Protein and small non-coding RNA-enriched extracellular vesicles are released by the pathogenic blood fluke Schistosoma mansoni.
Penetration of skin, migration through tissues and establishment of long-lived intravascular partners require Schistosoma parasites to successfully manipulate definitive host defences. While previous studies of larval schistosomula have postulated a function for excreted/secreted (E/S) products in initiating these host-modulatory events, the role of extracellular vesicles (EVs) has yet to be considered. Here, using preparatory ultracentrifugation as well as methodologies to globally analyse both proteins and small non-coding RNAs (sncRNAs), we conducted the first characterization of Schistosoma mansoni schistosomula EVs and their potential host-regulatory cargos. Transmission electron microscopy analysis of EVs isolated from schistosomula in vitro cultures revealed the presence of numerous, 30-100 nm sized exosome-like vesicles. Proteomic analysis of these vesicles revealed a core set of 109 proteins, including homologs to those previously found enriched in other eukaryotic EVs, as well as hypothetical proteins of high abundance and currently unknown function. Characterization of E/S sncRNAs found within and outside of schistosomula EVs additionally identified the presence of potential gene-regulatory miRNAs (35 known and 170 potentially novel miRNAs) and tRNA-derived small RNAs (tsRNAs; nineteen 5' tsRNAs and fourteen 3' tsRNAs). The identification of S. mansoni EVs and the combinatorial protein/sncRNA characterization of their cargo signifies that an important new participant in the complex biology underpinning schistosome/host interactions has now been discovered. Further work defining the role of these schistosomula EVs and the function/stability of intra- and extra-vesicular sncRNA components presents tremendous opportunities for developing novel schistosomiasis diagnostics or interventions.


Topology of the global regulatory network of carbon limitation in Escherichia coli.
One fundamental shortcoming of biotechnological processes operating under carbon-limiting conditions is the high-energy demand (maintenance) of the cells. Although the function of the central carbon metabolism in supplying precursors and energy for biosynthesis has been thoroughly characterized, its regulation and dynamic behaviour during carbon-limited growth has not yet been revealed. The current work demonstrates a time series of metabolic flux distributions during fed-batch cultivation of Escherichia coli K-12 W3110 applying a constant feed rate. The fluxes in glycolysis, pentose phosphate pathway and biosynthesis fell significantly, whereas TCA cycle fluxes remained constant. The flux redistribution resulted in an enhanced energy generation in the TCA cycle and consequently, in a 20% lower biomass yield. The intracellular alarmones ppGpp and cAMP accumulated in large quantities after the onset of nutrient limitation, subsequently declining to basal levels. The network topology of the regulation of the central metabolic pathways was identified so that the observed metabolic and regulatory behaviour can be described. This provides novel aspects of global regulation of the metabolism by the cra, crp and relA/spoT modulons. The work constitutes an important step towards dynamic mathematical modelling of regulation and metabolism, which is needed for the rational optimization of biotechnological processes.


The Ketogenic Diet: Making a Comeback.
Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.


The effect of virtual reality cognitive training for attention enhancement.
Our main goal in this research was to validate the possibility of virtual reality (VR) for attention enhancement in cognitive training program. Then, we developed some cognitive training tasks using VR technology. Thirty subjects who had little behavioral problems and social problems were randomly assigned into three groups: VR group, non-VR group, and control group. Only the VR group used the head-mounted display (HMD) and position sensor. While the VR group and non-VR group performed cognitive training, the control group received no special treatment. All participants took their eight session tasks over 2 weeks. Participants executed a continuous performance task (CPT) before and after training sessions. We found that immersive VR with cognitive training is effective for attention enhancement. Also, we confirmed that our cognitive training can improve the attention span of children and adolescents with behavioral problems and help them learn to focus on some tasks.


Comparative Evaluation of Remineralizing Effect of Novamin and Tricalcium Phosphate on Artificial Caries: An in vitro Study.
The aim of the present study was to compare the remineralizing efficacy of novamin and tricalcium phosphate (TCP). Nail varnish was coated to a total of 30 sound human premolars except for 5 mm × 5 mm window. Baseline microhardness was measured for all test samples. Artificial carious lesions were created for all teeth by subjecting them to demineralization process. Then microhardness of demineralized lesion was measured. Later artificial caries teeth were equally divided into two groups to treat with remineralization solution for 10 days; group I: novamin and group II: TCP. After 10 days of pH cycling, microhardness was measured. The data were statistically analyzed using Statistical Package for the Social Sciences (SPSS) statistical software from Chicago SPSS Inc., version 21 and using analysis of variance (ANOVA) post hoc multiple comparisons test for intergroup and significant difference at p < 0.05. In the present study, group I indicated a higher value for remineralization compared with group II (p < 0.05). The present study showed that both novamin and TCP were effective in remineralizing the carious lesions. This study evaluates the remineralizing potential of novamin and TCP on initial carious lesions.


Changes in bone histoquantitative parameters and histochemical staining reactions for aluminium in a group of patients with chronic renal failure following a reduction in the aluminium concentration of the haemodialysis fluid.
Bone biopsies from a group of 16 patients in chronic renal failure treated by intermittent haemodialysis were available for histoquantitative and histochemical assessment before and after the introduction of reverse osmosis treatment of the dialysis fluid. This treatment reduced the aluminium concentration of the fluid from 1.15 mg/l to less than 0.06 mg/l. After the changeover there was an increase in the extent of calcification fronts. Overall, there was a decrease in the histochemical staining reactions for aluminium, although a few cases showed increased reactions. A large percentage of cases showing decreased reactions also had decreased osteoid volumes. It is concluded that reduction of the concentration of aluminium in the dialysis fluid is associated with an improvement in mineralisation state, and this is further evidence of the importance of minimising the aluminium burden of patients with chronic renal failure.


Effects of Siraitia grosvenorii seed flour on the properties and quality of steamed bread.
Siraitia grosvenorii seeds are rich in abundant active compounds beneficial to human health. To clarify the digestion characteristics of Siraitia grosvenorii seed flour (SSF) and promote the use of SSF in the processing of functional staple foods, SSF was prepared, its composition and physicochemical properties were studied, and the processing characteristics of SSF-wheat flour were systematically investigated. The results showed that the torque curve and other parameters of the dough were significantly affected by the amount of SSF added. With the increase of SSF proportion, the water absorption showed an increasing trend, while the degree of protein weakening first weakened and then enhanced. At 20% SSF, the dough was more resistant to kneading. In response to an increase in SSF, the L* value decreased significantly, and the a* and b* values increased gradually, while the specific volume decreased gradually. Additionally, the hardness, adhesiveness, and chewiness of the bread enhanced gradually, while its elasticity, cohesiveness, and resilience decreased gradually. After the addition of 30% SSF, the inner tissue of steamed bread was more delicate. With an increase in SSF proportion, the predicted glycemic index (pGI) of steamed bread weakened markedly. Overall, these results showed that SSF, as a kind of food ingredient with hypoglycemic activity, can be used in the production of new functional steamed bread products. This study provides basic research data for the development of products containing S. grosvenorii seed.


Genomic profiling of breast cancers.
To describe recent advances in the application of advanced genomic technologies towards the identification of biomarkers of prognosis and treatment response in breast cancer. Advances in high-throughput genomic profiling such as massively parallel sequencing have enabled researchers to catalogue the spectrum of somatic alterations in breast cancers. These tools also hold promise for precision medicine through accurate patient prognostication, stratification, and the dynamic monitoring of treatment response. For example, recent efforts have defined robust molecular subgroups of breast cancer and novel subtype-specific oncogenes. In addition, previously unappreciated activating mutations in human epidermal growth factor receptor 2 have been reported, suggesting new therapeutic opportunities. Genomic profiling of cell-free tumor DNA and circulating tumor cells has been used to monitor disease burden and the emergence of resistance, and such 'liquid biopsy' approaches may facilitate the early, noninvasive detection of aggressive disease. Finally, single-cell genomics is coming of age and will contribute to an understanding of breast cancer evolutionary dynamics. Here, we highlight recent studies that employ high-throughput genomic technologies in an effort to elucidate breast cancer biology, discover new therapeutic targets, improve prognostication and stratification, and discuss the implications for precision cancer medicine.


Effects of a Brief Mindfulness Induction on Death-Related Anxiety.
This study examined effects of a mindfulness induction on proximal and distal defense responses to mortality salience and negative affect. Three experimental conditions were included: mindfulness, mind-wandering, and worrying. Participants in the mindfulness condition underwent a mindfulness induction at the experiment's outset, while participants in the other two conditions underwent a mind-wandering or worry induction. Inductions involved following guided audio instructions presented via headphones. All conditions (N = 77) underwent a mortality salience induction after experimental manipulation, involving a written exercise pertaining to one's death. Results indicated fewer proximal responses in the mindfulness and mind-wandering groups, compared with the worrying group, but no differences in distal responses. Negative affect was lower in the mindfulness group than in the worrying group following mortality salience. Results suggest that mindfulness exercises effectively buffer against negative affect and some responses to mortality salience, although these effects are not different from those of mind-wandering.


[Natural coagulation inhibitors; antithrombin III, protein C, protein S in children with hypercoagulation due to nephrotic syndrome].
Activity of AT HI, protein C and protein S was evaluated in 58 children with nephrotic syndrome aged between 2-17 years and in 50 healthy children aged between 2-16 years serving as a control group. In children with nephrotic syndrome measurements were conducted at three different stages of disease: onset, improvement and remission. The aim was to assess the effect of steroid therapy on activity of the above inhibitors. At the onset of the disease, activity of AT III and protein S were found to be significantly decreased whereas activity of protein C was significantly increased as compared with the control group. Activity of AT III lowered at the onset of the disease, was significantly higher during both the improvement and the remission stage. Activity of protein C, increased at the onset of the nephrotic syndrome, decreased progressively and significantly during the improvement stage and then again increased markedly during the remission. Activity of protein S, lowered at the onset and during the improvement stage of the nephrotic syndrome, significantly rose during the remission, but never reached levels observed in the control group. Activity of AT III and protein C within 72 hours after introduction of steroids increased without any marked alterations in the clinical and biochemical course of the nephrotic syndrome. Activity of protein S was not changed. There are marked changes in AT III and protein C activity in children with nephrotic syndrome. It is expected that these proteins are involved in inhibition of the inflammatory process and of the local and systemic coagulopathy. Raised activity of protein C is not accompanied by increased activity of protein. This arouses doubts as to whether protein C-protein S complex is effective in inhibition of inflammation and limitation of coagulopathy. That role may be played AT III, which with its sufficient rise at the early stage of treatment may limit the risk of thromboembolic complications in children with nephrotic syndrome.


Characterization and Classification of Keratinized Odontogenic Cysts in 29 Dogs.
This retrospective case series presents a unique group of odontogenic cysts that are lined by heavily keratinized epithelium and contain laminated keratin. Keratinized odontogenic cyst (KOC) is proposed as appropriate terminology for the described lesions. The series evaluates cysts from 29 dogs, including clinical presentation, diagnostic imaging, and histopathology. All 29 lesions occurred in tooth bearing regions of the jaws; 21 were maxillary and 8 were mandibular. These keratinized odontogenic cysts were unilocular or multilocular, and some demonstrated considerable expansion resulting in bone destruction. In 13 of 29 cases, there was evidence of tooth displacement associated with the expansion of the KOC. The KOCs did not have a distinctive radiographic appearance. 48% of the cysts had a soft tissue defect through which the keratin contents could be visualized. Cyst contents ranged from hard mineralized keratin to fluid consistency with soft flecks of keratin. The pathoetiology of KOCs is unknown; however, the biological behavior is benign and thought to be slowly progressive despite potential for locally destructive growth. Recurrence is uncommon when cyst enucleation and debridement are aggressive or when solid cysts are excised en bloc.


Preeclampsia associated focal and segmental glomerulosclerosis and glomerular hypertrophy: a morphometric analysis.
Renal biopsies from hypertensive pregnant women performed 8 to 10 days postpartum were processed by morphometric analysis. We allocated the 74 patients into four groups according to the respective forms of pregnancy hypertension, i.e. preeclampsia and gestational hypertension. Groups I and II included preeclamptic women, with (group I) or without (group II) de novo FSGS. Groups III and IV included biopsies of women with isolated gestational hypertension, appeared during the third trimester (group III) or earlier (group IV). The control group included 17 biopsies from age-matched nonpregnant women presenting with isolated hematuria. Glomerular lesions of typical preeclampsia were seen in all the biopsies of groups I and II, and in some of women with gestational hypertension of groups III and IV. Our morphometric analysis of these renal biopsies showed a progressive increase in glomerular size from early gestational hypertension, gestational hypertension of the 3rd trimester, isolated preeclampsia, and finally preeclamptic nephropathy associated with FSGS. The largest glomeruli were seen in preeclamptic women with severe hypertension and histologic lesions of preeclampsia with FSGS. Thus, both systemic hypertension and glomerular hypertrophy seem necessary to induce FSGS in this type of pathology.


Time, music, and reverie.
Time is an important source of containment vis-à-vis the pressure of affects and the nondimensional immensity of mental space experienced by difficult patients. A more articulated spatiotemporal integration can be facilitated by the analyst's musical "reverie" during intense emotional exchanges in analytic sessions. This reverie can be visual, olfactory, kinaesthetic, etc., no less than auditory or musical. Music is indeed connected with both the concrete world of bodily sensations and the symbolic expressions of culture, and may be an important transitional phenomenon in analytic communication on both unconscious and conscious levels. Two clinical cases are presented in which the patient's awareness of the passage of time, associated with the analyst's internal musical experiences, made it possible in one case to reduce intense panic attacks and, in the other, to overcome the patient's rigid obsessive defenses, giving him access to fluid and unforeseen emotions. In these two instances of working through, the perception of time helped establish confidence in the creative contribution of the "unheard melodies" (Keats) of affects to the functioning of thought.


Biodegradation of Structurally Diverse Phthalate Esters by a Newly Identified Esterase with Catalytic Activity toward Di(2-ethylhexyl) Phthalate.
Herein, we report a double enzyme system to degrade 12 phthalate esters (PAEs), particularly bulky PAEs, such as the widely used bis(2-ethylhexyl) phthalate (DEHP), in a one-pot cascade process. A PAE-degrading bacterium, Gordonia sp. strain 5F, was isolated from soil polluted with plastic waste. From this strain, a novel esterase (GoEst15) and a mono(2-ethylhexyl) phthalate hydrolase (GoEstM1) were identified by homology-based cloning. GoEst15 showed broad substrate specificity, hydrolyzing DEHP and 10 other PAEs to monoalkyl phthalates, which were further degraded by GoEstM1 to phthalic acid. GoEst15 and GoEstM1 were heterologously coexpressed in Escherichia coli BL21 (DE3), which could then completely degrade 12 PAEs (5 mM), within 1 and 24 h for small and bulky substrates, respectively. To our knowledge, GoEst15 is the first DEHP hydrolase with a known protein sequence, which will enable protein engineering to enhance its catalytic performance in the future.


Asymmetric synthesis of (+)-galbelgin, (-)-kadangustin J, (-)-cyclogalgravin and (-)-pycnanthulignenes A and B, three structurally distinct lignan classes, using a common chiral precursor.
The enantioselective synthesis of three structurally distinct classes of lignan from a single, aza-Claisen-derived, chiral morpholine amide is reported. The class of lignan formed is dependent on the substitution pattern in the aryl rings and choice of protecting group on a key benzylic hydroxyl group. The methodology has been used to asymmetrically synthesize and determine the absolute stereochemistry of lignans (+)-cyclogalgravin 3, (-)-pycnanthulignene A 4, (-)-pycnanthulignene B 5, and (-)-kadangustin J 8.


Characterization and identification of glyceryl ether diesters present in tumor cells.
The previously unidentified neutral lipid present in tumor tissues has been isolated from Ehrlich ascites cells and unequivocally identified as a lipid class of glyceryl ether diesters containing various degrees of unsaturation, and ranging in approximate molecular weight from 760 to 990. The glyceryl ether diester fraction was shown to be free from neutral plasmalogens (glyceryl diacyl alk-1'-enyl ethers). The tumor lipid was subjected to saponification, transesterification, and lithium aluminum hydride reduction. The glyceryl monoethers that resulted from deacylation were the 1-isomers ranging in hydrocarbon chain length from C(12) to C(24). The predominant glyceryl ethers were the hexadecyl (49%), octadecyl (21%), and octadecenyl (14%) derivatives. Saturated and mono- and polyunsaturated fatty acids ranging in chain length from C(12) to C(24) carbon atoms were esterified to the glyceryl monoether. Gas-liquid chromatography, thin-layer chromatography, and nuclear magnetic resonance and infrared spectroscopy were used to characterize and identify the intact tumor lipid and its derived products.


Recycling of the Ca2+-activated K+ channel, KCa2.3, is dependent upon RME-1, Rab35/EPI64C, and an N-terminal domain.
Regulation of the number of Ca(2+)-activated K(+) channels at the endothelial cell surface contributes to control of the endothelium-derived hyperpolarizing factor response, although this process is poorly understood. To address the fate of plasma membrane-localized KCa2.3, we utilized an extracellular epitope-tagged channel in combination with fluorescence and biotinylation techniques in both human embryonic kidney cells and the human microvascular endothelial cell line, HMEC-1. KCa2.3 was internalized from the plasma membrane and degraded with a time constant of 18 h. Cell surface biotinylation demonstrated that KCa2.3 was rapidly endocytosed and recycled back to the plasma membrane. Consistent with recycling, expression of a dominant negative (DN) RME-1 or Rab35 as well as wild type EPI64C, the Rab35 GTPase-activating protein, resulted in accumulation of KCa2.3 in an intracellular compartment. Expression of DN RME-1, DN Rab35, or wild type EPI64C resulted in a decrease in steady-state plasma membrane expression. Knockdown of EPI64C increased cell surface expression of KCa2.3. Furthermore, the effect of EPI64C was dependent upon its GTPase-activating proteins activity. Co-immunoprecipitation studies confirmed an association between KCa2.3 and both Rab35 and RME-1. In contrast to KCa2.3, KCa3.1 was rapidly endocytosed and degraded in an RME-1 and Rab35-independent manner. A series of N-terminal deletions identified a 12-amino acid region, Gly(206)-Pro(217), as being required for the rapid recycling of KCa2.3. Deletion of Gly(206)-Pro(217) had no effect on the association of KCa2.3 with Rab35 but significantly decreased the association with RME-1. These represent the first studies elucidating the mechanisms by which KCa2.3 is maintained at the plasma membrane.


Outcome in systemic lupus erythematosus: a prospective study of patients from a defined population.
All adult patients with systemic lupus erythematosus (SLE) (greater than or equal to 15 years old, n = 86) from a defined population (approximately 160,000 population at risk) were followed prospectively over 6 years. The study area comprised 2 health care districts served by only 1 hospital. Retrieval was based on clinical case finding and computerized diagnosis and laboratory registers. The incidence of the disease was 4.0 cases/100,000 adults/year and was stable during the 6 years, suggesting that completeness of retrieval was high. Point prevalence by the end of 1986 was 42 cases/100,000 population at risk and 5-year survival in the prospective group 97%. Immunologically the group was characterized by a high frequency of positive anti-dsDNA (73%), and a low frequency of rheumatoid factor positivity (10%). The frequency of ARA criteria (median, 6) was comparable with previous larger series of selected patients. Sixteen percent of the patients were males, and they had more serositis and renal manifestations than females. In view of the low mortality we studied the more sensitive outcome measures: disease activity, irreversible organ damage, and functional impairment. After the diagnosis year, disease flares occurred with a constant frequency of 0.2 flares/year/patient, even after long duration of disease. Patients with neuropsychiatric disease, history of drug reactions, and immunological abnormalities such as persistent hypocomplementemia, antibodies to dsDNA, and cardiolipin had a high frequency of relapse. In contrast, elderly patients with serositis during their first flare seldom relapsed. The number of gainfully employed individuals was normal. Neuropsychiatric disease and joint involvement were principal causes of long-standing functional impairment. Notably, patients with renal disease usually fared well, as reflected by preserved renal function and little functional by preserved renal function and little functional impairment. Disease duration and glucocorticoid treatment were major denominators for morbidity due to infections and vascular disease with the incidence of myocardial infarctions being 9 times more common than that in a Swedish control population. Prolonged glucocorticoid treatment was also related to mortality, which was predominantly due to cardiovascular or central nervous system disease. The present prospective and epidemiologically based study of outcome in SLE was made possible by a uniquely coordinated health care system, enabling complete identification of the patients within the study area.(ABSTRACT TRUNCATED AT 400 WORDS)


Antibacterial and antifungal activity of sulfur-containing compounds from Petiveria alliacea L.
A total of 18 organosulfur compounds originating from Petiveria alliacea L. roots have been tested for their antibacterial and antifungal activities. These represent compounds occurring in fresh homogenates as well as those present in various macerates, extracts and other preparations made from Petiveria alliacea. Of the compounds assayed, the thiosulfinates, trisulfides and benzylsulfinic acid were observed to be the most active, with the benzyl-containing thiosulfinates exhibiting the broadest spectrum of antimicrobial activity. The effect of plant sample preparation conditions on the antimicrobial activity of the extract is discussed.


A Bayesian approach to estimate the prevalence of Schistosomiasis japonica infection in the Hubei Province Lake Regions, China.
A Bayesian inference model was introduced to estimate community prevalence of Schistosomiasis japonica infection based on the data of a large-scale survey of Schistosomiasis japonica in the lake region in Hubei Province. A multistage cluster random sampling approach was applied to the endemic villages in the lake regions of Hubei Province in 2011. IHA test and Kato-Katz test were applied for the detection of the S. japonica infection in the sampled population. Expert knowledge on sensitivities and specificities of IHA test and Kato-Katz test were collected based on a two-round interview. Prevalence of S. japonica infection was estimated by a Bayesian hierarchical model in two different situations. In Situation 1, Bayesian estimation used both IHA test data and Kato-Katz test data to estimate the prevalence of S. japonica. In Situation 2, only IHA test data was used for Bayesian estimation. Finally 14 cities and 46 villages from the lake regions of Hubei Province including 50,980 residents were sampled. Sensitivity and specificity for IHA test ranged from 80% to 90% and 70% to 80%, respectively. For the Kato-Katz test, sensitivity and specificity were from 20% to 70% and 90% to 100%, respectively. Similar estimated prevalence was obtained in the two situations. Estimated prevalence among sampled villages was almost below 13% in both situations and varied from 0.95% to 12.26% when only using data from the IHA test. The study indicated that it is feasible to apply IHA test only combining with Bayesian method to estimate the prevalence of S. japonica infection in large-scale surveys.


Sexual Harassment Policies and Training in State Legislatures.
(1) Sexual harassment is a violation of The Civil Rights Act of 1964. (2) Most states do not require employers to conduct sexual harassment training. (3) Most sexual harassment training for state legislators occurs at their orientation.


Chronic inflammatory demyelinating polyradiculoneuropathy associated with pregnancy.
In a series of 61 patients with the relapsing variety of chronic inflammatory demyelinating polyneuropathy, there were 16 women of childbearing age, 9 of whom became pregnant. In 4 of these women, the onset of neuropathy occurred in pregnancy and in the other 5 relapses occurred during pregnancy. There was a significant increase in the number of relapses during the year of pregnancy, and a tendency for symptoms to worsen during the third trimester or immediate postpartum period. It is concluded that there is an increased risk of relapse of chronic inflammatory demyelinating polyneuropathy in pregnancy.


Effects of brief repetitive ischemia on contractility, relaxation, and coronary flow. Exaggerated postischemic diastolic dysfunction in pressure-overload hypertrophy.
The recovery of systolic and diastolic function during unstable angina may be modified by the repetition of brief episodes of ischemia and by the presence of left ventricular hypertrophy (LVH). We studied the effects of six consecutive 5-minute cycles of no-flow ischemia and reperfusion followed by 25 minutes of recovery in isovolumic red blood cell-perfused hearts from aortic-banded rats with chronic LVH (n = 8) and sham-operated control rats (n = 8). At baseline (left ventricular end-diastolic pressure [LVEDP], 10 mm Hg), left ventricular developed pressure (123 +/- 5 versus 114 +/- 5 mm Hg/g) and coronary flow [2.5 +/- 0.3 versus 2.2 +/- 0.2 (mL/min)/g] were similar in LVH versus control rats. Repetitive ischemia was associated with progressive depression of postischemic recovery of left ventricular systolic function, and the recovery of left ventricular developed pressure after the final 25-minute reperfusion period was similar in LVH versus control rats (61 +/- 6% versus 72 +/- 4% of baseline, P = NS). Although there was no increase in isovolumic LVEDP during the initial cycle of transient ischemia, both groups showed a rapid and similar rise in LVEDP during subsequent ischemic cycles (delta 82 +/- 8 versus delta 89 +/- 7 mm Hg/g in response to the final ischemia cycle for LVH versus control rats, respectively; P = NS). The control hearts showed complete restoration of LVEDP to baseline during final reperfusion, whereas the LVH hearts showed prolonged and severe postischemic diastolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)


Human T-Lymphotropic Virus-1/2 Infection in Central Brazil Prisons: A Multicenter Study.
Human T-lymphotropic virus (HTLV) infection is endemic in some group populations. Prisoners are at high risk of acquiring HTLV infection mainly due to the environment of closed penal institutions, socioeconomic conditions, and risk behaviors. This study aimed to investigate the prevalence, the occurrence of new cases of HTLV infection after a 1-year follow-up, and circulating subtypes of HTLV-1 among prisoners from twelve closed prisons in Mato Grosso do Sul state, Central Brazil. A total of 1,507 prisoners were randomly enrolled in the cross-sectional study. Out of the 1,507 participants, 1,000 prisoners, susceptible to HTLV infection, were included in the prospective cohort study. In the cross-sectional study, serological evidence of HTLV infection was 0.4% (CI 95%: 0.1-0.7), tested for anti-HTLV antibodies by enzyme-linked immunosorbent assay (ELISA). Three samples were positive for HTLV-1, two samples were positive for HTLV-2, and 1 sample was indeterminate by the Western blot method. The presence of HTLV proviral DNA was detected in all positive samples by amplification of the HTLV tax gene through nested-PCR. Phylogenetic analysis showed that HTLV-1 samples belonged to the Cosmopolitan subtype Transcontinental subgroup. From a cohort of 1,000 individuals, no new case of HTLV infection was detected. Although the prevalence rate of HTLV infection found in this study was similar to that observed in the Brazilian general population, the lack of access to preventive interventions and harm reduction measures all contribute to increasing the risk of HTLV transmission and acquisition among this key and vulnerable population.


Frequency and correlates of anticholinergic use among patients with schizophrenia in Denmark: A Nation-wide pharmacoepidemiological study.
Anticholinergic medications are used to treat extrapyramidal adverse effects induced by antipsychotics. Anticholinergics are associated with adverse effects: constipation, dry mouth and worsening of cognitive function. Anticholinergics have potential for abuse and are not recommended for long term-treatment. We aimed to investigate the use of anticholinergics in patients with schizophrenia. The national health registers in Denmark were used to examine: The prevalence of anticholinergics in 1996-2012 using a cross-sectional design; geographic variations in the prescription of anticholinergics in 2012; correlates of treatment with anticholinergics. The proportion of patients using anticholinergics decreased significantly from 11.7% in 1996 to 5.7% in 2012. The prescription pattern varied considerably between national regions in 2012, ranging from 4.0% in the Capital Region to 8.1% in the Northern Denmark Region. Long-term use of anticholinergics was predicted by older age, age at debut of schizophrenia, receiving early retirement pension, typical antipsychotic use, antipsychotic polypharmacy, typical + atypical antipsychotics, antidepressant treatment, high doses of antipsychotics measured in defined-daily-dose, physical comorbidity and psychiatrists` greater caseload. Use of anticholinergics declined during the study period, and showed substantial variation across the regions in 2012. Long-term use was linked to typical antipsychotic use and variables that are associated with greater illness severity.


DR beta peptides block the antigen-specific response but not the alloresponse of a dual-reactive T-cell clone.
It is generally assumed that alloreactivity and the response to foreign antigens are equivalent T-cell recognition events. We have addressed this issue by examining the antigen presentation of beef insulin by two DR1-restricted human T-clones. One of the clones was dual-reactive and exhibited alloreactivity. By employing 20 synthetic consecutive overlapping peptides representing the entire extracellular (residues 1-198) and intracellular (residues 222-273) parts of the DR2 beta molecule, the effects of each of these peptides on antigen presentation and alloreactivity were examined. The DR1-restricted response to beef insulin by both clones was inhibited by peptides from DR2 beta region 1-25. Other DR2 beta (residues 21-198 en 222-237) or control peptides had no effect. The DR3-associated alloresponse of the dual-reactive clone was not inhibited by any peptide. These observations suggest that recognition of antigen is fundamentally different from allorecognition.


Parametric studies of ethanol production form xylose and other sugars by recombinant Escherichia coli.
The conversion of xylose to ethanol by recombinant Escherichia coli has been investigated in pH-controlled batch fermentations. Chemical and environmental parameters were varied to determine tolerance and to define optimal conditions. Relatively high concentrations of ethanol (56 g/L) were produced from xylose with excellent efficiencies. Volumetric productivities of up to 1.4 g ethanol/L h were obtained. Productivities, yields, and final ethanol concentrations achieved from xylose with recombinant E. coli exceeded the reported values with other organisms. In addition to xylose, all other sugar constituents of biomass (glucose, mannose, arabinose, and galactose) were efficiently converted to ethanol by recombinant E. coli. Unusually low inocula equivalent to 0.033 mg of dry cell weight/L were adequate for batch fermentations. The addition of small amounts of calcium, magnesium, and ferrous ions stimulated fermentation. The inhibitory effects of toxic compounds (salts, furfural, and acetate) which are present in hemicellulose hydrolysates were also examined.


Precise role of dermal fibroblasts on melanocyte pigmentation.
Dermal fibroblasts are traditionally recognized as synthesizing, remodeling and depositing collagen and extracellular matrix, the structural framework for tissues, helping to bring thickness and firmness to the skin. However, the role of fibroblasts on skin pigmentation arouses concern recently. More is known about the interactions between epidermal melanocytes and keratinocytes. This review highlights the importance of fibroblast-derived melanogenic paracrine mediators in the regulation of melanocyte activities. Fibroblasts act on melanocytes directly and indirectly through neighboring cells by secreting a large number of cytokines (SCF), proteins (DKK1, sFRP, Sema7a, CCN, FAP-α) and growth factors (KGF, HGF, bFGF, NT-3, NRG-1, TGF-β) which bind to receptors and modulate intracellular signaling cascades (MAPK/ERK, cAMP/PKA, Wnt/β-catenin, PI3K/Akt) related to melanocyte functions. These factors influence the growth, the pigmentation of melanocytes via the expression of melanin-producing enzymes and melanosome transfer, as well as their dendricity, mobility and adhesive properties. Thus, fibroblasts are implicated in both skin physiological and pathological pigmentation. In order to investigate their contribution, various in vitro models have been developed, based on cellular senescence. UV exposure, a major factor implicated in pigmentary disorders, may affect the secretory crosstalk between dermal and epithelial cells. Therefore, identification of the interactions between fibroblasts and melanocytes could provide novel insights not only for the development of melanogenic agents in the clinical and cosmetic fields, but also for a better understanding of the melanocyte biology and melanogenesis regulation.


Computer-Assisted Decision Support System in Pulmonary Cancer detection and stage classification on CT images.
Pulmonary cancer is considered as one of the major causes of death worldwide. For the detection of lung cancer, computer-assisted diagnosis (CADx) systems have been designed. Internet-of-Things (IoT) has enabled ubiquitous internet access to biomedical datasets and techniques; in result, the progress in CADx is significant. Unlike the conventional CADx, deep learning techniques have the basic advantage of an automatic exploitation feature as they have the ability to learn mid and high level image representations. We proposed a Computer-Assisted Decision Support System in Pulmonary Cancer by using the novel deep learning based model and metastasis information obtained from MBAN (Medical Body Area Network). The proposed model, DFCNet, is based on the deep fully convolutional neural network (FCNN) which is used for classification of each detected pulmonary nodule into four lung cancer stages. The performance of proposed work is evaluated on different datasets with varying scan conditions. Comparison of proposed classifier is done with the existing CNN techniques. Overall accuracy of CNN and DFCNet was 77.6% and 84.58%, respectively. Experimental results illustrate the effectiveness of proposed method for the detection and classification of lung cancer nodules. These results demonstrate the potential for the proposed technique in helping the radiologists in improving nodule detection accuracy with efficiency.


Prospective, open-label safety study of intravenous recombinant tissue plasminogen activator in wake-up stroke.
It is estimated that one of four ischemic strokes are noticed upon awakening and are not candidates for intravenous recombinant tissue plasminogen activator (rtPA) because their symptoms are >3 hours from last seen normal (LSN). We tested the safety of rtPA in a multicenter, single-arm, prospective, open-label study (NCT01183533) in patients with wake-up stroke (WUS). We aimed to enroll 40 WUS patients with disabling deficits. Patients were 18 to 80 years of age, National Institutes of Health Stroke Scale (NIHSS) ≤25, and selected only on the appearance of noncontrast computed tomography (ie, over one-third middle cerebral artery territory hypodensity). Standard-dose (0.9mg/kg) intravenous rtPA had to be started ≤3 hours of patient awakening. The primary safety outcome was symptomatic intracerebral hemorrhage (sICH) with preplanned stopping rules and data safety board oversight. Other endpoints included: asymptomatic intracerebral hemorrhage; clinical improvement in NIHSS; and 90-day modified Rankin Scale (mRS) score. Between October 2010 and October 2013, all 40 preplanned patients were enrolled (50% men) at five stroke centers. Four patients (10%) were subsequently determined to be mimics. Patients had a mean age of 60.8, median NIHSS of 6.5 (range, 2-24), and received thrombolysis at a mean time of 10.3 ± 2.6 LSN and 2.6 ± 0.6 hours from awakening with deficits. No sICH or parenchymal hematomas occurred. At 3 months, 20 of 38 (52.6%) patients achieved excellent recovery with mRS scores of 0 or 1 (2 patients were lost to follow-up). Intravenous thrombolysis was safe in this prospective WUS study of patients selected by noncontrast CT. A randomized effectiveness trial appears feasible using a similar, pragmatic design. Ann Neurol 2016;80:211-218.


[A bowel perforation with metallic stent placement for advanced rectal cancer during bevacizumab-based chemotherapy].
A 61-year-old woman with an unresectable malignant rectal stricture underwent placement of an expandable metallic stent under endoscopic guidance. The stent was successfully implanted and her bowel obstruction was relieved. After treatment with bevacizumab for unresectable rectal cancer, she was admitted to our hospital because of rectal perforation. This case suggests that placement of a metallic stent in colorectal cancer cases may increase the risk of bowel perforation during bevacizumab-based chemotherapy.


Ruthenium-Catalyzed Oxidative Homocoupling of Arylboronic Acids in Water: Ligand Tuned Reactivity and Mechanistic Study.
Molecular catalysts based on water-soluble arene-Ru(II) complexes ([Ru]-1-[Ru]-5) containing aniline (L1), 2-methylaniline (L2), 2,6-dimethylaniline (L3), 4-methylaniline (L4), and 4-chloroaniline (L5) were designed for the homocoupling of arylboronic acids in water. These complexes were fully characterized by (1)H, (13)C NMR, mass spectrometry, and elemental analyses. Structural geometry for two of the representative arene-Ru(II) complexes [Ru]-3 and [Ru]-4 was established by single-crystal X-ray diffraction studies. Our studies showed that the selectivity toward biaryls products is influenced by the position and the electronic behavior of various substituents of aniline ligand coordinated to ruthenium. Extensive investigations using (1)H NMR, (19)F NMR, and mass spectral studies provided insights into the mechanistic pathway of homocoupling of arylboronic acids, where the identification of important organometallic intermediates, such as σ-aryl/di(σ-aryl) coordinated arene-Ru(II) species, suggested that the reaction proceeds through the formation of crucial di(σ-aryl)-Ru intermediates by the interaction of arylboronic acid with Ru-catalyst to yield biaryl products.


Enhancement of collagen-degrading enzymes in the dermis after one topical application of tumor-promoting phorbol esters.
The effect of tumor-promoting and non-promoting skin mitogens on the induction of matrix degradation in the dermis of mouse skin has been examined. A stimulation of active collagenolytic and proteolytic enzyme levels was observed after application of the tumor promoters 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 12-O-retinoylphorbol-13-acetate (RPA) as well as the non-promoting skin irritant Ca-ionophore A 23187, but not with the non-irritant mitogen 4-O-methyl-TPA. It therefore appears that the enhancement of collagenolytic and proteolytic enzymes after tumor promoter treatment is mainly due to the inflammation that is always caused by the promoter. However, a subfraction of collagenolytic enzymes that is not extracted from the dermis with 0.5 M NaCl but only with 5 M urea is specifically increased after treatment with TPA and RPA. This fraction is absent in A 23187- or 4-O-methyl-TPA-treated dermis. This indicates that apart from inflammation-induced matrix degradation there is also stimulation of enzymes which are directly related to tumor promotion.


Residual beta-cell function in type II diabetes and evaluation of the hepatic insulin extraction.
Insulin and C-peptide (free insulin and C-peptide in insulin-treated patients) were measured after glucose stimulation in nine Type II diabetics on chlorpropamide, eleven insulin-treated maturity-onset diabetics and in 8 normal controls. Dissociation between C-peptide and insulin response to glucose was observed in several diabetics. The relation between incremental molar areas under C-peptide and insulin curves, after glucose challenge (delta CPR - delta IRI/delta CPR) were used to evaluate the hepatic insulin extraction in all but the insulin-treated diabetics. The lower insulin requirements and better control of the short-duration insulin-treated maturity-onset diabetics in relation to the long-term ones could not be explained either by the residual insulin secretion or by the level of "insulin antibodies". The chlorpropamide-responsive patients presented higher insulin levels after the glucose challenge and a lower hepatic insulin extraction than the non-responsive ones.


Use of data from the Health Survey for England in obesity policy making and monitoring.
Health data and statistics are the foundation of health policy. Over the last 20 years, numerous government documents have been commissioned and published to inform obesity strategies in the UK. The Health Survey for England, an annual cross-sectional survey of a nationally representative random general population sample in England, collects information on health, lifestyle and socioeconomic factors, physical measurements and biological samples. Heights and weights measured by the Health Survey for England are believed to have played a major part in promoting, shaping and evaluating obesity strategies. A formal review of how these data have been used has not been conducted previously. This paper reviews government documents demonstrating the contribution of Health Survey for England examination data to every stage of the policy making process: quantifying the obesity problem in England (e.g. Chief Medical Officer's reports); identifying inequalities in the burden of obesity (Acheson report); modelling potential future scenarios (Foresight); setting and monitoring specific, measurable, attainable targets (calorie reduction challenge in manufacturers' Responsibility Deal); developing and informing strategies and clinical guidance; and evaluating the success of obesity strategies (Healthy Weights, Healthy Lives progress report). Measurement data are needed and used by governments to produce evidence-based strategies to combat obesity.


Efficacy and safety of oral Pentasa (prolonged-release mesalazine) in mild-to-moderate ulcerative colitis: a systematic review and meta-analysis.
Pentasa (prolonged-release mesalazine [5-ASA]) has been available for >30 years as an effective treatment for mild-to-moderate ulcerative colitis (UC). A systematic literature review and meta-analysis was undertaken to provide an up-to-date evaluation of oral Pentasa efficacy and safety for induction and maintenance of remission. Literature searches were conducted in PubMed, Embase and Cochrane databases, from inception to 02 December 2020. Unpublished studies were also sourced. Meta-analyses using a random-effects model and Bayesian inference compared Pentasa (tablets, granules, capsules) against placebo and other 5-ASAs. Twelve studies involving 3674 patients treated with Pentasa were identified. Pentasa 2-4 g/day was superior to placebo at inducing (absolute risk difference [ARD] at 8 weeks 0.14, 95% CI 0.07‒0.21; p < .001) and maintaining (ARD 6-12 months 0.18, 95% CI 0.04‒0.33; p < .05) remission (clinical/endoscopic). Against other 5-ASAs, Pentasa had similar efficacy for induction (ARD <0.001, 95% CI -0.05‒0.05) and maintenance (ARD 0.01, 95% CI -0.07‒0.08) treatment using randomized controlled trial data. Upon inclusion of real-world study data, Pentasa was significantly better at maintaining remission compared both to Eudragit-S mesalazine and sulfasalazine (ARD 0.04, 95% CI 0.02‒0.06; p < .001). Pentasa (1-4 g/day) had similar treatment-related adverse event rates to placebo (ARD 0.02, 95% CI -0.03‒0.06) and Eudragit-L/S mesalazines (2.25-3 vs 2.4-3 g/day, respectively; ARD -0.03, 95% CI -0.12‒0.05), but was better tolerated than sulfasalazine (3 g/day) (ARD 0.07, 95% CI 0.003‒0.14; p < .05). This study confirms oral Pentasa is efficacious and well-tolerated in treating active UC and maintaining remission. The availability of multiple forms of Pentasa supports physicians' ability to individualize treatment and optimize dosing to improve outcomes.


Manufacturing of Peptide Microarrays Based on Catalyst-Free Click Chemistry.
Immobilization of peptides to a solid surface is frequently an important first step before they can be probed with a variety of biological samples in a heterogeneous assay format for research and clinical diagnostic purposes. Peptides can be derivatized in many ways to subsequently covalently attach them to an activated solid surface such as epoxy-functionalized glass slides. Here, we describe a clean, efficient, and reproducible fabrication process based on catalyst-free click chemistry compatible with the construction of low- to high-density peptide microarrays.


Synthesis and insertion, both in vivo and in vitro, of rat-liver cytochrome P-450 and epoxide hydratase into Xenopus laevis membranes.
We described whole cell and cell-free systems capable of inserting into membranes cytochrome P-450 and epoxide hydratase made under the direction of rat liver RNA. The systems have been used to study the pathways followed by newly made secretory and integral membrane proteins. The cell-free system contains Xenopus laevis embryo membranes, and demonstrates competition for a common receptor between cytochrome P-450 and epoxide hydratase, and normal secretory proteins: evidence is provided for differential membrane receptor affinity. Thus, synthesis of secretory and membrane proteins appears to involve a common initial pathway. Microinjection of rat liver RNA into whole oocytes suggests that membrane insertion is neither cell type nor species specific, because functional rat liver enzymes are found inserted in the endoplasmic reticulum of the frog cell. Nonetheless, insertion is highly selective since albumin and several other proteins made under the direction of the injected liver RNA are sequestered within membrane vesicles and are then secreted by the oocyte, whilst epoxide hydratase and cytochrome P-450 are inserted into membranes but are not secreted.


Experimental Observation of a Time-Driven Phase Transition in Quantum Chaos.
We report the first experimental observation of the time-driven phase transition in a canonical quantum chaotic system, the quantum kicked rotor. The transition bears a firm analogy to a thermodynamic phase transition, with the time mimicking the temperature and the quantum expectation of the rotor's kinetic energy mimicking the free energy. The transition signals a sudden change in the system's memory behavior: before the critical time, the system undergoes chaotic motion in phase space and its memory of initial states is erased in the course of time; after the critical time, quantum interference enhances the probability for a chaotic trajectory to return to the initial state, and thus the system's memory is recovered.


The molecular basis of T-cell specificity.
Studies of TCR expression in antigen-specific immune responses have provided a large body of information correlating the primary structure of the TCR with specificity. Much has been learned regarding the mechanisms for the generation of TCR diversity and the selection of TCR V elements in immune responses. However, the exact nature of the trimolecular complex found during the TCR/antigen/MHC interaction awaits the structural characterization of the TCR by crystallography. Just as describing the three-dimensional structure of MHC molecules and defining their putative antigen-binding site have made it possible to interpret with fresh insight the wealth of functional data regarding antigen/MHC binding and alloreactivity, similar characterization of the TCR structure will allow more definitive interpretation of all the current data with respect to TCR usage in antigen-specific immune responses. It should also facilitate the study of the molecular basis of positive and negative TCR selection during thymic ontogeny. Finally, the identification of T-cell superantigens and their ability to stimulate T cells on the basis of TCR V beta expression alone has defined a new and distinct type of TCR/ligand interaction. The fact that bacterial products such as staphylococcal and streptococcal toxins as well as the mitogenic moiety produced by some mycoplasma are included within this class of antigens suggests that TCR recognition of superantigens may have major clinical significance. It is important to determine the structural basis of T-cell activation by these antigens.


Deregulation of the cyclin D1/Cdk4 retinoblastoma pathway in rat mammary gland carcinomas induced by the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a suspected human breast carcinogen found in cooked meat that induces mammary gland cancer in rats. By real time PCR analysis, PhIP-induced rat mammary gland carcinomas showed statistically higher expression of the G(1)-S cyclin D1 (5-fold) and its kinase partner cyclin-dependent kinase (Cdk)-4 (37-fold) in comparison with normal mammary gland, whereas cyclin D2, cyclin D3, and Cdk6 were not statistically changed. Amplification of cyclin D1 was observed by real time PCR in 24% of carcinomas (15 of 63). Only 1 of 47 carcinomas showed Cdk4 amplification. By Western blotting, the level of phospho-Rb was >2-fold higher in carcinomas than in normal mammary gland. By immunohistochemical analysis, cyclin D1, Cdk4, and phospho-Rb nuclear protein expression was 5.7-, 3.9-, and 2.3-fold higher, respectively, in carcinomas than in normal mammary gland, whereas the expression of cyclin D2, cyclin D3, and Cdk6 was similar. Among carcinomas, Cdk4 and phospho-Rb levels were positively correlated with cell proliferation. Previous studies by this laboratory indicated that these carcinomas harbor a high frequency of H-ras mutations. The H-ras pathway is linked to the cell cycle via cyclin D1. The results from the current study implicate cyclin D1/Cdk4, phospho-Rb as a central pathway in PhIP-induced rat mammary gland carcinogenesis.


Rec8 cleavage by separase is required for meiotic nuclear divisions in fission yeast.
Sister chromatid cohesion in meiosis is established by cohesin complexes, including the Rec8 subunit. During meiosis I, sister chromatid cohesion is destroyed along the chromosome arms to release connections of recombined homologous chromosomes (homologues), whereas centromeric cohesion persists until it is finally destroyed at anaphase II. In fission yeast, as in mammals, distinct cohesin complexes are used depending on the chromosomal region; Rec8 forms a complex with Rec11 (equivalent to SA3) mainly along chromosome arms, while Psc3 (equivalent to SA1 and SA2) forms a complex mainly in the vicinity of the centromeres. Here we show that separase activation and resultant Rec8 cleavage are required for meiotic chromosome segregation in fission yeast. A non-cleavable form of Rec8 blocks disjunction of homologues at meiosis I. However, displacing non-cleavable Rec8 restrictively from the chromosome arm by genetically depleting Rec11 alleviated the blockage of homologue segregation, but not of sister segregation. We propose that the segregation of homologues at meiosis I and of sisters at meiosis II requires the cleavage of Rec8 along chromosome arms and at the centromeres, respectively.


[Enzymatic activity and therapeutic action of pepsin K in chronic gastritis with secretory failure].
Pepsin K (chicken pepsin) in the test for hemoglobin proteolysis is 1.7 times superior to abomin (porcine pepsin) in the medium pH 2 and 44 times more potent in the medium pH 3. Even in pH 4 chicken pepsin retains its enzymatic activity while porcine pepsin in pH 4 looses its activity. These biochemical findings show that pepsin K is more effective in the treatment of enzymatic insufficiency of the stomach. Intake of 1-3 pepsin K tablets after meal for 4 weeks by 82 patients having chronic gastritis with secretory insufficiency was effective in 75% of patients.


Parenting with PTSD: A Review of Research on the Influence of PTSD on Parent-Child Functioning in Military and Veteran Families.
Posttraumatic stress disorder (PTSD) is strongly associated with exposure to war related trauma in military and veteran populations. In growing recognition that PTSD may influence and be influenced by social support and family systems, research has begun to explore the effects that war related trauma and the ensuing PTSD may have on varied aspects of close relationship and family functioning. Far less research, however, has examined the influence of war-related PTSD on parent-child functioning in this population. This paper provides a timely review of emergent literature to examine the impacts that PTSD may have on parenting behaviors and children's outcomes with a focus on studies of military and veterans of international conflicts since post-9/11. The review sheds light on the pathways through which PTSD may impact parent-child relationships, and proposes the cognitive-behavioral interpersonal theory of PTSD as a theoretical formulation and extends this to parenting/children. The review identifies the strengths and limitations in the extant research and proposes directions for future research and methodological practice to better capture the complex interplay of PTSD and parenting in military and veteran families.


The positive moderating effect of absorptive capacity on R&D investment: the case of Argentina's ict firms.
The model analyzes the positive moderating role of absorptive capacity (ACAP) in the innovative outcomes of the firms. It focuses on ACAP as a moderating variable of the innovative efforts that firms develop or have the chance of incorporating from outside and not just as an antecedent of the innovation results. The empirical evidence collected comes from a study conducted on 189 SMEs working in IT services in Argentina and the results prove the main hypothesis of how ACAP is a positive moderating factor of the innovative effort of firms, even in the case of the connections created by their the participation in international networks not having a high correlation. Some suggestions for policymaker managers and future lines of research are provided.


Citrate-cleavage enzyme, 'malic' enzyme and certain dehydrogenases in embryonic and growing chicks.
The activities of several enzymes possibly implicated in lipogenesis were measured in the soluble fraction of homogenates of liver and adipose tissue of embryonic and growing chicks. The activities of adipose-tissue enzymes showed little or no change. The activities of hepatic hexose monophosphate-shunt dehydrogenases, malate dehydrogenase, 3-phosphoglyceraldehyde dehydrogenase and NAD-linked alpha-glycerophosphate dehydrogenase also showed little or no change. Isocitrate dehydrogenase activity in liver rose to a peak on the day of hatching and fell to half the peak value during the next 12 days, where it remained to 26 days after hatching. The activities of ;malic' enzyme and citrate-cleavage enzyme showed very low stable values in embryonic liver and remarkable rises during the early part of the post-hatching period. An 85-fold increase in the activity of ;malic' enzyme activity was completed in 7 days and a 15-fold increase in that of citrate-cleavage enzyme in 5 days. The activities then attained were maintained up to 26 days after hatching. 2. The increases in the activities of hepatic citrate-cleavage enzyme and ;malic' enzyme occurred simultaneously with a marked increase in lipogenesis, suggesting a relationship of these enzymes to lipogenesis in chick liver. By contrast, activity of the hexose monophosphate-shunt dehydrogenases does not appear to be thus associated.


Glycoprotein B (gB) vaccines adjuvanted with AS01 or AS02 protect female guinea pigs against cytomegalovirus (CMV) viremia and offspring mortality in a CMV-challenge model.
The transmission of cytomegalovirus (CMV) from mother to fetus can give rise to severe neurodevelopment defects in newborns. One strategy to prevent these congenital defects is prophylactic vaccination in young women. A candidate vaccine antigen is glycoprotein B (gB). This antigen is abundant on the virion surface and is a major target of neutralization responses in human infections. Here, we have evaluated in a challenge model of congenital guinea pig CMV (GPCMV) infection, GPCMV-gB vaccines formulated with the clinically relevant Adjuvant Systems AS01B and AS02V, or with Freund's adjuvant (FA). Fifty-two GPCMV-seronegative female guinea pigs were administered three vaccine doses before being mated. GPCMV-challenge was performed at Day 45 of pregnancy (of an estimated 65 day gestation). Pup mortality rates in the gB/AS01B, gB/AS02V, and gB/FA groups were 24% (8/34), 10% (4/39) and 36% (12/33), respectively, and in the unvaccinated control group was 65% (37/57). Hence, efficacies against pup mortality were estimated at 64%, 84% and 44% for gB/AS01B (p<0.001), gB/AS02V (p<0.001) and gB/FA (p=0.014), respectively. Efficacies against GPCMV viremia (i.e. DNAemia, detected by PCR) were estimated at 88%, 68% and 25% for the same vaccines, respectively, but were only significant for gB/AS01B (p<0.001), and gB/AS02V (p=0.002). In dams with viremia, viral load was approximately 6-fold lower with vaccination than without. All vaccines were highly immunogenic after two and three doses. In light of these results and of other results of AS01-adjuvanted vaccines in clinical development, vaccine immunogenicity was further explored using human CMV-derived gB antigen adjuvanted with either AS01B or the related formulation AS01E. Both adjuvanted vaccines were highly immunogenic after two doses, in contrast to the lower immunogenicity of the unadjuvanted vaccine. In conclusion, the protective efficacy and immunogenicity of adjuvanted vaccines in this guinea pig model are supportive of investigating gB/AS01 and gB/AS02 in the clinic.


[Intraoperative autotransfusion in gynecology and surgery (author's transl)].
The technique of intraoperative autotransfusion (AT) is being used to date only in a few individual clinics. Since there is a clinically safe and economical AT-apparatus available the routine application of this rational blood replacement method is easy to perform. The authors have used this technique altogether in 111 patients, applying the Bentley-ATS-machine in the last 69 cases. In a previous series of 42 cases AT was used for ruptured ectopic pregnancy, in the series of 69 surgical cases for hemothorax or intraabdominal hemorrhages of mainly traumatic origin. The most frequent indications for AT in emergency surgical operations were ruptures of spleen and liver, and in elective surgery for portocaval shunt. Altogether 247 litres of blood have been retransfused with an AT-volume per patient ranging from 0,5 to 15 litres. For anticoagulation generally ACD was used, only in vascular surgery was heparin preferred. Methodical complications have not been seen. Technique, indications, consequences and possible complications of AT are described. The main advantages of autologous intraoperative transfusion are the immediate availability of blood, the absence of the risk of hepatitis and of incompatibility reactions, reduction of pressure on the blood banks and lower transfusion costs. The authors therefore believe that the possibility of intraoperative AT should exist at every surgical and gynecological clinic.


Survey of Techniques Utilized to Access Ventricular Shunts and Reservoirs.
This study assessed variations in pediatric neurosurgical technique when accessing shunts and ventricular access devices (VADs). A 12-question survey was developed and sent to members of the American Association of Neurological Surgeons (AANS) whose self-identified subspecialty was pediatric neurosurgery. Four hundred and twenty surveys were sent out, and 149 responses were received (35.5% response rate); 95.3% of respondents always use sterile gloves, 55.0% never use a sterile gown, and 69.8% always have a member of the neurosurgery team perform the procedure. The majority of respondents answered "sometimes" for use of a facemask (38.3%), sterile drapes (39.6%), site shaving (45.6%), having an attending present (68.5%), and having an assistant hold the patient's head (78.5%). The majority reported using a 23- or 25-gauge butterfly needle for site entry (96.6%), and betadine or ChloraPrep™ as the preferred antiseptic solution (64.4%). The frequency in which CSF is sent for analysis is not standardized in 31.5% of respondents, and wait time for the antiseptic solution to dry is not standardized in 62.4%. There is great variation in the technique for accessing shunts and VADs. Future studies are needed to assess whether these discrepancies affect infection rates.


Incidental carcinoid tumor next to vascular malformation.
Dedicated linear endobronchial ultrasound (EBUS) is an established modality in sampling central pulmonary lesions, mediastinal and hilar lymph nodes to diagnose and stage lung malignancies as well as evaluate a number of inflammatory conditions. In addition, power Doppler modality of EBUS allows for vascular evaluation. We describe a case where EBUS visualized a submucosal lesion within a vascular malformation, which was eventually proven to be a carcinoid tumor. Computed tomographic scan of the chest failed to differentiate the 2 structures and bronchoscopy showed no endobronchial component. This case underscores the added diagnostic capabilities of endobronchial Doppler ultrasonography. We suggest considering EBUS in investigating central opacities associated with vascular features within the lung parenchyma when technically feasible.


The healthy diver: A cross-sectional survey to evaluate the health status of recreational scuba diver members of Divers Alert Network (DAN).
Scuba diver fitness is paramount to confront environmental stressors of diving. However, the diving population is aging and the increasing prevalence of diseases may be a concern for diver fitness. The purpose of this study is to assess the demographics, lifestyle factors, disease prevalence, and healthcare access and utilization of Divers Alert Network (DAN) members and compare them with those from the general population. DAN membership health survey (DMHS) was administered online in 2011 to DAN members in the United States (US). Health status of DMHS respondents was compared with the general US population data from the Center for Disease Control and Prevention's Behavioral Risk Factor Surveillance System using two-sided student's t-tests and Mantel-Haenszel chi-square tests. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with healthcare utilization among the DMHS participants. Compared to the general US population, the DMHS population had lower prevalence of asthma, heart attack, angina, stroke, diabetes, hypertension, hypercholesterolemia, and disabilities (p<0.01); more heavy alcohol drinkers, and fewer smokers (p<0.01); and greater access and utilization (routine checkup) of healthcare (p<0.01). Healthcare utilization in males was lower than among females. Increasing age and increase in the number of chronic illnesses were associated with increased healthcare utilization. DAN members are healthier than the general US population. DAN members also have better access to healthcare and utilize healthcare for preventive purposes more often than the general population. DAN members appear to have a better fitness level than their non-diving peers.


Insulin and IGF binding by IGFBP-3 fragments derived from proteolysis, baculovirus expression and normal human urine.
Recombinant human IGFBP-3 was proteolysed with different concentrations of plasmin for various periods of time. The major IGFBP-3 fragment resulting from this digestion migrated at ca. 15 kDa in nonreducing SDS-PAGE. Following the identification of this fragment as an N-terminal IGFBP-3 fragment, by use of N-terminus-specific monoclonal antibody and amino acid sequence analysis, we constructed and expressed a similar fragment in a baculovirus expression system. The fragments resulting from plasmin digestion, as well as the baculovirus-expressed recombinant human IGFBP-3(1-97), retain weak IGF binding and show specific insulin binding on cross-linking and western ligand blot. RhIGFBP-3(1-97) can inhibit insulin receptor autophosphorylation in insulin receptor-overexpressing NIH 3T3 cells. Insulin and IGF binding to IGFBP-3 fragments could be further demonstrated in normal urine. These data indicate the physiological significance of IGFBP-3 fragments derived from proteolysis in vivo.


Spontaneous isolated intra-abdominal mesenteric fibromatosis. Case report.
Magnetic resonance imaging in a 54-year-old Japanese man showed a huge low-intensity abdominal mass on T1 WI and a high-intensity tumoral structure with low-intensity bundles on T2 WI. The histologic diagnosis was intra-abdominal mesenteric fibromatosis. As the levels of tissue estrogen and progesterone receptors were not elevated (both less than 5 FMOL/mg), tamoxifen treatment was not indicated.


SmeOP-TolCSm efflux pump contributes to the multidrug resistance of Stenotrophomonas maltophilia.
A five-gene cluster, tolCSm-pcm-smeRo-smeO-smeP, of Stenotrophomonas maltophilia was characterized. The presence of smeOP and smeRo-pcm-tolCSm operons was verified by reverse transcription (RT)-PCR. Both operons were negatively regulated by the TetR-type transcriptional regulator SmeRo, as demonstrated by quantitative RT-PCR and a promoter-fusion assay. SmeO and SmeP were associated with TolCSm (the TolC protein of S. maltophilia) for the assembly of a resistance-nodulation-cell-division (RND)-type pump. The compounds extruded by SmeOP-TolCSm mainly included nalidixic acid, doxycycline, amikacin, gentamicin, erythromycin, leucomycin, carbonyl cyanide 3-chlorophenylhydrazone, crystal violet, sodium dodecyl sulfate, and tetrachlorosalicylanilide.


Anchoring High-Concentration Oxygen Vacancies at Interfaces of CeO(2-x)/Cu toward Enhanced Activity for Preferential CO Oxidation.
Catalysts are urgently needed to remove the residual CO in hydrogen feeds through selective oxidation for large-scale applications of hydrogen proton exchange membrane fuel cells. We herein propose a new methodology that anchors high concentration oxygen vacancies at interface by designing a CeO2-x/Cu hybrid catalyst with enhanced preferential CO oxidation activity. This hybrid catalyst, with more than 6.1% oxygen vacancies fixed at the favorable interfacial sites, displays nearly 100% CO conversion efficiency in H2-rich streams over a broad temperature window from 120 to 210 °C, strikingly 5-fold wider than that of conventional CeO2/Cu (i.e., CeO2 supported on Cu) catalyst. Moreover, the catalyst exhibits a highest cycling stability ever reported, showing no deterioration after five cycling tests, and a super long-time stability beyond 100 h in the simulated operation environment that involves CO2 and H2O. On the basis of an arsenal of characterization techniques, we clearly show that the anchored oxygen vacancies are generated as a consequence of electron donation from metal copper atoms to CeO2 acceptor and the subsequent reverse spillover of oxygen induced by electron transfer in well controlled nanoheterojunction. The anchored oxygen vacancies play a bridging role in electron capture or transfer and drive molecule oxygen into active oxygen species to interact with the CO molecules adsorbed at interfaces, thus leading to an excellent preferential CO oxidation performance. This study opens a window to design a vast number of high-performance metal-oxide hybrid catalysts via the concept of anchoring oxygen vacancies at interfaces.


Nitrite binding to cytochrome P-450 from liver microsomes of trout (Salmo gairdneri Rich.) and effects on two microsomal enzymes.
Addition of nitrite to dithionite-reduced trout liver microsomes leads to the conversion of cytochrome P-450 into a cytochrome P-420-NO complex, as it does in mammalian microsomes. A loss in cytochrome P-450 and an inhibition of aminopyrine demethylase (AP) activity were observed in vitro at nitrite-concentrations found in the liver of trout exposed in vivo to this toxin. Nitrite had no effect on dimethylaniline monooxygenase (DMA), a cytochrome P-450-independent enzyme.


[Schwannoma of the infratemporal fossa].
A rare case of infratemporal fossa Schwannoma is reported together with an outline description of Schwannoma and a discussion on the aetiology, macroscopic and histological aspects and therapy.


Effect of porcine somatotropin (pST) treatment and withdrawal on performance and adipose tissue cellularity in finishing swine.
A 10-wk trial was conducted with 60 barrows and 60 gilts (initial weight = 47 kg) to investigate the effect of pST treatment (3 mg/d) for wk 0 to 5, 5 to 10, or 0 to 10 on performance, carcass traits, and adipose tissue cellularity of finishing hogs. The primary objective of the study was to determine the effect of 5 wk of pST treatment followed by 5 wk of withdrawal on performance and carcass traits relative to a control or to pigs treated for the entire period. After 5 wk, pST-treated pigs exhibited improved (P < .001) gain (11%) and efficiency (22%) and decreased (P < .001) feed intake (-22%) and 10th rib backfat accretion (-93%, P < .001). There was an increase in adipose cell number/gram of tissue (control, 2.57 vs pST, 3.36 x 10(6)/g; P < .005) and a decrease in cell diameter (control, 72.4 vs pST, 67.2 microns; P < .005). Backfat thickness and cell diameter increased in control pigs from wk 5 to 10. During the last 5-wk period, pST-treated animals continued to exhibit improved performance and maintained adipose cell size distribution and number similar to the pST-treated pigs at wk 5. Pigs treated for the first 5 wk and withdrawn from treatment for the second 5 wk had decreased efficiency (-12%, P < .05) and a twofold increase in backfat accretion (P < .001) relative to control. The increase in backfat thickness was accompanied by an increase in adipocyte diameter, indicative of lipid filling. Most of the benefits of pST observed during the first 5 wk were lost during the withdrawal period. Reductions in carcass fat in response to pST treatment are at least partially accounted for by inhibition of lipid filling in adipose tissue, an effect that is reversed upon cessation of treatment.


Wearable Intrinsically Soft, Stretchable, Flexible Devices for Memories and Computing.
A recent trend in the development of high mass consumption electron devices is towards electronic textiles (e-textiles), smart wearable devices, smart clothes, and flexible or printable electronics. Intrinsically soft, stretchable, flexible, Wearable Memories and Computing devices (WMCs) bring us closer to sci-fi scenarios, where future electronic systems are totally integrated in our everyday outfits and help us in achieving a higher comfort level, interacting for us with other digital devices such as smartphones and domotics, or with analog devices, such as our brain/peripheral nervous system. WMC will enable each of us to contribute to open and big data systems as individual nodes, providing real-time information about physical and environmental parameters (including air pollution monitoring, sound and light pollution, chemical or radioactive fallout alert, network availability, and so on). Furthermore, WMC could be directly connected to human brain and enable extremely fast operation and unprecedented interface complexity, directly mapping the continuous states available to biological systems. This review focuses on recent advances in nanotechnology and materials science and pays particular attention to any result and promising technology to enable intrinsically soft, stretchable, flexible WMC.


cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity.
Signaling pathways targeting mitochondria are poorly understood. We here examine phosphorylation by the cAMP-dependent pathway of subunits of cytochrome c oxidase (COX), the terminal enzyme of the electron transport chain. Using anti-phospho antibodies, we show that cow liver COX subunit I is tyrosinephosphorylated in the presence of theophylline, a phosphodiesterase inhibitor that creates high cAMP levels, but not in its absence. The site of phosphorylation, identified by mass spectrometry, is tyrosine 304 of COX catalytic subunit I. Subunit I phosphorylation leads to a decrease of V(max) and an increase of K(m) for cytochrome c and shifts the reaction kinetics from hyperbolic to sigmoidal such that COX is fully or strongly inhibited up to 10 mum cytochrome c substrate concentrations, even in the presence of allosteric activator ADP. To assess our findings with the isolated enzyme in a physiological context, we tested the starvation signal glucagon on human HepG2 cells and cow liver tissue. Glucagon leads to COX inactivation, an effect also observed after incubation with adenylyl cyclase activator forskolin. Thus, the glucagon receptor/G-protein/cAMP pathway regulates COX activity. At therapeutic concentrations used for asthma relief, theophylline causes lung COX inhibition and decreases cellular ATP levels, suggesting a mechanism for its clinical action.


Calibration atmosphere generator for operating theatre pollution studies. A system for the controlled production of trace concentrations of inhalation anaesthetics.
The design and performance of an apparatus for producing accurately known trace concentrations of anaesthetic agents in air is described. The generator was constructed to facilitate the testing and calibration of equipment used in measuring the personal exposure of operating theatre staff to waste anaesthetic gases, and operates on the principle of the controlled injection of the pure anaesthetic agent into a diluting air stream. It is compact, simple to construct and easy to operate. Furthermore, it has a short stabilization time and can provide a wide range of predetermined concentrations with very good repeatability. It appears to be considerably more flexible than systems which have been described previously and should be of interest to groups involved in monitoring pollution in the operating theatre.


[Pregnancy diagnosis by the ultrasonographical device and observation of fetal growth in the squirrel monkey (Saimiri sciureus)].
This paper describes usefulness of the ultrasonographical device (USD) for the diagnosis of pregnancy and the observation of fetal growth in the squirrel monkeys (Saimiri sciureus) conceived under group breeding conditions. Pregnancy was diagnosed on the basis of the detection of gestational sac (GS) in the uterus. The GS was first detected 127 +/- 10 days before delivery. The heart beat of embryo was detected around 114 days before delivery. It was able to judge conditions of fetal growth by measuring the size of GS and the biparietal diameter. No difference in uterine size between nonpregnant and pregnant animals was observed 135 days before delivery.


[Automatic segmentation of the sequential images of neural stem cell based on geometric active contour].
A rapid and robust segmentation system is the base of the research on the change process of neural stem cells. In order to improve this system, against the segmentation of the multiple connected and blurred border cells, we present an improved geometric active contour algorithm based on the level set method and the curve evolution theory. This method can solve the topological change by itself and obtain the more real edges of the cells. This method has been adopted in the segmentation of the sequence of neural stem cell. The results prove the validity and veracity.


The floating first metacarpal: A rare case.
A floating metacarpal is defined as the simultaneous dislocation of the metacarpophalangeal (MCP) and carpometacarpal (CMC) joints. Metacarpal dislocations are rare, and floating metacarpals with double dislocations are extremely rare. In this article, we present a very rare case of floating metacarpal in which the first MCP and CMC dislocations were found simultaneously and successfully treated with closed reduction, open reduction, and Kirschner wire fixation methods.


Immunotherapy for fungal infections with special emphasis on central nervous system infections.
Opportunistic fungal infections are major causes of morbidity and mortality in the immunocompromized. Fungi have evolved complex and coordinated mechanisms to survive in the environment and the mammalian host. Fungi must adapt to "stressors" in the host, including nutrient scarcity, pH and reactive oxygen and nitrogen intermediates, in addition to evading host immunity. Knowledge of the immunopathogenesis of fungal infections has paved the way to promising strategies for immunotherapy. These include strategies that increase phagocyte number, activate innate host defense pathways in phagocytes and dendritic cells and stimulate antigen-specific immunity (e.g, vaccines). Immunotherapy must be tailored to specific immunocompromized states. Our review focuses on cryptococcosis and coccidioidomycosis because of the propensity of these diseases to involve the central nervous system (CNS). The CNS has long been considered "immunologically privileged" in the sense of being isolated from normal immune surveillance. This notion is only partially accurate. Immune-based therapies for fungal CNS disease are at an exploratory level and merit further evaluation in clinical trials.


Wire Guided Cannulation Facilitates Endoscopic Management of Buried Bumper Syndrome: A Novel Technique.
Buried bumper syndrome is a rare but potentially severe complication of percutaneous endoscopic gastrostomy tube insertion. Though this complication is uncommon, it may lead to pressure necrosis, bleeding, perforation, peritonitis, sepsis, or death. Each case of buried bumper syndrome is unique in terms of patient comorbidities and anatomic positioning of the buried bumper. For this reason, many approaches have been described in the management of buried bumper syndrome. In this case report, we describe the case of an adolescent Caucasian female who developed buried bumper syndrome three years after undergoing percutaneous endoscopic gastrostomy insertion. We review diagnosis and management of buried bumper syndrome and describe a novel technique for bumper removal in which we use a guide wire in combination with external traction to maintain a patent gastrostomy lumen while removing the internal percutaneous endoscopic gastrostomy bumper.


Pharmacogenomics of warfarin in populations of African descent.
Warfarin is the most commonly prescribed oral anticoagulant worldwide despite its narrow therapeutic index and the notorious inter- and intra-individual variability in dose required for the target clinical effect. Pharmacogenetic polymorphisms are major determinants of warfarin pharmacokinetic and dynamics and included in several warfarin dosing algorithms. This review focuses on warfarin pharmacogenomics in sub-Saharan peoples, African Americans and admixed Brazilians. These 'Black' populations differ in several aspects, notably their extent of recent admixture with Europeans, a factor which impacts on the frequency distribution of pharmacogenomic polymorphisms relevant to warfarin dose requirement for the target clinical effect. Whereas a small number of polymorphisms in VKORC1 (3673G > A, rs9923231), CYP2C9 (alleles *2 and *3, rs1799853 and rs1057910, respectively) and arguably CYP4F2 (rs2108622), may capture most of the pharmacogenomic influence on warfarin dose variance in White populations, additional polymorphisms in these, and in other, genes (e.g. CALU rs339097) increase the predictive power of pharmacogenetic warfarin dosing algorithms in the Black populations examined. A personalized strategy for initiation of warfarin therapy, allowing for improved safety and cost-effectiveness for populations of African descent must take into account their pharmacogenomic diversity, as well as socio-economical, cultural and medical factors. Accounting for this heterogeneity in algorithms that are 'friendly' enough to be adopted by warfarin prescribers worldwide requires gathering information from trials at different population levels, but demands also a critical appraisal of racial/ethnic labels that are commonly used in the clinical pharmacology literature but do not accurately reflect genetic ancestry and population diversity.


Sertoli cell synthesizes and secretes a protease inhibitor, alpha 2-macroglobulin.
The mechanism by which the seminiferous epithelium limits the damaging effects of proteases that are released from degenerating late spermatids does not depend upon protease inhibitors in the systemic circulation since these proteins are excluded from the seminiferous tubule by the blood-testis barrier. The purpose of this study was to identify the major protease inhibitor of the testis and determine its cellular origin. Sertoli cells, the major epithelial component of the seminiferous epithelium, release a protease inhibitor, testicular alpha 2-macroglobulin, in vitro. Immunoprecipitation using [35S]methionine and a monospecific polyclonal antibody prepared against purified testicular alpha 2-macroglobulin establishes that this protein is actively synthesized and secreted by Sertoli cells. Measurements of immunoreactive protease inhibitors in tubular and rete testis fluids collected by micropuncture suggest that alpha 2-macroglobulin rather than alpha 1-antitrypsin is the major protease inhibitor in the seminiferous tubules in vivo. The ability of alpha 2-macroglobulin to inactivate proteases and growth factors such as TGF-beta by a common mechanism suggests that this protein may have a dual function in the testis.


Lengthscale-Dependent Solvation and Density Fluctuations in n-Octane.
Much attention has been focused on the solvation and density fluctuations in water over the past decade. These studies have brought to light interesting physical features of solvation in condensed media, especially the dependence of solvation on the solute lengthscale, which may be general to many fluids. Here, we focus on the lengthscale-dependent solvation and density fluctuations in n-octane, a simple organic liquid. Using extensive molecular simulations, we show a crossover in the solvation of solvophobic solutes with increasing size in n-octane, with the specifics of the crossover depending on the shape of the solute. Large lengthscale solvation, which is dominated by interface formation, emerges over subnanoscopic lengthscales. The crossover in n-octane occurs at smaller lengthscales than that in water. We connect the lengthscale of crossover to the range of attractive interactions in the fluid. The onset of the crossover is accompanied by the emergence of non-Gaussian tails in density fluctuations in solute shaped observation volumes. Simulations over a range of temperatures highlight a corresponding thermodynamic crossover in solvation. Qualitative similarities between lengthscale-dependent solvation in water, n-octane, and Lennard-Jones fluids highlight the generality of the underlying physics of solvation.


Expression and correlation analysis of RegIV and vascular endothelial growth factors (VEGF-A and VEGF-C) in metastatic spinal tumors.
The expression and correlation analysis of the regenerating gene family member 4 (RegIV) and vascular endothelial growth factors (VEGF-A and VEGF-C) in metastatic spinal tumors were studied. Fifteen patients with metastatic spinal tumors who underwent operation in our hospital from January 2011 to January 2013 were selected into this study. The expression level of tumor tissues in patients with spinal metastasis and RegIV, VEGF-A and VEGF-C of the corresponding paracancer normal tissue samples were evaluated by immunohistochemical staining method and the correlation between the expression of RegIV, VEGF-A and VEGF-C was analyzed. qRT-PCR results showed that the expression of RegIV was increased (P<0.05) in paracancer normal tissues and spinal metastatic tumor tissues. Compared with normal tissues, expression of RegIV, VEGF-A and VEGF-C was higher in metastatic spinal tumor tissues and the difference had statistical difference (P<0.05). Spearman's correlation analysis showed that the expression of RegIV was positively correlated with VEGF-A (r=0.683, P<0.05); the expression of RegIV positively correlated with VEGF-C (r=0.717, P<0.05). Cox regression analysis showed that RegIV, VEGF-A, VEGF-C expression and microvessel density counts are prognostic factors affecting spine metastasis (P<0.05), RegIV expression affected the survival of patients with relative risk. The high expression of RegIV in spinal metastatic tumors may promote the expression of VEGF-A and VEGF-C to increase the microvascular density, promote angiogenesis, and accelerate the occurrence and progression of spinal metastatic tumors.


Migration Spurs Changes in the Human Microbiome: a Review.
International migration often results in major changes in living environments and lifestyles, and these changes may lead to the observed increases in obesity and diabetes among foreign-born people after resettling in higher-income countries. A possible mechanism linking changes in living environments to the onset of health conditions may be changes in the microbiome. Previous research has shown that unfavorable changes in the composition of the microbiome can increase disposition to diseases such as diabetes, obesity, kidney disease, and inflammatory bowel disease. We investigated the relationship between human migration and microbiome composition through a review using microbiome- and migration-related search terms in PubMed and Web of Science. We included articles examining the gut, oral, or oropharyngeal microbiome in people who migrated internationally. Nine articles met eligibility criteria. All but one examined migration from a non-Western to a Western country. Four of these found a difference in the microbiome of migrants compared with non-migrating residents of their country of birth, seven found differences in the microbiome of migrants compared with the native-born population in the country of resettlement, and five found microbiome differences associated with duration of stay in the country of resettlement. Microbiome composition varies with country of birth, age at migration, time since immigration, and country of resettlement. The results suggest that migration may lead to changes in the microbiome; thus, microbiome characteristics are a plausible pathway to examine changes in health after resettlement in a new country.


[Prognostic factors of pediatric patients with Ph-positive acute lymphoblastic leukemia].
Objective: To explore the clinical features and prognostic factors of Ph-positive and/or BCR-ABL positive acute lymphoblastic leukemia (Ph+ ALL) in children. Methods: The clinical data of 68 Ph+ ALL children who were treated at Peking University People's Hospital from December 2006 to December 2016 was retrospectively reviewed. Survival analysis were estimated by Kaplan-Meier method. Univariate analysis was estimated by Log-rank test and Chi-square, and multivariate analysis was estimated by Cox proportional hazards regression model. Results: In the 68 cases, the proportion of male to female was 2.1∶1, with a median age of 8 (1-16) years, and the median overall survival (OS) and disease free survival (DFS) were 16.8 months and 13.5 months, respectively. The early response rate to treatment was 43.9%, with myeloid-antigens-expression group lower than the non-expression group (29.6% vs 61.3%, χ2=5.814, P=0.020); The complete remission (CR) rate after one-course induction therapy was 86.2% (56/65), with good-response group higher than the poor-response group (100.0% vs 74.2%, χ2=6.680, P=0.003);The CR rate after induction in patients receiving imatinib plus chemotherapy was higher than the patients receiving chemotherapy only (94.9% vs 73.1%, χ2=5.185, P=0.024). The 2-and 5-year OS were (61.4±7.0)% and (50.8±8.1)%, respectively. The 2-and 5-year DFS were (54.6±6.8)% and (48.6±7.3)%, respectively. Univariate analysis showed that the initial WBC, LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year OS rate (all P<0.05). LDH, spleen size, liver size, with-myeloid-antigens-expression, early response to treatment, MRD (BCR-ABL) after one-course induction, application of imatinib and different treatment options affected 2-year DFS rate (all P<0.05). Multivariate prognostic analysis for OS (RR=45.7, 95% CI 1.4-1 528.2, P=0.033) and DFS (RR=52.3, 95% CI 1.6-1 725.9, P=0.026) showed that the spleen ≥ 3 cm was the independent risk factor. Conclusions: Pediatric Ph+ ALL is a special condition with unique clinical and biological features. The early response to treatment was poor in patients with myeloid-antigens-expression, which resulted in a low CR rate after one-course induction and the administration of imatinib can remarkably improve the CR rate. Initial spleen ≥ 3 cm is an independent prognostic factor. The efficacy of chemotherapy alone is poor, and imatinib combined with chemotherapy is applauded in the aim of improving outcomes.


Transfection of primary brain capillary endothelial cells for protein synthesis and secretion of recombinant erythropoietin: a strategy to enable protein delivery to the brain.
Treatment of chronic disorders affecting the central nervous system (CNS) is complicated by the inability of drugs to cross the blood-brain barrier (BBB). Non-viral gene therapy applied to brain capillary endothelial cells (BCECs) denotes a novel approach to overcome the restraints in this passage, as turning BCECs into recombinant protein factories by transfection could result in protein secretion further into the brain. The present study aims to investigate the possibility of transfecting primary rat brain endothelial cells (RBECs) for recombinant protein synthesis and secretion of the neuroprotective protein erythropoietin (EPO). We previously showed that 4% of RBECs with BBB properties can be transfected without disrupting the BBB integrity in vitro, but it can be questioned whether this is sufficient to enable protein secretion at therapeutic levels. The present study examined various transfection vectors, with regard to increasing the transfection efficiency without disrupting the BBB integrity. Lipofectamine 3000™ was the most potent vector compared to polyethylenimine (PEI) and Turbofect. When co-cultured with astrocytes, the genetically modified RBECs secreted recombinant EPO into the cell culture medium both luminally and abluminally, and despite lower levels of EPO reaching the abluminal chamber, the amount of recombinant EPO was sufficient to evolve a biological effect on astrocytes cultured at the abluminal side in terms of upregulated gene expression of brain-derived neurotropic factor (BDNF). In conclusion, non-viral gene therapy to RBECs leads to protein secretion and signifies a method for therapeutic proteins to target cells inside the CNS otherwise omitted due to the BBB.


A Rare Case of Acute Pancreatitis in the Setting of Hemorrhagic Cholecystitis.
Hemorrhagic cholecystitis is a rare form of acute cholecystitis with very few cases reported in the literature. We report a novel case of a 79-year-old male who developed hemorrhagic cholecystitis and concomitant acute pancreatitis. The patient presented to the emergency department with a one-day history of severe epigastric pain radiating to his back. The patient was on an anticoagulant therapy for a history of pulmonary embolism. He had an elevated serum lipase and on a right upper quadrant ultrasound, a mildly distended gallbladder without stones was noted. Computed tomography (CT) the following day demonstrated heterogenous material in the gallbladder concerning for blood clots. Laparoscopic cholecystectomy with intraoperative cholangiogram (IOC) was performed that revealed a gallbladder filled with clots. He had an uneventful post-operative recovery.