Myocarditis: unresolved issues in diagnosis and treatment.
Myocarditis is an enigmatic disease. Lymphocytic myocarditis is most commonly viral in origin. Considerable evidence suggests that myocardial damage is due to an immune-mediated mechanism rather than to direct effects of the virus itself. The presentation is variable, ranging from a clinically inapparent or relatively benign illness to acute progressive heart failure and death. Although examination of the endomyocardial biopsy specimen is the "gold standard" for the diagnosis of myocarditis there are problems with this technique, relating particularly to sampling error and histologic interpretation. Considerable evidence, both animal and human, suggests that a link between viral myocarditis and dilated cardiomyopathy does exist. There is a rational basis for the use of immunosuppressive therapy in myocarditis. Although many favorable responses have been reported with the use of these agents, the results of more definitive studies are awaited to determine the role of immunosuppressive therapy in myocarditis more clearly. Recommendations for the practical management of patients with myocarditis are made. Whenever possible, patients with this diagnosis should be entered into the ongoing NIH trial.


A critical review of HPLC-based analytical methods for quantification of Linezolid.
Linezolid is a synthetic antimicrobial agent belonging to the oxazolidinone class. Since its approval in the year 2000 until now, linezolid remains the main representative drug for the oxazolidinone class of drugs, which is used in therapy due to its unique mode of action, which involves inhibition of protein synthesis. As linezolid holds great importance in antimicrobial therapy, it is necessary to compile the various analytical methods that have been reported in the literature for its analysis. Analytical techniques used for pharmaceutical analyses and therapeutic drug monitoring play an important role in comprehending the aspects regarding bioavailability, bioequivalence, and therapeutic monitoring during patient follow-ups. Even though linezolid has had the approval for clinical use for more than 18 years now, most of the analytical methods for its determination reported in the scientific literature are the ones which utilize HPLC. Therefore, the present review provides a summary of the HPLC-based methods used in the determination and quantification of linezolid in different matrices since the time of its discovery.


Intrahepatic splenosis mimicking liver metastasis in a patient with gastric cancer.
A 54 year old man was referred to our hospital with gastric cancer. The patient had a history of splenectomy and a left nephrectomy as a result of a traffic accident 15 years earlier. The endoscopic findings were advanced gastric cancer at the lower body of the stomach. Abdominal ultrasonography (USG) and magnetic resonance imaging demonstrated a metastatic nodule in the S2 segment of the liver. Eventually, the clinical stage was determined to be cT2cN1cM1 and a radical distal gastrectomy, lateral segmentectomy of the liver were performed. The histopathology findings confirmed the diagnosis of intrahepatic splenosis, omental splenosis. Hepatic splenosis is not rare in patients with a history of splenic trauma or splenectomy. Nevertheless, this is the first report describing a patient with gastric cancer and intrahepatic splenosis that was misinterpreted as a liver metastatic nodule. Intra-operative USG guided fine needle aspiration should be considered to avoid unnecessary liver resections in patients with a suspicious hepatic metastasis.


Numerical and experimental investigation of a negative-curvature variable-shell flextensional transducer.
Type IV flextensional transducers do not have broadband characteristics due to the deep valley between their first- and second-order response curves arising from the sound pressure cancellation produced by the vibration in different areas of the shell. In this paper, the cause of the deep valley is examined by analyzing the equivalent radiated sound field of the transducer. Simplifying the three-dimensional vibration equation to a two-dimensional equation shows that the vibration state of the shell is related to the positive and negative curvature. Therefore, a variable-shell flextensional transducer with a negative curvature is proposed, which changes the second-order vibration of the transducer by introducing a negative curvature structure. The transducer avoids acoustic pressure cancellation, achieves broadband characteristics, and has continuous high efficiency in the frequency band. After optimization, a prototype of the transducer is fabricated and a pool test is completed. The test results show that the transducer realizes the coupling of the first three vibration mode, forming a broad band with an in-band fluctuation of less than 8 dB at 1200-5600 Hz, and the efficiencies of the first to third resonance peaks are 30.2 %, 16.6 %, and 9.4 %, respectively.


Elevation of free fatty acids induces inflammation and impairs vascular reactivity in healthy subjects.
To test the possible acute proinflammatory effects of fatty acids, we induced an increase in plasma free fatty acid (FFA) concentrations after a lipid and heparin infusion for 4 h in 10 healthy subjects. We determined the nuclear factor-kappaB (NF-kappaB) binding activity in mononuclear cells (MNCs), the p65 subunit of NF-kappaB, reactive oxygen species (ROS) generation by MNC, and polymorphonuclear leukocytes (PMN). Brachial artery reactivity, using postischemic flow-mediated dilation, was also measured. NF-kappaB binding activity in the MNC nuclear extracts increased to 163 +/- 17% and 144 +/- 14% as compared with basal levels at 2 and 4 h (P < 0.005) and remained elevated (P < 0.05) at 6 h (2 h after cessation of lipid infusion). NF-kappaB p65 subunit protein expression in MNC homogenates also increased at 2, 4, and 6 h (P < 0.05). ROS generation by PMNs increased significantly at 2 and 4 h (P < 0.005), whereas that by MNCs increased at 4 h (P < 0.05). Plasma macrophage migration inhibitory factor increased at 2 (P < 0.05) and 4 h (P < 0.005), respectively, and declined to baseline at 6 h. The postischemic flow-mediated dilation of brachial artery decreased from 6.3 +/- 1.1% at baseline to 4.3 +/- 1.9% and 2.7 +/- 2.1% (P < 0.01) at 2, 4, and 6 h, respectively. We conclude that an increase in FFA concentration induces oxidative stress and has a proinflammatory effect; it also impairs postischemic flow-mediated vasodilation of the brachial artery.


Use of vacuum-assisted closure in pediatric open fractures with a focus on the rate of infection.
The use of the vacuum-assisted closure device (VAC; KCI, San Antonio, Texas) has given the orthopedist a new tool for the successful management of severe traumatic wounds and open fractures. While the VAC's role in the adult population is proving itself as an improved therapy compared to "traditional wound care," it's role within pediatric orthopedics remains less well defined. Questions remain whether VAC therapy provides benefit regarding decreased infection rates as well as decreased need for extensive soft tissue coverage procedures. A review was therefore performed of a pediatric level I trauma center's experience using the VAC therapy for pediatric open fractures with a focus on the rate of superficial, deep, and chronic infection. A retrospective chart review spanning 4.5 years of all pediatric patients younger than 18 years with an open fracture initially treated with VAC therapy was conducted at a level I pediatric trauma center. This yielded 28 patients with 37 open fractures aged 2 to 17 years who were initially treated with wound VAC therapy. Subsequent chart review of these patients was performed examining in-hospital records, operative notes, and clinical follow-up visits for documented cases of superficial, deep, or chronic infection. Of 37 open pediatric fractures treated with a wound VAC, there were no cases of superficial infection and 2 cases of deep infection for an overall infection rate of 5%. Both infections resolved with surgical intervention and antibiotics without chronic infection development. When compared with historical controls, the use of VAC therapy for pediatric open fractures appears to be an equally safe and effective modality to help reduce infection in pediatric open fractures and should be considered a valuable tool in treating these injuries.


Renal hyperfiltration in prediabetes confirmed by fasting plasma glucose and hemoglobin A1c.
The aim of the study was to confirm that glomerular hyperfiltration, an early and reversible stage of kidney damage, is associated in patients with prediabetes and prehypertension. In total, 5003 people aged between 35 and 69 years who had participated in the Shizuoka part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study took part in the study. Prevalence of hyperfiltration [the estimated glomerular filtration rate (eGFR) above the age- /sex-specific 95th percentile] was compared among different stages of prediabetes [fasting plasma glucose (FPG) < 100, 100-109, 110-125, and ≥126 mg/dL; and/or hemoglobin A1c (HbA1c) < 5.7, 5.7-6.0, 6.1-6.4 and ≥6.5% for no prediabetes, stage 1 prediabetes, stage 2 prediabetes, and overt diabetes, respectively] and prehypertension (blood pressure <120/80, 120-129/80-84, 130-139/85-89, and ≥140/90 mmHg for no prehypertension, stage 1 prehypertension, stage 2 prehypertension, and overt hypertension, respectively). The prevalence of hyperfiltration increased with increasing stages of prediabetes (odds ratios: 1.25, 1.68, and 2.37 using FPG, and 1.26, 2.15, and 2.45 using HbA1c for stage 1 prediabetes, stage 2 prediabetes, and diabetes, respectively, relative to no prediabetes). Prehypertension, however, was not associated with hyperfiltration. The results confirmed that the prevalence of glomerular hyperfiltration increased with increasing stages (i.e., worsening) of prediabetes. Because both FPG and HbA1c showed similar association with hyperfiltration, either of these can be used to identify subjects who are at increased risk of nephropathy. Therefore, the functioning of kidneys should be monitored in subjects with prediabetes. Prompt treatment of hyperglycemia is necessary in subjects with hyperfiltration to prevent it to cause nephropathy.


Prooxidant-antioxidant balance in animals with enhanced hemoglobin-oxygen affinity under acute normobaric hypoxia.
The content of main lipid peroxidation (LPO) products and antioxidant defense (AD) factors were investigated in rats without a treatment and with preliminary rise of hemoglobin-oxygen affinity (HOA) by cyanate under acute normobaric environmental hypoxia. Under acute hypoxia the cyanate-treated rats expressed the lower contents of conjugated dienes (CD), thiobarbituric acid-reactive substances (TBARS), Schiff bases (SB) and higher alpha-tocopherol (alpha-T) concentration, and catalase (CAT) activity than in control animals (mainly in tissues). The regression analysis of HOA, LPO and AD parameters in investigated material indicated the close positive correlations of oxygen pressure for hemoglobin half-saturation (p50) with CD, TBARS, and SB, and negative correlation of p50 with alpha-T and CAT. The results of experiments with intended HOA increase during the hypoxia and observed weakened activities of the free radical processes suggest that blood oxygen-binding properties can have an important role in the mechanisms of prooxidant-antioxidant balance.


Change in Intraocular Pressure and Ocular Perfusion Pressure Due to Trendelenburg Positioning.
This study increases foundational knowledge about the dynamic relationships between intraocular pressure (IOP), blood pressure (BP), and mean ocular perfusion pressure (MOPP) in the setting of steep Trendelenburg positioning and may inform medical decision making for patients in which this positioning is planned. The purpose of this study was to explore the demographic and clinical factors related to IOP, MOPP, and BP change during Trendelenburg positioning in a large sample of subjects. A single-cohort interventional study was conducted at the American Academy of Optometry 2017 annual meeting. Baseline demographic data were collected by a secure survey tool. IOP and BP were then measured while seated and again after 1 and 2 minutes in a steep Trendelenburg position. Raw and percentage differences for each variable were compared between time points, and regression analyses demonstrated factors related to change in IOP, BP, and MOPP during steep Trendelenburg positioning. Median IOP increased from 16.3 mmHg (13.3 to 18.3 mmHg) at baseline to 25.0 mmHg (21.7 to 28.7 mmHg) at 1 minute after assuming the Trendelenburg position. More than 95% of individual eyes exhibited an IOP increase of at least 10%, and 45% had an IOP increase of 10 mmHg or greater. Correspondingly, MOPP fell from 50.3 mmHg (43.4 to 55.4 mmHg) at baseline to 36.3 mmHg (31.9 to 43.3 mmHg). Mean ocular perfusion pressure decreased by at least 10 in 90% of eyes. In multivariate regression analysis, factors independently related to percentage IOP increase were increasing weight, less myopic refractive error, lower baseline pulse, and lower baseline IOP (total r = 0.31, P < .001). Conversely, weight was the only variable independently related to percent MOPP change, and this relationship was weak (r = 0.05, P = .008). Our results confirm that steep Trendelenburg positioning causes an increase in IOP and a decrease in MOPP in almost all eyes. Considering the identified causative factors will inform clinical education and provide foundational knowledge for future investigations.


A palmtop PCR system with a disposable polymer chip operated by the thermosiphon effect.
A small thermocyling system to perform DNA amplification by polymerase chain reaction (PCR) is presented in this report. PCR reactants are convected along a triangular closed-loop channel in a polymer chip by the thermosiphon effect. In an effort to develop a convection-based PCR for real application, we adopted a molded channel to define the flow path inside the chip, so that the chip may be suitable for disposability together with the merits of LOC; mass production, versatile integration and facile handling. We developed the geometry of the flow loop that made it easier to load the PCR reactants without air pockets inside. Based on systematic simulations and theoretical considerations of buoyant flows, the loop channel was designed to acquire an optimized flow for PCR. A PCR sample was dropped on a chip to fill the loop channel, and the chip was inserted into a slot of a heating block unit that was composed of three metal blocks with different temperatures. The temperature differences within the closed loop gave rise to buoyancy differences and the liquid reactant continuously circulated along the closed loop by the thermosiphon effect. Because there was no loss of time among the temperature shifts in the reaction steps, approximately 10 min were sufficient for the detectable amplification of 127 bp target gene from 10 pg microl(-1) of PCR fragments. In addition, it took 20 min for the mass amplification of 470 bp gene from PCR fragments or genomic DNA. The entire PCR system is compact enough even to be palmtop because it requires only a tiny temperature controller for a self-actuated thermosiphon flow. This thermocycling system would be a prototypical model for the field application of PCR.


Transcriptional activity of human epidermal growth factor receptor family and angiogenesis effectors in locoregionally recurrent head and neck squamous cell carcinoma and correlation with patient outcome.
Locoregional recurrence is the most common failure pattern in patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively identified 41 HNSCC patients with locoregional relapse and used kinetic reverse transcription-polymerase chain reaction (kRT-PCR) in order to study fresh-frozen tumour messenger RNA (mRNA) levels of the Human Epidermal growth factor family members HER1-4, the Vascular Endothelial Growth Factors (VEGFs) A, B, C, D, and their receptors VEGFR1, 2, 3. High VEGF-C and VEGFR3 tumour mRNA expression correlated with relapse beyond the primary locus (neck nodes or soft tissues, P < .05). Tumours with regional nodal involvement at diagnosis more often exhibited high transcriptional activity of VEGFR1 and VEGFR3 at the time of relapse (P < .05). At a median follow-up of 52 months from the time of locoregional recurrence, patients with high VEGF-C tumours at relapse had significantly poorer postrelapse progression-free survival (R-PFS, 5 versus 47 months, log-rank P = .052) and a trend for inferior postrelapse overall survival (R-OS, 22 versus 44 months, log-rank P = .076) in comparison to low VEGF-C tumours. Similar association with dismal outcome was seen for its receptor, VEGFR3 tumoural mRNA levels (log-rank P = .060). In contrast, suppressed tumour transcription of VEGF-D was associated with poorer post-relapse survival, though statistical significance was not reached. Active transcription of the VEGF-C/VEGFR3 axis in recurrent HNSCC is associated with failure at neck soft tissues/lymph nodes and inferior survival post-relapse.


Computed Tomography Evaluation of the Paranasal Sinuses in Adults with Primary Ciliary Dyskinesia.
Introduction Primary ciliary dyskinesia is a rare inherited disease that results in a malfunction of mucociliary clearance and sinonasal complaints. Aplasia/hypoplasia of the frontal and sphenoid sinuses has been described as more frequent in this population. However, to date, no studies have provided a detailed description of computed tomography findings in adult patients with a diagnosis of this condition. Objective To describe the computed tomography (CT) findings of adult patients with primary ciliary dyskinesia. Methods Retrospective observational study of adult patients with primary ciliary dyskinesia who underwent CT. Results Twenty-one adults were included in the study. Aplasia occurred in 38.1% of frontal sinuses and in 14.3% of sphenoid sinuses. Likewise, hypoplasia occurred in 47.6% of the frontal sinuses, in 54.8% of the sphenoid sinuses and in 40.5% of the maxillary sinuses. Furthermore, trabecular loss was identified in 61.9% ethmoidal sinuses. The mean Lund-Mackay score was 13.5. In addition, 9.5% of the patients had concha bullosa, 47.6% had marked bilateral inferior turbinate hypertrophy, 38.1% had marked middle turbinate hypertrophy, and 47.6% had marked septal deviation. Finally, we identified images suggestive of fungus ball, mucocele, osteoma, a possible antrochoanal polyp, and frontal bone erosions. Conclusion The present study provides a detailed description of CT findings in patients with primary ciliary dyskinesia. We also describe abnormalities that must be identified for safer surgical planning and that suggest a diagnosis of primary ciliary dyskinesia if found in patients with a consistent clinical picture.


Reassessment of biases in predicted nitrogen flows to the duodenum by NRC 2001.
The appearance of numerous plots in recent literature from which the residuals are plotted against observed values (Y) to assess a model's potential bias raises this question: should residuals be regressed against Y or against predicted values (Y)? The answer requires knowing the expected relationship under the assumption of an unbiased model. The objectives of this paper are: 1) to derive the expected relationship between residuals, Y, and Y; 2) to determine whether Y or Y should be used for the assessment of bias; and 3) to reassess the extent of mean and linear bias in the prediction of N flows to the duodenum by the NRC (2001). In the simplest case, we can assume a true model of the form Y = Xbeta + epsilon. This model is estimated by Y = Xb + e, and Y = Xb. The correlation between the residual vector e and the vector of observations Y can easily be derived. The numerator of the correlation coefficient is shown to be equal to e'e, the residual sum of squares. The denominator of this correlation is equal to the square root of e'e multiplied by the total sum of squares. Algebraic simplifications show that the correlation between e and Y is equal to the square root of (1-R2). That is, under the assumption of an unbiased model, the residuals are correlated with the observed values and the slope of e regressed on Y is equal to (1-R2). Thus, a graph of e versus Y will show a positive slope between e and Y unless the model is a perfect predictor (i.e., R2 is equal to 1.0). Significant slopes linking e to Y have been erroneously interpreted as evidence of biased models in the NRC (2001). Conversely, the slope of e regressed on Y is expected to be zero under the assumption of an unbiased model. Therefore, residuals should be regressed against Y and not Y. When Y, as opposed to Y, was used to assess biases in the prediction of flows to the duodenum of microbial N, nonammonia-nonmicrobial N and nonammonia N in NRC (2001), mean biases became nonsignificant and linear biases over the range of predicted values are of the same magnitude or smaller than the standard errors of measurements reported in literature. Thus, although N flow predictions from NRC (2001) may not be precise, they appear to have insignificant and inconsequential biases.


[Allergy to mercurothiolate in an infant during heparinization of an intracaval catheter].
A 4-month old infant developed an immediate and proven systemic allergic reaction to mercurothiolate. The acute accident occurred while an intracaval catheter was being treated with a dry-frozen heparin which excipient contains mercurothiolate. This conservative agent is present in numerous pharmaceutical preparations for topical and systemic use.


Solvent controlled sugar-rhodamine fluorescence sensor for Cu(2+) detection.
A "turn-on" fluorescence probe for Cu(2+) detection has been reported according to a Cu(2+) triggered spirolactam ring-opening reaction. The probe is a double-responsive fluorescent and colorimetric Cu(2+)-specific sensor in aqueous solution containing 20% of acetonitrile with high selectivity and excellent sensitivity (limit of detection is 12 μg L(-1)). Furthermore, the significant color changes visible to the naked eye at the concentration of 3 μM (ca. 0.20 mg L(-1)) are about ten times lower than the WHO (World Health Organization) recommended level (2.0 mg L(-1)) for Cu(2+) ions in drinking water.


Decision-making impairment in anorexia nervosa: New insights into the role of age and decision-making style.
Patients with anorexia nervosa (AN) often report difficulties in decision making, which may interfere with treatment. The aim of this study was to investigate decision making in a large sample of adolescent and adult patients with AN, by using the Iowa gambling task. Participants were 611 female individuals (310 patients and 301 controls) who underwent neuropsychological and clinical assessment. Significantly poorer decision-making performance was observed in adult patients, whereas no difference emerged between affected and nonaffected adolescents. Both adolescent and adult patients were characterized by trends for higher levels of attention to losses in comparison with healthy controls. Although healthy adult women exhibited better decision-making performance than healthy adolescents, in AN, there was no improvement of decision making with age. A cluster analysis identified 2 different styles of decision making in both patients and controls: a conservative style and an impulsive style. Our study provides evidence of dysfunctional decision making in adult patients with AN and reveals an association between poor decision making and excessive punishment sensitivity in AN. The clinical and scientific implications of these findings merit further exploration.


[Role of lipid peroxidation, prostanoids and cyclic nucleotides in the individual resistance of animals to exogenous catecholamines].
The role of the lipid peroxidation, power of the antioxidants, peculiarities of synthesis of some prostanoids and cyclic nucleotides in determination of the rabbit individual sensitivity to exogenous catecholamines was studied. Some peculiarities of the initial state of homeostasis both of the survived and lost rabbits are demonstrated. It is determined that the low stability to izadrine's administration of the lost rabbits may be associated with the higher basal activity of the lipid peroxidation and the smaller antioxidative power. The peculiarities of the arachidonic acid's metabolism, which are associated with this, modulate the activity of the cyclic nucleotide enzymes. The latter may mobilize the cAMP-dependent mechanisms of the intracellular hormone signal transduction.


The effect of charge display on cost of care and physician practice behaviors: a systematic review.
While studies have been published in the last 30 years that examine the effect of charge display during physician decision-making, no analysis or synthesis of these studies has been conducted. We aimed to determine the type and quality of charge display studies that have been published; to synthesize this information in the form of a literature review. English-language articles published between 1982 and 2013 were identified using MEDLINE, Web of Knowledge, ABI-Inform, and Academic Search Premier. Article titles, abstracts, and text were reviewed for relevancy by two authors. Data were then extracted and subsequently synthesized and analyzed. Seventeen articles were identified that fell into two topic categories: the effect of charge display on radiology and laboratory test ordering versus on medication choice. Seven articles were randomized controlled trials, eight were pre-intervention vs. post-intervention studies, and two interventions had a concurrent control and intervention groups, but were not randomized. Twelve studies were conducted in a clinical environment, whereas five were survey studies. Of the nine clinically based interventions that examined test ordering, seven had statistically significant reductions in cost and/or the number of tests ordered. Two of the three clinical studies looking at medication expenditures found significant reductions in cost. In the survey studies, physicians consistently chose fewer tests or lower cost options in the theoretical scenarios presented. In the majority of studies, charge information changed ordering and prescribing behavior.


Esterified estrogen and conjugated equine estrogen and the risk of incident myocardial infarction and stroke.
Clinical trials of conjugated equine estrogen (CEE) or estradiol vs placebo in postmenopausal women have found no effect or an elevated risk of myocardial infarction (MI) and stroke. The association of these end points with the use of esterified estrogen (EE) is unknown. We examined the risk of MI and stroke associated with current use of CEE, use of EE, or nonuse of hormones in a population-based case-control study in a health maintenance organization. Cases were all postmenopausal women with an incident MI (n = 1644) or stroke (n = 1080). Controls (n = 4205) consisted of a random sample of postmenopausal women without MI or stroke. Current use of postmenopausal hormones was assessed using a computerized pharmacy database. There was no difference in risk of MI or stroke associated with current use of CEE or EE compared with nonuse or for current use of CEE compared with EE. In analyses restricted to hormone users, there was a suggestion of higher ischemic stroke risk associated with CEE alone (without progestin) compared with EE alone (odds ratio, 1.57; 95% confidence interval, 0.98-2.53). There was also a suggestion that when initiated in the previous 6 months, CEE was associated with a higher risk of MI than EE (odds ratio, 2.33; 95% confidence interval, 0.93-5.82). Further study may be warranted of the effects of EE on the risk of cardiovascular end points.


The aperture problem in contoured stimuli.
A moving object elicits responses from V1 neurons tuned to a broad range of locations, directions, and spatiotemporal frequencies. Global pooling of such signals can overcome their intrinsic ambiguity in relation to the object's direction/speed (the "aperture problem"); here we examine the role of low-spatial frequencies (SF) and second-order statistics in this process. Subjects made a 2AFC fine direction-discrimination judgement of 'naturally' contoured stimuli viewed rigidly translating behind a series of small circular apertures. This configuration allowed us to manipulate the scene by randomly switching which portion of the stimulus was presented behind each aperture or by occluding certain spatial frequency bands. We report that global motion integration is (a) largely insensitive to the second-order statistics of such stimuli and (b) is rigidly broadband even in the presence of a disrupted low SF component.


Fine structure and metamorphosis of the wax gland cells in a psyllid insect, Anomoneura mori schwartz (Homoptera).
The fine structure of the wax gland of Anomoneura nymph and its metamorphic change were investigated. In the nymph, this organ encircles the anus, and consists of two kinds of cells, derived from epidermal cells: (1) very tall, slim wax cells, which produce and secrete the wax, and (2) flat interstitial cells found among the wax cells. The whole gland is covered by a wax-secreting cuticle with a delicate surface sculpture. Each wax cell has a long, wide duct which opens at the cuticle and penetrates the entire cell. Its cytoplasm is rich in mitochondria and smooth endoplasmic reticulum while that of interstitial cells contains rough endoplasmic reticulum. During each nymphal molt, the cluster of primordial wax gland cells - derived from the epidermis - proliferates rapidly and forms the gland of the next instar. The gland of the preceding instar meanwhile degenerates. Interstitial cells play an important role in cuticle formation and shedding at each molt. These cells alone produce and deposit the new cuticle of the next instar; the wax cells, specialized for wax production, cannot produce cuticle. The apical portion of the wax cell is cut off from the main cell body by growth of the surrounding interstitial cells. Thereafter, the wax cells degenerate, resulting in the rapid disappearance of the previous instar's wax gland. Adults lack this gland entirely.


Exploring the Association of Age with Depressive Symptomatology in Childhood and Adolescence: A Network Study.
This study aimed to explore the association of age with individual depression and anxiety symptoms and their connectivity (i.e., number/strength of connections with other symptoms) in girls and boys. Our study comprised cross-sectional data from 31,960 Dutch girls and 32,162 Dutch boys aged 8 to 18 and considered 11 depression symptoms and 14 anxiety symptoms measured by the Revised Child Anxiety and Depression Scale. Network estimations were used to examine whether age was associated with individual symptoms and, in a separate step, with the connectivity of depression symptoms with other depression symptoms and with the connectivity of depression symptoms with anxiety symptoms. Age was, in general, positively associated with depression symptoms in girls, but not in boys, and with the connectivity of depression symptoms with other depression symptoms in both sexes. These findings were the most profound for energy-related symptoms in girls. Age was, in general, negatively associated with anxiety symptoms and not or negatively associated with the connectivity of depression symptoms with anxiety symptoms in girls and boys, respectively. Substantial differences across symptoms were found. This study shows that it is important to focus on individual symptoms, for age is mainly associated with energy-related depression symptoms and their connectivity in girls. Future etiologic studies may examine the role of energy-related depression symptoms in the development of depressive symptomatology in girls as these symptoms seem potential targets for the prevention of depression in the female population.


Isolation and characterization of hantavirus carried by Apodemus peninsulae in Jilin, China.
To provide a better understanding of hantavirus epidemiology in China, Korean field mice (Apodemus peninsulae) and striped field mice (Apodemus agrarius) were captured in Jilin province, China, where haemorrhagic fever with renal syndrome (HFRS) is endemic. Hantavirus antigens were detected in eight of the 130 A. peninsulae individuals and in four of the 193 A. agrarius individuals by using an immunofluorescence assay. Partial S and M segments were amplified from all of the antigen-positive samples. Furthermore, two hantaviruses (CJAp89 and CJAp93) were isolated successfully in cell culture and the entire S and M segments were amplified from one of them (CJAp93). Phylogenetic analysis of these sequences (partial or complete) showed that hantaviruses carried by A. peninsulae and A. agrarius form two distinct lineages, although viruses carried by A. peninsulae are similar to those isolated previously from A. agrarius in China and from HFRS patients in Russia. However, the viruses detected in A. peninsulae in China are genetically different from those detected in A. peninsulae in other countries. These data suggest that A. peninsulae is also a natural host for HTNV in north-eastern China.


Environmental biodegradation of halophenols by activated sludge from two different sewage treatment plants.
Halophenols make a group of aromatic compounds that are resistible to biodegradation by environmental microorganisms. In this study, the biodegradation of 4-bromo-, 4-chloro- and 4-fluorophenols was studied with two types of activated sludges (from a small rural plant and from a bigger municipal plant) as an inoculum. Because of their wide use, surfactants are present in the wastewater and inhibitors enhance the biodegradation of different pollutants; the influence of natural surfactants on halophenols' biodegradation was also tested. Both types of activated sludge contained bacterial strains which were active in the halophenols' biodegradation process. The coexistence of surfactants and halophenols in the wastewater does not prevent microorganisms from effective halophenols' biodegradation. Moreover, surfactants can enhance the effectiveness of halophenols' removal from the environment. Different cell surface modifications of two isolated bacterial strains were observed in the same system of halophenols with or without surfactants. Halophenols and surfactants may also induce changes in bacteria cell surface properties.


Pro-Inflammatory Profile of Adipokines in Obesity Contributes to Pathogenesis, Nutritional Disorders, and Cardiovascular Risk in Chronic Kidney Disease.
Obesity is a disease which leads to the development of many other disorders. Excessive accumulation of lipids in adipose tissue (AT) leads to metabolic changes, including hypertrophy of adipocytes, macrophage migration, changes in the composition of immune cells, and impaired secretion of adipokines. Adipokines are cytokines produced by AT and greatly influence human health. Obesity and the pro-inflammatory profile of adipokines lead to the development of chronic kidney disease (CKD) through different mechanisms. In obesity and adipokine profile, there are gender differences that characterize the male gender as more susceptible to metabolic disorders accompanying obesity, including impaired renal function. The relationship between impaired adipokine secretion and renal disease is two-sided. In the developed CKD, the concentration of adipokines in the serum is additionally disturbed due to their insufficient excretion by the excretory system caused by renal pathology. Increased levels of adipokines affect the nutritional status and cardiovascular risk (CVR) of patients with CKD. This article aims to systematize the current knowledge on the influence of obesity, AT, and adipokine secretion disorders on the pathogenesis of CKD and their influence on nutritional status and CVR in patients with CKD.


Effects of morphological characteristics of Cucumis sativus seedlings grown at different vapor pressure deficits on initial colonization of Bemisia tabaci (Hemiptera: Aleyrodidae).
We investigated the effects of morphological characteristics of cucumber, Cucumis sativus L., seedlings grown at different vapor pressure deficits (VPDs) on initial colonization of whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) biotype B. The seedlings were grown at a VPD of 3.8 or 0.4 kPa for 9 d at 30 degrees C under a photoperiod of 12:12 (L:D) h. Pairs of seedlings, one grown at high VPD and the other at low VPD, were then installed in cages with a VPD of 1.3 kPa, and adults of B. tabaci between 150 and 200 were released. Leaves of high-VPD seedlings had fewer B. tabaci than those of low-VPD seedlings 24 h after release. They also had higher relative chlorophyll content, were thicker and tougher, and had abaxial trichomes with higher density. Water stress caused by the high VPD probably decreased the initial colonization of B. tabaci through changes in these leaf morphological characteristics.


Parent and child reports of sleep problems associated with early-onset bipolar spectrum disorders.
Despite sleep problems being part of the diagnostic criteria for mood disorders, research on sleep difficulties related to early-onset bipolar spectrum disorders (EBSDs) is sparse. The authors examined the parent and child agreement, frequency, and severity of EBSD-related manic, depressive, and comorbid sleep problems. A sample of one hundred thirty-three 8- to 11-year-olds with EBSDs was assessed with parental and self-report measures of EBSD-related sleep problems. Dimensional and categorical measures indicated low agreement and high discrepancy between parent and child reports of EBSD sleep problems. Subsequent combination of parent-child data revealed the majority (96.2%) of children had moderate-to-severe sleep problems related to manic, depressive, or comorbid symptoms, either currently or during their worst mood period. More depression-related sleep problems than mania-related sleep problems were reported, especially initial insomnia. Over half the sample had sleep problems associated with current comorbidity, particularly separation anxiety disorder. These findings, their implications, and study limitations are discussed.


Latent tuberculous infection among foreign-born individuals applying to shelters in the metropolitan area of Milan.
Screening for latent tuberculous infection (LTBI) of groups at high risk of active tuberculosis (TB) is a key component of the End TB Strategy. To conduct a retrospective descriptive analysis of LTBI rates among foreign-born individuals applying to shelters in the metropolitan area of Milan, Italy. All foreign-born individuals registering for accommodation centres in the city of Milan from November 2009 to April 2017 were screened for active TB and LTBI. Individuals aged <36 years with a tuberculin skin test (TST) induration of >10 mm were offered confirmatory testing with QuantiFERON®-TB Gold In-Tube (QFT-GIT). Of the 2666 TST-positive migrants aged <36 years who underwent LTBI confirmation testing, 1322 (49.6%) tested negative, 1339 (50.2%) were positive and five (0.2%) had indeterminate results. In the multivariate analysis, TB incidence in the country of origin and age were significantly associated with QFT-GIT positivity. Although estimated TB incidence in Eritrea, Morocco and Romania was 100/100 000 person-years (py), the probability of being QFT-GIT-positive in individuals from these countries were not statistically significantly different from individuals from countries with TB incidence > 250/100 000 person-years. Our data showed a high proportion of LTBI among individuals coming from intermediate TB burden countries.


Thiol-ene click reaction as a general route to functional trialkoxysilanes for surface coating applications.
Functionalized trialkoxysilanes are widely used to modify the surface properties of materials and devices. It will be shown that the photoinitiated radical-based thiol-ene "click" reaction provides a simple and efficient route to diverse trialkoxysilanes. A total of 15 trialkoxysilanes were synthesized by reacting either alkenes with 3-mercaptopropyltrialkoxysilane or thiols with allyltrialkoxysilanes in the presence of a photoinitiator. The functionalized trialkoxysilanes were obtained in quantitative to near-quantitative yields with high purity. The photochemical reactions can be run neat in standard borosilicate glassware using a low power 15-W blacklight. A wide range of functional groups is tolerated in this approach, and even complex alkenes click with the silane precursors. To demonstrate that these silanes can be used as surface coating agents, several were reacted with iron oxide superparamagnetic nanoparticles and the loadings quantified. The photoinitiated thiol-ene reaction thus offers a facile and efficient method for preparing surface-active functional trialkoxysilanes.


Diagnostic virology and patient care: from vaguely interesting to vitally important.
The existence of pathogenic viruses was inferred by experiments at the turn of the twentieth century. Key developments in detection of viruses, including electron microscopy and monolayer cell culture, were made in the middle of that century. However, in terms of patient care, the results from the virology laboratory often arrived the patient was 'better or dead'. The advent of molecular techniques, particularly polymerase chain reaction and more recently whole genome sequencing made timely and accurate diagnosis of viral infections feasible. A range of approaches have been taken to identify and characterise new viruses. Vaccines against viruses have made it possible to eliminate two pathogenic mammalian viruses altogether, with several others close to eradication. The role of biomedical scientists working in diagnostic virology is more relevant to patient care than ever.


Comparison of innervation and agrin-induced tyrosine phosphorylation of the nicotinic acetylcholine receptor.
Studies of the regulation of tyrosine phosphorylation at the neuromuscular junction during development and following denervation suggest that tyrosine phosphorylation of the nicotinic acetylcholine receptor is regulated by neuronal innervation of muscle. The finding that agrin, a neuronally derived extracellular matrix protein also induces tyrosine phosphorylation of the nicotinic receptor, suggests that nerve-induced tyrosine phosphorylation may be mediated by agrin. To study this further, we have examined the regulation of tyrosine phosphorylation of the nicotinic receptor by innervation in vitro using muscle-neuron cocultures. Innervation of chick myotubes by chick ciliary ganglia neurons induced tyrosine phosphorylation of the nicotinic receptor with the same subunit specificity seen with bath applied purified agrin. Both innervation and agrin-induced phosphorylation of the nicotinic receptor resulted in an increase in tyrosine and serine phosphorylation. In addition, thermolysin phosphopeptide maps of the subunits after innervation or agrin-treatment were identical. The similarity in the agrin- and nerve-induced phosphorylation of the acetylcholine receptor suggests that agrin mediates the nerve-induced phosphorylation during development in vivo and that phosphorylation of the acetylcholine receptor may play an important role in the development of the neuromuscular junction.


MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model.
We introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding-site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.


[MspI-POLYMORPHISM IN FOURTH INTRON OF THE GROWTH HORMONE GENE IN CHICKEN POPULATIONS OF DIFFERENT BREEDS. ANALYSIS OF THE CAUSES OF ADDITIONAL RESTRICTION PATTERN ORIGIN].
The MspI-polymorphism in the fourth intron of the growth hormone gene in populations of White Plymouth Rock, Poltava Clay, Rhode Island Red and Borkovskaya Barvistaya chicken breeds was studied. It is shown that in all examined chicken populations the growth hormone gene is polymorphic. It was found that the presence of "additional" phenotype (restriction pattern) is not associated with duplication of the growth hormone gene. The possibility of formation of heteroduplex DNA of two different types in the course of amplification of heterozygous samples B/C, containing the site 'CCGG', which leads to formation the additional DNA fragment which do not contain the site 'CCGG', was described. The nucleotide sequences of alleles A, B, C and "additional" fragment is described. Frequencies of alleles A, B and C in chicken population of White Plymouth Rock breed were 0.56; 0.16 and 0.28; Poltava Clay--0.10; 0.07 and 0.83; Rhode Island Red--0.27; 0.31 and 0.42; Borkovskaya Barvistaya--0.75; 0.08 and 0.17 respectively.


Professor Decker replies.
Replies to comments by Allen Frances (see record 2016-05673-005) and Ronald W. Pies (see record 2016-05673-006) on the article by Hannah Decker (see record 2016-05673-004). Frances' sophisticated fine-tuning of Decker's dichotomies is most welcome. Nevertheless, the impact of reductionism on an era does persist. As for Pies, Decker wishes she could share Pies' hopes for the future of an integrated psychiatry, but we are in a biological period that shows little evidence of becoming inclusive of the psychological and the social. (PsycINFO Database Record


[Association of occipital encephalocele with vesicoureteral reflux].
Occipital encephalocele was associated with vesicoureteral reflux and agenesis of the os coccygeum in a small-for-gestational age newborn girl. The symptoms did not correspond to any of the syndromes with encephalocele. The present observation and data of the literature suggest that the significance of vesicoureteral reflux in syndrome diagnosis is generally underestimated.


Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa.
The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, with mice dying between 9.5 and 10 days postcoitum. At the time of death, no abnormalities were apparent in the embryo proper. Nervous system development, in particular, was not impaired, as might have been expected in analogy to Drosophila GCM. Instead, placental failure was the cause of death. In agreement with the selective expression of mGCMa in labyrinthine trophoblasts, mutant placentas did not develop a functional labyrinth layer, which is necessary for nutrient and gas exchange between maternal and fetal blood. Only a few fetal blood vessels entered the placenta, and these failed to thrive and branch normally. Labyrinthine trophoblasts did not differentiate. All other layers of the placenta, including spongiotrophoblast and giant cell layer, formed normally. Our results indicate that mGCMa plays a critical role in trophoblast differentiation and the signal transduction processes required for normal vascularization of the placenta.


Early worsening of diabetic retinopathy due to intensive glycaemic control.
The prevalence of diabetes and diabetic retinopathy is increasing around the world. Glycaemic control is important in reducing the long-term risk of complications of diabetes, however intensive glycaemic control, particularly in patients with longstanding and poorly controlled diabetes, is associated with the risk of early worsening of diabetic retinopathy and vision loss. We present two clinical cases to illustrate the presentation of early worsening and to highlight a role for intravitreal anti-vascular endothelial growth factor therapies in ameliorating this phenomenon, as well as a review of the current understanding of this phenomenon. We emphasise the importance of identifying individuals at risk of early worsening of diabetic retinopathy and recommend regular ophthalmological review during the period of intensive glycaemic control to ensure optimal visual outcomes.


[Biology of ovarian carcinoma and the hope of individualised therapy].
For ovarian cancer therapy, the detailed analysis of the individual case becomes more and more important. The stage of growth is very significant. Owing to a more comprehensive primary diagnosis and to a more aggressive surgery, recently diagnosed cases cannot be compared with corresponding stages of past years. The experiences of therapies based on passed staging are not valid any more. The traditional staging (FIGO or UICC) takes in too little account the different forms of growth: so, f.i., tumors with solitary metastases and/or node involvement on one hand and tumors of primarily diffuse growth on the other one. The size of the tumor remaining after surgery depends not only from the surgeon's technique and experience but also from the type of growth of the individual carcinoma. As for morphology, the different types characterized by different growth and probably by different reaction to chemotherapy, have to be taken into consideration. The grade, however, is of special importance. The cancer of low malignant potential must be defined and be treated in a different way from invasive carcinoma. Unfortunately, we still do not have a standard definition of the different grades. Nowadays, biological investigations of tumor tissue come more and more to the fore, such as chemosensitivity testing, investigation of estrogen and progesterone receptors, of membrane receptors, and studies in transplantation of tumor tissue in nu/nu mice. They will more and more have therapeutic consequences. General condition has been very much neglected until now though it is very important for the development of the disease. Age is an important but not the essential factor and must be put in correlation with many other factors of prognosis.


Multiplet splittings and intensities of fine structure components of the Q1(0)H2 + S0(0)N2 transition in a solid parahydrogen matrix.
A comprehensive analysis of theoretical multiplet splittings and intensities of the fine structure components of the Q(1)(0)H(2) + S(0)(0)N(2) transition in a solid parahydrogen crystal is presented. The consideration of higher order anisotropic term responsible for splittings is essential to explain the observed splitting of the three components. The pair interaction parameters DeltaB and DeltaC have been determined by comparing the theoretical splittings with the experimental values. The information about the small splittings (approximately 0.1 cm(-1)) due to crystal-field interaction is completely obscured due to fast hopping of v(') = 1, J(') = 0 H(2) vibron. Also, the theoretical expressions are derived for the intensities of the fine structure components of the Q(v(H(2)))(0) + S(v(N(2)))(0) transition and the theoretical results are compared with the experimental findings.


Assessment of Pediatric Telemedicine Using Remote Physical Examinations With a Mobile Medical Device: A Nonrandomized Controlled Trial.
The number of innovations in health care based on the use of platforms, digital devices, apps, and artificial intelligence has grown exponentially in recent years. When used correctly, these technologies allow inequities in access to health care to be addressed by optimizing care and reducing social and geographic barriers. However, most of the technological health care solutions proposed have not undergone rigorous clinical studies. To assess the concordance between measurements from a remote physical examination using a mobile medical device and measurements from a conventional in-person physical examination. This nonrandomized controlled trial was conducted from January 1 to December 31, 2020. The clinical parameters compared were heart rate; body temperature; heart, lung, and abdominal auscultation; otoscopy; throat and oral examination; and skin examination. A total of 690 patients with clinical stability and various symptoms who were seen in the emergency department of 2 Brazilian pediatric hospitals were eligible to enter this study. The primary outcome was concordance between measurements from a telemedicine physical examination using a mobile medical device and measurements from a conventional in-person physical examination. The secondary outcome was the specificity and sensitivity of the digital device, considering the conventional in-person consultation as the gold standard. Among 690 patients, the median (IQR) age at study entry was 5 (1-9) years; 348 (50.4%) were female, and 331 (48.0%) presented with a chronic disease. Regarding the primary outcome, the concordance values were 90% or greater for skin examination (94% for rash, 100% for hemorrhagic suffusion, and 95% for signs of secondary infection), characteristics of the mucosa (98% for hydration and 97% for coloring), and heart (95% for murmur, 97% for rhythms, and 98% for sounds), lung (91% for adventitious sounds, 97% for vesicular sounds, and 90% for fever), and abdominal (92% for abdominal sounds) auscultations. Concordance values were lower for otoscopy (72% for the ear canal and 86% for the tympanic membrane), throat and oral examination (72%), and rhinoscopy (79% for mucosa and 81% for secretion). The specificity was greater than 70% (ranging from 74.5% for the ear canal to 99.7% for hemorrhagic suffusion) for all variables. The sensitivity was greater than 52% for skin examination (58.0% for rash and 54.8% for signs of secondary infection), throat and oral examination (52.7%), and otoscopy (66.1% for the ear canal and 64.4% for the tympanic membrane). In this study, measurements from remote physical examination with a mobile medical device had satisfactory concordance with measurements from in-person physical examination for otoscopy, throat and oral examination, skin examination, and heart and lung auscultation, with limitations regarding heart and lung auscultation in infants and abdominal auscultation in children of all ages. Measurements from remote physical examination via a mobile medical device were comparable with those from in-person physical examination in children older than 2 years. These findings suggest that telemedicine may be an alternative to in-person examination in certain contexts and may help to optimize access to health care services and reduce social and geographic barriers. Brazilian Registry of Clinical Trials Identifier: RBR-346ymn.


Comparison of two pretransplant predictive models and a flexible HCT-CI using different cut off points to determine low-, intermediate-, and high-risk groups: the flexible HCT-CI Is the best predictor of NRM and OS in a population of patients undergoing allo-RIC.
Patient comorbidities are being increasingly analyzed as predictors for outcome after hematopoietic stem cell transplantation (HSCT), especially in allogeneic HSCT (Allo-HSCT). Researchers from Seattle have recently developed several pretransplant scoring systems (hematopoietic cell transplantation comorbidity index [HCT-CI] and the Pretransplantation Assessment of Mortality (PAM) model) from large sets of HSCT recipients with the aim of improving non-transplant models, mainly the Charlson Comorbidity Index (CCI). The validation of these comorbidity indexes in other institutions and in different disease and conditioning-related settings is of interest to determine whether these models are potentially applicable in clinical practice and in research settings. We performed a retrospective study in our institution including 194 consecutive reduced-intensity conditioning (RIC) AlloHSCT (allo-RIC) recipients to compare the predictive value of the PAM score, CCI, the original HCT-CI, and the flexible HCT-CI using a different risk group stratification. The median patient pretransplant scores for the HCT-CI, PAM, and CCI were 3.5, 22, and 0, respectively. The flexible HCT-CI risk-scoring system (restratified as: low risk [LR] 0-3 points, intermediate risk [IR] 4-5 points, and high risk [HR] >5 points) was the best predictor for non-relapse mortality (NRM). The 100-day and 2-year NRM incidence in these risk categories was 4% (95% confidence interval C.I. 2%-11%), 16% (95% C.I. 9%-31%), and 29% (95% C.I. 19%-45%), respectively (P < .001), and 19% (95% C.I. 12%-28%), 33% (95% C.I. 22%-49%), and 40% (95% C.I. 28%-56%), respectively (P=.01). However, we found no predictive value for NRM using neither the original HCT-CI nor the PAM or CCI models. The better predictive capacity for NRM of the flexible HCT-CI than PAM and CCI was confirmed with the c-statistics (c-statistics of 0.672, 0.634, and 0.595, respectively). Regarding the 2-year overall survival (OS), the flexible HCT-CI score categories were also associated with the highest predictive HR. In conclusion, our single-center study suggests that the flexible HCT-CI is a good predictor of 2-year NRM and survival after an allo-RIC.


Loss of latent activity of liver microsomal membrane enzymes evoked by lipid peroxidation. Studies of nucleoside diphosphatase, glucose-6-phosphatase, and UDP glucuronyltransferase.
The effects of lipid peroxidation on latent microsomal enzyme activities were examined in NADPH-reduced microsomes from phenobarbital-pretreated male rats. Lipid peroxidation, stimulated by iron or carbon tetrachloride, was assayed as malondialdehyde formation. Independent of the stimulating agent of lipid peroxidation, latency of microsomal nucleoside diphosphatase activity remained unaffected up to microsomal peroxidation equivalent to the formation of about 12 nmol malondialdehyde/mg microsomal protein. However, above this threshold a close correlation was found between lipid peroxidation and loss of latent enzyme activity. The loss of latency evoked by lipid peroxidation was comparable to the loss of latency attainable by disrupting the microsomal membrane by detergent. Loss of latent enzyme activity produced by lipid peroxidation was also observed for microsomal glucose-6-phosphatase and UDPglucuronyltransferase. In contrast to nucleoside diphosphatase, however, both enzymes were inactivated by lipid peroxidation, as indicated by pronounced decreases of their activities in detergent-treated microsomes. According to the respective optimal oxygen partial pressure (po2) for lipid peroxidation, the iron-mediated effects on enzyme activities were maximal at a po2 of 80 mmHg and the one mediated by carbon tetrachloride at a po2 of 5 mmHg. Under anaerobic conditions no alterations of enzyme activities were detected. These results demonstrate that loss of microsomal latency only occurs when peroxidation of the microsomal membrane has reached a certain extent, and that beyond this threshold lipid peroxidation leads to severe disintegration of the microsomal membrane resulting in a loss of its selective permeability, a damage which should be of pathological consequences for the liver cell. Because of its resistance against lipid peroxidation nucleoside diphosphatase is a well-suited intrinsic microsomal parameter to estimate this effect of lipid peroxidation on the microsomal membrane.


The Evolving Role of Immune Checkpoint Inhibitors in Hepatocellular Carcinoma Treatment.
Hepatocellular carcinoma (HCC) is one of most common cancers and the fourth leading cause of death worldwide. Commonly, HCC development occurs in a liver that is severely compromised by chronic injury or inflammation. Liver transplantation, hepatic resection, radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), and targeted therapies based on tyrosine protein kinase inhibitors are the most common treatments. The latter group have been used as the primary choice for a decade. However, tumor microenvironment in HCC is strongly immunosuppressive; thus, new treatment approaches for HCC remain necessary. The great expression of immune checkpoint molecules, such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activating gene 3 protein (LAG-3), and mucin domain molecule 3 (TIM-3), on tumor and immune cells and the high levels of immunosuppressive cytokines induce T cell inhibition and represent one of the major mechanisms of HCC immune escape. Recently, immunotherapy based on the use of immune checkpoint inhibitors (ICIs), as single agents or in combination with kinase inhibitors, anti-angiogenic drugs, chemotherapeutic agents, and locoregional therapies, offers great promise in the treatment of HCC. This review summarizes the recent clinical studies, as well as ongoing and upcoming trials.


Prognostic relevance of a novel semiquantitative classification of Bcl2 immunohistochemical expression in human infiltrating ductal carcinomas of the breast.
Bcl2 is an important prognostic parameter in human breast cancer. However, the evaluation of Bcl2 expression by immunohistochemistry is carried out using arbitrary scoring criteria. In the present study, we evaluated the clinical relevance of a novel, semiquantitative classification of the Bcl2 immunostaining based on both the distribution and the intensity of the staining reaction. The proposed classification was first validated in 69 breast cancer specimens by comparing the Bcl2 immunostaining with the Bcl2 messenger RNA (mRNA) levels evaluated by real-time RT-PCR. Since a highly significant association was found between protein and mRNA for Bcl2, the immunohistochemical scoring system was applied to 442 patients with infiltrating ductal carcinomas of the breast with long-term follow-up (median observation time 106 months). In the entire series, the Bcl2 variable was an independent predictor of clinical outcome, and its prognostic independence was maintained when lymph node-negative and -positive patients were considered separately. In this regard, of particular interest was the observation of a subgroup of node-negative breast cancer patients with a negative Bcl2 immunostaining, who had a very high probability of relapse or death (respectively about five and seven times greater than patients with a positive Bcl2 immunostaining). Moreover, the Bcl2 variable retained prognostic significance also in subgroups of patients treated with either adjuvant endocrine therapy or chemotherapy. Our results demonstrated that in breast cancer, Bcl2 protein expression parallels its mRNA level, and it has a highly significant and independent prognostic relevance.


Listeria monocytogenes mutants that fail to compartmentalize listerolysin O activity are cytotoxic, avirulent, and unable to evade host extracellular defenses.
Listeria monocytogenes is a facultative intracellular bacterial pathogen that escapes from a phagosome and grows in the host cell cytosol. Escape of the bacterium from the phagosome to the cytosol is mediated by the bacterial pore-forming protein listeriolysin O (LLO). LLO has multiple mechanisms that optimize activity in the phagosome and minimize activity in the host cytosol. Mutants that fail to compartmentalize LLO activity are cytotoxic and have reduced virulence. We sought to determine why cytotoxic bacteria have attenuated virulence in the mouse model of listeriosis. In this study, we constructed a series of strains with mutations in LLO and with various degrees of cytotoxicity. We found that the more cytotoxic the strain in cell culture, the less virulent it was in mice. Induction of neutropenia increased the relative virulence of the cytotoxic strains 100-fold in the spleen and 10-fold in the liver. The virulence defect was partially restored in neutropenic mice by adding gentamicin, an antibiotic that kills extracellular bacteria. Additionally, L. monocytogenes grew more slowly in extracellular fluid (mouse serum) than within tissue culture cells. We concluded that L. monocytogenes controls the cytolytic activity of LLO to maintain its nutritionally rich intracellular niche and avoid extracellular defenses of the host.


Eruption of Permanent Teeth As Risk Factor for Allergic Reactions During Oral Immunotherapy.
Background: Oral immunotherapy (OIT) increases the threshold of reaction in children older than 4 years with food allergy. The risk for severe allergic reactions (ARs) during OIT has been reported in several studies, often in the presence of concomitant cofactors such as physical exercise, empty stomach, medications, poorly controlled asthma, menses, and alcohol consumption. Cases Presentation: We describe a case series of 5 scholar age patients undergoing OIT who showed ARs to a known, previously tolerated dose of allergen during permanent tooth eruption, in which other known cofactors were excluded. Conclusions: Patients may be exposed to cofactors due to behavioral habits not only in the second and third decades of life, but also in the first decade of life, due to the timing of mixed dentition. More studies are needed to estimate the frequency and entity of tooth eruption as cofactor, as well as to know the correct management of children undergoing dentition during OIT.


Numerical simulation of blood flow inside an artery under applying constant heat flux using Newtonian and non-Newtonian approaches for biomedical engineering.
In this paper, different behaviors of blood flow are simulated inside the artery under applying a constant heat flux on the artery boundary walls. To simulate the blood flow, the Sisko model is employed. Then, the temperature and Nusselt number of blood flow are reported for different Sisko parameters. Afterward, the effects of different artery radiuses are studied on the Nusselt number. Medical treatment by replenishes fluid and electrolytes in the body vessels can change blood flow properties from non-Newtonian behavior to Newtonian behavior, which increases heat transfer in blood flow and causes to reduce blood flow temperature. In this research, the maximum temperature of Newtonian blood fluid flow is reported as much as 310.0045 K, whereas; maximum flow temperature in non-Newtonian blood fluid is 310.007 K. These results emphasize the effects of the type of Newtonian and non-Newtonian fluid model on the thermal behavior of blood inside body vessels. Since medical science does not permit body temperature to be changed from the normal condition, this small variation can be noticeable and sensible on the health. Hence, medical scientific research centers and institutes of vaccine and serum have to be careful in the mechanical design of drugs for blood fluid. The results of this research show the application of mechanical engineering for some of the medical concerns in designing the drugs which are effective on the behavior of human body blood.


Measuring social support among older adults.
The purpose of this study is to introduce a measure of natural supportive behaviors for use in studies that examine the relationship between stress, social support, and health among older adults. The index improves on existing measures in three ways: it avoids problems arising from confounding potentially supportive relationships with support that is actually received; the scale also assesses variations in individual support needs; and it measures four distinct dimensions of social support (informational support, tangible help, emotional support, and integration). Based on data from a random community survey of 351 older adults, the basic psychometric properties and the factor structure of the scale are explored. The predictive validity of the scale is demonstrated by showing that the dimensions of support buffer the stressful effects of bereavement on depressive symptoms.


Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial nucleus: a role in migraine?
Migraine is a common, debilitating condition affecting up to 15% of the population. The ventroposteromedial nucleus of the thalamus relays trigeminal sensory input to the primary somatosensory cortex. In vivo electrophysiological recordings were made from the cell bodies of thalamocortical relay neurons in rats. We investigated whether microiontophoretic ejection of beta antagonists could inhibit thalamocortical activity in response to superior sagittal sinus (SSS) stimulation. We also studied 'postsynaptic' actions of these drugs through their modulatory actions on L-glutamate-evoked third order neuronal firing. Propranolol inhibited responses to SSS stimulation (P < 0.001) and L-glutamate ejection (P < 0.001). This was due to an action on beta receptors as it could be partially reversed by co-ejection of isoproterenol (SSS, P = 0.02; L-glutamate, P = 0.006). Serotonin (5-HT) receptor antagonism did not contribute to propranolol's action since the 5-HT1A receptor antagonist, (S)-WAY 100135 (P = 0.2), and the 5-HT1B/1D receptor antagonist, GR127935 (P = 0.6), did not affect L-glutamate-evoked neuronal firing. Atenolol inhibited both responses (SSS, P = 0.003; L-glutamate, P < 0.001). The beta2 antagonist ICI 118,551 had no effect (SSS, P = 0.9; L-glutamate, P = 0.4), nor did the beta2 agonist procaterol (SSS, P = 0.6; L-glutamate, P = 0.9). SR 59230A (beta3 antagonist) also produced no significant inhibition (SSS, P = 0.7; L-glutamate, P = 0.2), indicating an inhibitory role for beta1 antagonists only. beta Blockers therefore may exert some of their therapeutic effects in migraine through beta1 adrenoceptor antagonist actions in the thalamus. Thalamic involvement in migraine is attractive given the complex and widespread nature of the sensory disturbance.


Epithelial keratitis mimicking herpes simplex keratitis in a patient after cataract surgery: A case report.
Epithelial keratitis is a common complication after cataract surgery. Many factors have been attributed to this clinical phenomenon. An 82-year-old woman without previous herpes simplex keratitis (HSK) underwent an uncomplicated clear corneal phacoemulsification procedure in the right eye. In the late postoperative period, epithelial keratitis developed in this same eye. An initial diagnosis of HSK was made clinically. The lesion was refractory to antiviral treatment and had progressed. After topical acyclovir cessation and vigorous lubrication, a diagnosis of toxic keratitis was finally made. The corneal epithelial defect and dendritic lesion presented initially. Responding to antiviral treatment, this corneal lesion aggravated and revealed large epithelial erosion. After topical acyclovir cessation and initiation of vigorous lubrication, the toxic keratitis was completely resolved. Epithelial keratitis following cataract surgery is a common complication and can be misdiagnosed early in its disease course. Physicians should be alert to the possibility of HSK. Polymerase chain reaction detection is helpful in diagnosing this disease.


GRANT Motif Regulates CENP-A Incorporation and Restricts RNA Polymerase II Accessibility at Centromere.
Precise chromosome segregation is essential for maintaining genomic stability, and its proper execution centers on the centromere, a chromosomal locus that mounts the kinetochore complex to mediate attachment of chromosomes to the spindle microtubules. The location of the centromere is epigenetically determined by a centromere-specific histone H3 variant, CENP-A. Many human cancers exhibit overexpression of CENP-A, which correlates with occurrence of aneuploidy in these malignancies. Centromeric targeting of CENP-A depends on its histone fold, but recent studies showed that the N-terminal tail domain (NTD) also plays essential roles. Here, we investigated implications of NTD in conferring aneuploidy formation when CENP-A is overexpressed in fission yeast. A series of mutant genes progressively lacking one amino acid of the NTD have been constructed for overexpression in wild-type cells using the intermediate strength nmt41 promoter. Constructs hosting disrupted GRANT (Genomic stability-Regulating site within CENP-A N-Terminus) motif in NTD results in growth retardation, aneuploidy, increased localization to the centromere, upregulated RNA polymerase II accessibility and transcriptional derepression of the repressive centromeric chromatin, suggesting that GRANT residues fine-tune centromeric CENP-A incorporation and restrict RNA polymerase II accessibility. This work highlighted the importance of CENP-A NTD, particularly the GRANT motif, in aneuploidy formation of overexpressed CENP-A in fission yeast.


Factors Associated With Adherence to Helicobacter pylori Testing During Hospitalization for Bleeding Peptic Ulcer Disease.
Guidelines recommend testing patients with peptic ulcer disease for Helicobacter pylori infection. We sought to identify factors associated with adherence to testing for H pylori in patients hospitalized for bleeding ulcers and to evaluate whether performing these tests affect risk for rebleeding. We performed a retrospective study of 830 inpatients who underwent endoscopy from 2011 through 2016 for gastrointestinal bleeding from gastric or duodenal ulcers. We searched electronic medical records for evidence of tests to detect H pylori by biopsy, serologic, or stool antigen analyses. We used multivariable models to identify clinical, demographic, and endoscopic factors associated with testing for H pylori. Kaplan-Meier analysis was performed to determine whether H pylori testing altered risk for the composite outcome of rebleeding or death within 1 year of admission. Among the patients hospitalized for bleeding peptic ulcer disease during the 6-year period, 19% were not tested for H pylori within 60 days of index endoscopy. Hospitalization in the intensive care unit (ICU) was the factor most frequently associated with nonadherence to H pylori testing guidelines (only 66% of patients in the ICU were tested vs 90% of patients not in the ICU; P < .01), even after we adjusted for ulcer severity, coagulation status, extent of blood loss, and additional factors (adjusted odds ratio, 0.42; 95% CI, 0.27-0.66). Testing for H pylori was associated with a 51% decreased risk of rebleeding or death during the year after admission (adjusted hazard ratio 0.49; 95% CI, 0.36-0.67). In an analysis of hospitalized patients who underwent endoscopy for gastrointestinal bleeding from gastric or duodenal ulcers, we found admission to the ICU to be associated with failure to test for H pylori infection. Failure to test for H pylori was independently associated with increased risk of rebleeding or death within 1 year of hospital admission. We need strategies to increase testing for H pylori among inpatients with bleeding ulcers.


Insecticidal activity of different extracts from Scrophularia canina L. against Culex pipiens molestus Forskal (Diptera, Culicidae).
The insecticidal activity of different extracts (aqueous, methyl alcohol, hexane and petroleum ether) of the aerial part of Scrophularia canina against the second and fourth-instar larvae and adult females of Culex pipiens molestus was investigated. The larvicidal activity of all the extracts was tested in the dose range from 7.8 to 1000 ppm. The highest toxicity was exhibited by the petroleum ether extract against second-instar larvae (48 h LC₅₀ = 23.5 ppm) and by the hexane extract against fourth-instar larvae (48 h LC₅₀ = 23.6 ppm). Methyl alcohol and aqueous extracts did not show any larvicidal activity. Sub-lethal doses of petroleum ether and hexane extracts induced increasing mortalities during 13 days after treatment but did not affect the duration of larval and pupal stages. In persistence tests, the hexane extract retained a satisfactory larvicidal activity after a 10-day period of test solutions incubation. Topical treatment of adult females with doses from 0.25 to 8 μg per mg of female body weight of different extracts showed a similar toxicity for the hexane (24 h LD₅₀ = 1.7 μg mg⁻¹) and petroleum ether (24 h LD₅₀ = 1.8 μg mg⁻¹) extracts which were significantly more toxic than methyl alcohol extract (4.2 μg mg⁻¹). Aqueous extract did not induce adult mortality. The marked mosquitocidal activity of petroleum ether and hexane extracts of the aerial part of S. canina against different life stages of C. pipiens molestus is promising to develop effective alternatives to synthetic insecticides.


Lung function decline and blood lead among residents nearby to industrial complex.
PURPOSE: This study was to ascertain the risk factors of pulmonary function decline (forced expiratory volume in 1 s [FEV(1)], forced vital capacity [FVC]) among those exposed to lead in the vicinity of industrial complex. METHODS: In total, 263 men and women, aged over 30, were recruited from two cities during a 2-year follow-up. Spirometry testing was conducted first at baseline and then after 2-years of follow-up. The change in FVC and FEV(1) during the study period was analyzed according to blood lead (BPb), urinary cotinine, and 1-hydroxypyrene, after controlling for sex, height, baseline FVC or FEV(1), and airway hyperresponsiveness. RESULTS: With increase in age, both FEV(1) and FVC declined. More marked decline in FVC was noted for men than for women (p < 0.05), while the decline in FEV(1) was not. Biological variables, especially height (p < 0.05) and pulmonary status (p < 0.0001), were associated with the decline in both FEV(1) and FVC. Even after controlling these other variables, blood lead level was also significantly associated with the decline of FVC. CONCLUSIONS: Even though the decline in FEV(1) and FVC with aging was within a normal range, people with smaller height were more vulnerable to the decline of both FEV(1) and FVC and especially higher level of BPb was accompanied with larger decline of FVC. Oxidative stress in relation to lead accumulation in adult may contribute to rapid aging of pulmonary function.


Mood disorders in patients with COPD: overview of current research and future needs.
Depression is major problem for the medically ill population but few recommendations have been made regarding treatment with specific compounds in many of these illnesses. This review attempts to consider the inter-relationship between smoking, pulmonary disease and mood disorders. It has been reported that nearly 50% of patients with chronic pulmonary illnesses report depressive symptoms at some time during the course of their illness, but with the complex issues regarding respiratory drive and substance dependence, little in the way of specific clinical information have been made for this group. In this review, the theorectical relationship that exists between dopamine, serotonin and nicotine and how the biochemical nicotine dependence issues (with regard to mood) may actually be a key element in the understanding and treatment of depression later in the life of the development of chronic lung disease and depression, are discussed.


The influence of perturbing the working surface during reaching and grasping in children with hemiplegic cerebral palsy.
To examine unimanual and bimanual reaching and grasping in children with hemiplegic cerebral palsy with particular emphasis on the nature and extent of interlimb coupling when the working surface is perturbed. Nine children with hemiplegic cerebral palsy and 7 control children with no movement difficulties took part in the study. Children were asked to pick up a cube unimamually and bimanually when the surface it was placed on was either sloping away from the child (Experiment 1) or towards the child (Experiment 2). Both 3D kinematic data and video data were gathered and qualitative descriptions of video data were made. The working surface did indeed influence the nature and extent of interlimb coupling and this varied from participant to participant. Analysis of the displacement data revealed that during the bimanual condition lower trajectories were produced by both the hemiplegic and non hemiplegic sides, especially in Experiment 2. The control group showed little difference between the unimanual and bimanual condition. Evidence of interlimb coupling is found, these studies support the findings of our previous work that indicates that there are some benefits to performing bimanual movements in children with hemiplegic cerebral palsy.


Active site prediction using evolutionary and structural information.
The identification of catalytic residues is a key step in understanding the function of enzymes. While a variety of computational methods have been developed for this task, accuracies have remained fairly low. The best existing method exploits information from sequence and structure to achieve a precision (the fraction of predicted catalytic residues that are catalytic) of 18.5% at a corresponding recall (the fraction of catalytic residues identified) of 57% on a standard benchmark. Here we present a new method, Discern, which provides a significant improvement over the state-of-the-art through the use of statistical techniques to derive a model with a small set of features that are jointly predictive of enzyme active sites. In cross-validation experiments on two benchmark datasets from the Catalytic Site Atlas and CATRES resources containing a total of 437 manually curated enzymes spanning 487 SCOP families, Discern increases catalytic site recall between 12% and 20% over methods that combine information from both sequence and structure, and by >or=50% over methods that make use of sequence conservation signal only. Controlled experiments show that Discern's improvement in catalytic residue prediction is derived from the combination of three ingredients: the use of the INTREPID phylogenomic method to extract conservation information; the use of 3D structure data, including features computed for residues that are proximal in the structure; and a statistical regularization procedure to prevent overfitting.


Is There a Dark Side to Mindfulness? Relation of Mindfulness to Criminogenic Cognitions.
In recent years, mindfulness-based interventions have been modified for use with inmate populations, but how this might relate to specific criminogenic cognitions has not been examined empirically. Theoretically, characteristics of mindfulness should be incompatible with distorted patterns of criminal thinking, but is this in fact the case? Among both 259 male jail inmates and 516 undergraduates, mindfulness was inversely related to the Criminogenic Cognitions Scale (CCS) through a latent variable of emotion regulation. However, in the jail sample, this mediational model also showed a direct, positive path from mindfulness to CCS, with an analogous, but nonsignificant trend in the college sample. Post hoc analyses indicate that the Nonjudgment of Self scale derived from the Mindfulness Inventory: Nine Dimensions (MI:ND) largely accounts for this apparently iatrogenic effect in both samples. Some degree of self-judgment is perhaps necessary and useful, especially among individuals involved in the criminal justice system.


Fas cross-linking induces apoptosis in human airway smooth muscle cells.
Hypertrophy and hyperplasia lead to excess accumulation of smooth muscle in the airways of human asthmatic subjects. However, little is known about mechanisms that might counterbalance these processes, thereby limiting the quantity of smooth muscle in airways. Ligation of Fas on the surface of vascular smooth muscle cells and nonmuscle airway cells can lead to apoptotic cell death. We therefore tested the hypotheses that 1) human airway smooth muscle (HASM) expresses Fas, 2) Fas cross-linking induces apoptosis in these cells, and 3) tumor necrosis factor (TNF)-alpha potentiates Fas-mediated airway myocyte killing. Immunohistochemistry using CH-11 anti-Fas monoclonal IgM antibody revealed Fas expression in normal human bronchial smooth muscle in vivo. Flow cytometry using DX2 anti-Fas monoclonal IgG antibody revealed that passage 4 cultured HASM cells express surface Fas. Surface Fas decreased partially during prolonged serum deprivation of cultured HASM cells and was upregulated by TNF-alpha stimulation. Fas cross-linking with CH-11 antibody induced apoptosis in cultured HASM cells, and this effect was reduced by long-term serum deprivation and synergistically potentiated by concomitant TNF-alpha exposure. TNF-alpha did not induce substantial apoptosis in the absence of Fas cross-linking. These data represent the first demonstration that Fas is expressed on HASM and suggest a mechanism by which Fas-mediated apoptosis could act to oppose excess smooth muscle accumulation during airway remodeling in asthma.


Spatio-temporal dynamics, differentiation and viability of human neural stem cells after implantation into neonatal rat brain.
Neural stem cells (NSCs) have attracted major research interest due to their potential use in cell replacement therapy. In patients, human cells are the preferred choice, one source of human NSCs being the brain of fetuses. The aims of the present study were to explore the long-term differentiation, mobility and viability of NSCs derived from the human fetal striatum in response to intracerebral implantation. To investigate long-term spatio-temporal and functional dynamics of grafts in vivo by magnetic resonance imaging, these cells were labeled with superparamagnetic iron oxide (SPIO) nanoparticles prior to implantation. SPIO-labeling of human NSCs left the quantitative profile of the proliferation, cell composition and differentiation capacity of the cells in vitro unaltered. Also after transplantation, the phenotypes after long-term cell differentiation were not significantly different from naïve cells. Upon transplantation, we detected a hypointensity corresponding to the striatal graft location in all animals and persisting for at least 4 months. The hypointense signal appeared visually similar both in location and in volume over time. However, quantitative volumetric analysis showed that the detectable, apparent graft volume decreased significantly from 3 to 16 weeks. Finally, the human NSCs were not proliferating after implantation, indicating lack of tumor formation. These cells are thus a promising candidate for translationally relevant investigations for stem cell-based regenerative therapies.


Nonhost resistance to Phytophthora: novel prospects for a classical problem.
Members of the oomycete genus Phytophthora are the most devastating pathogens of dicot plants. Recent developments in the study of these organisms have led to improved understanding of their phylogenetic relationships and trends in their evolution. Molecular analyses of nonhost (species-level) resistance offer exciting prospects for disease management. A model that evokes a complex interplay of several layers of specific resistance, mediated by a set of ancient broad-spectrum R-gene loci, is sufficient to explain existing cellular and molecular data on nonhost resistance to Phytophthora.


[Peri-operative management in patients with thoracic aortic aneurysm complicated with cardiac tamponade].
We retrospectively summarized the peri-operative hemodynamic status and respiratory function in patients with thoracic aneurysms complicated with cardiac tamponade (Tamponade Group; n = 6) in comparison with patients complicated with hemorrhagic pericardial effusion without symptom of cardiac tamponade (Effusion Group; n = 10). There were no difference with regard to preoperative heart rate, pericardial effusion quantity, frequency of emergent operation and operation time. Preoperative hemodynamic status was worse in Tamponade Group than in Effusion Group. The cardiac indices of 12 h, 24 h, 48 h after operation in Tamponade Group were 2.60 +/- 0.60, 2.29 +/- 0.42, 1.95 +/- 0.33 l/min/m2 respectively, those were not different in Effusion Group. The differences between O2 tension in alveolar and arterial blood O2 tension (A-aDO2) and oxygenation indices (OI) of 12 h and 24 h after operation were significantly worse in Tamponade Group than in Effusion Group, but those of 48 h were not different. The operative mortality was 50% in Tamponade Group, and none in Effusion Group. It is very important to maintain hemodynamic status before operation, to perform complete repair (graft replacement) as early as possible and to care intensively after operation for thoracic aortic aneurysm complicated with cardiac tamponade.


Novel therapies and preventative strategies for primary and recurrent Clostridium difficile infections.
Clostridium difficile is the leading infectious cause of antibiotic-associated diarrhea and colitis. C. difficile infection (CDI) places a heavy burden on the healthcare system, with nearly half a million infections yearly and an approximate 20% recurrence risk after successful initial therapy. The high incidence has driven new research on improved prevention such as the emerging use of probiotics, intestinal microbiome manipulation during antibiotic therapies, vaccinations, and newer antibiotics that reduce the disruption of the intestinal microbiome. While the treatment of acute C. difficile is effective in most patients, it can be further optimized by adjuvant therapies that improve the initial treatment success and decrease the risk of subsequent recurrence. Finally, the high risk of recurrence has led to multiple emerging therapies that target toxin activity, recovery of the intestinal microbial community, and elimination of latent C. difficile in the intestine. In summary, CDIs illustrate the complex interaction among host physiology, microbial community, and pathogen that requires specific therapies to address each of the factors leading to primary infection and recurrence.


Differential Alterations in Resting State Functional Connectivity Associated with Depressive Symptoms and Early Life Adversity.
Depression and early life adversity (ELA) are associated with aberrant resting state functional connectivity (FC) of the default mode (DMN), salience (SN), and central executive networks (CEN). However, the specific and differential associations of depression and ELA with FC of these networks remain unclear. Applying a dimensional approach, here we analyzed associations of FC between major nodes of the DMN, SN, and CEN with severity of depressive symptoms and ELA defined as childhood abuse and neglect in a sample of 83 healthy and depressed subjects. Depressive symptoms were linked to increased FC within the SN and decreased FC of the SN with the DMN and CEN. Childhood abuse was associated with increased FC within the SN, whereas childhood neglect was associated with decreased FC within the SN and increased FC between the SN and the DMN. Our study thus provides evidence for differential associations of depressive symptoms and ELA with resting state FC and contributes to a clarification of previously contradictory findings. Specific FC abnormalities may underlie specific cognitive and emotional impairments. Future research should link specific clinical symptoms resulting from ELA to FC patterns thereby characterizing depression subtypes with specific neurobiological signatures.


[Cartilage damage caused by a dislocated resorbable interference screw of poly(L-lactide) 46 months after anterior cruciate ligament reconstruction].
The case of a 44-year-old male patient is reported, who was operated 4 years after a cruciate ligament replacement. A nearly completely intact biodegradable screw was removed arthroscopically. The screw dislocated from the tibial canal into the joint and caused damage to the retropatellar cartilage which was treated by debridement and lateral release. A material analysis was done on the explanted screw which showed no material fault. A review of the literature reporting adverse events connected to biodegradable implants was carried out. Nine papers reporting about adverse event are cited. There seem to be three main problems: delayed degradation, foreign body reaction and the filling of graft tunnels with non-ossified tissue. Instructions for the use of biodegradable interference screws were requested from seven manufacturers to compare the given information about the degradation behaviour. The information given on the period of time until the screws would be completely resorbed were heterogeneous, ranging from no specific information about the time span at all up to 24 months. More research is needed to identify the degradation behaviour more precisely and clarify the potential risks connected to biodegradable implants. Their use should be reconsidered critically.


Cleavage and degradation of Claspin during apoptosis by caspases and the proteasome.
Apoptosis plays a crucial role in development and tissue homeostasis. Some key survival pathways, such as DNA damage checkpoints and DNA repair, have been described to be inactivated during apoptosis. Here, we describe the processing of the human checkpoint protein Claspin during apoptosis. We observed cleavage of Claspin into multiple fragments in vivo. In vitro cleavage with caspases 3 and 7 of various fragments of the protein, revealed cut sites near the N- and C-termini of the protein. Using mass spectrometry, we identified a novel caspase cleavage site in Claspin at Asp25. Importantly, in addition to cleavage by caspases, we observed a proteasome-dependent degradation of Claspin under apoptotic conditions, resulting in a reduction of the levels of both full-length Claspin and its cleavage products. This degradation was not dependent upon the DSGxxS phosphodegron motif required for SCF(beta-TrCP)-mediated ubiquitination of Claspin. Finally, downregulation of Claspin protein levels by short interfering RNA resulted in an increase in apoptotic induction both in the presence and absence of DNA damage. We conclude that Claspin has antiapoptotic activity and is degraded by two different pathways during apoptosis. The resulting disappearance of Claspin from the cells further promotes apoptosis.


Air pollution and emergency department visits for depression in Edmonton, Canada.
Depression is a common cause of morbidity. Sufferers are very sensitive to many external factors. Emergency department (ED) visits for this condition can be associated with the concentration of ambient air pollutants. The study objective was to examine and assess the associations between ED visits for depression and ambient air pollution. The present study analyzed 15,556 ED visits for depression (ICD-9: 311) at Edmonton hospitals between 1992 and 2002. The data were clustered based on the triplet {year, month, day of the week}. The generalized linear mixed models (GLMM) technique was used to regress the logarithm of the clustered counts for ED visits for depression on the levels of air pollutants (CO, NO2, SO2, O3, PM10 and PM2.5) and the meteorological variables. The number of ED visits for depression was analyzed separately for all patients, and males and females. An analysis by season was also conducted: for the whole year (I-XII), warm season (IV-IX), and cold season (X-III). After adjusting for temperature and relative humidity, the following increments in daily depression-related ED visits could be noted: 6.9% (95% CI: 1.3, 12.9) for carbon monoxide (CO) for all patients in warm season; 7.4% (95% CI: 0.5, 14.8) for nitrogen dioxide (NO2) for female patients in warm season; 4.5% (95% CI: 0.1, 9.1) for sulphur dioxide (SO2) for female patients in warm season; 6.9% (95% CI: 0.6, 13.6) for ground level ozone (O3, 1-day lagged) for female patients in warm season; 7.2% (95% CI: 2.7, 12.0) for particulate matter (PM10) for females in cold season; and 7.2% (95% CI: 2.0, 12.8) for particulate matter (PM2.5) for females in cold season. The findings provide support for the hypothesis that ED visits for depression are associated with exposure to ambient air pollution.


Time squared: repeated measures on phylogenies.
Studies of gene expression profiles in response to external perturbation generate repeated measures data that generally follow nonlinear curves. To explore the evolution of such profiles across a gene family, we introduce phylogenetic repeated measures (PR) models. These models draw strength from 2 forms of correlation in the data. Through gene duplication, the family's evolutionary relatedness induces the first form. The second is the correlation across time points within taxonic units, individual genes in this example. We borrow a Brownian diffusion process along a given phylogenetic tree to account for the relatedness and co-opt a repeated measures framework to model the latter. Through simulation studies, we demonstrate that repeated measures models outperform the previously available approaches that consider the longitudinal observations or their differences as independent and identically distributed by using deviance information criteria as Bayesian model selection tools; PR models that borrow phylogenetic information also perform better than nonphylogenetic repeated measures models when appropriate. We then analyze the evolution of gene expression in the yeast kinase family using splines to estimate nonlinear behavior across 3 perturbation experiments. Again, the PR models outperform previous approaches and afford the prediction of ancestral expression profiles. To demonstrate PR model applicability more generally, we conclude with a short examination of variation in brain development across 4 primate species.


Recent progress in carbon nanotube-based gas sensors.
The development of carbon nanotube-(CNTs-)based gas sensors and sensor arrays has attracted intensive research interest in the last several years because of their potential for the selective and rapid detection of various gaseous species by novel nanostructures integrated in miniature and low-power consuming electronics. Chemiresistors and chemical field effect transistors are probably the most promising types of gas nanosensors. In these sensors, the electrical properties of nanostructures are dramatically changed when exposed to the target gas analytes. In this review, recent progress on the development of different types of CNT-based nanosensors is summarized. The focus was placed on the means used by various researchers to improve the sensing performance (sensitivity, selectivity and response time) through the rational functionalization of CNTs with different methods (covalent and non-covalent) and with different materials (polymers and metals).