalock-Taussig and one central. All four types of shunts provided good palliation, but the Great Ormond Street type of Blalock-Taussig shunt is our preferred shunt because of (1) low operative risk, (2) predictable patency (100% in our series), (3) lack of distortion of pulmonary arterial anatomy, and (4) technical ease of insertion as well as takedown.


Anti-inflammatory effect of a sulphated polysaccharide fraction extracted from the red algae Hypnea musciformis via the suppression of neutrophil migration by the nitric oxide signalling pathway.
The aim of this study was to evaluate the anti-inflammatory effect of a sulphated polysaccharide fraction (PLS) extracted from the alga Hypnea musciformis and investigate the possible involvement of the nitric oxide (NO) pathway in this effect. The anti-inflammatory activity of PLS was evaluated using inflammatory agents (carrageenan and dextran) to induce paw oedema and peritonitis in Swiss mice. Samples of paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity, NO3 /NO2 levels, and interleukin-1β (IL-1β) level. The involvement of NO in the modulation of neutrophil migration in carrageenan-induced paw oedema or peritonitis was also investigated. Compared with vehicle-treated mice, mice pretreated with PLS (10 mg/kg) inhibited carrageenan-induced and dextran-induced oedema; it also inhibited total and differential peritoneal leucocyte counts in a model of peritonitis. These PLS effects were reversed by l-arginine treatment and recovered with the administration of a NO synthase blocker (aminoguanidine). Furthermore, PLS reduced the MPO activity, decreased IL-1β levels, and increased NO3 /NO2 levels in the peritoneal cavity. PLS reduced the inflammatory response by modulating neutrophil migration, which appeared to be dependent on the NO pathway.


Behavior and lineage progression of neural progenitors in the mammalian cortex.
The cerebral cortex is a central structure in the mammalian brain that enables higher cognitive functions and intellectual skills. It is the hallmark of the mammalian nervous system with enormous complexity, consisting of a large number of neurons and glia that are diverse in morphology, molecular expression, biophysical properties, circuit connectivity and physiological function. Cortical neurons and glia are generated by neural progenitor cells during development. Ensuring the correct cell cycle kinetics, fate behavior and lineage progression of neural progenitor cells is essential to determine the number and types of neurons and glia in the cerebral cortex, which together constitute neural circuits for brain function. In this review, we discuss recent findings on mammalian cortical progenitor cell types and their lineage behaviors in generating neurons and glia, cortical evolution and expansion, and advances in brain organoid technology that allow the modeling of human cortical development under normal and disease conditions.


[How do Psychiatric Executives Evaluate the Inclusion of Experienced Patients as Peer Workers? - Results from an Explorative Interview Study].
This study aimed at investigating the perspective of executives on the implementation of peer support in psychiatric facilities - an aspect that has been insufficiently addressed in research so far. We guided qualitative interviews with eleven executives of psychiatric institutions from Germany and Switzerland, in which peer workers are employed. The interview transcripts were evaluated according to the principles of content analysis. The study participants evaluated the inclusion of peer workers very positively overall. Peer support was described as a special quality feature of a psychiatric institution. In addition, improvements were reported with regard to a more respectful and conscious interaction with colleagues and patients as well as a more positive therapeutic climate. Based on their experience, the executives named a number of change management tasks, e. g. with regard to the preparation of the organization, personnel selection and financing, job descriptions and the integration of the peer workers in the team. Our results underline the specific advantages of peer support for the further development of psychiatric practice. Some implications for personnel management are discussed.


Demonstration of dose dependent cytotoxic activity in SW480 colon cancer cells by ¹⁷⁷Lu-labeled siRNA targeting IGF-1R.
The radiolabeling of targeting biomolecules with gamma emitter radionuclides for tracing and beta emitters for therapy involves the conjugation of such biomolecules to the chelating agents to form complexes with the radionuclide of interest. In this study, radioconjugate of IGF-1R siRNA with lutetium-177 ((177)Lu) was produced, and the anti-proliferation and apoptosis effects elicited by this (177)Lu-siRNA complex in the SW480 colon cancer cells were evaluated. IGF-1R and Luciferase siRNAs were conjugated with p-SCN-Bn-DTPA, and then radiolabeled with (177)Lu. The effects of labeled and non-labeled IGF-1R siRNAs on IGF-1R expression were assessed with RT-PCR analysis and ELISA assay. IGF-1R siRNAs induced cell death and apoptosis were investigated using MTT assay and Annexin-V/propidium iodide (PI) double staining, respectively. Combined purification using Vivaspin and PD-10 columns resulted in a radiochemical purity of 97.32% ± 1.97%. Knockdown effect of the labeled IGF-1R siRNA was not significantly different from the non-labeled duplex of the same sequence (P<0.05), but it was significant compared to the Luciferase siRNAs (P<0.001). Proliferation decreased significantly, but apoptosis increased in the cells treated with the (177)Lu-IGF-1R siRNA in comparison with either (177)Lu or IGF-1R siRNA (P<0.001). Radioconjugate of IGF-1R siRNA, p-SCN-Bn-DTPA and (177)Lu was successfully produced and characterized as radiopharmaceutical. The present study demonstrates the involvement of (177)Lu-labeled IGF-1R siRNA in the inhibition of cell growth and induction of apoptosis in colon cancer cells.


Inhibition of the Na,K-ATPase by fluoride. Parallels with its inhibition of the sarcoplasmic reticulum CaATPase.
Addition of lithium fluoride to a suspension of Na,K-ATPase undergoing turnover produced a slow (minutes) complete loss of ouabain-sensitive ATPase activity. Persistence of the effect in the presence of deferoxamine showed that fluoride inhibits independent of aluminum. The time course of onset of inhibition was adequately fit by a function corresponding to a monophasic transformation with a pseudo first-order rate constant (k(obs)). This constant varied hyperbolically with [Mg2+] (half-maximal effect at 9 mM Mg2+), whereas it increased with no sign of approaching saturation as the square of [F-], implying that inhibition requires binding of two fluorides/ATPase. The value of k(obs) was found to be increased by greater than 10-fold in the presence of potassium ([K+]1/2 = 0.6 mM) or ouabain. Sodium, ATP, and ADP, which favor the E1 form of the enzyme, had a protective effect. These results implicate the potassium-occluded MgE2(K2) complex as the main fluoride-susceptible form. Protection by Pi and orthovanadate suggests that fluoride exerts its effect at the phosphorylation site. Inhibition was reversible, although slowly, with t1/2 = 7 h at 37 degrees C. Sodium greatly accelerated reversal (t1/2 = 3 min with 150 mM Na+ present), and potassium antagonized this acceleration. The value of k(obs) for reactivation increased steeply with [Na+], with the sodium dependence being about the same at pH 8.0 as at pH 7.4. All of these effects have parallels to effects of fluoride on the sarcoplasmic reticulum CaATPase (Murphy, A. J., and Coll, R. J. (1992) J. Biol. Chem. 267, 5229-5235).


Perforated marginal ulcer after palliative gastrojejunostomy.
We describe a patient in whom biliary bypass and gastrojejunostomy for palliation of carcinoma of the head of the pancreas led to the late development of a marginal ulcer, which perforated and may have hastened the patient's death.


Zoledronic acid decreased osteolysis but not bone metastasis in a nude mouse model of canine prostate cancer with mixed bone lesions.
Bone metastasis is the most common cause of morbidity and mortality in patients with advanced prostate cancer and is manifested primarily as mixed osteoblastic and osteolytic lesions. However, the mechanisms responsible for bone metastases in prostate cancer are not clearly understood, in part due to the lack of relevant in vivo models that mimic the clinical presentation of the disease in humans. We previously established a nude mouse model with mixed bone metastases using intracardiac injection of canine prostate cancer cells (Ace-1). In this study, we hypothesized that tumor-induced osteolysis promoted the incidence of bone metastases and osteoblastic activity. We studied the effect of inhibition of osteolysis with zoledronic acid (ZA) on the prevention and progression of Ace-1 bone metastases in nude mice using prophylactic and delayed treatment protocols. Bioluminescent imaging, radiography, and histopathological evaluation were performed to monitor the effect of ZA on the incidence, progression and nature of bone metastases. Unexpectedly, there was no significant difference in tumor burden and the incidence of metastasis between control and treatment groups as detected by bioluminescent imaging and bone histomorphometry. However, radiographic and histopathological analysis showed a significant treatment-related decrease in osteolysis, but no effect on tumor-induced trabecular bone thickness in both treatment groups compared to controls. Our results demonstrated that the incidence of prostate cancer bone metastases in vivo was not reduced by zoledronic acid even though zoledronic acid inhibited bone resorption and bone loss associated with the mixed osteoblastic/osteolytic bone metastases in the Ace-1 model.


Inhibition of class-3 aldehyde dehydrogenase and cell growth by restored lipid peroxidation in hepatoma cell lines.
Hepatoma cells have a below-normal content of polyunsaturated fatty acids; this reduces lipid peroxidation and the production of cytotoxic and cytostatic aldehydes within the cells. In proportion to the degree of deviation, hepatoma cells also show an increase in the activity of Class-3 aldehyde dehydrogenase, an enzyme important in the metabolism of lipid peroxidation products and also in that of several drugs. When hepatoma cells with different degrees of deviation were enriched with arachidonic acid and stimulated to peroxidize by ascorbate/iron sulphate, their growth rate was reduced in proportion to the quantity of aldehydes produced and to the activity of aldehyde dehydrogenase. Therefore, 7777 cells, less deviated and with low Class-3 aldehyde dehydrogenase activity, were more susceptible to lipid peroxidation products than JM2 cells. It is noteworthy that repeated treatments with prooxidant also caused a decrease in mRNA and activity of Class-3 aldehyde dehydrogenase, contributing to the decreased growth and viability. Thus, Class-3 aldehyde dehydrogenase could be considered relevant for the growth of hepatoma cells, since it defends them against cell growth inhibiting aldehydes derived from lipid peroxidation.


Green alga Chlamydomonas reinhardtii can effectively remove diclofenac from the water environment - A new perspective on biotransformation.
The use of unicellular algae to remove xenobiotics (including drugs) from wastewaters is one of the rapidly developing areas of environmental protection. Numerous data indicate that for efficient phycoremediation three processes are important, i.e. biosorption, bioaccumulation, and biotransformation. Although biosorption and bioaccumulation do not raise any serious doubts, biotransformation is more problematic since its products can be potentially more toxic than the parent compounds posing a threat to organisms living in a given environment, including organisms that made this transformation. Thus, two questions need to be answered before the proper algae strain is chosen for phycoremediation, namely what metabolites are produced during biotransformation, and how resistant is the analyzed strain to a mixture of parent compound and metabolites that appear over the course of culture? In this work, we evaluated the remediation potential of the model green alga Chlamydomonas reinhardtii in relation to non-steroidal anti-inflammatory drugs (NSAIDs), as exemplified by diclofenac. To achieve this, we analysed the susceptibility of C. reinhardtii to diclofenac as well as its capability to biosorption, bioaccumulation, and biotransformation of the drug. We have found that even at a relatively high concentration of diclofenac the algae maintained their vitality and were able to remove (37.7%) DCF from the environment. A wide range of phase I and II metabolites of diclofenac (38 transformation products) was discovered, with many of them characteristic rather for animal and bacterial biochemical pathways than for plant metabolism. Due to such a large number of detected products, 18 of which were not previously reported, the proposed scheme of diclofenac transformation by C. reinhardtii not only significantly contributes to broadening the knowledge in this field, but also allows to suggest possible pathways of degradation of xenobiotics with a similar structure. It is worth pointing out that a decrease in the level of diclofenac in the media observed in this study cannot be fully explained by biotransformation (8.4%). The mass balance analysis indicates that other processes (total 22%), such as biosorption, a non-extractable residue formation, or complete decomposition in metabolic cycles can be involved in the diclofenac disappearance, and those findings open the prospects of further research.


A retention modification for the limbal ring method of foreign body localization.
For intraocular foreign body localization, we used a modification of the limbal ring method with surgical adhesive instead of limbal sutures. After taking x-ray films of the eyeball, we removed the ring and the adherent glue with toothless forceps.


Stem cell mobilisation in lymphoproliferative diseases.
A number of different regimens have evolved for the mobilisation of peripheral blood stem cells for autologous transplantation in patients with lymphoma or myeloma. A successful regimen could be defined as one which consistently resulted in the collection of an optimal number of CD34+ cells with a minimum number of apheresis procedures with minimal toxicity. Initial protocols, which used chemotherapy alone as a mobilising agent, have now been replaced by regimens involving the use of haematopoietic growth factors either alone or in combination with variable doses of cyclophosphamide. Although there is good evidence that high-dose cyclophosphamide (6-7 g/m2) is an effective mobilising agent it is associated with significant toxicity and many groups have now utilised lower doses of cyclophosphamide with reduced toxicity which have still proven to be effective in the majority of patients. More recently a number of 'second generation' combined salvage chemotherapy and mobilisation regimens have been reported for use in the lymphomas which have the advantage of avoiding a specific stem cell mobilisation step and at the same time appear more consistently effective at mobilising stem cells than cyclophosphamide and G-CSF. These regimens are associated with fewer 'poor-mobilisers' and indeed some patients who have failed previous mobilisation with cyclophosphamide and G-CSF have been successfully re-mobilised. It is clear that in both lymphoma and myeloma patients the success of PBSC mobilisation is affected by the amount and type of previous chemotherapy and radiotherapy and probably other pre-treatment factors as exemplified by variability seen in normal donors mobilised with G-CSF alone. In myeloma most groups have utilised cyclophosphamide in variable doses in combination with G-CSF or GM-CSF. However, recent randomised studies have confirmed that G-CSF alone is an effective and nontoxic alternative although it appears that the efficacy of G-CSF as a single agent is related to the dosage used with daily doses of 16 microg/kg/day or greater being most effective. Thus, disease-specific mobilisation strategies appear to be emerging and these will undoubtedly be modified further as more is understood concerning the biology of blood stem cell mobilisation.


Electroneutral polymersomes for combined cancer chemotherapy.
Combination cancer chemotherapy provides an important treatment tool, both as an adjuvant and neoadjuvant treatment, this shift in focus from mono to combination therapies has led to increased interest in drug delivery systems (DDS). DDSs, such as polymersomes, are capable of encapsulating large amounts of multiple drugs with both hydrophilic and hydrophobic properties simultaneously, as well as offering a mechanism to combat multi drug resistant cancers and poor patient tolerance of the cytotoxic compounds utilised. In this article, we report the formulation and evaluation of a novel electroneutral polymersome capable of high encapsulation efficacies for multiple drugs (Doxorubicin, 5-Fluorouracil and leucovorin). The in-vivo biodistribution of the polymersome were established and they were found to accumulate largely in tumour tissue. Polymersome encapsulating the three chemotherapeutic drugs were assessed both in-vitro (BxPC-3 cell line) and in-vivo (following intratumoral and intravenous administration) and compared with the same concentration of the three drugs in solution. We report better efficacy and higher maximum tolerated dose for our combination drug loaded polymersomes in all experiments. Furthermore, intratumorally injected combination drug loaded polymersomes exhibited a 62% reduction in tumour volume after 13 days when compared with the free combination solutions. A smaller differential of 13% was observed for when treatment was administered intravenously however, importantly less cardiotoxicity was displayed from the polymersomal DDS. In this study, expression of a number of survival-relevant genes in tumours treated with the free chemotherapy combination was compared with expression of those genes in tumours treated with the polymersomes harbouring those drugs and the significance of findings is discussed. STATEMENT OF SIGNIFICANCE: The shift in focus from mono to combination chemotherapies has led to an increased interest in the role of drug delivery systems (DDS). Liposomes, although commercialized for mono therapy, have lower loading capacities and stability than their polymeric counterpart, polymersomes. Polymersomes are growing in prevalence as their advantageous properties are better understood and exploited. Here we present a novel polymersome for the encapsulation of three anticancer compounds. This is the first time this particular polymersome has been used to encapsulate these three compounds with both an in-vitro and in-vivo evaluation carried out. This work will be of interest to those in the field of combination therapy, drug delivery, drug toxicity, multidrug resistance, liposomes, DDS and polymersomes.


Sequential imaging studies of cerebral gnathostomiasis with subdural hemorrhage as its complication.
Cerebral gnathostomiasis is a severe form of human infection caused by Gnathostoma spinigerum. We report sequential brain imaging in serologically proven cerebral gnathostomiasis. The clinical and radiographic correlation showed the probable route taken by the parasite during its migration through the central nervous system. We offer additional insight into pathogenesis of cerebral gnathostomiasis and its rare complication, subdural hemorrhage, a finding not previously reported in the literature.


Correction to: CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis.
The article titled "CircCPA4 Promotes the Malignant Phenotypes in Glioma via miR-760/MEF2D Axis", written by Yunjuan Zhang, Zengyan Cai, Jin Liang, Erqing Chai, Anqing Lu, Yinwu Shang was originally published electronically on the publisher's internet portal (currently SpringerLink) on 17 October 2020 with open access.


Nephrotoxicity during tenofovir treatment: a three-year follow-up study in a Brazilian reference clinic.
In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10(®) was used for statistical analysis. The patients' mean age was 43.2±10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF+3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F=3.95; p=0.048), SAH (F=6.964; p=0.009), and age over 50 years (F=45.81; p<0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F=2.437; p=0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F=32.02; p<0.05) and there was a significant time-by-sex interaction (F=3.117; p=0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.


Kidney development and function: ECM cannot be ignored.
The extracellular matrix (ECM) is an essential network entity surrounding and supporting cells to guarantee their physiological function and homeostasis. It is important to choose the most appropriate ECM for in vitro experiments of mammalian cells for tissue engineering and functional analyses. Although most studies have examined optimization of the correct ECM that can be used to assess mammalian cells, a comprehensive study has not been conducted. In this review, we present the factors to be taken into consideration when designing or optimizing an appropriate ECM for development and maintenance of kidney tissues and compare the previously reported ECMs.


Synthesis, crystal structures, luminescence properties of two metal coordination polymers derived from 5-substituted isophthalate and flexible bis (triazole) ligands.
Two new metal complexes, [Ni(btx)(nip)(H2O)]n (1), {[Cd(btx)(mip)(H2O)]·H2O}n (2) (btx=1,4-bis(1,2,4-triazol-1-ylmethyl)benzene, H2nip=5-nitroisophthalic acid, H2mip=5-methyisophthalic acid) were synthesized under hydrothermal conditions and characterized by single-crystal X-ray diffraction methods, IR spectroscopy, TGA and elemental analysis. Complex 1 features a 3D metal-organic framework with three-fold interpenetrating CdSO4-type topology. Complex 2 exhibits a 2D network with square grid units, which is further extended into a rare 3,5T1 three-dimensional supramolecular network via three modes of classical OH⋯O hydrogen bonds. In addition, luminescence properties of 1 and 2 have also been investigated in the solid state.


European rabbits versus native rodents in Central Chile: effects on shrub seedlings.
The importance of the introduced rabbit Oryctolagus cuniculus and of the native rodent Octodon degus (=degu) as browsers of shrub seedlings in the Central Chilean evergreen shrublands (=matorral) was experimentally assessed. Seedlings were planted in several spatial arrangements in two open successional stands and in two mature stands of different cover and exposure. The browsing impact of rabbits and degus was evaluated separately after about one year since the start of the experiments. It was found that degus cause important seedling mortality only within a 5 m-radius centered at the border of their retreats. Rabbits, on the other hand, cause heavier seedling mortality, forage more widely, and consequently have a greater impact than do degus. It is speculated that rabbits may be halting the secondary succession process, shifting the matorral composition toward less palatable shrub species, and/or broadening the spacing between shrub clumps.


Use of a novel pedal-operated compressor is non-inferior to the use of a standard hand-compressed bag-valve mask.
The standard bag-valve mask (BVM) used universally requires that a single healthcare practitioner affix the mask to the face with 1 hand while compressing a self-inflating bag with the second hand. Studies have demonstrated that creating a 2-handed seal (with 2 healthcare practitioners) is superior. Our study aims to assess the efficacy of a novel single-practitioner BVM device that uses a foot pedal as the bag compressor, allowing both hands to be available for the seal to facilitate delivery of appropriate tidal volumes during single-practitioner resuscitation. This was a prospective, randomized, cross-over study. Participants with various BVM ventilation experience performed 2 minutes of metronome-guided BVM ventilation using a standard BVM and the pedal-operated compressor on a high-fidelity simulation mannequin. Analysis examining differences in mean tidal volume delivered was conducted using a regression model that adjusted for covariates. A secondary analysis using a series of Wilcoxon tests was conducted to compare differences in the additional out-of-range sensed breaths metrics to compare differences by prior BVM ventilation experience. A total of 58 subjects participated. The pedal-operated compressor unadjusted mean tidal volume delivered was 446.5 mL (95% confidence interval [CI], 425.9-467.1) compared with 340.6 mL (95% CI, 312.2-369.0) by standard BVM (mean change, 105.9 mL [95% CI, 71.2-140.6]; P < .001). When modeling a generalized estimation equation regression model, standard BVM ventilation provided a mean difference of 105.9 mL less than pedal-operated compressor ventilation after adjusting for covariates (P = 0.01). For the secondary outcome, the pedal-operated compressor did have a significantly lower median number of out-of-range breaths (median, 3; interquartile range [IQR], 1-11.5) compared with the standard device (median, 13.5; IQR, 6-19; P < 0.001). Use of a novel pedal-operated compressor may allow a single healthcare practitioner, regardless of prior experience, to deliver consistent, appropriate tidal volumes with more ease compared with the standard BVM during manual respiratory resuscitation.


Towards characterization and identification of solid state pharmaceutical mixtures through second harmonic generation.
In this paper, we report improvements to a previously developed method based on optical nonlinearity for characterizing polymorphism and concentration of pharmaceuticals in powdered and tablet form. An apparatus that measures the nonlinear optical response of a sample through second harmonic generation (SHG) is described. The response of several enalapril maleate-polyvinylpyrrolidone (PVP) tablets was measured, the results of which were used to determine the concentration of the drug. The current limit of detection of the apparatus was found to be approximately 1%-2%. Ranitidine hydrochloride (RN) polymorph forms I and II were also characterized using SHG. It was found that pure samples of forms I and II could be clearly and rapidly distinguished. Mixtures consisting of 50% form I and 50% form II were also distinguishable from the respective pure forms. An investigation was performed into the size dependence of the SHG response for crystalline lactose. It was found that the SHG response was a slowly decreasing monotonic function of particle size. Additional investigation into the angular dependence of the scattered SHG light was also undertaken for crystalline lactose. This new technique based on optical nonlinearity offers promise for application in monitoring of pharmaceutical manufacturing processes.


Regulation of the biosynthesis of cytochrome P-450 in brewer's yeast. Role of cyclic AMP.
The drug metabolising enzyme cytochrome P-450 has been studied in great detail in mammalian systems and its presence in microorganisms is also well established. However, neither its function nor its means of control in brewer's yeast, Saccharomyces cerevisiae, has been investigated. We demonstrate here using yeast protoplasts that it is the intracellular concentration of cyclic AMP which controls, by repression, the de novo synthesis of the enzyme, and also that cyclic AMP concentrations are in turn inversely related to the concentration of glucose in the yeast growth medium.


An Update on Gonorrhea and Chlamydia.
Gonorrhea and chlamydia infections remain a significant public health concern with most cases occurring in adults younger than 25 years old. Diagnosis relies on nucleic acid amplification testing as this is the most sensitive and specific test. Treatment with doxycycline or ceftriaxone is recommended for chlamydia and gonorrhea, respectively. Expedited partner therapy is cost-effective and acceptable by patients as a means to reduce transmission. Test of cure is indicated in persons at risk for reinfection or during pregnancy. Future directions include identifying effective strategies for prevention.


Malalignment: signs and significance.
Malalignment of the vertebrae, in patients suspected of blunt spinal trauma, is the quintessential sign of spinal injury. Malalignment is obvious in displaced fractures and dislocations but is rarely considered in the diagnosis because of the obvious injury. In patients with more subtle injuries such as those limited to ligamentous structures, vertebral malalignment is the only radiographic sign that leads one to the recognition of the injury. Equally important is the fact that vertebral malalignment may be congenital and may be due to physiologic movement as well as radiographic patient positioning. Recognition of the pattern of traumatic malalignment as distinguished from the appearance of non-traumatic malalignment is essential to accurate radiologic diagnosis. Because malalignment is critical to the radiographic assessment of blunt cervical spine injury, this presentation is limited to the cervical spine. The format of the article includes signs of physiologic and traumatic malaignment as seen on antero-posterior and lateral radiographs of the cervico-cranium and the lower cervical spine.


Superficial malignant schwannoma on the face: a case for early radical surgery.
A case of superficial epithelioid schwannoma is presented. The lesion arose as a skin papule in the infra-orbital region and recurring repeatedly over a five-year period, caused significant local morbidity without metastasis. Radical surgery was delayed in the hope of preserving binocular vision. The similarity of this tumour with a rare variant of malignant melanoma, the neurotropic melanoma, is discussed.


The Use of TnSeq to Identify Essential Alphaproteobacterial Genes Reveals Operational Variability in Conserved Developmental and Cell Cycle Systems.
A powerful method for examining genetic fitness and function on a large scale is to couple saturating transposon mutagenesis with high-throughput sequencing (TnSeq). By mapping where transposon insertions can be tolerated in a genome, it is possible to analyze the fitness of every gene in a genome simultaneously under a given growth condition. While this technique can describe genes as essential or nonessential under those growth conditions, sufficient mutagenesis and sequencing depth can provide more subtle differences in fitness. In this paper, TnSeq was used to analyze gene fitness of two Alphaproteobacteria from different environments: the freshwater oligotroph Brevundimonas subvibrioides (Caulobacterales) and the soil plant pathogen Agrobacterium tumefaciens (Rhizobiales) for the purpose of comparing conservation of gene function.


Role of PERK-mediated pathway in the effect of mild hypothermia after cerebral ischaemia/reperfusion.
Hypothermia is an effective method of reducing brain injury caused by a variety of neurological insults. It is aimed to elucidate whether a change in the expression of PERK-mediated pathway proteins is an indicator of the neuroprotective effect of mild hypothermia after cerebral ischaemia/reperfusion. One hundred and ninety-two male C57BL/6 mice were randomly divided into three groups: a sham group, a cerebral normothermic ischaemia/reperfusion (I/R) group and a cerebral hypothermic I/R group. A cerebral ischaemia model was established by ligating the bilateral common carotid artery for 15 min. Mice in the hypothermia group stayed in a cage that was set at 33°C, sprayed with a spray of 70% ethanol, and blown with two high-speed fans. The state of neurons was assessed on micropreparations stained with haematoxylin-eosin and TUNEL. The expressions of GRP78, p-perk, p-eif2α, ATF4 and CHOP were measured by western blot analysis 6, 12, 24 and 72 h after reperfusion. The number of surviving cells was significantly higher in the hypothermia group than in the group without hypothermia (p < .05). The GRP78 expression in the hypothermia group was statistically higher (p < .05) than in the ischaemia/reperfusion group. Optical densities of p-perk, p-eif2α and ATF4 in hippocampus CA1 neurons ischaemia were statistically significantly lower in the hypothermia group than in the ischaemia/reperfusion group (p < .05). The CHOP expression in the hypothermia group was statistically lower (p < .05) than in the ischaemia/reperfusion group. Mild hypothermia for 6 h promoted moderate neuroprotection by mediating the expression of GRP78, p-PERK, p-eIF2α, ATF4 and CHOP.