Longitudinal Relationships Between Self-Management Skills and Substance Use in an Urban Sample of Predominantly Minority Adolescents.
We explored changes in self-management skills and substance use from 7th to 11th grade in a multiwave study of predominantly minority adolescents (N = 1,756). Using latent growth curve analysis, we found that substance use significantly increased, whereas self-management skills significantly decreased. In a parallel process model, we found that participants who reported higher self-management skills in the 7th grade had smaller increases in substance use. Participants who had larger decreases in self-management skills tended to have greater increases in substance use. We also explored the influence of grades and gender and found that (a) participants with higher grades at baseline had lower initial substance use, higher initial self-management skills, and smaller increases in substance use, and (b) male participants had greater increases in substance use. These results suggest that the provision of self-management skills may be an effective strategy for preventing substance-use initiation and escalation during adolescence.


Synaptic distribution and plasticity in primary auditory cortex (A1) exhibits laminar and cell-specific changes in the deaf.
The processing sequence through primary auditory cortex (A1) is impaired by deafness as evidenced by reduced neuronal activation in A1 of cochlear-implanted deaf cats. Such a loss of neuronal excitation should be manifest as changes in excitatory synaptic number and/or size, for which the post-synaptic correlate is the dendritic spine. Therefore, the present study sought evidence for this functional disruption using Golgi-Cox/light microscopic techniques that examined spine-bearing neurons and their dendritic spine features across all laminae in A1 of early-deaf (ototoxic lesion <1 month; raised into adulthood >16 months) and hearing cats. Surprisingly, in the early-deaf significant increases in spine density and size were observed in the supragranular layers, while significant reductions in spine density were observed for spiny non-pyramidal, but not pyramidal, neurons in the granular layer. No changes in dendritic spine density consistent with loss of excitatory inputs were seen for infragranular neurons. These results indicate that long-term early-deafness induces plastic changes in the excitatory circuitry of A1 that are laminar and cell-specific. An additional finding was that, unlike the expected abundance of stellate neurons that characterize the granular layer of other primary sensory cortices, pyramidal neurons predominate within layer 4 of A1. Collectively, these observations are important for understanding how neuronal connectional configurations contribute to region-specific processing capabilities in normal brains as well as those with altered sensory experiences.


"Paradoxical embolism" - a misnomer?
Dear Editor, I wish to comment on two articles published in the December 2007 issue. Firstly I sympathise with the plight of the European doctors wishing to perform diving medicals that are accepted by the Queensland Government. As you will be aware SPUMS is not a regulatory body and had no input into the decision of the Queensland Government to use the SPUMS Diving Doctors List (DDL) as a reference list for doctors able to perform diving medicals. The DDL is a service offered to the SPUMS membership, and not all doctors who are members of SPUMS are included on the list. Rather it contains only those who have done the appropriate courses/training and then have applied annually to be listed. Doctors who are not members of SPUMS but are 'qualified' are also not on the DDL. To me the solution is easy for our European colleagues - become a SPUMS member and apply. As Dr J Wendling indicated the EDTC/ECHM standards are acceptable to SPUMS so the process would be simple. The application forms can be found on the SPUMS website: www.spums.org.au. Secondly the term;'paradoxical embolisation' was used in the book review by Dr Boon von Ochsèe. It was an excellent review and has prompted me to buy the book but I would like to question the use of the word 'paradoxical' when referring to air embolism associated with a patent foramen ovale. I know it is a term frequently used and, therefore, I am not arguing with Dr Boon. However, the word 'paradox' means "statement contrary to accepted opinion;…person or thing conflicting with preconceived notions of what is reasonable or possible". By this definition, surely there is nothing paradoxical about an air embolism associated with two connected chambers of the heart - any connection would mean a mixing of the chamber's contents? I believe the term should be reserved for embolisation in which no communication between the atria or any other right-to-left communication is found.


Diabetogenic effects of N-nitrosomethylurea in rats.
The influence of a single i.v. injection of 75 or 175 mg N-nitrosomethylurea (NMU)/kg into Wistar rats on plasma glucose, i.p. glucose tolerance, plasma insulin and glucagon, glucose stimulated insulin secretion and release as well as on the biosynthesis of insulin in isolated pancreatic islets have been investigated at set intervals between the 3rd day and the 6th week post injectionem. At the end of the experimental period all NMU-treated animals were alive but had significantly reduced body mass. All animals remained normoglycemic even after the glucose load. 3 days after drug application plasma insulin decreased only insignificantly in the 175 mg NMU-group, whereas plasma glucagon was significantly reduced in both drug-groups; after 3 and 6 weeks the reduction of plasma glucagon was still about 30 percent. In isolated islets the glucose stimulated insulin secretion, the percent stimulation of insulin release and insulin biosynthesis were significantly decreased.


An open, randomized, comparative study of efficacy and safety of risperidone and haloperidol in schizophrenia.
In the last decade there have been numerous randomized controlled trials comparing the efficacy and safety of second generation antipsychotics and conventional antipsychotics in the treatment of schizophrenia, but most of them have been conducted in the western population. This study compared the efficacy and safety of risperidone versus haloperidol in the Nepalese context, in order to add on to the very few literatures available on this topic in the South East Asia region and compare them. Patients with the diagnosis of schizophrenia were randomly assigned to receive risperidone 4-6 milligrams (mg) per day and haloperidol 10-20 mg per day, and were followed up for 6 weeks. Assessment were done on the day of the diagnostic interview and days 7, 14, 28 and 42 (end point). During the assessment periods Positive and Negative Syndrome Scale (PANSS) was administered to monitor the progress in psychopathology and Udvalg for Kliniske Undersogelser (UKU) side effects rating scale was applied to rate the treatment emergent adverse effects. Both risperidone and haloperidol were associated with substantial baseline- to- endpoint reduction in symptom severity. After one week of treatment, the improvement in schizophrenia with risperidone was significantly better than haloperidol in terms of PANSS- total Score (-45.4 versus -29.5), negative subscale score (-14.3 versus -6.68) and general psychopathology subscale score (-20.9 versus -13.7). At the end point of the study, the benefit was maintained in total score (-52.1 versus -43.1), though the negative subscale score still showed tendency for greater improvement in psychopathology with risperidone. The side effects profile did not show significant differences except in extrapyramidal symptoms. Thirty-eight percent of risperidone treated patients had to resort to anti-parkinsonian treatment compared to 78% in haloperidol treatment group. Similar to the studies in the western countries, Asia and Indian subcontinent, both risperidone and haloperidol were effective in the reduction of psychopathological symptoms in this group of Nepalese population with the diagnosis of schizophrenia. However, risperidone was quicker and better then haloperidol and risperidone had a better safety profile. This is important, because extrapyramidal side effects of neuroleptics are responsible for non-compliance and increased cost in terms of us of anti-parkinsonian medication.


Comparative hemostatic protein alterations accompanying pregnancy and parturition.
Pregnancy and parturition represent adaptive, physiological stress situations that elicit both blood coagulation protein changes and endocrine alterations. This paper briefly reviews the interrelationships of these responses by comparing the available data in several mammalian species including man, dog, cow, and pig. Hemostasis is an enzymatically controlled cascade process involving platelets and specific coagulation proteins that results in the formation of insoluble strands of fibrin. Although qualitatively similar in most mammals, quantitative differences exist in the circulating levels of individual coagulation proteins which may contribute towards the different rates of clot formation. In the late gestation stage of human pregnancy, significant increases are observed in the circulating biological activities of the coagulation factors VII, VIII:C, IX, and X. In the dog, the activities of factors VII and IX reach peak values in midpregnancy, while in the cow little or no changes are observed except for factor VII values which show a significant increase only around the time of parturition. These coagulation changes appear to be associated with fluctuations in circulating hormone values, particularly plasma estrogen. In human pregnancy, the circulating levels of fibrinogen, the precursor of fibrin, increase during the gestation period reaching maximum values during and immediately following parturition. In the dog and the cow two distinct increases in fibrinogen values are observed, the first in the midgestation period and the second in the immediate postparturition period. In the pig, fibrinogen values also rise significantly at parturition. Oral contraceptive studies in the human female have indicated that changes in circulating activities of coagulation proteins are hormonally influenced.(ABSTRACT TRUNCATED AT 250 WORDS)


Exacerbation of oxaliplatin neurosensory toxicity following surgery.
Combination of chemotherapy and surgical resection of metastases is the most promising strategy to improve the fraction of long-term survivors and cured patients in metastatic colorectal cancer. We reproducibly observed evidence of exacerbation of the oxaliplatin-induced neurosensory toxicity following surgery. Total, protein-bound and intra-erythrocytic concentrations of oxaliplatin were measured, whenever possible, immediately prior to surgery and 4, 24 and 48 h following surgical resection. Among 12 patients, seven (58%) patients reported immediate post-operative aggravation of the pre-existing neurotoxicity. At the time of surgery, we detected high intra-erythrocytic platinum concentrations in all patients (median: 1365 micro g/l, range: 820-2968 micro g/l). While ultrafilterable oxaliplatin was not detectable prior to surgery, it could be detected immediately after surgery and during 48 h. These results suggest that patients heavily pretreated with oxaliplatin may experience aggravation of neurotoxicity after surgery, probably through a redistribution of the pool of intra-erythrocytic oxaliplatin biotransformation products into the plasma. This clinical observation might be the consequence of peroperative hemolysis.


Quantum chemical study of the geometrical and electronic structures of ScSi3 (-/0) clusters and assignment of the anion photoelectron spectra.
The geometrical and electronic structures of ScSi3 (-/0) clusters have been studied with the B3LYP, CCSD(T), and CASPT2 methods. The ground state of the anionic cluster was evaluated to be the (1)A1 of rhombic η(2)-(Si3)Sc(-) isomer, whereas that of the neutral cluster was computed to be the (2)A1 of the same isomer. All features in the 266 and 193 nm photoelectron spectra of ScSi3 (-) cluster were interpreted by the one- and two-electron detachments from the (1)A1 of rhombic η(2)-(Si3)Sc(-) isomer. The Franck-Condon factor simulation results show that the first broad band starting at 1.78 eV in the spectra comprises several vibrational progression peaks of two totally symmetric modes with the corresponding frequencies of 296 and 354 cm(-1).


Preoperative Serum Alkaline Phosphatase and Clinical Outcome of Off-Pump Coronary Artery Bypass Surgery.
Serum alkaline phosphatase (ALP) is related to vascular calcification. In a recent study on percutaneous coronary intervention (PCI) with a drug-eluting stent, higher ALP was associated with poor clinical outcomes in terms of mortality, myocardial infarction, and stent thrombosis. The aim of this study was to evaluate the relationship between preoperative ALP and clinical outcome of off-pump coronary artery bypass surgery (OPCAB).Methods and Results:We retrospectively enrolled and reviewed a total of 1,335 patients who underwent OPCAB. Patients were divided into tertiles based on preoperative serum ALP (<60, 60-76, and >76 IU/L). As preoperative ALP increased, the HR of mortality remained constant after adjusting for confounders. On Cox proportional hazards regression analysis, there was no association between ALP and all-cause mortality. The adjusted HR for all-cause mortality for the middle tertile was 0.882 (95% CI: 0.592-1.314, P=0.537), and 0.915 (95% CI: 0.605-1.383, P=0.672) for the highest tertile. In addition, no associations between ALP and cardiovascular mortality, myocardial infarction, revascularization, or major adverse cardiac events were found. Unlike after PCI, high ALP is not related to adverse clinical events, such as mortality, myocardial infarction, or revascularization after OPCAB. ALP might be considered when determining the optimal revascularization technique.


Coverage of Acta Dermatovenerologica Alpina, Pannonica et Adriatica in Elsevier's CiteScore index: a new tool for measuring the citation impact of academic journals.
In December 2016, Elsevier launched a new tool that helps measure the citation impact of academic journals, called the CiteScore index. The CiteScore index values for 2015 confirmed the status of Acta Dermatovenerologica Alpina, Pannonica et Adriatica (Acta Dermatovenerol APA) as the leading journal in dermatology and sexually transmitted infections in the region. Sixty-five articles published in Acta Dermatovenerol APA from 2012 to 2014 received a total of 77 citations in 2015, resulting in a CiteScore index value of 1.18 for the journal. More than half of the articles published from 2012 to 2014 received at least one citation in 2015. Acta Dermatovenerol APA performed well in all three categories listed because it is ranked 384th out of 1,549 journals in the category General Medicine (75th percentile), 53rd out of 122 journals in the category Dermatology (56th percentile), and 142nd out of 246 journals in the category Infectious Diseases (42nd percentile).


Purification and characterization of an amidase from an acrylamide-degrading Rhodococcus sp.
A constitutively expressed aliphatic amidase from a Rhodococcus sp. catalyzing acrylamide deamination was purified to electrophoretic homogeneity. The molecular weight of the native enzyme was estimated to be 360,000. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified preparation yielded a homogeneous protein band having an apparent molecular weight of about 44,500. The amidase had pH and temperature optima of 8.5 and 40 degrees C, respectively, and its isoelectric point was pH 4.0. The amidase had apparent K(m) values of 1.2, 2.6, 3.0, 2.7, and 5.0 mM for acrylamide, acetamide, butyramide, propionamide, and isobutyramide, respectively. Inductively coupled plasma-atomic emission spectometry analysis indicated that the enzyme contains 8 mol of iron per mol of the native enzyme. No labile sulfide was detected. The amidase activity was enhanced by, but not dependent on Fe(2+), Ba(2+), and Cr(2+). However, the enzyme activity was partially inhibited by Mg(2+) and totally inhibited in the presence of Ni(2+), Hg(2+), Cu(2+), Co(2+), specific iron chelators, and thiol blocking reagents. The NH2-terminal sequence of the first 18 amino acids displayed 88% homology to the aliphatic amidase of Brevibacterium sp. strain R312.


Laboratory diagnosis of infectious diarrhoea syndrome; a three years study in two hospitals of infectious diseases.
Infectious diarrhoea is a syndrome caused by a variety of bacterial, viral and parasitic organisms which represents a major cause of morbidity and mortality all over the world. The wide diversity of etiological agents impairs the surveillance and the diagnosis and affects the correct treatment applied to reduce the long-term complications. Besides well known enteric pathogens such as Salmonella, Shigella and Yersinia, a high number of emergent and re-emergent aetiologies are now recognised to be at the origin of diarrhoea. The lack of a correct diagnostic algorithm and adequate methods of analyses leads to under-evaluation and incertitude in an important number of clinical cases. Our study was designed as a complex analysis of the stool specimens collected from the patients, in the purpose to improve the laboratory diagnostic and to enhance the number of confirmed cases of infectious diarrhoea. A number of 756 samples from inpatients with diarrhoea were tested targeting pathogenic and opportunistic bacteria, viruses and parasites by classical and molecular methods. We documented that, in case of non-Salmonella, non-Shigella, non-Yersinia diarrhoea, the quality of diagnostic was improved by increasing the percentage of positive specimens to 22.49% compared to 11.12% when only bacteria, 5.56% when only viruses and 4.10% when only parasites were investigated. The laboratory data are of great value in evaluating the diarrhoea syndrome offering the documentation for an accurate epidemiological response and an adequate treatment.


Increased sensitivity of mouse mammary gland for hormones and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate in tissues containing the Mtv-2 gene.
We have compared the response of mammary explants obtained from GR mice with those derived from GR/Mtv-2- congenic mice towards hormones and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In explants of the mammary glands of virgin GR mice, insulin, prolactin, progesterone and TPA stimulated the rate of (3H)-thymidine incorporation into DNA. A significantly lower response towards prolactin and TPA was observed in mammary explants derived from GR/Mtv-2-mice. The differential sensitivity of mammary tissues from GR and GR/Mtv-2-mouse strains to the actions of prolactin and tumor promoter is directly correlated to their different incidences of spontaneous tumor formation; it is not known if there is a causal relationship.


Hereditary Neuropathies.
This article provides an overview of hereditary neuropathies, describes the different hereditary neuropathy subtypes and the clinical approach to differentiating between them, and summarizes their clinical management. Increasingly available clinical genetic testing has broadened the clinical spectrum of hereditary neuropathy subtypes and demonstrated a significant overlap of phenotypes associated with a single gene. New subtypes such as SORD -related neuropathy and CANVAS (cerebellar ataxia, neuropathy, vestibular areflexia syndrome) have emerged. The optimization of clinical management has improved gait and motor function in the adult and pediatric populations. Novel therapeutic approaches are entering clinical trials. Hereditary neuropathies constitute a spectrum of peripheral nerve disorders with variable degrees of motor and sensory symptoms, patterns of involvement, and clinical courses.


The effect of ethyl pyruvate supplementation on rat fatty liver induced by a high-fat diet.
Continuous positive energy imbalance leads to obesity, which increases the risk of developing non-alcoholic fatty liver disease. The hepatoprotective effect of ethyl pyruvate has been revealed in several studies. Therefore, we examined the effect of ethyl pyruvate supplementation on liver cell damage, metabolism, membrane fluidity, and oxidative stress markers in rats fed a high-fat diet. After 6-wk feeding of a control or high-fat diet, Wistar rats were divided into 4 groups: control diet, control diet and ethyl pyruvate, high-fat diet, and high-fat diet and ethyl pyruvate. Ethyl pyruvate was administered as a 0.3% solution in drinking water, for the following 6 wk. Ethyl pyruvate intake attenuated the increase in activities of plasma transaminases and liver TNF-α. However, the supplementation was without effect in the lipid profiles, membrane fluidity or oxidative metabolism in liver induced by the high-fat diet. Our data confirm the potency of ethyl pyruvate against cell liver damage. Nevertheless, prolonged intake did not affect the development of a fatty liver.


Lanthanum staining of the surface coat of cells. Its enhancement by the use of fixatives containing Alcian blue or cetylpyridinium chloride.
Among the techniques which have been reported to stain the surface coat of cells, for electron microscopy, is lanthanum staining en bloc. Similarly, the presence of the cationic dye, Alcian blue 8GX, in a primary glutaraldehyde fixative has been reported to improve the preservation of the surface coat of cells of many types; however, the preserved coat is not very electron opaque unless thin sections are counterstained. The present paper shows that for several rat tissues lanthanum staining en bloc is an effective electron stain for the cell surface, giving excellent contrast, if combined sequentially with prefixation in an aldehyde fixative containing Alcian blue. The cationic substance cetylpyridinium chloride was found to have a similar effect to that of Alcian blue in enhancing the lanthanum staining of the surface coat material of the brush border of intestinal epithelial cells. The patterns of lanthanum staining obtained for the tissues studied strikingly resemble those reported in the literature where tissues are stained by several standard methods for demonstrating mucosubstances at the ultrastructural level. This fact and the reproduction of the effect of Alcian blue by cetylpyridinium chloride constitute a persuasive empirical argument that the material visualized is a mucopolysaccharide or mucopolysaccharide-protein complex.


Impact of the COVID-19 pandemic lockdown on public sector ophthalmic work by New Zealand's ophthalmologists.
In response to the COVID-19 pandemic, the New Zealand government enforced a nationwide 'alert level 4' lockdown from 26 March to 27 April 2020. We assessed the impact of this lockdown on New Zealand's public ophthalmology service. An anonymous online survey was sent to all New Zealand-based fellows of the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) after lockdown. Respondents provided retrospective assessment of practice patterns and their personal health during the COVID-19 lockdown. This was supported by national-level administrative data, allowing survey findings to be contextualised. Fifty-seven respondents (response rate 49%) working in the public health system participated. A large majority of respondents reduced elective clinic and surgical volumes by at least 75% (82% and 98%, respectively). National-level information confirmed clinic reduced to 38.2% of normal and elective operating volumes to 11.5%, with virtual visits increasing 17.9-fold. Elective clinic and elective operating volumes promptly recovered to usual volumes on the second month post lockdown. Most respondents (58%) followed the RANZCO triaging guideline, and 28% triaged emergencies only. At a personal level, respondents reported a significant physical health benefit (p<0.001) associated with the lockdown experience, but no change in mental health or social wellbeing. Publicly employed ophthalmologists experienced dramatic reductions to elective clinic and operating volumes during the COVID-19 lockdown. The prompt recovery of service delivery volumes back to pre-lockdown levels supports the value of a COVID-19 elimination strategy in New Zealand. Virtual visits for selected patients allowed ongoing management without risking virus transmission.


Visual attention in children with normal hearing, children with hearing aids, and children with cochlear implants.
Previous studies have reported both positive and negative effects of deafness on visual attention. The purpose of this study was to replicate and expand findings of previous studies by examining visual attention abilities in children with deafness and children with normal hearing. Twenty-eight children, ages 8-14 years, were evaluated. There were two groups of children with prelingual deafness and one group with normal hearing. The children with deafness were divided further into two groups: those with cochlear implants and those with conventional hearing aids. Unlike previous studies, the current study found no substantial differences in performance among these three groups of children on a continuous-performance visual attention task or on a letter cancellation task. Children in all three groups performed very well on the visual attention tasks. Furthermore, there was little association between performance on the visual attention tasks and parent or teacher ratings of behavior and attention. Age and nonverbal intelligence were significantly correlated with performance on visual attention tasks. The theoretical implications of these findings are discussed, along with directions for future research.


A squaraine-linked metalloporphyrin two-dimensional polymer photocatalyst for hydrogen and oxygen evolution reactions.
Efficient water splitting photocatalysts are an energetically demanding and cost-effective method for generating renewable energy. Significant research has been reported to advance this approach. However, the use of organic photocatalysts and the presence of residual catalysts trapped in the porous frameworks present major concerns about the efficiency of this strategy. Herein, we report the photocatalytic evolution of H2 and O2 by a multi-hydroxyl group-decorated metalloporphyrin-based two-dimensional catalyst developed via metal catalyst-free synthetic route. Though metalloporphyrins have long been used for catalytic functions, a heterogeneous photocatalyst delivering both H2 and O2 has not yet been realized. This polymer catalyst design enables the photocatalytic diatomic O2 release, a bottleneck in water splitting, in a facile way. Photocatalytic release of H2 as well as O2 occurs with long-term durability of 20 cycles in 300 days with negligible decrease in efficiency, thus demonstrating the excellent performance of this new catalyst.


The assessment of IFN-gamma and its regulatory cytokines in the plasma and bronchoalveolar lavage fluid of patients with active pulmonary tuberculosis.
To assess the role of IFN-gamma and its regulatory cytokines in active pulmonary tuberculosis (TB). Cytokines were measured in the plasma of TB patients and healthy subjects with different risk for TB exposure. In addition, cytokine profile was assessed in the bronchoalveolar lavage fluid (BALf) of six TB patients and nine normal controls. Circulating IFN-gamma, IL-10 and IL-18 were higher in TB patients than in control groups. Plasma IL-12 levels were extremely variable, and no difference was observed among study groups. An inverse correlation between plasma IFN-gamma and IL-10 levels was found in TB patients. Furthermore, circulating IL-18 correlated with IL-10 but not with IFN-gamma levels. Finally, IFN-gamma, IL-18 and IL-12 were increased in the BALf of TB patients, whereas no difference was observed in IL-10 levels. In human TB, at least at certain disease stages, there is a differential compartmentalization of the IFN-gamma-regulatory factors IL-12 and IL-10, the former being concentrated in the lungs and the latter being present in peripheral circulation. In addition, our findings address more critically the role of IL-18 in the host response to tuberculosis infection in humans.


Clenbuterol and salbutamol in the symptomatic treatment of patients with reversible airways obstruction.
In a single-blind, partially randomized, crossover study, 48 patients with reversible airways obstruction were treated with 4 mg salbutamol 3-times daily, 20 micrograms clenbuterol twice daily and 40 micrograms clenbuterol twice daily, each regimen being given for 2 weeks. With all treatments there was an improvement in lung function, as indicated by daily monitoring of PEFR and subjective assessment of breathing, and there were no significant differences between them. Side-effects were few. It is considered, therefore, that twice daily regimens of clenbuterol can be as effective as salbutamol given 3-times daily and this may help to improve patient compliance.


An Unusual Case of Acute Cholecystitis Caused by Lactobacillus paracasei.
Lactobacillus paracasei is a gram-positive rod commonly found in probiotic foods and is well known to promote healthy gastrointestinal tracts. However, there have been a few case reports that have found Lactobacillus paracasei to be the causative agent in complications such as endocarditis, meningitis, peritonitis, pancreatitis, and cholecystitis. We present the case of a 76-year-old woman who was admitted for decompensated heart failure. The patient also reported abdominal pain in the right upper quadrant. Ultrasound findings suggested cholelithiasis and a subsequent hepatobiliary iminodiacetic acid (HIDA) scan confirmed acute cholecystitis. This patient was not a good candidate for cholecystectomy because of the risk of cardiac complications. Hence, percutaneous cholecystostomy tube (PCT) placement was done, and the aspirate drained during the procedure was sent for pathology. This bile culture was positive for Lactobacillus paracasei and negative for any other kinds of bacteria. The incidence of Lactobacillus species-induced cholecystitis makes up only 0.08% to 0.2% of cases, which makes this an unusual case of acute cholecystitis caused by Lactobacillus paracasei. We will discuss several pathogenic aspects of Lactobacillus paracasei, such as its ability to generate biofilms, pore-forming toxins, drug transporters, and antibiotic susceptibility.


Growth parameters in normal fetuses.
A total of 14 linear measurements, seven ratios of linear measurements, and the weights of eight organs were taken from 100 normal fetuses. The fetuses had been therapeutically aborted between 11 and 19 weeks of gestational age by prostaglandin induction or hysterotomy. Measurements were obtained from at least five fetuses for each week of development age. A correlation matrix was calculated in order to identify those variables that showed a significant relationship with each other and with total body measurements. Significant correlations were obtained between crown-rump length and the following: head circumference, femur length, and humerus length. These three measurements were also significantly correlated with body weight. First-order regression equations were produced for these significantly correlated variables. This information can be used to estimate fetal growth even when the fetus is incomplete.


Management of Persistent Air Leaks.
Alveolar-pleural fistulas causing persistent air leaks (PALs) are associated with prolonged hospital stays and high morbidity. Prior guidelines recommend surgical repair as the gold standard for treatment, albeit it is a solution with limited success. In patients who have recently undergone thoracic surgery or in whom surgery would be contraindicated based on the severity of illness, there has been a lack of treatment options. This review describes a brief history of treatment guidelines for PALs. In the past 20 years, newer and less invasive treatment options have been developed. Aside from supportive care, the literature includes anecdotal successful reports using fibrin sealants, ethanol injection, metal coils, and Watanabe spigots. More recently, larger studies have demonstrated success with chemical pleurodesis, autologous blood patch pleurodesis, and endobronchial valves. This manuscript describes these treatment options in detail, including postprocedural adverse events. Further research, including randomized controlled trials with comparison of these options, are needed, as is long-term follow-up for these interventions.


ACL transection influences mRNA levels for collagen type I and TNF-alpha in MCL scar.
To assess the mRNA expression of extracellular matrix genes which might correlate with or contribute to mechanically weaker medial collateral ligament (MCL) scars in the ACL-deficient rabbit knee joint compared to those in anterior cruciate ligament (ACL) intact knee joints, a bilateral MCL injury was induced in 10 skeletally mature female NZW rabbits. As part of the same surgical procedure, the ACL was transected in one of the knees while the contralateral knee had a sham procedure. The side having the combined MCL and ACL injury was randomly assigned. After six weeks, the rabbits were euthanized. Histological assessments were performed on samples of the MCL scars from each operated knee (n = 3 animals) and mRNA levels for collagen type I, III, V, decorin, biglycan, lumican, fibromodulin, TGF-beta, IL-1, TNF-alpha, MMP-1, MMP-13, and a housekeeping gene (GAPDH) were assessed using semiquantitative RT-PCR on RNA isolated from the MCL scar tissue of the remaining animals (n = 7 animals). Levels of mRNA for each gene were normalized using the corresponding GAPDH value. Results showed that the total RNA yield (per mg wet weight) in the MCL scar of the ACL-deficient knee was significantly greater than that in the MCL scar from the ACL-intact knee. Collagen type I mRNA levels were significantly lower and mRNA levels for TNF-alpha were significantly greater in the scars of ACL-deficient knees compared to scars from ACL-intact joints. There were no significant differences between ACL-deficient and ACL-intact knees with respect to MCL scar mRNA levels for the remaining genes assessed. Histologically, the "flaw" area, which has been shown to correlate with mechanical properties in previous studies, was significantly greater in MCL scars from ACL-deficient knees than in the ACL-intact MCL scars. The mean number of cells/mm2 in MCL scars from ACL-deficient knees was significantly greater than in MCL scars from ACL-intact knees. The present study suggests that MCL scar cell metabolism is differentially influenced by the combined injury environment.


Human Naa50 Protein Displays Broad Substrate Specificity for Amino-terminal Acetylation: DETAILED STRUCTURAL AND BIOCHEMICAL ANALYSIS USING TETRAPEPTIDE LIBRARY.
Amino-terminal acetylation is a critical co-translational modification of the newly synthesized proteins in a eukaryotic cell carried out by six amino-terminal acetyltransferases (NATs). All NATs contain at least one catalytic subunit, and some contain one or two additional auxiliary subunits. For example, NatE is a complex of Naa10, Naa50, and Naa15 (auxiliary). In the present study, the crystal structure of human Naa50 suggested the presence of CoA and acetylated tetrapeptide (AcMMXX) that have co-purified with the protein. Biochemical and thermal stability studies on the tetrapeptide library with variations in the first and second positions confirm our results from the crystal structure that a peptide with Met-Met in the first two positions is the best substrate for this enzyme. In addition, Naa50 acetylated all MXAA peptides except for MPAA. Transcriptome analysis of 10 genes that make up six NATs in humans from eight different cell lines suggests that components of NatE are transcribed in all cell lines, whereas others are variable. Because Naa10 is reported to acetylate all amino termini that are devoid of methionine and Naa50 acetylates all other peptides that are followed by methionine, we believe that NatE complex can be a major contributor for amino-terminal acetylation at the ribosome exit tunnel.


Molecular profiling of ADAM12 in human bladder cancer.
We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. ADAM12 gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12 could be detected in the urine by Western blotting; ADAM12 was present in higher levels in the urine from patients with bladder cancer compared with urine from healthy individuals. Significantly, following removal of tumor by surgery, in most bladder cancer cases examined, the level of ADAM12 in the urine decreased and, upon recurrence of tumor, increased. ADAM12 is a promising biomarker of bladder cancer.


Linking Autophagy and the Dysregulated NFκB/ SNAIL/YY1/RKIP/PTEN Loop in Cancer: Therapeutic Implications.
The role of autophagy in the pathogenesis of various cancers has been well documented in many reports. Autophagy in cancer cells regulates cell proliferation, viability, invasion, epithelial-to-mesenchymal transition (EMT), metastasis, and responses to chemotherapeutic and immunotherapeutic treatment strategies. These manifestations are the result of various regulatory gene products that govern autophagic, biochemical, and molecular mechanisms. In several human cancer cell models, the presence of a dysregulated circuit-namely, NFκB/SNAIL/YY1/RKIP/PTEN-that plays a major role in the regulation of tumor cell unique characteristics just listed for autophagy-regulated activities. Accordingly, the autophagic mechanism and the dysregulated circuit in cancer cells share many of the same properties and activities. Thus, it has been hypothesized that there must exist a biochemical/molecular link between the two. The present review describes the link and the association of each gene product of the dysregulated circuit with the autophagic mechanism and delineates the presence of crosstalk. Crosstalk between autophagy and the dysregulated circuit is significant and has important implications in the development of targeted therapies aimed at either autophagy or the dysregulated gene products in cancer cells.


Buprenorphine management: a conundrum for the anesthesiologist and beyond - a one-act play.
We have witnessed a worldwide upsurge of streamlined enhanced recovery after surgery (ERAS) pathways advocating for consistency and compliance within their guidelines. At a recent national conference, two experts defended their institutional policies on perioperative management of buprenorphine, one defending its continuation, while the other suggesting its discontinuation. The moderator diplomatically proclaimed the need to have guidance at the institutional level and following it for favorable patient outcomes. Unfortunately, perioperative management of buprenorphine remains an understudied topic with a lack of national guidelines leading to variations at a local level despite its increased use nationally in the current opioid crisis. Although the moderator made a valid statement, we demonstrate via our one-act play the importance of recognizing a subset of the population within an ERAS pathway that necessitates multidisciplinary discussion, communication, and patient-centric care to formulate a perioperative plan coordinating a patient's care. More robust research is needed to minimize variability in current practices and to further develop comprehensive evidence-based guidelines that encompass risk factors and anticipated postsurgical and peripartum pain for patients on buprenorphine.


An Australian experience of managing pressure ulcers in persons with SCI.
Pressure ulcers are a difficult and complex problem, frequently resulting in poor patient outcomes and significantly increased cost of care. This project evolved from a desire to improve the management and subsequent outcomes for persons with spinal cord injury (SCI) who experience pressure ulcers acquired in the community. The vast body of work related to pressure ulcers has focused on risk assessment and prevention. However, there has been little interest in the management of prevailing pressure ulcers. Using a retrospective case history audit and interviews with patients and health care workers from an Australian spinal services unit, current practices associated with the care of pressure ulcers are described. A number of issues are identified that relate to funding, diet, attitudes, consistency of care, and low levels of staff interest in pressure ulcer management. This work provides baseline data from which current management practices can be reviewed, revised, and empirically evaluated.


Protein effective rotational correlation times from translational self-diffusion coefficients measured by PFG-NMR.
Molecular rotational correlation times are of interest for many studies carried out in solution, including characterization of biomolecular structure and interactions. Here we have evaluated the estimates of protein effective rotational correlation times from their translational self-diffusion coefficients measured by pulsed-field gradient NMR against correlation times determined from both collective and residue-specific (15)N relaxation analyses and those derived from 3D structure-based hydrodynamic calculations. The results show that, provided the protein diffusive behavior is coherent with the Debye-Stokes-Einstein model, translational diffusion coefficients provide rapid estimates with reasonable accuracy of their effective rotational correlation times. Effective rotational correlation times estimated from translational diffusion coefficients may be particularly beneficial in cases where i) isotopically labelled material is not available, ii) collective backbone (15)N relaxation rates are difficult to interpret because of the presence of flexible termini or loops, or iii) a full relaxation analysis is practically difficult because of limited sensitivity owing to low protein concentration, high molecular mass or low temperatures.


Ultrastructure of the peripheral zone of a Glugea-induced xenoma.
The Glugea stephani-induced xenoma in the winter flounder, Pseudopleuronectes americanus, is a large spherical host-parasite complex, up to 4.0 mm in diameter, with the host and parasite components of the xenoma being most active in the peripheral zone. The xenoma has an extensive periodic acid-silver methenamine-positive surface coat covering the plasma membrane. The surface of this membrane is amplified by the presence of numerous folds and fine tubular extensions. The peripheral zone of the xenoma contains many host-cell mitochondria in addition to numerous microsporidan parasites. At the ultrastructural level, the peripheral zone of the host-cell cytoplasm appears normal. Inside the peripheral region of the 0.4-1.0 mm xenoma, the host-cell component largely disintegrates in the presence of microsporidan parasites undergoing sporogenesis.


Natural products and diabetes treatment.
Many natural products are promoted to improve the health status of patients with diabetes by people making a profit on these products. Few of these claims have any scientific basis. Certain natural products are potentially damaging to patients with chronic diseases, especially if the products are used instead of proven scientific treatment regimens. Many individuals believe that if a product is natural it must be effective and safe. What is ironic is that if the products were safe and effective, and if studies would have been done on humans to prove safety and effectiveness, the sales of the products would greatly increase (as opposed to present limited sales as herbs from health food stores). Some of the products do have a beneficial effect, especially as a placebo if the patient believes that the product is going to work. As can be seen from the summary of products that are listed here that claim to improve the treatment of patients with diabetes, very few are available in a standard form that would produce a known positive effect. The few products that do have a mild impact on lowering blood glucose levels are much less effective than standard treatments. In a recent review of the role of plant-derived drugs and herbal medicines in healthcare, no natural products were listed as having a beneficial effect on diabetes. Diabetes care providers need to confront the issue of the use of natural products with their patients. Patients should be taught the importance of using proven, effective treatment regimens. Any patient who decides to use a natural product should be followed closely to make sure that no toxic effects occur and that treatment objectives are achieved.


Integrating community-based health promotion programs and primary care: a mixed methods analysis of feasibility.
Implementation of evidence-based programs (EBPs) for disease self-management and prevention is a policy priority. It is challenging to implement EBPs offered in community settings and to integrate them with healthcare. We sought to understand, categorize, and richly describe key challenges and opportunities related to integrating EBPs into routine primary care practice in the United States. As part of a parent, participatory action research project, we conducted a mixed methods evaluation guided by the PRECEDE implementation planning model in an 11-county region of Southeast Minnesota. Our community-partnered research team interviewed and surveyed 15 and 190 primary care clinicians and 15 and 88 non-clinician stakeholders, respectively. We coded interviews according to pre-defined PRECEDE factors and by participant type and searched for emerging themes. We then categorized survey items-before looking at participant responses-according to their ability to generate further evidence supporting the PRECEDE factors and emerging themes. We statistically summarized data within and across responder groups. When consistent, we merged these with qualitative insight. The themes we found, "Two Systems, Two Worlds," "Not My Job," and "Seeing is Believing," highlighted the disparate nature of prescribed activities that different stakeholders do to contribute to health. For instance, primary care clinicians felt pressured to focus on activities of diagnosis and treatment and did not imagine ways in which EBPs could contribute to either. Quantitative analyses supported aspects of all three themes, highlighting clinicians' limited trust in community-placed activities, and the need for tailored education and system and policy-level changes to support their integration with primary care. Primary care and community-based programs exist in disconnected worlds. Without urgent and intentional efforts to bridge well-care and sick-care, interventions that support people's efforts to be and stay well in their communities will remain outside of-if not at odds with-healthcare.


Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry.
Risk of bias (ROB) may threaten the internal validity of a clinical trial by distorting the magnitude of treatment effect estimates, although some conflicting information on this assumption exists. The objective of this study was evaluate the effect of ROB on the magnitude of treatment effect estimates in randomized controlled trials (RCTs) in periodontology and implant dentistry. A search for Cochrane systematic reviews (SRs), including meta-analyses of RCTs published in periodontology and implant dentistry fields, was performed in the Cochrane Library in September 2014. Random-effect meta-analyses were performed by grouping RCTs with different levels of ROBs in three domains (sequence generation, allocation concealment, and blinding of outcome assessment). To increase power and precision, only SRs with meta-analyses including at least 10 RCTs were included. Meta-regression was performed to investigate the association between ROB characteristics and the magnitudes of intervention effects in the meta-analyses. Of the 24 initially screened SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the meta-analyses. Three SRs (two from periodontology field) generated information for conducting 27 meta-analyses. Meta-regression did not reveal significant differences in the relationship of the ROB level with the size of treatment effect estimates, although a trend for inflated estimates was observed in domains with unclear ROBs. In this sample of RCTs, high and (mainly) unclear risks of selection and detection biases did not seem to influence the size of treatment effect estimates, although several confounders might have influenced the strength of the association.


Hemodynamic effects of anesthesia in patients with ischemic heart failure chronically treated with angiotensin-converting enzyme inhibitors.
Anesthesia may induce hemodynamic instability in patients treated with angiotensin-converting enzyme inhibitors (ACEIs). To assess the hemodynamic effects of anesthesia in patients treated (n = 9) or not treated (n = 9) with ACEIs for ischemic left ventricle dysfunction after myocardial infarction, we studied 18 patients scheduled for elective coronary artery bypass graft surgery. Induction of anesthesia with fentanyl (5 micrograms/kg), flunitrazepam (30 micrograms/kg), and pancuronium (100 micrograms/kg) was followed by a significant decrease in mean arterial blood pressure in both groups (-18.6% +/- 8.1% in controls and -25.7% +/- 7.8% in ACEI-treated patients, P = 0.01). In controls, cardiac index and systemic vascular resistance were not significantly altered (-11.2% +/- 9.4% and -16.2% +/- 4.6%, respectively, not significant [NS]). In ACEI-treated patients, cardiac index decreased significantly (-27.3% +/- 11.6%, P = 0.01 from baseline and P = 0.03 when compared with controls), and systemic vascular resistance was unchanged (1.0% +/- 18.7%, NS from baseline and P = 0.04 when compared with controls). Two patients from each group experienced a transient severe hypotensive episode. ACEI treatment in patients with infarction-induced myocardial dysfunction does not increase the incidence of severe hypotension after induction of anesthesia.


[Preventive administration of new UDCA derivatives in experimental alcoholic steatohepatitis].
We have studied the prophylactic effect of new derivatives of ursodeoxycholic acid (UDCA), including UDCA-N-acetylcysteine, UDCA-L-acetylcysteine, and nor-UDCA (in doses equivalent to 40 mg/kg of UDCA) on the development of experimental alcoholic steatohepatitis induced by the Lieber-DeCarli liquid ethanol-containing diet. Results demonstrated that most of the investigated compounds produced a hepatoprotective effect, improving biochemical tests and liver morphology, as manifested by decreasing steatosis intensity, activity of alkaline phosphatase and gamma-glutamyltranspeptidase, triglyceride level in blood serum and liver, and TNF alpha content. However, nor-UDCA was most effective as compared to UDCA in preventing the accumulation of triglycerides in the liver.


[Clinical efficacy of aztreonam in patients with complicated urinary tract infections].
Aztreonam (AZT) (2 g daily) was intravenously administered for 5 to 7 days to 65 patients with complicated urinary tract infections (UTI). Ninety one organisms were isolated from these patients' urine. Among them 66 organisms were eliminated following AZT administration. The elimination rate for Gram negative organisms was 94.7% and that for Gram positive organisms was 33.3%. Thirty one organisms appeared newly by the replacement of organisms. Among them, 12 organisms were E. faecalis. The efficacy rate of AZT in single infection and in mixed infection was 55.8% and 13.7%, respectively. The overall clinical efficacy rate of AZT in the present study was 41.5%. As side effects, skin rash and itching were observed in 3 patients and slight elevations in blood chemistry were observed in 10 patients. The results indicate that AZT is an effective drug for the treatment of patients with complicated UTI, especially those caused by Gram negative organisms.


Endoscopic treatment of Zenker's diverticulum by complete septotomy: initial experience in 19 patients.
Background and study aims Endoscopic treatment of Zenker's Diverticulum (ZD) using a flexible endoscope and a diverticuloscope consists of myotomy of the cricopharyngeus muscle, sparing the lower part of the diverticular septum. However, recurrence occurs in up to 54 % of patients at 4 years. We assessed the feasibility and safety of a complete septotomy in endoscopic treatment of ZD. Patients and methods We conducted a retrospective analysis of a prospectively collected database at a single referral center. All consecutive patients treated by complete resection of the diverticular wall were included. The endoscopic technique used a distal attachment cap and division of the ZD septum using a Dual Knife or a Triangle Tip knife in endocut mode, until the esophageal muscularis propria was seen and no residual diverticulum remained. Symptoms were evaluated using the Augsburger questionnaire. Results Nineteen patients, 10 of whom were men with mean age 79 ± 12 years, were treated by complete septotomy for a symptomatic ZD with a median size of 2.5 cm (range 1-5 cm). The clinical success rate was 100 % and the complication rate was 10 % (one pneumonia and one atrial fibrillation). Median hospital stay was 2 days (range 1-3 days). On Day 1 esophagogram, no extraesophageal contrast leakage was seen, periesophageal CO 2 was still visible in two patients, and complete ZD regression was seen in 63 % of patients. The 6-month clinical success rate was 100 %, with two patients lost to follow-up, and a median symptom score of 0 (range 0-4). After a mean ± SD follow-up of 9 ± 5 months, the clinical success rate was 94 % (16/17). Conclusion Complete endoscopic septotomy is a feasible and safe therapeutic modality in patients with symptomatic ZD that does not require use of a diverticuloscope, and with good short-term efficacy. The complete regression of the diverticulum observed on Day 1 in 63 % of patients could be a marker of long-term clinical success.


miR-122, a mammalian liver-specific microRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1.
These studies show that miR-122, a 22-nucleotide microRNA, is derived from a liver-specific noncoding polyadenylated RNA transcribed from the gene hcr. The exact sequence of miR-122 as well as the adjacent secondary structure within the hcr mRNA are conserved from mammalian species back to fish. Levels of miR-122 in the mouse liver increase to half maximal values around day 17 of embryogenesis, and reach near maximal levels of 50,000 copies per average cell before birth. Lewis et al. (2003) predicted the cationic amino acid transporter (CAT-1 or SLC7A1) as a miR-122 target. CAT-1 protein and its mRNA are expressed in all mammalian tissues but with lower levels in adult liver. Furthermore, during mouse liver development CAT-1 mRNA decreases in an almost inverse correlation with miR-122. Eight potential miR-122 target sites were predicted within the human CAT-1 mRNA, with six in the 3'-untranslated region. Using a reporter construct it was found that just three of the predicted sites, linked in a 400-nucleotide sequence from human CAT-1, acted with synergy and were sufficient to strongly inhibit protein synthesis and reduce mRNA levels. In summary, these studies followed the accumulation during development of miR-122 from its mRNA precursor, hcr, through to identification of what may be a specific mRNA target, CAT-1.


Rendering Molecular Sketches for Publication Quality Output.
The creation of 2D molecular structure diagrams that make full use of the capabilities of modern display systems, using only input data expressed in file formats used for cheminformatics, is a complex task that requires a number of additional algorithms. Assuming that atom positions have been well chosen, the rendering engine is required to micromanage the precise positioning of atom labels, bonds and atom adjuncts, in such a way that the final output is correct, consistent with convention, and as pleasing to the eye as a diagram produced by a graphic designer. The techniques must be equally applicable when creating output for low-resolution screens and high resolution printed output, and make use of contemporary graphics file formats in such a way that the largest possible number of software platforms are able to display the output at any resolution without degradation or inconsistency. The main issues involved in meeting these criteria are discussed, and algorithms for satisfying them are presented.


Synthesis, conformational analysis, and antiarrhythmic properties of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one, 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate, and 7-benzyl-9-phenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ol hydroperchlorate and derivatives: single-crystal X-ray diffraction analysis and evidence for chair-chair and chair-boat conformers in the solid state.
The synthesis of the title ketone has been completed via a type of Mannich reaction starting from 4- thianone . An X-ray diffraction analysis has revealed that the solid system is a chair-boat conformer with the sulfur atom in the boat portion of the bicyclic ring compound. Wolff- Kishner reduction of the ketone group gave 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane, which was isolated as the hydroperchlorate . However, X-ray diffraction analysis of the salt showed this solid to be a chair-chair conformer. Addition of phenylmagnesium bromide to the ketone gave a tertiary alcohol with the C-C6H5 bond being equatorial with respect to the thiane ring and axial with respect to the piperidine ring. The reaction of the Grignard reagent with the ketone to give this alcohol seems to be very stereospecific. An X-ray analysis of the hydroperchlorate of the alcohol confirmed the system to be a chair-chair form in the solid. The title compounds were screened for antiarrhythmic activity in anesthetized mongrel dogs in which myocardial infarctions had been created when the left anterior descending coronary artery was ligated. Vagal-induced slowing of the sinus mode firing rate was used to determine the underlying ventricular automaticity in the dogs, which averaged 164 +/- 27 beats/min. Ventricular pacing was initiated to rates between 240 and 390/min. This technique resulted in the induction of rapid and sustained ventricular tachycardia. At doses of 3 and 6 mg/kg of body weight, 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane hydroperchlorate in alcohol (the solution was administered intravenously) was able to suppress markedly the induced ventricular tachycardia in five of six dogs. The compound also caused a 10-15% increase in blood pressure within a few minutes. The antiarrhythmic properties of this compound and others of related structure are discussed, and some comparison is made with the action of lidocaine in similar dog preparations.


Engineering plants for a changing climate.
Climate change is affecting the types of plant varieties we can cultivate, as well as how and where we can do so. A new collection of articles explores the twin challenges of engineering plants for resilience to climate change and enhancing their carbon-capture potential.


Raman spectroscopy using plasmonic and carbon-based nanoparticles for cancer detection, diagnosis, and treatment guidance. Part 2: Treatment.
Raman spectroscopy and surface-enhanced raman scattering (SERS) have the potential to improve the detection and monitoring of various diseases, particularly cancer, with or without the support of multifunctional active nanosystems. This review is focused on the recent advances that have made Raman a major tool for treatment guidance for surgical tumor resection or for analytical monitoring of various therapies, such as photodynamic therapy, photothermal therapy, and drug delivery. The potential of Raman spectroscopy and nanosytems to further improve cancer treatments is also discussed.


Laparoscopic versus open major hepatectomy: a systematic review and meta-analysis of individual patient data.
The role of laparoscopy for major hepatectomies remains a matter of development to be further assessed. The purpose of this study is to compare the short- and long-term outcomes between laparoscopic and open major hepatectomies meta-analyzing individual patient data from published comparative studies. All retrospective studies comparing between laparoscopic and open major hepatectomies published until March 2017 were identified independently by 2 reviewers by searching in PubMed and Cochrane Central Register of Controlled Trials. Individual patient data were sought from all selected studies. Postoperative outcomes, including intraoperative blood loss, operative time, hospital stay, postoperative complications, mortality rates, and long-term survival were analyzed. A total of 917 patients were divided into the laparoscopic (427) and open (490) groups from 8 selected studies. The hospital stay was significantly shorter, and the total morbidity was lower in the laparoscopic group. When classified by severity, the incidence of postoperative minor complications was lower; however, that of major complications was not significantly different. The operative time was longer in the laparoscopic group; however, intraoperative blood loss, perioperative mortality, and blood transfusions were comparable between the 2 groups. The overall survival in the patients with colorectal liver metastases and hepatocellular carcinoma was not significantly different between the 2 groups. Laparoscopic major hepatectomies offer some perioperative advantages, including fewer complications and shorter hospital stay, without increasing the blood loss volume and mortality. Whether these results can anticipate the outcomes in future randomized controlled trials has not been determined.


Effects of 5-hydroxytryptamine on the short-circuit current across the small intestine of the gerbil (Gerbillus cheesmani) in different dietary states.
The effects of serosally added 5-hydroxytryptamine (5-HT, 100 microM) on the short circuit-current (Isc) across jejunum and ileum taken from fed, starved and undernourished (Gerbillus cheesmani) were investigated. The effects of the neurotoxin, tetrodotoxin (TTX, 10 microM) on the basal Isc as well as on the maximum increase in Isc induced by 5-HT were also studied. There were regional variations in the basal Isc as well as in the way by which the small intestine responds to 5-HT. The basal Isc was greater in jejunum than in ileum and such differences were TTX-sensitive. The maximum increase in Isc, which results from addition of 5-HT, was higher in jejunum than in ileum under all three feeding conditions. TTX reduced the maximum increase in Isc induced by 5-HT across stripped and intact intestine of the two regions in the three nutritional states. The 5-HT-induced Isc in the jejunum of both starved and undernourished gerbils and in the ileum of starved animals was the function of both submucosal and myenteric plexus. In jejunum and ileum taken from starved and undernourished gerbils the 5-HT-induced Isc was both chloride- and bicarbonate-dependent. Thus the results indicated that both starvation and undernourishment increase that response and such increases were TTX-sensitive and both chloride- and bicarbonate-dependent.


Perinatal outcomes associated with intrahepatic cholestasis of pregnancy.
The objective of this study is to examine perinatal outcomes associated with cholestasis of pregnancy according to bile acid level and antenatal testing practice. Retrospective cohort study of women with symptoms and bile acid testing from 2005 to 2014. Women were stratified by bile acid level: no cholestasis (<10 μmol/L), mild (10-39 μmol/L), moderate (40-99 μmol/L), and severe (≥100 μmol/L). The primary outcome was composite neonatal morbidity (hypoxic ischemic encephalopathy, severe intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, or death). 785 women were included; 487 had cholestasis (347 mild, 108 moderate, 32 severe) and 298 did not. After controlling for gestational age (GA), severe cholestasis was associated with the composite neonatal outcome (aRR 5.6, 95% CI 1.3-23.5) and meconium-stained fluid (aRR 4.82, 95%CI 1.6-14.2). Bile acid levels were not correlated with the frequency of testing (p = .50). Women who underwent twice weekly testing were delivered earlier (p = .016) than women tested less frequently, but the difference in GA was ≤4 d. Abnormal testing prompting delivery was uncommon. Among women with cholestasis, there were three stillbirths. One of these women was undergoing antenatal testing, which was normal 1 d prior to the fetal demise. Severe cholestasis is associated with neonatal morbidity which antenatal testing may not predict.


Achondroplasia and multiple-suture craniosynostosis.
Genetic mutations in the fibroblast growth factor receptor 3 gene may lead to achondroplasia or syndromic forms of craniosynostosis. Despite sharing a common genetic basis, craniosynostosis has rarely been described in cases of confirmed achondroplasia. We report an infant with achondroplasia who developed progressive multiple-suture craniosynostosis to discuss the genetic link between these clinical entities and to describe the technical challenges associated with the operative management.


Development of a Multichannel Dialysis Microchip for Bioassay of Drug Efficacy and Retention.
Here, we developed a multichannel dialysis microchip having three sets of dialysis systems, which consisted of three independent circulation channels with a common micropump. Each dialysis system was composed of a pneumatic micropump (heart), dialysis unit (renal corpuscle), and cell culture chamber (drug target) as well as circulation and dialysate channels to mimic the circulation system. Small molecules were successfully separated in parallel from macromolecules at the dialysis components. Anticancer tests using this microchip showed results that considered both serum protein-binding nature and drug activity. In the anticancer bioassay, the multichannel chip showed similar reproducible and reliable results as those of the single-channel system but with higher throughput.


Seizure prediction: the long and winding road.
The sudden and apparently unpredictable nature of seizures is one of the most disabling aspects of the disease epilepsy. A method capable of predicting the occurrence of seizures from the electroencephalogram (EEG) of epilepsy patients would open new therapeutic possibilities. Since the 1970s investigations on the predictability of seizures have advanced from preliminary descriptions of seizure precursors to controlled studies applying prediction algorithms to continuous multi-day EEG recordings. While most of the studies published in the 1990s and around the turn of the millennium yielded rather promising results, more recent evaluations could not reproduce these optimistic findings, thus raising a debate about the validity and reliability of previous investigations. In this review, we will critically discuss the literature on seizure prediction and address some of the problems and pitfalls involved in the designing and testing of seizure-prediction algorithms. We will give an account of the current state of this research field, point towards possible future developments and propose methodological guidelines for future studies on seizure prediction.


Preimplantation diagnosis for aneuploidies in assisted reproduction.
At least one half of oocytes and preimplantation embryos are aneuploid and have to be avoided from transfer in in vitro fertilization (IVF) patients of advanced reproductive age. This can now be done by preimplantation genetic diagnosis, which has recently become an integral part of assisted reproduction technologies and was shown to improve implantation rate and reduce spontaneous abortions after implantation. The experience of approximately 5000 preimplantation genetic diagnosis (PGD) cycles performed for poor prognosis IVF patients have already resulted in birth of approximately 1000 apparently healthy children, suggesting that this novel technique is safe and reliable, and may in future replace the current IVF practice of preselection of embryos for transfer based on morphological parameters.


Termination of photorefractoriness in golden hamsters-photoperiodic requirements.
The photorefractory period of golden hamsters is characterized by the failure of short daylengths (less than 12.5 hours per 24) to induce gonadal regression. Photorefractoriness is terminated by prolonged exposure to long daylengths (greater than 12.5 hours per 24). This study was designed to determine the precise duration of long day (LD 14 hours light/24) exposure necessary to terminate refractoriness. The data indicate that 11 weeks of LD 14:10 terminate refractoriness in nearly every hamster. Exposure for fewer than 11 weeks is less effective whereas exposure for more than 11 weeks is no more effective. The data show that hamsters begin measuring long days to terminate photorefractoriness irrespective of the physiological state of the reproductive system, and, therefore, that photorefractoriness is induced some time during the period of testicular regression (during the first 10-12 weeks of short day exposure).


Immediate Implants: Clinical Guidelines for Esthetic Outcomes.
Research has shown that tooth loss results in morphological changes in alveolar ridge that may influence the subsequent implant placement. Immediate implant placement was introduced as a possible means to limit bone resorption and reduce the number of surgical procedures following tooth extraction. Histological and clinical evidence from human clinical studies showing efficacy of immediate implants has come to light over the last decade or so. However, immediate implant placement is a challenging surgical procedure and requires proper case selection and surgical technique. Furthermore, there appears to be a lack of clinical guidelines for immediate implant placement case selection. Therefore, the aim of this mini-review is to analyze critical evidence from human studies in order to establish clinical guidelines which may help clinicians in case selection when considering immediate implant placement protocol.


Late Emergence of an Imatinib-Resistant ABL1 Kinase Domain Mutation in a Patient with Chronic Myeloid Leukemia.
The introduction of the tyrosine kinase inhibitor (TKI) imatinib has revolutionised the outlook of chronic myeloid leukemia (CML); however, a significant proportion of patients develop resistance through several mechanisms, of which acquisition of ABL1 kinase domain mutations is prevalent. In chronic-phase patients, these mutations become evident early in the disease course. A case is described of a chronic-phase CML patient who achieved a sustained, deep molecular response but who developed an Y253H ABL1 kinase domain mutation nearly nine years after commencing imatinib. Switching therapy to bosutinib resulted in a rapid reachievement of a major molecular response. Long-term TKI treatment impacts on quality of life and late losses of responses are usually due to lack of adherence. This case highlights the requirement for ABL1 kinase domain mutation analysis in those CML patients on long-term imatinib who lost their molecular response, regardless of whether nonadherence is suspected.


[Houttuynia Cordata induces expression of human beta-defensin-2 mRNA in pulmonary epithelial cells in vitro].
To explore the effects of Houttuynia Cordata on expression of human beta-defensin-2 (HBD-2) in pulmonary epithelial cells (SPC-A-1) in vitro; and to observe the correlationship between the level of HBD-2 mRNA and the concentrations or treatment times of Houttuynia Cordata. The SPC-A-1 cells were cultured with different concentrations of Houttuynia Cordata in vitro, including 0, 12.5, 25, 50, 100 and 200 microg/ml. And then, the SPC-A-1 cells were cultured with the optimal concentration of Houttuynia Cordata in different lengths of time, including 1, 2, 4, 8, 16 and 24 hours. After the treatment, the mRNA level of HBD-2 in pulmonary epithelial cells was detected by means of semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). After being cultured with Houttuynia Cordata, the expression of HBD-2 mRNA had positive correlation with the stimulus concentrations (rs=0.829, P=0.042) and stimulus time (rs=0.914, P=0.003). The highest expression of HBD-2 mRNA was induced by 100 microg/ml Houttuynia Cordata after 8-hour treatment. In comparison with the normal control group and the interleukin-1beta group, 100 microg/ml Houttuynia Cordata could significantly up-regulate the expression of HBD-2 mRNA in SPC-A-1 cells after 8-hour treatment (P<0.01). Houttuynia Cordata can up-regulate expression of HBD-2 mRNA in SPC-A-1 cells, and the highest expression level of HBD-2 mRNA can be obtained by culture with 100 microg/ml Houttuynia Cordata for 8 hours.


Interleukin-1β accelerates the onset of stroke in stroke-prone spontaneously hypertensive rats.
High blood levels of inflammatory biomarkers and immune cells in stroke lesions have been recognized as results of stroke. However, recent studies have suggested that inflammation occurs prior to stroke onset. In this study, we aimed to clarify the role of inflammation in stroke onset among stroke-prone spontaneously hypertensive rats (SHRSP). At 4 weeks of age (before stroke onset), the plasma level of IL-1β was significantly higher in SHRSP (153.0 ± 49.7 pg/ml) than in Wistar Kyoto rats (WKY) (7.7 ± 3.4 pg/ml, P < 0.001 versus SHRSP) or spontaneously hypertensive rats (SHR) (28.0 ± 9.1 pg/ml, P < 0.001 versus SHRSP) (n = 6 per strain). Stimulated IL-1β signal was also observed in cerebrovascular endothelial cells of SHRSP. Gene expressions of IL-1β, IL-1 receptors, caspase-1, and downstream genes (MCP-1 and ICAM-1), which associated with immune cell recruitment, were significantly greater in SHRSP than in WKY or SHR, coincident with greater NFκB protein levels in SHRSP compared to WKY or SHR. In addition, continuous administration of IL-1β (2 μg/day) using an osmotic pump slightly increased the incidence of stroke in SHR (P = 0.046) and significantly accelerated the onset of stroke in SHRSP (P = 0.006) compared to each control (n = 10 per group). These results suggest that a stimulated IL-1β signal might be a cause of stroke onset when concomitant with severe hypertension.


[Immunoglobulin therapy].
Kawasaki disease(KD) is an acute, self-limited vasculitis of unknown etiology that predominantly affects infants and children. Coronary artery(CA) aneurysms, the most severe complication, occur in 25 % of untreated children and may lead to ischemic heart disease, myocardial infarction, or sudden death. While a single high dose of intravenous immunoglobulin (IVIG) terminates the fever and acute inflammation in most subjects and dramatically reduces the incidence of CA aneurysms, 10 to 20 % of KD patients are IVIG- resistant and these subjects are at higher risk of developing CA abnormalities. Several mechanisms have been reported for the anti-inflammatory activity of IVIG in different disease states. In this review, we describe the clinical utility and these mechanisms of IVIG in KD.


Time-Resolved Proteomic Visualization of Dendrimer Cellular Entry and Trafficking.
Our understanding of the complex cell entry pathways would greatly benefit from a comprehensive characterization of key proteins involved in this dynamic process. Here we devise a novel proteomic strategy named TITAN (Tracing Internalization and TrAfficking of Nanomaterials) to reveal real-time protein-dendrimer interactions using a systems biology approach. Dendrimers functionalized with photoreactive cross-linkers were internalized by HeLa cells and irradiated at set time intervals, then isolated and subjected to quantitative proteomics. In total, 809 interacting proteins cross-linked with dendrimers were determined by TITAN in a detailed temporal manner during dendrimer internalization, traceable to at least two major endocytic mechanisms, clathrin-mediated and caveolar/raft-mediated endocytosis. The direct involvement of the two pathways was further established by the inhibitory effect of dynasore on dendrimer uptake and changes in temporal profiles of key proteins.


Molecular identification of Anaplasma platys in cattle by nested PCR.
Anaplasmosis is a zoonotic disease caused by Gram-negative bacterium from Anaplasmataceae family. Anaplasma causes high economic losses worldwide. 16S rRNA analysis was used to diagnose Anaplasma platys in Cattle. Phylogenetic tree and estimation of evolutionary divergence between A. platys isolates were performed. A total of 60 blood samples were collected from a cattle farm in AL-Diwaniyah province. 16S rRNA gene was identified using nested PCR. Overall, 40% of cattle that were chosen to collect the blood were identified to be infected with A. platys. The results have shown presence of targeting partial region of 16S rRNA gene in 24 samples out of 60. Sequencing results of 10 samples have revealed that the phylogenetic tree was divided in to two separate clades. Five isolates of A. platys-Iraq (accession no. OP646782, OP646783, OP646784, OP646790, and OP646791) were located in one clade with the A. platys-China (accession no. MN193068.1). While, five isolates (accession no. OP646785, OP646786, OP646787, OP646788, OP646789) were in different clade with two isolates of A. platys-Africa and A. platys-Zambia in distinct branches, close to the Rickettsiales. The phylogenetic study of A. platys sequences indicated that the isolates were collected from a cattle farm in Al-Dewaniyah were similar and close related to A. platys-China, A. platys-Zambia and A. platys-Africa). This study suggests that cattle can be considered a reservoir of A. platys.


Blood flow in obstetrics using Doppler ultrasound.
We describe the history of obstetric blood flow research in the human fetal circulation (1978-1982) using both continuous wave (CW) Doppler and pulsed (PW) Doppler with linear array scanning. After the initial work (mainly in Ireland, Australia, Sweden, The Netherlands and the UK) it was recognized that CW Doppler velocity waveforms were of diagnostic significance and yielded as much useful clinical information as more complex PW duplex systems. PW duplex continues to be a useful research tool where accurate Doppler sampling or mean velocity measurement is required. The measurement of fetal Doppler velocity waveforms is clinically useful in the evaluation of the 'small-for-dates' fetus and abnormalities of cardiac anatomy or rhythm. Simple CW pencil probe study of the maternal utero-placental vasculature distinguishes normal from abnormal placentation and may be useful as a screening test to predict hypertensive disease of pregnancy.


Methodologies for Quantitative Systems Pharmacology (QSP) Models: Design and Estimation.
With the increased interest in the application of quantitative systems pharmacology (QSP) models within medicine research and development, there is an increasing need to formalize model development and verification aspects. In February 2016, a workshop was held at Roche Pharma Research and Early Development to focus discussions on two critical methodological aspects of QSP model development: optimal structural granularity and parameter estimation. We here report in a perspective article a summary of presentations and discussions.


Draft Genome Sequence of Vibrio penaeicida Strain TUMSAT-NU1, Isolated from Diseased Shrimp in Japan.
Vibrio penaeicida is a bacterial pathogen of cultured shrimp. The draft genome sequence of V. penaeicida strain TUMSAT-NU1 consists of 100 scaffolds with a total of 6.41 Mbp. We identified possible virulence factors, and we found that V. penaeicida and Vibrio nigripulchritudo are closely related.


[The use of efferent methods in the combined treatment of pyelonephritis in pregnant women].
After-treatment immune effects of therapy were assessed in 57 pregnant females with pyelonephritis. Eleven patients received standard antibacterial treatment (ABT), 25 patients ABT plus plasmapheresis, 21 patients underwent UV irradiation of blood and ABT. ABT alone resulted in improved general condition of the patients, in reduced renal inflammation, but it failed to remove completely signs of immunodeficiency, B-lymphocyte and Ig levels remained low. The combined treatment with UV blood irradiation and plasmapheresis promoted rapid disappearance of clinical and laboratory evidence indicating pyelonephritis. UV irradiation could not correct deficiency of cellular immunity, while adjuvant plasmapheresis led to a complete cure of immune deficiency symptoms.


Morphologic changes induced by neoadjuvant androgen ablation may result in underdetection of positive surgical margins and capsular involvement by prostatic adenocarcinoma.
Neoadjuvant androgen ablation (NAAA) causes significant cytoarchitectural changes in both benign and malignant prostatic epithelial cells that may contribute to underdetection of prostate cancer capsular involvement and positive surgical margins. The aim of this study is to determine the ability of cytokeratin immunohistochemistry to enhance the determination of pathologic stage of prostate cancer following NAAA. Cytokeratin AE1/AE3 immunohistochemistry identified 6 (27.3%), 15 (68.2%), 5 (22.7%), and 5 (22.7%) cases of organ-confined disease, capsule penetration, positive surgical margin, and seminal vesicle involvement, respectively, as compared with 10 (45.5%), 10 (45.5%), 3 (13.6%), and 5 (22.7%) cases by hematoxylin-eosin (H&E) staining, respectively. Two cases without detectable tumor by H&E staining had demonstrable residual tumor by cytokeratin immunohistochemical staining. Cytokeratin immunohistochemistry revealed more extensive intracapsular, capsular, and extracapsular tumor involvement and higher rate of positive surgical margin than did conventional H&E staining. Therefore, the beneficial pathologic effects of NAAA observed may, in part, be attributable to the artifact of observation.


[A case of advanced hepatocellular carcinoma with lung metastases and cirrhosis that responded to combination chemotherapy with interferon-alpha and 5-fluorouracil].
The prognosis for patients with hepatocellular carcinoma (HCC) with progressive liver cirrhosis or extrahepatic metastases remains dismal. We report a case of HCC with liver cirrhosis and lung metastases who had been treated successfully by combination chemotherapy of 5-fluorouracil (5-FU) and interferon-alpha (IFN-alpha). A 67-year-old male with a history of hepatitis C, liver cirrhosis and HCC was hospitalized because of cough and dyspnea. Computed tomography (CT) of chest revealed multiple lung metastases. Systemic combination chemotherapy with 5-FU and IFN-alpha was begun, and lung metastases disappeared after one course of treatment. He died of liver failure one year later, but no recurrence of lung metastases was seen. Although systemic combination chemotherapy of 5-FU and IFN-alpha induced the bone marrow suppression, it was effective for lung metastases and palliates symptoms and signs in our case of HCC.


Measuring lupus arthritis activity using contrasted high-field MRI. Associations with clinical measures of disease activity and novel patterns of disease.
Arthritis in SLE is poorly described, and there is no objective measure for quantification of arthritis. In this pilot study, we aim to assess the utility of the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for the quantification of lupus arthritis. Patients were eligible for entry into the study if they were evaluated at the Medical University of South Carolina Lupus Center and determined by their treating rheumatologist to have active hand arthritis due to SLE. Standard of care lupus activity measures were collected, along with a detailed physical exam. MRIs were obtained using standard musculoskeletal sequences with gadolinium contrast. Semiquantitative scoring of the images used the Outcome Measures in Rheumatology Clinical Trials RAMRIS system. RAMRIS demonstrates large amounts of synovitis, tenosynovitis, bone marrow oedema and erosive disease in only a minority of patients. Some patients were not scored as having any synovitis or tenosynovitis. We describe potential features of lupus arthritis that are not captured in the RAMRIS scores and may be contributing to symptoms. Lupus arthritis is an entity separate from rheumatoid arthritis and requires the development of new quantitative methods to describe and quantitate it. MRI findings suggest the inadequacy of a typical lupus musculoskeletal measure including swollen/tender joint counts to assess the level of disease activity.


Pseudo-Meigs' syndrome caused by a Krukenberg tumour of gastric cancer.
A 50-year-old woman who presented with a one-month history of abdominal fullness and dyspnoea was admitted to our hospital. Esophagogastroduodenoscopy showed the scirrhous-type gastric cancer on the greater curvature of the gastric body. Computed tomography revealed bilateral large ovarian tumours with massive right pleural effusion and ascites. A repeated cytological examination of pleural effusion and ascites revealed no malignant cells. The definitive diagnosis of pseudo-Meigs' syndrome was made by confirming the fact that pleural effusion and ascites disappeared after bilateral oophorectomy. Resection of ovarian tumours may also lead to long-term survival, even in the patients with pseudo-Meigs' syndrome caused by gastric cancer.


It Suddenly Occurred: Extensive Subcutaneous Emphysema after Bipolar Transurethral Resection of Prostate.
Subcutaneous emphysema is a very rare and good-natured complication after transurethral resection of prostate (TURP). It has been reported as colon perforation, diverticulitis, and bladder perforation associated complication previously. We report the first case of a wide subcutaneous emphysema due to microperforations of prostatic capsule, without a bladder perforation after TURP. Any sign of clinic situation should lead to ceasing of the procedure immediately; otherwise, it can cause a life-threatening problem of abdominal compartment syndrome.


Behavior analysis and ecological psychology: past, present, and future. a review of Harry Heft's Ecological Psychology in context.
Relations between behavior analysis and ecological psychology have been strained for years, notwithstanding the occasional comment on their affinities. Harry Heft's (2001)Ecological Psychology in Context provides an occasion for reviewing anew those relations and affinities. It describes the genesis of ecological psychology in James's radical empiricism; addresses Holt's neorealism and Gestalt psychology; and synthesizes Gibson's ecological psychology and Barker's ecobehavioral science as a means for understanding everyday human behavior. Although behavior analysis is excluded from this account, Heft's book warrants a review nonetheless: It describes ecological psychology in ways that are congruent and complementary with behavior analysis (e.g., nonmediational theorizing; the provinces of natural history and natural science). After introducing modern ecological psychology, I comment on (a) Heft's admirable, albeit selective, historiography; (b) his ecological psychology-past and present-as it relates to Skinner's science and system (e.g., affordances, molar behavior); (c) his misunderstandings of Skinner's behaviorism (e.g., reductionistic, mechanistic, molecular); and (d) the theoretical status of Heft's cognitive terms and talk (i.e., in ontology, epistemology, syntax). I conclude by considering the alliance and integration of ecological psychology and behavior analysis, and their implications for unifying and transforming psychology as a life science, albeit more for the future than at present.


Synaptosomes containing large agranular vesicles isolated from developing rat brain.
Using the subcellular fractionation technique the fine structure of the isolated nerve endings (synaptosomes) from the hemispheres and brain stem of the 1-day old and adult rat was examined. In the synaptosomal fractions of the brain of 1-day old rats we observed a new type of nerve endings containing predominantly large agranular vesicles about 1,000 A in diameter. After incubation with alpha-methylnoradrenaline or 5-hydroxydopamine these vesicles remained agranular. It is assumed that the new type of large vesicles represent developing synaptic vesicles.


[Comparison of the in vitro activity of amoxycillin + clavulanic acid and ampicillin + sulbactam combinations against 50 Haemophilus influenzae strains producing beta lactamase].
We compared the ability of two beta lactamase inhibitors, clavulanic acid and sulbactam, to reduce the minimal inhibitory concentrations (MICs) respectively of amoxycillin and ampicillin against fifty strains of Haemophilus influenzae producing a beta lactamase. The reduction of MICs of aminopenicillins was studied using low concentrations of beta lactamase inhibitors (0.125 to 0.5 mg/l). Moreover, the synergic effect of each association was evaluated against a heavy bacterial inoculum (10(8) cfu/ml). The combination of amoxycillin + clavulanic acid was more synergic on these strains than the association of ampicillin + sulbactam.


The cGAS-STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy.
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS-STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS-STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS-STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.


Probing electronic communication in stable benzene-bridged verdazyl diradicals.
Two benzene-bridged N,N'-bis(isopropyl)6-oxoverdazyl diradicals 7a (1,4-benzene-bridged) and 7b (1,3-benzene-bridged) were prepared and studied by an array of physicochemical techniques aimed at elucidating the intramolecular electronic and magnetic coupling between verdazyl chromophores. The very high stability of these diradicals permits comprehensive investigations of their properties for the first time. The UV-vis spectra suggest negligible direct conjugative overlap involving the radical SOMOs, although significant differences in higher energy absorptions suggest that radical orbitals other than the SOMO are likely communicating via the central p-phenylene bridge in 7a. The electrochemical features of the two diradicals are nearly identical; in each derivative, both radicals are oxidized essentially independently while the reductions occur in a stepwise manner with differences of approximately 100 mV between the two reductions. EPR and magnetic susceptibility collectively indicate that the para-bridged diradical is weakly antiferromagnetically coupled while the meta analogue is weakly ferromagnetically coupled, in accord with the topology of the substitution pattern on the central benzene ring.


Cortisol binding in uremic plasma. I. Absence of abnormal cortisol binding to cortisol binding to corticosteroid-binding globulin.
Increased morning plasma free cortisol levels have been reported previously in chronic renal failure (CRF) patients. To see whether binding abnormalities of plasma proteins contributed to the increase in morning free cortisol, binding characteristics of corticosteroid-binding globulin (CBG) were studied in pooled plasma from CRF patients and normal subjects. Using an isocolloidosmolar equilibrium dialysis method the unbound, albumin-bound, and CBG-bound fractions of plasma cortisol were measured within the physiologic range of plasma cortisol levels. Cortisol binding to CBG was equal in uremic and nonuremic plasma as determined by the affinity constants and the binding capacities of CBG for cortisol. In addition, the distribution of cortisol binding was identical in uremic and in nonuremic plasma samples at equal total cortisol concentrations. By confirming that cortisol binding properties of CBG are unaltered in CRF patients, these data support the assertion that elevated morning free cortisol levels in CRF patients are probably due to increases of plasma total cortisol.


Real-time online photonic random number generation.
We present a real-time scheme for ultrafast random number (RN) extraction from a broadband photonic entropy source. Ultralow jitter mode-locked pulses are used to sample the stochastic intensity fluctuations of the entropy source in the optical domain. A discrete self-delay comparison technology is exploited to quantize the sampled pulses into continuous RN streams directly. This scheme is bias free, eliminates the electronic jitter bottleneck confronted by currently available physical RN generators, and has no need for threshold tuning and post-processing. To demonstrate its feasibility, we perform a proof-of-principle experiment using an optically injected chaotic laser diode. RN streams at up to 7 Gb/s with verified randomness were thereby successfully extracted in real time. With the provision of a photonic entropy source with sufficient bandwidth, the present approach is expected to provide RN generation rates of several tens of gigabits per second.


Ramps remain a barrier to safe wheelchair user transit bus ingress/egress.
Background: Wheelchair users (WCUs) often rely on ramps for access to transit buses. Previous studies indicate WCUs have difficulty using ramps for bus ingress/egress and many transportation-related incidents occur on ramps. However, experiences of WCU ramp usage during ingress/egress have not been fully described.Methods: Cross-sectional, internet-based survey of WCUs who ride transit buses was conducted. The participants were queried on frequency of bus usage, difficulty and incidents involving ramps, and factors contributing to difficulty and incidents. Wheelchair characteristics, primary condition, and whether participants received travel training were also captured. Chi-square was used to describe relationships between wheelchair type and frequency of difficulties and incidents, and odd ratios were used to determine likelihood of the incidents.Results: The majority (55.7%) of 384 participants reported using public transportation ≥ 1 per week. Seventy-eight percent of WCUs had ≥ 1 ramp incident over the past 3 years, with an increased likelihood of incidents occurring during ingress (OR = 1.53; CI 1.21-1.86). Of those who had an incident, 22% were injured or had damage to their wheelchair. Over 60% of those who had an incident identified steep ramp slope as being the contributing factor. Steep ramp slope, exterior ramp thresholds and wet surfaces were the most common contributing factors to difficulty using ramps.Conclusion: This is the first large-scale US study enabling WCUs to describe their experiences using transit bus ramps. Despite ADA guidelines, steep ramps remain the primary factor contributing to incidents and difficulty when using ramps to access transit buses.Implications for rehabilitationThe discrepancy between ADA maximum allowable ramp slopes for the built environment and transit buses may require an increased level of effort that is a barrier to transportation accessibility for some wheelchair users.Wheelchair users who access transit buses should be made aware of, and trained, to navigate ramp configurations found in the environment.We suggest rehabilitation therapists provide skills training specific to navigating transit bus ramp slopes that may be steeper and narrower than building ramps.


Brightness fading during Ganzfeld adaptation.
The time course and extent of brightness fading in a Ganzfeld were determined for adapting luminances ranging from 0.01 to 100 cd/m2. Magnitude estimation and interocular brightness matching were used. During Ganzfeld adaptation, perceived brightness decreased slowly and leveled off, on average, after 5-7 min (adapting time increasing with luminance). On average, the total brightness loss was equivalent to a 1.2 log unit reduction in luminance, independent of adapting luminance. The residual brightness perceived at the final plateau was generally higher than the brightness of the Eigengrau, suggesting a partially sustained luminance channel.