Validation of Andrews Analysis in the Virtual Environment.
Andrews analysis is a tool to establish the aesthetic anteroposterior position of the maxilla. Andrews analysis has not been evaluated through computer-aided surgical simulation (CASS). The purpose of this study was to evaluate the accuracy of Andrews profile analysis when performed in the virtual environment. A retrospective cohort study was implemented with consecutive patients undergoing orthognathic surgery between February 2020 and February 2022 at the University of Alabama, Birmingham. Traditional Andrews analysis with lateral smiling photographs were taken during the presurgical appointment in adjusted natural head position (aNHP). The standard cone-beam CT obtained for CASS and archived on the KLS Martin (Jacksonville, Florida) database was accessed for retrospective measurement. Lateral facial photographs in aNHP were imported into the virtual environment and the three dimensional (3D) composite model was then oriented into aNHP. The software engineer, blinded to the traditional measurements, then performed the Andrews analysis in the virtual environment by placing a vertical glabella line on the 3D composite model in aNHP. The linear horizontal distance of the maxillary central incisor perpendicular to the vertical glabella line was recorded. Method of Andrews analysis measurement (traditional photographic evaluation vs CASS) MAIN OUTCOME VARIABLE: Linear Andrews analysis measurement. Additional covariates evaluated were sex, age at surgery, and dentofacial deformity diagnosis. Descriptive statistics were computed to compare photographic analysis versus CASS analysis. A P value of <.05 was considered statistically significant. The average age was 25.7 years old and 54% of patients were female. For the photographic analysis, the mean incisor-goal anterior limit line distance was -0.44 ± 7.12 mm (95% CI, -1.13 to 0.37 mm; P = .46). For the virtual analysis, the mean incisor-goal anterior limit line distance was 0.13 ± 7.21 (95% CI, -0.004 to 0.30; P = .89). The Pearson correlation coefficients between the photograph and 3D analysis were very strong (0.93). The root mean square deviation between the photographic and 3D analysis cohorts was 2.7 mm. Given the high correlation coefficients between all demographics, CASS can be utilized for Andrews analysis to determine ideal anteroposterior maxillary position to streamline data collection and the planning process.


Synthesis and biological activity of 5-hydroxy-4-quinolones and 5-methoxy-4-quinolones as truncated acridones.
A series of 5-hydroxy-4-quinolone (3) and 5-methoxy-4-quinolone (4) derivatives were synthesized as truncated acridone analogues and evaluated for antitumor, antiherpes and antituberculosis activities. Among them 5-hydroxy-8-methoxy-quinolone showed potent antitumor activity (IC50 = 17.7 microM for HL60) which was greater than that of acronycine. However, these compounds didn't show any significant antiherpes or antituberculosis activity.


A case of cortical deafness.
At the age of 42 Lothar H. suffered a left-sided ischaemic brain lesion with transient aphasia, followed at the age of 49 by a right-sided ischemic infarction, which caused a continuous inability to understand spoken language and to identify tones and noises. He was still able to discriminate between single qualities of pure tones. The ERA-results showed the central acoustic pathways of the brain-stem to be intact. The occurrence of cortical deafness following bilateral lesions of the acoustic cortex and adjoining cortical centres supports the view that human auditory recognition is represented in both temporoparietal areas.


Computer-aided resection and reconstruction in a case of aneurysmal bone cyst of the mandibular condylar head.
A case is presented of a 16-year-old girl with an aneurysmal bone cyst (ABC) of the mandibular condyle of the temporomandibular joint (TMJ). This lesion rarely involves the mandibular condyle, and involvement of condylar head is even rarer. To our knowledge, only 12 cases have been reported in the literature so far. This is the first case of ABC of the mandibular condyle with 3D planning of costochondral graft reconstruction described in the literature.


Crystal structure of (n-but-yl)[2-(2,6-di-meth-oxy-phen-yl)-6-methyl-phen-yl](2-meth-oxy-phen-yl)phospho-nium chloride monohydrate.
The title hydrated salt, C26H32O3P(+)·Cl(-)·H2O, contains four different substit-uents (H, alkyl, aryl, and biar-yl) on the P atom. The P-H hydrogen atom of the phospho-nium ion was located in a difference Fourier map and refined without imposing additional restraints. In the crystal, the Cl(-) ions and water mol-ecules are linked by pairs of Owater-H⋯Cl(-) hydrogen bonds and further linked to the phospho-nium cation by P-H(+)⋯Cl(-) and CAr/OMe-H⋯Owater hydrogen bonds to form an infinite one-dimensional chain along the [010] direction.


Expression of 8-oxoguanine DNA glycosylase is reduced and associated with neurofibrillary tangles in Alzheimer's disease brain.
Recent studies have confirmed the role of reactive oxygen species in the pathogenesis of Alzheimer's disease (AD). 8-Oxo-2'-deoxyguanosine accumulation in AD brain has been discussed, but few studies of DNA repair enzymes in AD brain have been done. Further, a relationship between mitochondrial function and oxidative stress has been noticed. In this study, to evaluate the repair mechanism for oxidative DNA damage in AD brain, we investigated brain tissues from autopsy cases of AD and control cases using an antibody against the mitochondrial form of 8-oxoguanine DNA glycosylase (hOGG1-2a), an enzyme that repairs 8-oxo-2'-deoxyguanosine. hOGGI-2a is expressed mainly in the neuronal cytoplasm in both AD and control cases in regionally different manners. Expression of hOGG1-2a is decreased in the orbitofrontal gyrus and entorhinal cortex in AD compared to that in control cases. Immunoreactivity to hOGG1-2a is associated with neurofibrillary tangles, dystrophic neurites and reactive astrocytes in AD. Our results indicate that the repair enzyme for oxidative damage in mitochondrial DNA may not function appropriately in AD, and thus oxidative DNA damage in mitochondria may be involved in the pathomechanism of AD.


Use of intraoperative technology in total knee arthroplasty is not associated with reductions in postoperative pain.
Our systematic review and meta-analysis sought to assess how technology-assistance impacts (1) post-operative pain and (2) opioid use in patients undergoing primary total knee arthroplasty (TKA). Four online databases were queried for studies published up to October 2021 that reported on pain and opioid usage between technology-assisted and manual TKA (mTKA) patients. Mantel-Haenszel (M-H) models were utilized to calculate pooled mean difference (MDs) and 95% confidence interval (CIs). Subgroup analyses were conducted to isolate robotic-arm assisted (RAA) and computed-assisted navigation (CAN) cohorts. Risk of bias was assessed for all included non-randomized studies with the Methodological Index for Non-Randomized Studies (MINORS) tool. For the randomized control trials included in our study, the Detsky scale was applied. Our analysis included 31 studies, reporting on a total of 761,300 TKAs (mTKA: n = 753,554; Computer-Assisted Navigation (CAN): n = 1,309; Robotic-Arm Assisted (RAA): n = 6437). No differences were demonstrated when evaluating WOMAC (MD: 0.00, 95% CI - 0.69 to 0.69; p = 1.00), KSS (MD: 0.01, 95% CI - 1.46 to 1.49; p = 0.99), KOOS (MD - 2.91, 95% CI - 6.17 to 0.34; p = 0.08), and VAS (MD - 0.54, 95% CI - 1.01 to - 0.007; p = 0.02) pain scores between cohorts. There was mixed evidence regarding how opioid consumption differed between TKA techniques. The present analysis demonstrated no difference in terms of pain across a variety of utilized patient-reported pain measurements. However, there were mixed results regarding how opioid consumption varied between manual and technology-assisted cohorts, particularly in the immediate post-operative period. III.


A New Type of Endometrial Cancer Models in Mice Revealing the Functional Roles of Genetic Drivers and Exploring their Susceptibilities.
Endometrial cancer (EC) is the most common female reproductive tract cancer and its incidence has been continuously increasing in recent years. The underlying mechanisms of EC tumorigenesis remain unclear, and efficient target therapies are lacking, for both of which feasible endometrial cancer animal models are essential but currently limited. Here, an organoid and genome editing-based strategy to generate primary, orthotopic, and driver-defined ECs in mice is reported. These models faithfully recapitulate the molecular and pathohistological characteristics of human diseases. The authors names these models and similar models for other cancers as organoid-initiated precision cancer models (OPCMs). Importantly, this approach can conveniently introduce any driver mutation or a combination of driver mutations. Using these models,it is shown that the mutations in Pik3ca and Pik3r1 cooperate with Pten loss to promote endometrial adenocarcinoma in mice. In contrast, the Kras G12D mutati led to endometrial squamous cell carcinoma. Then, tumor organoids are derived from these mouse EC models and performed high-throughput drug screening and validation. The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy.


Anterior spinal artery syndrome after peripheral angiography of the lower limbs.
A case report of temporary anterior spinal artery syndrome secondary to peripheral angiography of the lower limbs. To report a rare case of spinal cord ischemia following a straightforward peripheral angiography with femoral access. Istanbul, Turkey. A 70-year-old patient with peripheral vascular disease developed temporary paraplegia after angiography caused by anterior spinal ischemia. His motor weakness improved gradually over a 2 month period. Spinal complications are extremely rare after peripheral angiography. The possible mechanisms of spinal cord damage are discussed, and the relevant data regarding the etiology are reviewed.


Learned helplessness: an experimental model of the DST in rats.
Elevated ratings of anxiety and agitation in Dexamethasone Suppression Test (DST) nonsuppressors suggest a role for psychological stress in the generation of the hypothalamic-pituitary-adrenal cortical (HPAC) abnormalities characteristic of depression. We employed the learned helplessness model of depression to test the effectiveness of psychological stress in inducing a resistance of plasma corticosterone levels to dexamethasone suppression. Inescapably shocked rats exhibited corticosterone levels that were significantly more resistant to dexamethasone suppression than were the levels of rats receiving an equivalent amount of escapable shock or no shock. These results confirm the hypothesis that HPAC resistance to dexamethasone suppression is enhanced by the distress associated with the inefficacy of behavioral coping responses. The present findings represent the first analog of the DST in the learned helplessness model of depression. This DST model allows investigations into neurobiological mechanisms underlying the HPAC alterations in depression.


The Role of microRNAs in Epigenetic Regulation of Signaling Pathways in Neurological Pathologies.
In recent times, there has been a significant increase in researchers' interest in the functions of microRNAs and the role of these molecules in the pathogenesis of many multifactorial diseases. This is related to the diagnostic and prognostic potential of microRNA expression levels as well as the prospects of using it in personalized targeted therapy. This review of the literature analyzes existing scientific data on the involvement of microRNAs in the molecular and cellular mechanisms underlying the development of pathologies such as Alzheimer's disease, cerebral ischemia and reperfusion injury, and dysfunction of the blood-brain barrier.


Serum butyrylcholinesterase in type 2 diabetes mellitus: a biochemical and bioinformatics approach.
Butyrylcholinesterase is an enzyme that may serve as a marker of metabolic syndrome. We (a) measured its level in persons with diabetes mellitus, (b) constructed a family tree of the enzyme using nucleotide sequences downloaded from NCBI. Butyrylcholinesterase was estimated colorimetrically using a commercially available kit (Randox Lab, UK). Phylogenetic trees were constructed by distance method (Fitch and Margoliash method) and by maximum parsimony method. There was a negative correlation between serum total cholesterol and butyrylcholinesterase (-0.407; p < 0.05) and between serum LDL cholesterol and butyrylcholinesterase (-0.435; p < 0.05). There was no statistically significant correlation among the other biochemical parameters. In the evolutionary tree construction both methods gave similar trees, except for an inversion in the position of Sus scrofa (M62778) and Oryctolagus cuniculus (M62779) between Fitch and Margoliash, and maximum parsimony methods. The level of butyrylcholinesterase enzyme was inversely related to serum cholesterol; dendrogram showed that the structures from evolutionarily close species were placed near each other.


The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic.
The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.


Unexpected dramatic substituent effect for tuning the selectivity in the double ring-closing metathesis reaction of N-containing tetraenes. An efficient synthesis of bicyclic izidine alkaloid skeletons.
[reaction: see text] A double ring-closing metathesis reaction for the efficient construction of the fused bicyclic izidine alkaloid skeleton was developed. In this reaction, high selectivity was realized by tuning of electronic and steric effects of substituents in the N-containing tetraenes. It was observed that the reactivity of electron-rich carbon-carbon double bonds is higher than that of electron-deficient ones. A brief mechanistic study is also discussed.


Promoter analysis of the gene encoding the I kappa B-alpha/MAD3 inhibitor of NF-kappa B: positive regulation by members of the rel/NF-kappa B family.
In order to characterize the regulation of the gene encoding the I kappa B-alpha/MAD3 inhibitor of the transcription factor NF-kappa B, we have isolated a human genomic clone and sequenced the promoter of this gene. The MAD3 promoter exhibits a potential TATA element upstream of one of the two major transcription sites, and contains several potential NF-kappa B binding sequences, suggesting that the gene is positively regulated by members of this family. Transfection experiments demonstrate that the MAD3 promoter can be activated by various combinations of members of the rel/NF-kappa B family, as well as by phorbol esters and tumor necrosis factor. Specific deletion of one of the kappa B motifs, located 37 bp upstream of the TATA box, abolishes responses to PMA and TNF. This kappa B motif binds NF-kappa B (p50/relA), p50/c-rel and relA/c-rel heterodimers as well as KBF1 (p50 homodimer). These results help to explain the previously observed transient nature of the NF-kappa B response: following NF-kappa B activation, the expression of the inhibitor is increased, therefore the extent of nuclear translocation of the active complex is reduced, resulting in a decreased activation of its target genes.


Cancer patient perspectives on survivorship goals from the Smart Patients online community.
Cancer impacts individuals' life goals. Recent cancer care guidelines recommend discussing life goals as part of patient-provider communication. The goal of this study was to understand patients' attitudes toward goal sharing with their cancer care providers. Semi-structured questionnaires were conducted via email with cancer patients and survivors (n = 39) on an online social network called Smart Patients. Participants answered open-ended questions about their life goals. They then completed a survey regarding their attitudes toward goal sharing with healthcare providers. The study team used an integrated inductive-deductive qualitative analysis to identify conceptual themes. Participants listed goals related to improving physical activity, control, enjoyment/leisure, and inner strength while reducing pain, anxiety, fear of recurrence, and uncertainty. Most of these goals were life goals rather than goals specifically related to medical care. Across all goals, there was a focus on returning to normality. Our findings show that 87% of participants expect their cancer specialist to discuss their treatment preferences and goals regularly with them. However, participants were reluctant to share their goals with their providers. Respondents felt that their providers did not have an interest in their life goals or time to address them in addition to their medical treatment. Even though cancer patient-provider communication guidelines advocate for discussions around life goals, participants in this study expressed reluctance to share life goals with providers. Further efforts to align expectations of patients and providers may facilitate adherence to cancer communication guidelines about life goals. Cancer survivors should be aware that discussing life goals is part of recommended communication with their cancer care teams.


Decay rate measurement of the first vibrationally excited state of MgH+ in a cryogenic Paul trap.
We present a method to measure the decay rate of the first excited vibrational state of polar molecular ions that are part of a Coulomb crystal in a cryogenic linear Paul trap. Specifically, we have monitored the decay of the |ν = 1, J = 1)(X) towards the |ν = 0, J = 0)(X) level in MgH+ by saturated laser excitation of the |ν = 0, J = 2)(X)-|ν = 1, J = 1)(X) transition followed by state selective resonance enhanced two-photon dissociation out of the |ν = 0, J=2)(X) level. The experimentally observed rate of 6.32(0.69) s(-1) is in excellent agreement with the theory value of 6.13(0.03) s(-1) (this Letter). The technique enables the determination of decay rates, and thus absorption strengths, with an accuracy at the few percent level.


Function-modulating human monoclonal antibodies against platelet-membrane receptors isolated from a phage-display library.
Monoclonal antibodies to platelet membrane receptors have been used extensively for analysis of receptor structure and function. Function-blocking human antibodies are being used for the development of antiplatelet drugs. We isolated human monoclonal antibodies from a library of single-chain Fv (scFv) antibodies displayed on the surface of filamentous phage, by selection on whole platelets. Eight different platelet-binding clones were isolated, of which three bound to the platelet-membrane glycoprotein (GP) GPIb in an ELISA assay. Specific elution with a recombinant polypeptide of von Willebrand factor (VWF) spanning the GPIbalpha binding site, yielded the same three phage clones. Two of the three anti-GPIb clones could be purified as scFv monoclonal antibodies, and they competed with each other for binding to intact platelets, suggesting that they bind at or near the same site on GPIb. Their binding affinities differed, however, and the clone with higher affinity inhibited ristocetin-induced platelet aggregation. These data indicate that selection from a phage display library of human scFvs using whole platelets can be applied for the isolation of functional antiplatelet-GPIb antibodies useful for the development of new therapeutic and diagnostic strategies.


Osteolysis Following the Use of Polyetheretherketone Suture Anchors in Hand and Wrist Surgery: A Preliminary Study.
The objective of this study was to investigate and describe the presence of osteolysis after implantation of polyetheretherketone (PEEK) suture anchors in the hand and wrist. Patients who underwent hand or wrist surgery using PEEK suture anchor(s) at a large academic institution from January 2019 to January 2021 were identified. Patients without accessible intraoperative fluoroscopic imaging were excluded. Patient demographics, type of procedure, and suture anchor material were recorded. The suture anchor tunnel size was measured on sequential radiographs and recorded as percentage change. Descriptive statistics were used to summarize findings. A total of 26 PEEK suture anchors in 14 patients were included, with an average follow-up of 12.0 months (range, 1.5-24.1 months). Twenty-seven percent of the anchors (7/26) demonstrated osteolysis at final follow-up, as defined by enlargement of tunnel size by >30%. In all anchors, the tunnel size increased by 19.1% on average (range, -7.7% to 56.1%) by final follow-up. Polyetheretherketone suture anchors may be associated with the development of osteolysis in hand and wrist surgery. The clinical implications of osteolysis in the smaller bones of the hand and wrist remain unclear. Prognostic IV.


A Novel Approach to Developing Disease and Outcome-Specific Social Risk Indices.
A variety of industry composite indices are employed within health research in risk-adjusted outcome measures and to assess health-related social needs. During the COVID-19 pandemic, the relationships among risk adjustment, clinical outcomes, and composite indices of social risk have become relevant topics for research and healthcare operations. Despite the widespread use of these indices, composite indices are often comprised of correlated variables and therefore may be affected by information duplicity of their underlying risk factors. A novel approach is proposed to assign outcome- and disease group-driven weights to social risk variables to form disease and outcome-specific social risk indices and apply the approach to the county-level Centers for Disease Control and Prevention social vulnerability factors for demonstration. The method uses a subset of principal components reweighed through Poisson rate regressions while controlling for county-level patient mix. The analyses use 6,135,302 unique patient encounters from 2021 across seven disease strata. The reweighed index shows reduced root mean squared error in explaining county-level mortality in five of the seven disease strata and equivalent performance in the remaining strata compared with the reduced root mean squared error using the current Centers for Disease Control and Prevention Social Vulnerability Index as a benchmark. A robust method is provided, designed to overcome challenges with current social risk indices, by accounting for redundancy and assigning more meaningful disease and outcome-specific variable weights.


High-cholesterol diet enriched with onion affects endothelium-dependent relaxation and NADPH oxidase activity in mesenteric microvessels from Wistar rats.
The aim of the present study was to examine the effects of onion as functional ingredient on the oxidative status, lipoprotein levels (total cholesterol-TC, HDL-C, LDL-C), triacylglycerides (TAG) and vascular reactivity of mesenteric arteries in hypercholesterolemic Wistar rats. Twenty-four animals were fed with three different diets [control, high-cholesterol diet (HC) and high-cholesterol enriched with onion diet (HCO)]. After seven weeks of experimental feeding the rats were euthanized for blood and tissues collection. TC, HDL-C, LDL-C and TAG were measured, and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS(•+)) scavenging capacity and ferric reducing antioxidant power (FRAP) were determined in plasma. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzyme activities were assayed in erythrocyte lysates. Endothelium-dependent vasodilation to acetylcholine was evaluated in mesenteric arterial segments. NADPH oxidase (NOX) was also measured by lucigenin-derived chemiluminiscence. The dietary cholesterol content significantly affected plasma lipoprotein levels, increased superoxide generation from NOX, and caused impaired endothelium-dependent vasodilation in the rat mesenteric arteries. Onion ingredient improved antioxidant status in HCO group, as it was evidenced by ABTS(•+) and FRAP values and SOD and GPx enzyme activities compared to the HC-fed group, reduced the increment in NOX activity and reversed endothelial dysfunction promoted by the HC diet. Scavenging of superoxide with TEMPOL or inhibition of NOX with apocynin improved endothelium-dependent vasodilation only in HC-fed rats. Enrichment of diet with onion as functional ingredient could be proposed as a complementary approach to prevent or partially modulate vascular dysfunction, reducing some of the risk indexes linked to initial development of atherosclerosis.


Road related pollutants induced DNA damage in dragonfly nymphs (Odonata, Anisoptera) living in highway sedimentation ponds.
Nowadays, stormwater sedimentation ponds are popular in stormwater management because of their ability to mitigate flooding and treat polluted runoff from e.g. roads. In addition, they may provide other ecosystem services such as biodiversity. These man-made habitats will inevitably be polluted and the organisms living therein may be negatively affected by the chemical cocktail present in both the water and sediment compartments. The present study explored DNA damage in dragonfly nymphs (Odonata, Anisoptera) living in highway sedimentation ponds in comparison with natural ponds. The concentrations of Polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs and metals were also determined in sediment samples from the different ponds. The results showed that DNA damage was significantly higher in dragonfly nymphs living in sedimentation ponds compared to nymphs living in natural ponds. DNA damage was also highly and significantly correlated with the pollution levels in the sediment, i.e., PAH and Zinc. Finally, we report the concentrations of various alkylated PAHs which appeared to be very dominant in the sedimentation ponds. Our results show that there may be a conflict between the sedimentation ponds' primary function of protecting natural water bodies from polluted runoff and their secondary function as habitats for organisms. Overall, we suggest that this must be considered when planning and designing stormwater measures.


The role of pharmacogenetics in keloid scar treatment: A literature review.
The pathophysiology of keloid scars is still not fully understood and a universally reliable effective treatment has not been identified. Pharmacogenetics explores how drug response to a particular therapy can relate to genetic variations. To investigate how pharmacogenetics could be applied to keloid scars and the relevance of this to clinical practice. We reviewed the literature and discuss our current knowledge of pharmacogenomics in the treatment of keloid scars. A literature search was performed using the terms 'Pharmacogenetics', 'Pharmacogenomics', 'Keloid' and 'Scar'. We searched the PubMed, MEDLINE and EMBASE databases to find the relevant articles. Only articles in English were chosen. The level of evidence was evaluated and selected accordingly listing the studies with the highest level of evidence first. Treatments including corticosteroid injections and 5-fluorouracil can be effective in some patients, but less so in others. Polymorphisms of the glucocorticoid receptor and variants of CCL2, YAP1, miR-21-5p and NF-κβ might be responsible for different responses to treatments used in keloid scars such as 5-fluorouracil. Small molecule inhibitors might be utilised to target other implicated genes. Pharmacogenetics aims to produce the most efficacious patient outcomes while reducing adverse effects. Understanding the pharmacogenetics of keloid scars could lead to a new era of personalised medicine in the treatment of keloid scars. At present, there is some evidence (level 3b/4) to suggest genetic variations that are responsible to drug response in keloids, but further research in this field is required. The varied response to similar therapeutic treatments in keloids has prompted the consideration of the role of genetic variants on response in the form of pharmacogenetics. Pharmacogenetics refers to drugs and their metabolism and action based on genetic influences. The ideal scenario would involve the selection of treatment based on the individual's specific genetic variants to ensure maximum efficacy with minimal toxicity. Some evidence currently points to genetic variations in some keloid patients that might be of relevance to the treating clinician.


Volume and Patterns of Physical Activity Across the Health and Heart Failure Continuum.
The benefits of regular physical activity (PA) are well documented in patients with heart failure (HF), however the amount and intensity of objectively measured PA and sedentary behaviour in HF with preserved (HFPEF) or reduced ejection fraction (HFREF) is not well known. In a cross-sectional observational study the energy expenditure of 151 participants (HFPEF: n = 53; HFREF: n = 16; at-risk for HF: n = 48; control participants: n = 34) using SenseWear Mini Armbands (Body Media, Inc, Pittsburgh, PA) were monitored. PA outcomes included time spent in different PA intensities (light and moderate-vigorous PA), sedentary time, steps per day, total daily energy expenditure, PA energy expenditure, and the patterns of PA in bouts of ≥ 10 minutes of moderate-vigorous PA. The patients with HFPEF had the lowest volume of activity across the 4 groups. After adjusting for covariates, only steps per day remained significantly different across groups (P = 0.0005). A comparison of HFPEF vs HFREF indicated a higher amount of time in bouts of ≥ 10 minutes of moderate-vigorous PA for patients with HFREF (median, 2.4 [interquartile range, 0-13.5] vs 26 [3.7-46.8]; P = 0.0075). In the at-risk group, PA was lower than the recommended levels in the guidelines. Our findings suggest step count as the most robust outcome in evaluating daily PA in this population. Also, patients with HFPEF showed to be the least active group in the HF continuum. Monitoring volume and pattern of PA for those at risk of HF and patients with HFPEF could help to identify sedentary individuals and to develop tailored behavioural interventions for them.


Holmium: YAG laser lithotripsy for urolithiasis in dogs.
Laser lithotripsy has been used as an alternative to surgical removal of uroliths in a number of species. To determine the effectiveness of laser lithotripsy for removing urocystoliths, urethroliths, or both in dogs, and to determine the influence of dog (chronological order of lithotripsy, endoscope type, sex, body weight) and urolith (total urolith and urocystolith number, presence or absence of urethroliths, largest urolith dimension, and urolith composition) factors on outcome. Twenty-five client-owned dogs with urocystoliths, urethroliths, or both were included. Male dogs were required to weigh > or =6.8 kg. A single-arm prospective clinical trial. Laser lithotripsy was performed under general anesthesia. Main outcomes included procedure success and lithotripsy time. Predictors of procedure success and lithotripsy time were selected using logistic and linear regression modeling, respectively. The procedure was successful in 21 of 25 dogs. The procedure was successful more often and in less time in female spayed than in male neutered dogs. Sex was identified as a predictor of success. Univariable analysis showed that sex, endoscope type, and chronological order in which the dog received lithotripsy were significantly associated with lithotripsy time. Stepwise linear regression modeling identified sex, body weight, >10 uroliths, and largest urolith dimension as predictors of lithotripsy time. Laser lithotripsy is an effective procedure for the removal of urocystoliths, urethroliths, or both with rare important adverse effects and some limitations in male dogs.


Inhibition and recovery of rat hepatic glutathione S-transferase zeta and alteration of tyrosine metabolism following dichloroacetate exposure and withdrawal.
Dichloroacetate (DCA) is an investigational drug for certain metabolic disorders, a by-product of water chlorination and a metabolite of certain industrial solvents and drugs. DCA is biotransformed to glyoxylate by glutathione S-transferase zeta (GSTz1-1), which is identical to maleylacetoacetate isomerase, an enzyme of tyrosine catabolism. Clinically relevant doses of DCA (mg/kg/day) decrease the activity and expression of GSTz1-1, which alters tyrosine metabolism and may cause hepatic and neurological toxicity. The effect of environmental DCA doses (microg/kg/day) on tyrosine metabolism and GSTz1-1 is unknown, as is the time course of recovery from perturbation following subchronic DCA administration. Male Sprague-Dawley rats (200 g) were exposed to 0 microg, 2.5 microg, 250 microg, or 50 mg DCA/kg/day in drinking water for up to 12 weeks. Recovery was followed after the 8-week exposure. GSTz specific activity and protein expression (Western immunoblotting) were decreased in a dose-dependent manner by 12 weeks of exposure. Enzyme activity and expression decreased 95% after a 1-week administration of high-dose DCA. Eight weeks after cessation of high-dose DCA, GSTz activity had returned to control levels. At the 2.5 or 250 microg/kg/day doses, enzyme activity also decreased after 8 weeks' exposure and returned to control levels 1 week after DCA was withdrawn. Urinary excretion of the tyrosine catabolite maleylacetone increased from undetectable amounts in control rats to 60 to 75 microg/kg/24 h in animals exposed to 50 mg/kg/day DCA. The liver/body weight ratio increased in the high-dose group after 8 weeks of DCA. These studies demonstrate that short-term administration of DCA inhibits rat liver GSTz across the wide concentration range to which humans are exposed.


The effect of lactation educators implementing a telephone-based intervention among low-income Hispanics: A randomised trial.
To assess whether a phone-based breastfeeding intervention delivered by lactation educators influenced exclusive breastfeeding rates amongst low-income Hispanic women in the USA. Randomised two-group design. Pregnant low-income Hispanic women (298) were recruited from community health clinics in Los Angeles County (USA) and randomly assigned to either a control or an intervention group. Data relating to the factors associated with breastfeeding were collected during the third trimester. Breastfeeding outcome data was collected at 72 hours, one month, three months, and six months postpartum. There were no differences between the groups in rates of breastfeeding initiation. There was a significant difference in the duration of exclusive breastfeeding among participants during the infant's first week of life. While not significant, after controlling for covariates and intent to breastfeed at third trimester, the duration of exclusive breastfeeding amongst all participants was, on average, longer for intervention group mothers than control group mothers. Additionally, , the intervention group mothers were more likely to report exclusive and only breastfeeding at all data points compared to the control group, and less likely to discontinue breastfeeding. Findings from this study suggest that telephone-based breastfeeding interventions delivered by a lactation educator show promise as a cost-effective strategy for improving both the quantity and duration of breastfeeding among low-income Hispanic women in the USA. Intervention group mothers not only sustained breastfeeding for a longer durations, but also provided their infants with greater amounts of breast milk over these longer durations.


CCN3 increases BMP-4 expression and bone mineralization in osteoblasts.
The nephroblastoma overexpressed (NOV) gene, also called CCN3, regulates differentiation of skeletal mesenchymal cells. Bone morphogenetic proteins (BMPs) play important roles in osteoblast differentiation and bone formation, but the effects of CCN3 on BMP expression and bone formation in cultured osteoblasts are largely unknown. Here we found that CCN3 increased BMP-4 expression and bone nodule formation in cultured osteoblast. Monoclonal antibodies for α5β1 and αvβ5 integrins, and inhibitors of integrin-linked kinase (ILK), p38, and JNK, all inhibited CCN3-induced bone nodule formation and BMP-4 up-regulation of osteoblasts. CCN3 stimulation increased the kinase activity of ILK and phosphorylation of p38 and JNK. Inhibitors of activator protein-1 (AP-1) also suppressed bone nodule formation and BMP-4 expression enhanced by CCN3. Moreover, CCN3-induced c-Jun translocation into the nucleus, and the binding of c-Jun to the AP-1 element on the BMP-4 promoter were both inhibited by specific inhibitors of the ILK, p38, and JNK cascades. Taken together, our results provide evidence that CCN3 enhances BMP-4 expression and bone nodule formation in osteoblasts, and that the integrin receptor, ILK, p38, JNK, and AP-1 signaling pathways may be involved.


Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2.
Mast cells may activate fibroblasts and contribute to remodeling processes in the lung. However, the mechanism behind these actions needs to be further investigated. Fibroblasts are major regulators of on-going remodeling processes. Protease activated receptor 2 (PAR2) expressed by fibroblasts may be activated by serine proteases, such as the mast cell mediator tryptase. The objective in this study was to investigate the effects of mast cells and specifically mast cell tryptase on fibroblast migration and the role of PAR2 activation. Human lung fibroblasts (HFL-1) were cultured together with human peripheral blood-derived mast cells or LAD2 mast cells and stimulated with either conditioned medium from LAD2 cells or tryptase. Analyses of immunological stimulation of mast cells by IgE/anti IgE in the co-culture system were also performed. The importance of PAR2 activation by mast cells and mast cell tryptase for the migratory effects of fibroblasts was investigated by pre-treatment with the PAR2 antagonist P2pal-18S. The expression of PAR2 was analyzed on fibroblasts and mast cells. The migratory capacity of HFL-1 cells was enhanced by blood-derived mast cells (p < 0.02), LAD2 cells (p < 0.001), conditioned medium (p < 0.05) and tryptase (p < 0.006). P2pal-18S decreased the induced migration caused by mast cells (p < 0.001) and tryptase (p < 0.001) and the expression of PAR2 was verified in HFL-1 cells. Mast cells immunologically stimulated with IgE/Anti IgE had no further effects on fibroblast migration. Mast cells and the mast cell mediator tryptase may have crucial roles in inducing lung fibroblast migration via PAR-2 activation, which may contribute to remodeling processes in chronic lung diseases.


Breath-holding: helping parents cope.
Breath-holding is relatively rare but can occur in infants as young as six months. Ann Rowland describes some typical episodes and suggests strategies to help parents cope.


Degradation of Direct Black 38 dye under visible light and sunlight irradiation by N-doped anatase TIO₂ as photocatalyst.
The N-doped TiO(2) photocatalyst was prepared by calcination of a hydrolysis product composed of titanium (IV) isopropoxide with ammonia as the precipitator. X-ray diffraction, surface area, XPS and UV-vis spectra analyses showed a nanosized anatase structure and the appearance of a new absorption band in the visible region caused by nitrogen doping. The degradation of Direct Black 38 dye on the nitrogen-doped TiO(2) photocatalyst was investigated under visible light and sunlight irradiation. The N-doped anatase TiO(2) demonstrated excellent photocatalytic activity under visible light. Under sunlight irradiation, the N-doped sample showed slightly higher activity than that of the non-doped sample.


Applicability of photovoltaic panel rainwater harvesting system in improving water-energy-food nexus performance in semi-arid areas.
Growing food demand challenges the expansion of agriculture, while water and energy shortages have seriously jeopardized agricultural sustainability. Therefore, the water-energy-food (WEF) nexus must be integrated into sustainable agriculture management. However, despite the increasing sophistication of models for WEF optimization, more studies have considered only how to reduce resource consumption and less on how to increase resource supply. This paper outlines an agricultural WEF optimization model based on photovoltaic panel rainwater harvesting (PVRH). The model innovatively incorporates the PVRH system into the agricultural WEF nexus, providing a decision-making framework that exploits and conserves resources in parallel, while contributing to economic benefits. The model was applied in a rural case study in a semi-arid region of China. The results highlight the significant potential of the PVRH system to exploit water and energy, and the increased resources are allocated to irrigated alfalfa and vegetables, which would significantly increase revenue. However, the model does not recommend large-scale vegetable cultivation, which would increase water and energy consumption and reduce the WEF indicator values indicating agricultural sustainability. The final scheme will build a 98.92MWp PV power station, develop 1.31 × 108 kW·h of electricity and 1.97 × 107 m3 of rainwater into agricultural production. And through cropping restructuring, it will increase 23.61 % of economic revenue and save 57.74 % of water and 3.24 % of energy. In general, the model framework is transferable and applicable to similar agricultural areas under semi-arid climatic conditions.


Association of Mycobacterium tuberculosis Beijing genotype with tuberculosis relapse in Singapore.
The relationship of Mycobacterium tuberculosis Beijing genotype with tuberculosis relapse was examined. Beijing strains were detected from 32 out of 45 (71%) relapsed cases and 148 out of 290 (51%) non-relapsed cases. Multivariate logistic regression analysis revealed that Beijing genotype was significantly associated with tuberculosis relapse (OR 2.64, 95% CI 1.30-5.34, P=0.005).


Dynamics of the wetland ecosystem health in urban and rural settings in high altitude ecoregion.
The focus of the present study was to assess the dynamics of wetland ecosystem health in both urban and rural settings situated in the high-altitude Kashmir Himalayan ecoregion. The basic aim was to identify the drivers responsible for wetland degradation in order to sustain ecosystem services effectively. To achieve this, we examined water quality, trophic status, fish species diversity and human disturbances by analyzing changes in land use and land cover (LULC) since 1980. For the limnological characterization of the two wetlands, we evaluated a total of 21 physico-chemical parameters at 24 sites. Two-way analysis of variance revealed significant (p < 0.05) spatial and temporal variability in the water quality parameters. The trophic state index values of 67.7 and 76.7 indicated that the rural and urban wetlands were in eutrophic and hypertrophic status, respectively, signifying potential environmental stress. The data on fish fauna indicated a decline in fish species over the past 40 years, particularly the schizothoracine species. Urban wetlands showed a more significant decrease in species (06) compared to rural wetlands (01). LULC mapping and change analysis employing the visual interpretation technique showed significant transformations in the immediate catchment of wetlands. Substantial growth in the built-up (433.2 % and 2620 %) and decrease in aquatic vegetation (-83.4 % and - 97.5 %) in the immediate catchment was recorded in both the urban and rural wetlands respectively from 1980 to 2020. Our findings demonstrated a relationship between LULC classes and water quality parameters, with an increase in built-up and road areas showing a significant positive correlation with the rise in decadal mean values of total phosphorus, orthophosphorus, nitrate nitrogen, ammonical nitrogen, and calcium content. Based on these observations, we concluded that changes in land use and land cover within the immediate catchment areas of the wetlands were the primary drivers responsible for the deterioration of wetland ecosystem health.


Was millennial scale climate change during the Last Glacial triggered by explosive volcanism?
The mechanisms responsible for millennial scale climate change within glacial time intervals are equivocal. Here we show that all eight known radiometrically-dated Tambora-sized or larger NH eruptions over the interval 30 to 80 ka BP are associated with abrupt Greenland cooling (>95% confidence). Additionally, previous research reported a strong statistical correlation between the timing of Southern Hemisphere volcanism and Dansgaard-Oeschger (DO) events (>99% confidence), but did not identify a causative mechanism. Volcanic aerosol-induced asymmetrical hemispheric cooling over the last few hundred years restructured atmospheric circulation in a similar fashion as that associated with Last Glacial millennial-scale shifts (albeit on a smaller scale). We hypothesise that following both recent and Last Glacial NH eruptions, volcanogenic sulphate injections into the stratosphere cooled the NH preferentially, inducing a hemispheric temperature asymmetry that shifted atmospheric circulation cells southward. This resulted in Greenland cooling, Antarctic warming, and a southward shifted ITCZ. However, during the Last Glacial, the initial eruption-induced climate response was prolonged by NH glacier and sea ice expansion, increased NH albedo, AMOC weakening, more NH cooling, and a consequent positive feedback. Conversely, preferential SH cooling following large SH eruptions shifted atmospheric circulation to the north, resulting in the characteristic features of DO events.


Early interventions to prevent lower urinary tract dysfunction after spinal cord injury: a systematic review.
Systematic review. To synthetise the available scientific literature reporting early interventions to prevent neurogenic lower urinary tract dysfunction (NLUTD) after acute supra-sacral spinal cord injury (SCI). The present systematic review is reported according to the PRISMA guidelines and identified articles published through April 2021 in the PubMed, Embase, ScienceDirect and Scopus databases with terms for early interventions to prevent NLUTD after SCI. Abstract and full-text screenings were performed by three reviewers independently, while two reviewers performed data extraction independently. An article was considered relevant if it assessed: an in-vivo model of supra-sacral SCI, including a group undergoing an early intervention compared with at least one control group, and reporting clinical, urodynamic, biological and/or histological data. Of the 30 studies included in the final synthesis, 9 focused on neurotransmission, 2 on the inflammatory response, 10 on neurotrophicity, 9 on electrical nerve modulation and 1 on multi-system neuroprosthetic training. Overall, 29/30 studies reported significant improvement in urodynamic parameters, for both the storage and the voiding phase. These findings were often associated with substantial modifications at the bladder and spinal cord level, including up/downregulation of neurotransmitters and receptors expression, neural proliferation or axonal sprouting and a reduction of inflammatory response and apoptosis. The present review supports the concept of early interventions to prevent NLUTD after supra-sacral SCI, allowing for the emergence of a potential preventive approach in the coming decades.


Impact of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism on the risk of developing preeclampsia.
Preeclampsia is a multifactorial disease characterized by high blood pressure and protein in the urine. In this study, we investigated the association of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism with the risk of developing preeclampsia. 25-hydroxyvitamin D was measured using High-performance Liquid Chromatography. Vitamin D binding protein and vitamin D receptor gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. The control subjects have significant higher level of 25-hydroxyvitamin D (33.5 ± 1.194 ng/mL) relative to patients (23.97 ± 1.604 ng/mL) (p < 0.05). Vitamin D receptor rs1544410 and rs2228570 dominant model (GA + AA; TC + CC) showed significant higher risk of developing Preeclampsia (OR = 4.11, 95% CI = 0.62-27.09, p < 0.01; OR = 3.58, 95%CI = 0.78-16.38, p < 0.001 respectively). Similarly, vitamin D binding protein rs7041 and rs4588, dominant model (TG + GG; CA + AA) showed higher risk of preeclampsia development compared to control people (OR = 1.69, 95%CI = 0.35-8.19, p < 0.05; OR = 1.06, 95%CI = 0.25-4.44, p < 0.05 respectively). AA genotype of rs4588 of GC gene was significantly associated with 25-hydroxyvitamin D level in serum relative to CC and CA (p < 0.05). From our study, we can conclude that a low level of 25-hydroxyvitamin D, GC (rs1544410 and rs2228570), and VDR (rs4588 and rs7041) gene polymorphism is linked with an increased risk of developing preeclampsia.


Persistent Ambipolar Heptacenes and Their Redox Species.
Sixfold TIPS-ethynylation combined with fourfold bromination of the armchair edges furnishes a long-lived, soluble heptacene; π-extension via Stille coupling accesses a persistent tetrabenzononacene. Both types of acenes were stabilized best by double TIPS-ethynylation on every other benzene ring. Tetrabromoheptacene is an ambipolar transistor material (up to 0.036 cm2 V-1 s-1 n-channel), which was corroborated by generation of its monoanion and monocation.


CAPOS syndrome and hemiplegic migraine in a novel pedigree with the specific ATP1A3 mutation.
Identification and characterization of a novel pedigree with ATP1A3 mutations presenting with CAPOS syndrome and hemiplegic migraine. We have carried out clinical examinations of a three-generation pedigree with CAPOS syndrome and analyzed the ATP1A3 gene to identify causative mutations. The pedigree is of Slavic origin from Southeastern Europe. The clinical phenotype comprised cerebellar ataxia, areflexia, optic atrophy, and sensorineural hearing loss. Pes cavus was present in two of the four patients studied. The symptoms were triggered by fever and varied in severity in family members, exhibiting a chronic progressive course with or without relapses/remissions. The ATP1A3 c.2452G>A mutation was identified in the affected members of the family, while one of the mutation carriers exhibited both CAPOS and hemiplegic migraine. This study confirms that the specific c.2452G>A mutation in the ATP1A3 gene is associated with the CAPOS syndrome in pedigrees of different ethnic backgrounds. In patients with febrile episodes of ataxic encephalopathy or weakness, or both, genetic analysis of the ATP1A3 gene should be warranted. This is also the first report showing the co-occurrence of hemiplegic migraine and CAPOS syndrome in a patient with ATP1A3 mutations. Migraine has not been previously documented in ATP1A3 mutation carriers.


Antioxidant capacity of N-acetylcysteine against the molecular and cytotoxic implications of cadmium chloride leading to hepatotoxicity and vital progression.
Many studies have reported that cadmium (Cd) can induce liver cell injury; however, the toxicity mechanisms of Cd on the liver have not been fully explained. Thirty-two male albino rats were divided into four groups: the control group, the N-acetylcysteine (NAC) group orally as effervescent instant sachets with a concentration of 200 mg dissolved in distilled water and dosage was 200 mg/kg body weight freshly prepared, the cadmium chloride (CdCl2) group (treated with 3 mg/kg orally), and the N-acetylcysteine (NAC) + cadmium chloride group (treated with 200 mg/kg orally post to CdCl2) for 60 days. The NAC alone did not make notable changes in most of the parameters. The CdCl2 alone, compared to control, induced significant alterations in oxidative stress markers (increment in lipid peroxidation (LPO) and nitric oxide (NO)) and antioxidant defense system (decrement in superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx)), which resulted in a downregulation of pro-apoptotic Bcl2-associated X protein (Bax) and caspase-3 and upregulation of anti-apoptotic B-cell leukemia/lymphoma 2 (Bcl2) protein as well as the survival fate of hepatic cells. Post-administration of NAC to CdCl2 resulted in a reduction in oxidative stress markers, shifting of cells from the G2/M phase to the G0/G1 inhibiting signal-regulated kinase activation, and impairment of the anti-apoptotic signaling pathway when compared to the CdCl2 group alone. Accordingly, the Bcl2/Bax ratio was reduced to 1.17-fold change, as an adaptive process to hepatic tissue injury. These findings demonstrated that NAC would attenuate the possibility of oxidative stress and cytotoxicity of hepatic tissue induced by CdCl2.


Active-ion-gated room temperature acetone gas sensing of ZnO nanowires array.
Reducing the high operation temperature of gas sensor to room temperature (RT) have attracted intense interests for its distinct preponderances, including energy-saving and super stability, which presents great prospects in commercial application. The exciting strategies for RT gas sensing, such as unique materials with activated surface or light activation, do not directly modulate the active ions for gas sensing, limiting the RT gas sensing performances. Here, an active-ion-gated strategy has been proposed for RT gas sensing with high performance and low power consumption, in which gas ions in triboelectric plasma are introduced into metal oxide semiconductor (MOS) film to act as both floating gate and active sensing ions. The active-ion-gated ZnO nanowires (NWs) array shows a sensitivity of 38.3% to 10 ppm acetone gas at RT, and the maximum power consumption is only 4.5 mW. At the same time, the gas sensor exhibits excellent selectivity to acetone. More importantly, the response (recovery) time of this sensor is as low as 11 s (25 s). It is found that OH-(H2O)4 ions in plasma are the key for realizing RT gas sensing ability, and an accompanied resistive switch is also observed. It is considered that the electron transfer between OH-(H2O)4 and ZnO NWs will forms a hydroxyl-like intermediate state (OH*) on the top of Zn2+, leading to the band bending of ZnO and activating the reactive O2 - ions on the oxygen vacancies. The active-ion-gated strategy proposed here present a novel exploration to achieving RT gas sensing performance of MOS by activating sensing properties at the scale of ions or atoms.


An optimized nested polymerase chain reaction (PCR) approach allows detection and characterization of human immunodeficiency virus type 1 (HIV-1) env and gag genes from clinical samples.
The needs for development and/or improvement of molecular approaches for microorganism detection and characterization such as polymerase chain reaction (PCR) are of high interest due their sensitivity and specificity when compared to traditional microbiological techniques. Considering the worldwide importance of human immunodeficiency virus type 1 (HIV-1) infection, it is essential that such approaches consider the genetic variability of the virus, the heterogeneous nature of the clinical samples, the existence of contaminants and inhibitors, and the consequent needs for standardization in order to guarantee the reproducibility of the methods. In this work we describe a nested PCR assay targeting HIV-1 virus gag and env genes, allowing specific and sensitive diagnosis and further direct characterization of clinical samples. The method described herein was tested on clinical samples and allowed the detection of HIV-1 presence in all samples tested for the gag gene and 90.9% for the env gene, revealing sensitivities of 1 fg and 100 fg, respectively. Also, no cross-reactions were observed with DNA from infected and noninfected patients and the method allowed detection of the env and gag genes on an excess of 10(8) and 10(4) of human deoxyribonucleic acid (DNA), respectively. Furthermore, it was possible to direct sequence all amplified products, which allowed the sub typing of the virus in clinical samples.


Investigation of a rifampin, fusidic-acid and mupirocin releasing silicone catheter.
After strict hygienical measures have been exhausted the use of plastic materials with antibacterial activity may reduce catheter related-bacterial colonization. An antimicrobial silicone catheter was investigated by HPLC-measurement, SEM, antimicrobial assays and standard biocompatibility tests. The modified catheter was highly biocompatible and the antimicrobial leaching non-toxic. The initially release rate was governed by the drug solubility in the 'sink' and surface loading ('burst effect'). The second continuous period depended on the drug velocity in the silicone matrix and was extended up to 100 days with a proportionality to square root of t for each drug. Diffusion exponents were in range of 2 x 10(-8) to 1 x 10(-9) (cm2 sec(-1)). The lower diffusion exponent of mupirocin was explained by its higher cohesion energy and lower physico-chemical compatibility with the embedding silicone. The antimicrobial drugs were in a molecular-dispersed state with the silicone-matrix, whereas superficially located crystals of the antibiotics covering the catheter surface could be demonstrated by SEM.


Evaluation of cerebrospinal fluid EBV-DNA and IL-10 as markers for in vivo diagnosis of AIDS-related primary central nervous system lymphoma.
Acquired immunodeficiency syndrome (AIDS)-related primary central nervous system lymphoma (PCNSL) is almost always associated with the Epstein-Barr virus (EBV), and EBV-DNA in cerebrospinal fluid (CSF) has been indicated as a useful tumour marker for this HIV-related neoplasm. AIDS lymphomas also show an enhanced production of IL-10 which is generally associated with the presence of EBV in lymphoma cells. We performed a prospective study in 19 HIV seropositive patients with brain mass lesions, and in 21 other AIDS patients with or without other neurological disorders, to assess the in vivo diagnostic value of EBV-DNA and of IL-10 levels in the CSF for primary lymphoma of the central nervous system (CNS). EBV-DNA was detected by a nested polymerase chain reaction (PCR) in the CSF from seven of eight patients with PCNSL, diagnosed by brain biopsy (87.5% sensitivity) and in none of the 11 controls with brain mass lesions (100% specificity) and of the other 21 AIDS patients with or without neurological disorders. The only patient with PCNSL without detectable EBV-DNA in the CSF was also negative for EBV-DNA in the lymphoma tissue, whereas the samples of the other seven brain lymphomas were all positive for EBV-DNA by nested PCR. Therefore 100% of patients with an EBV-positive primary CNS lymphoma had detectable EBV-DNA in the CSF. No patient from the control group without PCNSL with EBV-negative CSF developed a lymphoma after a mean follow-up of 157 +/- 173 d. IL-10 levels in the CSF from the patients with PCNSL were not significantly different from those in the other groups of patients with AIDS. Due to uniformly high levels in the CSF from AIDS patients, IL-10 is not a useful diagnostic marker for AIDS-related brain lymphoma. The detection of EBV-DNA from the CSF by nested PCR is an extremely sensitive and specific diagnostic tool for AIDS-related PCNSL and should be further evaluated as a possible alternative in patients from whom brain biopsy is not advisable.


Comparison of CT scanning with photon absorptiometric measurement of bone mineral content in the appendicular skeleton.
Traditional methods of bone mineral analysis were compared to a new technique using computerized tomography (or CT scanning). The correlation between the CT values for long bones in the dog and actual calcium content was 0.9942. The correlation between two photon absorptiometric techniques and CT values were also 0.9981 and 0.9962. The precision of repeated scans was +/-2%. It is suggested that the CT scanner will allow bone mineral analysis to be performed with accuracy and precision.


Medullary branches of the vertebral artery: microsurgical anatomy and clinical significance.
Since the medullary arteries are of a great neurologic and neurosurgical significance, the aim was to perform a detailed microanatomic study of these vessels, as well as of the medullary infarctions in a group of patients. The arteries of 26 halves of the brain stem were injected with India ink and gelatin, microdissected and measured with an ocular micrometer. Neurologic and magnetic resonance imaging (MRI) examinations were performed in 11 patients. The perforating medullary arteries, averaging 6.7 in number and 0.26 mm in diameter, most often originated from the anterior spinal artery (ASA), and rarely from the vertebral (VA) (38.5%) and the basilar artery (BA) (11.6%). They supplied the medial medullary region. The anterolateral arteries, 4.8 in number and 0.2 mm in size, most often arose from the ASA and PerfAs, and nourished the anterolateral region. The lateral arteries, 2.2 in number and 0.31 mm in diameter, usually originated from the VA and the posterior inferior cerebellar artery (PICA). They supplied the lateral medullary region. The dorsal arteries, which mainly arose from the PICA and the posterior spinal artery (PSA), nourished the dorsal region, including the roof of the 4th ventricle. The anastomotic channels, averaging 0.3 mm in size, were noted in 42.3%. Among the medullary infarctions, the lateral ones were most frequently present (72.8%). The obtained anatomic data, which can explain the medullary infarctions symptomatology, are also important in order to avoid damage to the medullary arteries during neurosurgical and neuroradiologic interventions.


Stent-assisted coiling of intracranial aneurysms located on small vessels: midterm results with the LVIS Junior stent in 40 patients with 43 aneurysms.
The Low-profile Visualized Intraluminal Support (LVIS) Junior stent is dedicated for endovascular treatment of wide-neck intracranial aneurysms located on small-diameter vessels (2-3.5 mm). This study reports midterm clinical and anatomical results of this device. This study was approved by authors' ethical committees. A retrospective review of our prospectively maintained database identified all patients treated by this stent in three institutions. Technical issues and immediate and mid-term anatomical and clinical outcomes were evaluated. Forty patients (30 women/10 men, mean age of 55 years) with 43 aneurysms were identified. Mean aneurysm diameter was 5.6 mm (range, 2-13 mm). In all patients, treatment was successful and the stent could be precisely placed. There were three procedure-related complications, one stent thrombosis and two aneurysm ruptures, leading to immediate morbidity in one patient. Delayed ischemic events occurred in three patients including two transient attacks and one permanent deficit. The overall permanent morbidity rate was thus 5 %. No mortality occurred. Immediate aneurysm occlusion consisted of 36 complete occlusions (83.7 %), five neck remnants (11.6 %), and two incomplete occlusions (4.7 %). Twenty-seven patients (29 aneurysms) and 11 patients (11 aneurysms) had a 12- and 6-month angiographic follow-up, respectively. Final anatomical results included 36 complete occlusions (90 %) and four neck remnants (10 %). Two minor recanalizations were seen but did not require retreatment. Non-significant intrastent stenosis occurred in 7/40 followed-up cases (17.5 %). The LVIS Junior stent appears safe and effective for endovascular treatment of wide-neck intracranial aneurysms located on small vessels. Midterm results show high rates of adequate and stable occlusion.


Detection of benzylic adducts in DNA and nucleotides from 7-sulfooxymethyl-12-methylbenz[a]anthracene and related compounds by 32P-postlabeling using new TLC systems.
7,12-Dimethylbenz[a]anthracene (DMBA) is a highly potent experimental carcinogen, that must be transformed to its ultimate carcinogenic form in vivo. The meso-region theory of aromatic hydrocarbon carcinogenesis predicts that 7-hydroxymethyl sulfate (7-HMBA) ester plays a major role in the metabolic activation, benzylic DNA adduct formation and complete carcinogenicity of HMBA and DMBA. This study was undertaken to detect highly lipophilic benzylic DNA adducts resulting from the reaction between 7-hydroxymethy sulfate ester of HMBA (7-SMBA) and DNA as well as determine their DNA base selectivity. Synthetic 7-SMBA was incubated with DNA (800 microg/ml) and individual deoxynucleoside 3'-monophosphates (600 microg/ml) and benzylic adducts were analyzed by 32P-postlabeling/TLC following their enrichment with butanol extraction. Dilute ammonium hydroxide-based solvents were developed to detect the highly lipophilic aralkyl adducts. The reaction with DNA, dGp and dAp gave rise to multiple adducts; dCp and dTp showed no significant adducts. Chromatographic comparison revealed that the major DNA adduct was derived from dG. The methodology developed was also found applicable for highly lipophilic adducts resulting from sulfate esters of structurally-related metabolites of DMBA.


Implantation of rectal cancer cells in a fistula in ano: report of a case.
We report a case of implantation of tumor cells within a fistula in ano. A 36-year-old man with a 16-year history of an anal fistula underwent an operation for rectal carcinoma. Three weeks later, the anal fistula was resected. A histological examination of the specimen showed atypical cells; moreover, rectal carcinoma had proliferated in the granulation tissue lying underneath the intact squamous epithelium. Because there was no continuity to the rectal carcinoma or the anal glands, we diagnosed implantation of rectal cancer cells in a fistula in ano.


Covert Tracking to Immersive Stimuli in Traumatic Brain Injury Subjects With Disorders of Consciousness.
Eye tracking assessments are clinician dependent and can contribute to misclassification of coma. We investigated responsiveness to videos with and without audio in traumatic brain injury (TBI) subjects using video eye-tracking (VET). We recruited 20 healthy volunteers and 10 unresponsive TBI subjects. Clinicians were surveyed whether the subject was tracking on their bedside assessment. The Coma Recovery Scale-Revised (CRS-R) was also performed. Eye movements in response to three different 30-second videos with and without sound were recorded using VET. The videos consisted of moving characters (a dancer, a person skateboarding, and Spiderman). Tracking on VET was defined as visual fixation on the character and gaze movement in the same direction of the character on two separate occasions. Subjects were classified as "covert tracking" (tracking using VET only), "overt tracking" (VET and clinical exam by clinicians), and "no tracking". A k-nearest-neighbors model was also used to identify tracking computationally. Thalamocortical connectivity and structural integrity were evaluated with EEG and MRI. The ability to obey commands was evaluated at 6- and 12-month follow-up. The average age was 29 (± 17) years old. Three subjects demonstrated "covert tracking" (CRS-R of 6, 8, 7), two "overt tracking" (CRS-R 22, 11), and five subjects "no tracking" (CRS-R 8, 6, 5, 6, 7). Among the 84 tested trials in all subjects, 11 trials (13%) met the criteria for "covert tracking". Using the k-nearest approach, 14 trials (17%) were classified as "covert tracking". Subjects with "tracking" had higher thalamocortical connectivity, and had fewer structures injured in the eye-tracking network than those without tracking. At follow-up, 2 out of 3 "covert" and all "overt" subjects recovered consciousness versus only 2 subjects in the "no tracking" group. Immersive stimuli may serve as important objective tools to differentiate subtle tracking using VET.


Facile, eco-friendly, catalyst-free synthesis of polyfunctionalized quinoxalines.
A novel, facile and eco-friendly synthesis of quinoxalines from [Formula: see text] and 1,2-diamines was developed. An attractive feature of this protocol is that the desired products could be generated efficiently in water and without any catalyst, which is in accordance with the aim of green chemistry. A plausible mechanism has been proposed.


How linear response shaped models of neural circuits and the quest for alternatives.
In the past decades, many mathematical approaches to solve complex nonlinear systems in physics have been successfully applied to neuroscience. One of these tools is the concept of linear response functions. However, phenomena observed in the brain emerge from fundamentally nonlinear interactions and feedback loops rather than from a composition of linear filters. Here, we review the successes achieved by applying the linear response formalism to topics, such as rhythm generation and synchrony and by incorporating it into models that combine linear and nonlinear transformations. We also discuss the challenges encountered in the linear response applications and argue that new theoretical concepts are needed to tackle feedback loops and non-equilibrium dynamics which are experimentally observed in neural networks but are outside of the validity regime of the linear response formalism.


The axoplasmic reticulum within myelinated axons is not transported rapidly.
The axoplasmic reticulum in myelinated axons is an extensive system of branched smooth membranous tubules which is found throughout the length of large axons. To investigate its motility and possible role in fast axonal transport, a focal chilling method was used to arrest transport at two sites separated by a 3 mm wide warm region along the saphenous nerve of mice. The experiments ran for 3-4 h since axoplasmic material travelling faster than 25 mm/day would clear from the central warm region. The nerve was subsequently fixed and processed by a technique that enhances the electron density of the axoplasmic reticulum. Thin and thick sections from several regions along the nerve were then systematically studied using conventional and high voltage electron microscopy. In these studies we found that: 1. the axoplasmic reticulum does not accumulate against the proximal sides of the cold blocks; 2. although often closely associated, there is no evidence of continuity between the axoplasmic reticulum and the discrete membranous compartments that do accumulate proximal to the chilled regions; 3. the axoplasmic reticulum remains in the central 3 mm wide warm region; 4. the axoplasmic reticulum does not accumulate against the distal sides of the cold blocks; 5. retrogradely moving elements that do accumulate distal to the cold blocks do not fuse with the axoplasmic reticulum and are not contained in it; and 6. both retrograde and anterograde vector types are often closely associated with elements of axoplasmic reticulum. These results were supported by quantitative morphometric analysis. We conclude that the axoplasmic reticulum represents a discrete membrane system, separate from either anterogradely or retrogradely moving rapid transport vectors, and that this interconnected cisternal system itself is not rapidly transported.


Laponite assisted dispersion of carbon nanotubes in water.
The ability of Laponite to stabilize aqueous suspensions of multiwalled carbon nanotubes (MWCNTs) was investigated with the help of analytical centrifugation, microscopic image analysis, and measurements of electrical conductivity of hybrid Laponite+MWCNT suspensions. The impact of nanotube concentration C(n) (0.0025-0.5 wt%) and Laponite/MWCNTs ratio X (varied within 0-1 wt/wt) on the properties of Laponite+MWCNT hybrid suspensions was discussed. It was observed that sonication of MWCNTs at critical minimal concentration of Laponite X(c)≈0.25±0.05 resulted in efficient dispersion and formation of stabilized suspensions of individual nanotubes. The stabilization of nanotubes in the presence of Laponite was explained by adsorption of Laponite particles and formation of a hydrophilic charged shell on the surface of nanotubes. Increase of MWCNT concentration above the critical value resulted in percolation and formation of spatially extended electrically conductive networks of particles.


Pharmacologic enrichment of exosome yields and mitochondrial cargo.
In studies with human participants, exosome-based biospecimens can facilitate unique biomarker assessments. As exosome cargos can include mitochondrial components, there is interest in using exosomes to inform the status of an individual's mitochondria. Here, we evaluated whether targeted pharmacologic manipulations could influence the quantity of exosomes shed by cells, and whether these manipulations could impact their mitochondrial cargos. We treated human SH-SY5Y cells with bafilomycin A1, which interferes with general autophagy and mitophagy by inhibiting lysosome acidification and lysosome-autophagosome fusion; deferiprone (DFP), which enhances receptor-mediated mitophagy; or both. Exosome fractions from treated cells were harvested from the cell medium and analyzed for content including mitochondria-derived components. We found bafilomycin increased particle yields, and a combination of bafilomycin plus DFP consistently increased particle yields and mitochondria-associated content. Specifically, the exosome fractions from the bafilomycin plus DFP-treated cells contained more mitochondrial DNA (mtDNA), mtDNA-derived mRNA transcripts, and citrate synthase protein. Our data suggest pharmacologic manipulations that enhance mitophagy initiation, while inhibiting the lysosomal digestion of autophagosomes and multivesicular bodies, could potentially enhance the sensitivity of exosome-based biomarker assays intended to inform the status of an individual's mitochondria.


Is the future blue-green? A review of the current model predictions of how climate change could affect pelagic freshwater cyanobacteria.
There is increasing evidence that recent changes in climate have had an effect on lake phytoplankton communities and it has been suggested that it is likely that Cyanobacteria will increase in relative abundance under the predicted future climate. However, testing such a qualitative prediction is challenging and usually requires some form of numerical computer model. Therefore, the lake modelling literature was reviewed for studies that examined the impact of climate change upon Cyanobacteria. These studies, taken collectively, generally show an increase in relative Cyanobacteria abundance with increasing water temperature, decreased flushing rate and increased nutrient loads. Furthermore, they suggest that whilst the direct effects of climate change on the lakes can change the timing of bloom events and Cyanobacteria abundance, the amount of phytoplankton biomass produced over a year is not enhanced directly by these changes. Also, warmer waters in the spring increased nutrient consumption by the phytoplankton community which in some lakes caused nitrogen limitation later in the year to the advantage of some nitrogen-fixing Cyanobacteria. Finally, it is also possible that an increase in Cyanobacteria dominance of the phytoplankton biomass will lead to poorer energy flow to higher trophic levels due to their relatively poor edibility for zooplankton.


Relationships among HMO hospital utilization, physician visits, and years operational.
Statistical tests are performed on the membership of HMOs for which data are available (N = 124) to determine if (1) hospital utilization by HMO members is correlated with physician visits, (2) hospital utilization is correlated with the number of years a HMO is operational, and (3) physician visits is correlated with the number of years a HMO is operational. Statistical tests indicate that there is no correlation among the three pairs of variables.


Arterial injuries in two Bristol hospitals from 1974 to 1980.
Fifty-eight patients with 63 peripheral arterial injuries coming to the Bristol Royal Infirmary and Frenchay Hospital, Bristol over a six-year period from 1974-1980 were studied. The majority followed road traffic accidents, and over 70 per cent occurred in teenagers and young adults. Arterial reconstructions were undertaken in 51 cases (81 per cent) with concomitant fasciotomy in 3. Pulse volume recordings and on table arteriograms were used to detect and correct 2 reconstructions which were initially less than ideal. Forty-eight of 51 reconstructions were patent at follow up.


An efficient HPLC method for the analysis of isomeric purity of technetium-99m-exametazime and identity confirmation using LC-MS.
99mTc-exametazime (99mTc-d,l-HMPAO, 99mTc-d,l-hexamethylpropyleneamine oxime) is a neutral rather unstable complex of short-lived 99mTc (t(1/2)=6 h) with the d,l-isomer (mixture of D,D- and L,L-isomers) of a bis-amine bis-oxime tetraligand. It is widely used for measurement of regional cerebral perfusion in nuclear medicine. The meso-isomer (D,L-form) should not be present in a preparation as it is not retained in brain and thus does not provide clinically useful information. Meso-HMPAO is removed from the ligand during the synthesis procedure by repeated recrystallization, but can still be present as impurity in d,l-isomer. Due to the lack of a suitable chromatographic method for analysis of the isomeric purity of 99mTc-exametazime preparations, United States Pharmacopoeia 25 (USP 25) prescribes a biological test in rats for quality control purpose. In this study, we developed a suitable high-performance liquid chromatography (HPLC) method which allows to demonstrate the relative amounts of d,l- and meso-isomer in 99mTc-exametazime and so obviates the need for a biodistribution test in animals as part of the quality control. Due to the low concentrations in which 99mTc-d,l-HMPAO is obtained (typically 2-6 ng/ml), confirmation of the identity of 99mTc-d,l-HMPAO in the monograph of the European Pharmacopoeia is now performed only indirectly by TLC and assessment of its retention time on RP-HPLC. To investigate the potential of radio-LC-MS for assessment of the identity of 99mTc-exametazime, 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO prepared using a Tc-rich eluate were analyzed using a radio-LC-MS system equipped with a time-of-flight mass spectrometer with electrospray ionization. The main peak in the radiometric channel coincided with the molecular ion mass of 99mTc-d,l-HMPAO in the mass spectrometer channel and the measured accurate mass differed only by 0.26 ppm from the theoretical mass. The identity of 99mTc-meso-HMPAO was also confirmed. Thus, radio-LC-MS allowed to obtain strong evidence for the structure of 99mTc-d,l-HMPAO and 99mTc-meso-HMPAO at nanomolar concentration. It is concluded that radio-LC-MS can become a sensitive aid in quality control of "no carrier added" radiopharmaceutical preparations.


[Miniature quadrupole mass spectrometer array and its applications in manned spaceflight].
This paper explained the working method of the quadrupole mass spectrometer array and its features of volume, weight, power, sensitivity to many kinds of gases as well as flexibility when used together with a miniature gas chromatograph (GC) and a thermal-conductivity detector (TCD). Three types of structure formed in its development are also described. Finally, the applications of the quadrupole mass spectrometer array in the field of manned spaceflight were summarized.


Pediatric bacterial meningitis in French Guiana.
Controlling vaccine-preventable infectious diseases is a public health priority in French Guiana but there is currently no epidemiological data on pediatric bacterial meningitis in this overseas department. Our aim was to describe data related to pediatric bacterial meningitis in French Guiana and compare it with that of metropolitan France. We conducted a multicenter retrospective study from 2000 to 2010 to describe the clinical picture, biological data, epidemiology, and outcome of pediatric bacterial meningitis case patients in French Guiana. The median age of bacterial meningitis patients was 6months [0-15] and the sex ratio 1.06. We observed a total of 60 bacterial meningitis case patients. Most presented with pneumococcal meningitis (24 patients; 40%); 11 with Haemophilus influenzae type b meningitis (23%), five with group B streptococcal meningitis (8.5%), and five others (8.5%) with staphylococcal meningitis (three patients presented with coagulase-negative staphylococci and two with Staphylococcus aureus). Only one patient presented with group B meningococcal meningitis, an 18-month-old infant. We recorded 14 deaths (overall case fatality: 23%); eight were due to Streptococcus pneumoniae (case fatality: 33%). The overall sequelae rate was 28%. It was 32% for patients presenting with pneumococcal meningitis. We observed that 38% of children who had never been vaccinated were infected by a vaccine-preventable bacterium. We observed many differences in the distribution of the bacteria and in the patients' prognosis when comparing the French Guiana data with that of metropolitan France. Improving vaccination coverage would decrease the incidence of H. influenzae meningitis.


Spatial patterns in water quality and source apportionment in a typical cascade development river southwestern China using PMF modeling and multivariate statistical techniques.
River cascade development is one of the human activities that have the most significant impact on the water environment. However, the mechanism of cascade development affecting river hydrochemical components still needs to be further studied. In this study, water quality index(WQI), positive matrix factorization(PMF) model and multivariate statistical techniques were used to identify the mechanism of cascade development affecting river hydrochemical components in an typical cascade development Rivers, Lancang River, China. The results showed that the water quality of Lancang River is relatively good due to less affected by human activity. The spatial variation of river hydrochemistry is affected by the development of cascade reservoirs, and shows three patterns: irregular variation (pH and DO), fluctuating decreasing (Na+, Cl-, SO42- and HCO3-) and multi-peak variation (TN, TDN, NO3--N and NH4+-N). It's worth noting that the concentration of the most hydrochemical parameters is higher in the upper reaches (less human activities) than that in the middle and lower reaches of river due to the retention effect of the reservoir on the chemical composition. The PMF model outputs revealed that the rock weathering and internal source, sewage and soil nitrogen, and chemical fertilizer were primary material sources of Lancang River. Compared with the natural channel zone (41.0%), the interaction of water-rock has more influence on chemical component in the reservoir area (56.3%), while the contribution of fertilizer (11.2%) to the river hydrochemistry is less. The sites of downstream of the reservoir dam were affected by the retention of the reservoir and the disturbance of the bottom drainage, which leads to the weakening of the influence of the sewage (44.7%) on the river material and the increase of the contribution of fertilizer (25.0%). These results could provide valuable information in controlling the eutrophication of cascade reservoirs and the scientific construction of river cascade reservoirs.


Spinal traumas: some postoperative complications in experimental animals.
Animals with severe spinal traumas show paraplegic syndrome and various somatic and autonomic dysfunctions. Of the various dysfunctions those related to hypothermia, bladder problems, and autophagia are of serious nature. The condition of animals with these complications deteriorates rapidly, and the animals are sacrificed for histological and pathological analyses. The findings show that the postoperative complications are related to the degree of severity of the trauma, and that 50-80% animals are lost due to these complications. Most of these animals are lost during the first two weeks after surgery, and the remaining at later stages. Transplantation of neural tissue at the site of lesion does not ameliorate these postoperative complications and improve the survival rate of the animals.


A cDNA library functional screening strategy based on fluorescent protein complementation assays to identify novel components of signaling pathways.
Progress towards a deeper understanding of cellular biochemical networks demands the development of methods to both identify and validate component proteins of these networks. Here, we describe a cDNA library screening strategy that achieves these aims, based on a protein-fragment complementation assay (PCA) using green fluorescent protein (GFP) as a reporter. The strategy combines a simple cell-based cDNA-screening approach (interactions of a "bait" protein of interest with "prey" cDNA products) with specific functional assays that use the same system and provide initial validation of the cDNA products as being biologically relevant. We applied this strategy to identify novel interacting partners of the protein kinase PKB/Akt. This method provides very general means of identifying and validating genes involved in any cellular process and is particularly designed for identifying enzyme substrates or regulatory proteins for which the enzyme specificity can only be defined by their interactions with other proteins in cells in which the proteins are normally expressed.


Effect of elective surgical procedures on tissue protein synthesis.
The purpose of the study was to examine whether an early decrease in protein synthesis rates occurred in any tissues after abdominal surgery in postprandial rats. Leucine-specific radioactivity in mixed protein and on tRNA was determined after continuous infusion of L-[3H]leucine. Synthesis rates of mixed protein were significantly decreased in the gastrocnemius muscle, but not in the jejunum, liver, or heart, of rats 1-2 hr after splenectomy and ovariectomy or after combining the groups that had various types of abdominal surgery. These results suggest that a very early decrease in the protein synthesis rate of the gastrocnemius muscle occurs after laparotomy.


Modulation of steroidogenesis in choriocarcinoma cells by cholera toxin, phorbol ester, epidermal growth factor and insulin-like growth factor I.
The effects of cholera toxin (CT), which stimulates adenylate cyclase, 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C activator, epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on progesterone (P) and estradiol (E2) secretion by human choriocarcinoma JEG-3 cells were studied. During a 48 h incubation, CT, TPA and EGF stimulated P production in a concentration-dependent manner, whereas IGF-I was without effect. CT (1.0 ng/ml), TPA (10 ng/ml) and EGF (10 ng/ml) stimulated P production maximally 4.3-, 3.3- and 2.3-fold over basal, respectively. When added together with CT, TPA and EGF stimulated P production 10.0- and 5.0-fold over basal production showing that the effects of CT plus TPA were more than additive but those of CT plus EGF less than additive. Time-course studies indicated that the effects were detectable at 12 h, and continued to increase up to 48 h. The conversion of added dehydroepiandrosterone sulfate (DHEAS) to E2 was stimulated by CT and TPA and inhibited by IGF-I in a concentration-dependent manner. By contrast, EGF had no effect. The maximal responses in E2 production were 3.2- and 2.0-fold over unstimulated cells by CT (1.0 ng/ml) and TPA (10 ng/ml), respectively. When both agents were added together, their effects on E2 production were additive with 5.5-fold increase over unstimulated cells. IGF-I (30 ng/ml) inhibited maximally basal and CT-stimulated E2 production by 33% and 42%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstruction of the pharynx after laryngectomy and partial pharyngectomy.
Stricture formation may occur after pharyngolaryngectomy if less than one half of the circumference of the pharynx is available for primary closure. However, the alternative of total pharyngectomy with skin flap or visceral replacement carries with it a high mortality and morbidity rate. In an attempt to overcome these problems, a policy of patch grafting the pharyngeal defect with a myocutaneous flap or segment of free vascularised jejunum has been adopted whenever a strip of pharyngeal mucosa greater than one centimetre in width remains after excision of the tumour. A good post-operative swallow has been achieved in all cases.


Occurrence of nighttime gastroesophageal reflux in disturbed and normal sleepers.
It is not uncommon in a sleep laboratory to encounter individuals who have complaints of disturbed sleep, but who do not meet the criteria for a sleep disorder when evaluated by polysomnography. Because gastroesophageal reflux is known to occur in many individuals without their awareness, it is possible that some of these individuals might be suffering from reflux that is disturbing their sleep. Eighty-one individuals with complaints of disturbed or unrefreshing sleep, but no complaints of heartburn, were recruited. A comparison group of 39 individuals with neither sleep nor heartburn complaints also was studied. Both groups were studied on 2 separate occasions by simultaneous polysomnography and pH monitoring to detect the presence of nighttime gastroesophageal reflux and to determine sleep outcomes. In the disturbed-sleep group 27% of subjects had at least one reflux event compared with 33% in the normals. In the subjects who experienced reflux, the disturbed-sleep group had a significantly greater percentage of acid exposure time compared with the normals (9.5% vs 1.6%; P < .05). Participants in the disturbed-sleep group also had a longer sleep-onset latency (P < .05) and less total sleep time (P < .05) compared with the normal sleepers. Among individuals with complaints of disturbed sleep, there was a subset of individuals who had significant gastroesophageal reflux. We speculate that sleep-related gastroesophageal reflux may play a role in producing disturbed sleep in individuals without heartburn and otherwise unexplained sleep disturbance.


Reflection and transmission of laser light from the esophagus: the influence of incident angle.
The application of lasers in gastrointestinal endoscopy is rapidly expanding. Because of the tubular configuration of the gastrointestinal tract, endoscopists often deliver laser energy at large angles of incidence. As incident angle affects the fraction of radiation reflected from the tissue surface, we measured the transmittance and reflectance of laser light from in vitro esophagus as a function of incident angle, using integrating sphere and goniometric techniques. At a wavelength of 633 nm and angles of incidence less than 50 degrees, the total transmittance of the esophagus is approximately 25% and the total reflectance is approximately 45%; both are isotropically distributed. At larger angles of incidence, a specularly reflected component becomes evident and the total reflectance increases. The absorbed light per unit area illuminated decreases with increasing angle, because the area illuminated by the laser beam is proportional to the secant of the incident angle. The data suggest that during endoscopic laser procedures the incident laser beam should be directed within 50 degrees of normal for optimal performance and safety.


Secular trends of heart failure among US male physicians.
Heart failure (HF) remains a major public health issue. Data on long-term trends in the incidence of HF and survival after its onset are limited. A prospective cohort study conducted between 1985 and 2004 in 21,906 participants of the Physicians' Health Study I who were alive and free of HF on January 1, 1985. After an average follow-up of 16.8 years, a total of 909 incident cases of HF occurred in this cohort. There was no evidence for a substantial change in the incidence rate of HF across the 4 periods (P for trend .29). From 1985 through 2004, there were 457 deaths among 909 subjects with HF. Compared with the period of 1985 to 1989, the age-adjusted hazard ratio of all-cause mortality after onset of HF was 0.61 (0.46-0.81), 0.37 (0.28-0.48), and 0.10 (0.07-0.15) in the second, third, and fourth period, respectively (P for trend <.0001). Additional adjustment for treatment arm, diabetes, myocardial infarction, hypertension, atrial fibrillation, coronary angioplasty or bypass, valvular heart disease, and left ventricular hypertrophy did not alter these results. Similar findings were seen in subjects with HF with and without antecedent myocardial infarction (P for trend <.0001 each). Over the past 20 years, we observed a lower risk of all-cause mortality after onset of HF whereas no major change in the incidence of HF was seen among US male physicians.


Carbohydrate-functionalized surfactant vesicles for controlling the density of glycan arrays.
We report on the development of a method for rapidly characterizing the glycan binding properties of lectins. Catanionic surfactant vesicles, prepared from cationic and anionic surfactants, spontaneously formed in water and remained stable at room temperature for months. By varying the amount of glycoconjugate added during preparation, glycans were incorporated onto the outer surface of the vesicles in a controlled range of densities. The carbohydrate-functionalized vesicles were applied to commercially available, nitrocellulose-coated slides to generate glycan arrays. As proof of concept, the binding of two lectins, concanavalin A and peanut agglutinin, to the arrays was quantified using a biotin-avidin fluorescence sandwich assay. This facile method of preparing a glycan array by using vesicles to control the glycan density can be expanded to provide a platform for characterizing unknown lectins.


Factors effecting the solubilisation of stearoyl-coA desaturase of hen liver microsomes.
1. The lipid requirement for maximum desaturase activity was investigated using acetone/water mixtures. It was shown that for maximum stearoyl-CoA desaturase activity of hen liver microsomes neither the total neutral lipid fraction nor 44% of the phospholipid fraction were required. 2. The effect of sodium deoxycholate, Triton X-100, Nonidet P-40 and Bio-solv on the enzyme activity indicated that the neutral detergents had a milder effect than the ionic detergent but both classes could cause considerable irreversible loss of activity. 3. The treatment of the microsomes with 2.5% (v/v) water in acetone greatly improved the effective solubilising power of Triton X-100. The yield of desaturase in the 100 000 X g supernatant obtained by treating the microsomal fraction in this way was strongly dependent upon protein concentration. Maximum solubilisation was achieved with25 mg protein per ml 1% (w/v) Triton X-100 in 0.1 M potassium phosphate buffer pH 7.4. 4. A comparison of the properties of the solubilised and membrane-bound enzyme was made by an investigation of: (i) the temperature and pH optimum, (ii) activation energy and (iii) the effect of inhibitors on the enzyme activity.


A comparison of the Papanicolaou smear and the cervigram: sensitivity, specificity, and cost analysis.
A total of 3271 gynecology patients between the ages of 18-50 years were screened for cervical intraepithelial neoplasia and invasive cervical cancer by simultaneous Papanicolaou smears and cervigram, a noninvasive photographic method recently introduced for screening. The accuracy of each screening test, when positive or suspicious, was evaluated independently and the results compared with colposcopically directed biopsy results. The cervigram was significantly more sensitive than the Papanicolaou smear (P less than .001), whereas the Papanicolaou smear was significantly more specific than the cervigram in detecting cervical intraepithelial neoplasia (P less than .001). Cost analysis integrating sensitivity and specificity with cost per procedure indicated a greater yield of cervical intraepithelial neoplasia with the cervigram than with the Papanicolaou smear, by 3.7:1 case per dollar.