Sociodemographic and Psychosocial Factors Associated With Diet Quality in 6 Rural Native American Communities.
To identify psychosocial and household environmental factors related to diet quality among Native Americans (NA). Analysis of baseline data from a community-randomized obesity prevention trial. Six rural NA communities in the Midwest and the Southwestern US. A total of 580 tribal members, aged 18-75 years old (mean 45 years), 74% female, self-identified as the main household food purchaser. Diet quality (Healthy Eating Index-2015 [HEI]) was derived from a semiquantitative food frequency questionnaire. Sociodemographic, psychosocial, and home food environment factors were assessed via interviewer-administered questionnaires. One-way ANOVA, linear regression models, and 2-tailed t tests compared HEI scores among sociodemographic categories. Multiple linear regression models assessed the relationship between psychosocial factors, home food environment, and HEI. Prevalence of obesity was 59%. Mean HEI-2015 score was 49.3 (SD = 8.1). Average HEI scores were 3.0 points lower in smokers than nonsmokers (P < 0.001), and 2.2 points higher in females than males (P < 0.01). Higher self-efficacy (β = 0.97; P < 0.001) and healthier eating intentions (β = 0.78; P < 0.001) were positively associated with HEI. Healthier household food patterns score was associated with higher HEI (β = 0.48; P < 0.01). Psychosocial factors were associated with diet quality, a finding that supports the use of social-cognitive intervention approaches in rural NA communities in the Midwest and Southwest, and warrants evaluation in other locations. There remains a need to elucidate the association between the Food Distribution Program on Indian Reservations and diet quality.


Development and evaluation of a DGT sampler using functionalised cross-linked polyethyleimine for the monitoring of arsenic and selenium in mine impacted wetlands.
Arsenic and selenium are both carcinogenic and their presence in fresh water has attracted the development of robust and accurate monitoring techniques. A new diffusive gradients in thin-films (DGT) sampler was developed and evaluated for the in situ measurements of arsenic and selenium. The binding layer was made from a mixture of sulphonated and phosphonated cross-linked polyethylenimine (SCPEI and PCPEI, respectively). The optimum ratio of a SCPEI and PCPEI resin mixture was determined. The DGT sampler was calibrated under laboratory conditions to determine the influence of sample turbulence, concentration and pH. The optimised DGT passive sampler was field deployed in a mine impacted dam for 12 days. Binding layer optimisation shows that the polymers had to be mixed in a specific ratio of 80% sulphonated and 20% phosphonated per 0.8 g of the resin mixture, in the loose polymer form. Embedding the resin mixture in agarose gel reduced the uptake of both arsenic and selenium dramatically. At sample pH 3.0 and 5.0, the DGT sampler did not show significant differences in uptake of the two elements during the 15 day deployment. The passive sampler had limited adsorption capacity and was found better suited for dilute solutions, with concentrations below 0.5 mg L-1 of the target metals. This effect was more pronounced when exposed to dam water which had competing cations. Cations may have reduced the capacity by binding to the PEI backbone via the large number of amine groups. Nonetheless, these cations did not show linear uptake.


Periprostatic lymph node metastasis in prostate cancer and its clinical significance.
To evaluate the potential of periprostatic lymph node (LN) as a staging indicator, particularly with the use of methods for enhanced detection of micrometastasis. We retrieved cases with periprostatic LN from radical prostatectomy specimens accrued between 1997 and 2007 at our institution. Twenty-one (0.8%) of 2663 radical prostatectomy specimens had periprostatic LNs (total number of LNs = 22). LN size ranged from 0.8 to 4.7 mm. Most of the periprostatic LNs were located close to the posterior base. Seven (32%) of 22 LNs were involved by metastatic prostate cancer (PCa), including five detected on routine haematoxylin and ceosin slides and an additional two detected only by immunohistochemistry. Cases with periprostatic LNs had a significantly higher metastatic rate (29%; six of 21) compared to those with pelvic LNs sampled at radical prostectatomy in our institution (1.9%). When compared to cases with negative periprostatic LNs (n = 15), the tumour characteristics of cases with metastatic periprostatic LNs (n = 6) included higher tumour volume, Gleason score, stage and a greater propensity for prostate-specific antigen (PSA) recurrence. Despite their infrequent identification, periprostatic LNs if detected in the radical prostatectomy specimen should be evaluated with greater scrutiny (step sections and/or immunohistochemical studies) to evaluate their prognostic potential.


[Total synthesis and properties of prostaglandins. XXXVIII. Synthesis of 11-deoxyprostaglandin-E1 derivatives with amino acids and amines].
In order to study the physiological functions of 11-deoxyprostaglandin E1-alpha, a series of its amide derivatives with amino acids and some amines were synthesized using mixed anhydride technique. The myotropic properties of newly synthesized compounds were investigated.


Sudden infant and perinatal unexplained death: are we moving forward yet?
Autonomic nervous system and cardiac conducting system dysfunctions have been proposed to be implied in the pathogenesis of sudden infant death syndrome (SIDS). However, most clinicians and even pathologists lack experience with detailed examination of the brainstem and cardiac conducting system and may not recognize lesions within those systems that potentially could be crucial factors in the sudden unexpected perinatal and infant death. Recent anatomical, pathological, and bacteriological studies in SIDS confirm that the multidisciplinary approach provides the best approach to the challenging problems of SIDS and sudden unexplained perinatal death.


Chronic atrazine exposure causes disruption of the spontaneous locomotor activity and alters the striatal dopaminergic system of the male Sprague-Dawley rat.
The herbicide atrazine (ATR) is widely used around the world, and is a potential toxicant of the dopaminergic systems. Nigrostriatal and mesolimbic systems are the two major dopaminergic pathways of the central nervous system; they play key roles mediating a wide array of critical motor and cognitive functions. We evaluated the effects of exposing male rats for one year to 10 mg ATR/kg B.W. on these systems using motor and cognitive tasks and measuring monoamine content in the striatum, nucleus accumbens, prefrontal cortex, and hypothalamus. ATR administration resulted in impaired motor coordination and greater spontaneous locomotor activity only after 10 to 12 months of exposure. Chronic exposure to 10 mg ATR decreased striatal dopamine, but had no effect on accumbal, hypothalamic or cortical monoamine content. Chronic ATR exposure caused discrete changes in learning tasks that involve either the striatum or the nucleus accumbens. These results indicate that chronic exposure to ATR preferentially targets the nigrostriatal dopaminergic pathway, in comparison to the other dopaminergic pathways evaluated in this study, inducing behavioral and neurochemical alterations. In order to unveil the full extent of atrazine's effects on the nervous system, other neurochemical systems should be considered in future studies.


Sentiment Analysis of Conservation Studies Captures Successes of Species Reintroductions.
Learning from the rapidly growing body of scientific articles is constrained by human bandwidth. Existing methods in machine learning have been developed to extract knowledge from human language and may automate this process. Here, we apply sentiment analysis, a type of natural language processing, to facilitate a literature review in reintroduction biology. We analyzed 1,030,558 words from 4,313 scientific abstracts published over four decades using four previously trained lexicon-based models and one recursive neural tensor network model. We find frequently used terms share both a general and a domain-specific value, with either positive (success, protect, growth) or negative (threaten, loss, risk) sentiment. Sentiment trends suggest that reintroduction studies have become less variable and increasingly successful over time and seem to capture known successes and challenges for conservation biology. This approach offers promise for rapidly extracting explicit and latent information from a large corpus of scientific texts.


A review of antibiotics and antibiotic resistance genes (ARGs) adsorption by biochar and modified biochar in water.
Antibiotics have been used in massive quantities for human and animal medical treatment, and antibiotic resistance genes (ARGs) are of great concern worldwide. Antibiotics and ARGs are exposed to the natural environment through the discharge of medical wastewater, causing great harm to the environment and human health. Biochar has been widely used as a green and efficient adsorbent to remove pollutants. However, pristine and unmodified biochars are not considered sufficient and efficient to cope with the current serious water pollution. Therefore, researchers have chosen to improve the adsorption capacity of biochar through different modification methods. To have a better understanding of the application of modified biochar, this review summarizes the biochar modification methods and their performance, particularly, molecular imprinting and biochar aging are outlined as new modification methods, influencing factors of biochar and modified biochar in adsorption of antibiotics and ARGs and adsorption mechanisms, wherein adsorption mechanism of ARGs on biochar is found to be different than that of antibiotics. After that, the directions of biochar and modified biochar worthy of research and the issues that need attention are proposed. It can be noted that under the current dual carbon policy, biochar may have wider application prospects in future.


Promotion of axon regeneration and protection on injured retinal ganglion cells by rCXCL2.
In addition to rescuing injured retinal ganglion cells (RGCs) by stimulating the intrinsic growth ability of damaged RGCs in various retinal/optic neuropathies, increasing evidence has shown that the external microenvironmental factors also play a crucial role in restoring the survival of RGCs by promoting the regrowth of RGC axons, especially inflammatory factors. In this study, we aimed to screen out the underlying inflammatory factor involved in the signaling of staurosporine (STS)-induced axon regeneration and verify its role in the protection of RGCs and the promotion of axon regrowth. We performed transcriptome RNA sequencing for STS induction models in vitro and analyzed the differentially expressed genes. After targeting the key gene, we verified the role of the candidate factor in RGC protection and promotion of axon regeneration in vivo with two RGC-injured animal models (optic nerve crush, ONC; retinal N-methyl-D-aspartate, NMDA damage) by using cholera toxin subunit B anterograde axon tracing and specific immunostaining of RGCs. We found that a series of inflammatory genes expressed upregulated in the signaling of STS-induced axon regrowth and we targeted the candidate CXCL2 gene since the level of the chemokine CXCL2 gene elevated significantly among the top upregulated genes. We further demonstrated that intravitreal injection of rCXCL2 robustly promoted axon regeneration and significantly improved RGC survival in ONC-injured mice in vivo. However, different from its role in ONC model, the intravitreal injection of rCXCL2 was able to simply protect RGCs against NMDA-induced excitotoxicity in mouse retina and maintain the long-distance projection of RGC axons, yet failed to promote significant axon regeneration. We provide the first in vivo evidence that CXCL2, as an inflammatory factor, is a key regulator in the axon regeneration and neuroprotection of RGCs. Our comparative study may facilitate deciphering the exact molecular mechanisms of RGC axon regeneration and developing high-potency targeted drugs.


A novel variant of the aortic arch great vessels.
Congenital variants of the aortic arch are important to recognize not only for their association with congenital heart disease, vascular rings, and chromosomal abnormalities but also for the purposes of neurointerventional angiography. While many different variants have been reported in the literature, we present two rare cases of an aortic arch variant that, to the best of our knowledge, has not yet been described in the literature- an anteriorly-directed, independent common origin of both carotid arteries from the ascending aorta, with separate subclavian artery trunks originating from the arch.


Acute anterior uveitis: clinical and experimental aspects.
Acute anterior uveitis (AAU) or iritis is an inflammatory disorder of the anterior structures of the eye that may be associated with a number of disease entities. A significant proportion of patients will have no evidence of an underlying disorder and are labeled as idiopathic. Within this group approximately 50% will possess the human leukocyte antigen, HLA-B27, and some will have an associated spondyloarthropathy such as ankylosing spondylitis or Reiter's syndrome. Nevertheless, a number of HLA-B27-positive patients have no apparent underlying rheumatic disorder. The potential interplay of HLA-B27 and certain infective agents in the pathogenesis of AAU is discussed with particular reference to Yersinia species. Presentation of a uveitogenic peptide, similar to the arthritogenic peptide model in spondyloarthropathies, may be a mechanism involved in the development of AAU. Experimental models in animals have increased our understanding of the roles of retinal proteins and bacterial peptides, as well as T cells and cytokines, in the pathogenesis of uveitis. As in animal models of arthritis, certain retinal peptides (in conjunction with adjuvant therapy) can induce uveitis in animals. The treatment of isolated AAU usually involves topical medication and the prognosis is good. Occasional cases, especially those associated with systemic disorders, may require the addition of systemic corticosteroids or other immunosuppressive medications.


Diagnosis of gastro-oesophageal reflux disease is enhanced by adding oesophageal histology and excluding epigastric pain.
The diagnosis of gastro-oesophageal reflux disease (GERD) in clinical practice is limited by the sensitivity and specificity of symptoms and diagnostic testing. To determine if adding histology as a criterion and excluding patients with epigastric pain enhances the diagnosis for GERD. Patients with frequent upper gastrointestinal symptoms who had not taken a proton pump inhibitor in the previous 2 months and who had evaluable distal oesophageal biopsies were included (Diamond study: NCT00291746). Epithelial hyperplasia was identified when total epithelial thickness was at least 430 μm. Investigation-based GERD criteria were: presence of erosive oesophagitis, pathological oesophageal acid exposure and/or positive symptom-acid association probability. Symptoms were assessed using the Reflux Disease Questionnaire and a pre-specified checklist. Overall, 127 (55%) of the 231 included patients met investigation-based GERD criteria and 195 (84%) met symptom-based criteria. Epithelial hyperplasia was present in 89 individuals, of whom 61 (69%) met investigation-based criteria and 83 (93%) met symptom-based criteria. Adding epithelial hyperplasia as a criterion increased the number of patients diagnosed with GERD on investigation by 28 [12%; number needed to diagnose (NND): 8], to 155 (67%). The proportion of patients with a symptom-based GERD diagnosis who met investigation-based criteria including epithelial hyperplasia was significantly greater when concomitant epigastric pain was absent than when it was present (P < 0.05; NND: 8). Histology increases diagnosis of GERD and should be performed when clinical suspicion is high and endoscopy is negative. Excluding patients with epigastric pain enhances sensitivity for the diagnosis of GERD.


Pattern dystrophies in patients treated with deferoxamine: report of two cases and review of the literature.
Deferoxamine (DFO) is one of the most commonly used chelation treatments for transfusional hemosiderosis. Pattern dystrophies constitute a distinct entity of retinal disorders that has been occasionally identified in association with deferoxamine. We report two cases of bilateral macular pattern dystrophy in transfusion dependent patients undergoing chronic chelation therapy with deferoxamine due to thalassemias. Our patients were evaluated with multimodal imaging and the results are presented. Both patients had normal cone and rod responses in the full-field electroretinogram and continued the prescribed chelation therapy, after hematology consult. The patients were followed up every 3 months for 2 and 4 years respectively for possible deterioration. Their best corrected visual acuity remained stable with no anatomic change on Optical Coherence Tomography findings. Multimodal imaging of our patients allowed a better evaluation and possibly earlier detection of the DFO-related changes. Screening and close follow up of patients under chronic chelating therapy is important in order to promptly diagnose and manage possible toxicity either with discontinuation of the offending agent or dose modification.


Bakuchiol derivatives as novel and potent cytotoxic agents: a report.
A library of 28 compounds comprising of acyl, amino, halo, nitro, styryl and cyclized derivatives of bakuchiol have been evaluated against a panel of eight human cancer cell lines. Bioevaluation studies have resulted in the identification of potent cytotoxic molecules exhibiting concentration dependent growth inhibition against leukemia cancer cells with best results observed for compounds 17 and 22 exhibiting IC(50) 1.8 and 2.0 μM respectively. As evident from various biological end-points, inhibition of cell proliferation by inducing G2/M cell cycle arrest, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis is demonstrated.


Results of iliac branch devices for hypogastric salvage after previous aortic repair.
The aim of this multicentric study was to assess the "REsults of iliac branch deviceS for hypogastriC salvage after previoUs aortic rEpair (RESCUE)." All consecutive patients who underwent implantation of iliac branch devices (IBDs) after previous open aortic repair (OAR) or endovascular aortic repair (EVAR) at seven centers were captured. The study cohort was divided into two groups according to the type of repair originally performed. Early outcomes included immediate technical success and perioperative adverse events. Late outcomes included survival, side branch (SB) primary patency, SB instability, and new onset buttock claudication. A total of 94 patients (82 male) were included in the study, 10 of them received bilateral implantation of IBDs. This resulted in a total of 104 devices included in the final analysis. Indication for treatment were endoleak 1b or progressive iliac aneurysmal degeneration or distal para-anastomotic aortic aneurysms; 73 were implanted after previous EVAR and 31 after previous OAR. Technical success was 100% in both groups. The 3-year rate of freedom from SB instability was 90.1% after previous EVAR and 85.4% after previous OAR, respectively (P = .05). The 3-year estimates of SB primary patency were significantly lower in patients who had received OAR as compared with those that had received EVAR (89.8% vs 94.9%; P = .05). Endovascular treatment with IBDs following previous OAR or EVAR is safe and effective up to 3 years. Freedom from SB instability during follow-up was lower in patients who had previously undergone OAR than EVAR.


Cholesterol-fed ovariectomized monkeys are good animal models for human atherosclerosis of postmenopausal women.
Although it is well known that the incidence of atherosclerosis is markedly increased in postmenopausal women, antiatherosclerotic effects of estrogen replacement therapies are not clear. One of the reasons for this is due to the lack of appropriate animal models for atherosclerosis of postmenopausal women. Therefore, we attempted to develop an animal model for atherosclerosis of postmenopausal women and examined the antiatherosclerotic effects of estrogen replacement therapy. Adult ovariectomized Japanese monkeys were fed 2% cholesterol diet alone (C-group) or in combination with conjugated estrogen (CE-group) for 30 months. The serum estradiol-17beta levels of the CE-group were varied between 10 and 204.5 ng/dl during treatment. In the C-group, the serum total cholesterol levels were increased from 110 to 270 mg/dl, and atheroma was first observed after 3-months treatment with angioscopy. In the CE-group, the levels of the serum total cholesterol during treatment were 30% lower than those of the C-group, and the aortic lesions were first observed after 12-months treatment with angioscopy. The aortic intimal thickness of the CE-group was 58% of the C-group. This finding showed good agreement with the angioscopic observation. The aortic lesions were of a fibromuscular type in both groups. In conclusion, a cholesterol-fed ovariectomized monkey is an appropriate animal model for atherosclerosis of postmenopausal women. Furthermore, angiofiberscopic and histopathological observations suggested that estrogen replacement therapy was valid for atherosclerosis of postmenopausal women.


Imitators of preeclampsia: A review.
This review article describes disorders that may imitate preeclampsia (PET), preeclampsia with haemolysis, elevated liver enzymes and low platelets (HELLP syndrome) and eclampsia.


[Change in the carbohydrate metabolic indices in the hemolymph of freshwater molluscs infected with trematode parthenitae and larvae].
The effect of parthenites and larvae of trematodes on the contents of total sugar, glucose as well as on the variations in the activity of acid and alkaline phosphatases of the haemolymph of Lymnaea stagnalis, Planorbis corneus and Viviparus viviparus has been studied. The studies have revealed differences in the degree of effect of individual species of parasites on their hosts depending on their localisation, infection intensity and developmental stage.


Substrate specificity of the Rad3 ATPase/DNA helicase of Saccharomyces cerevisiae and binding of Rad3 protein to nucleic acids.
Rad3 protein from the yeast Saccharomyces cerevisiae is a single-stranded DNA-dependent ATPase which catalyzes the unwinding of DNA.DNA duplexes. In the present studies we have demonstrated that the purified enzyme additionally catalyzes the displacement of RNA fragments annealed to complementary DNA. Quantitative comparisons using otherwise identical partially duplex DNA.DNA and DNA.RNA substrates indicate a significant preference for the latter. Competition for ATPase or DNA helicase activity by various homopolymers suggests that Rad3 protein does not discriminate between ribonucleotide and deoxyribonucleotide homopolymers with respect to binding. However, neither single-stranded RNA nor various ribonucleotide homopolymers supported the hydrolysis of nucleoside 5'-triphosphates. Additionally, Rad3 protein was unable to catalyze the displacement of oligo(dA) annealed to poly(U), suggesting that the catalytic domain of the enzyme is exquisitely sensitive to chemical and/or or conformational differences between DNA and RNA. Hence, it appears that Rad3 protein is not an RNA helicase.


Bacterial diacetyl suppresses abiotic stress-induced senescence in Arabidopsis.
Premature plant senescence induced by abiotic stresses is a major cause of agricultural losses worldwide. Tools for suppressing stress-induced plant senescence are limited. Here, we report that diacetyl, a natural compound emitted by the plant-beneficial bacterium Bacillus amyloliquefaciens, suppresses abscisic acid -mediated foliar senescence in Arabidopsis thaliana under various abiotic stress conditions. Our results establish diacetyl as an effective protector against stress-induced plant senescence and reveal a molecular mechanism for bacteria-enhanced plant stress resistance.


Systematic differences between lean and obese adolescents in brain spin-lattice relaxation time: a quantitative study.
Emerging evidence suggests that obese adolescents show changes in brain structure compared with lean adolescents. In addition, obesity impacts body development during adolescence. We tested a hypothesis that T1, a marker of brain maturation, can show brain differences associated with obesity. Adolescents similar in sex, family income, and school grade were recruited by using strict entry criteria. We measured brain T1 in 48 obese and 31 lean adolescents by quantitative MR imaging at 1.5T. We combined MPRAGE and inversion-recovery sequences with normalization to standard space and automated skull stripping to obtain T1 maps with a symmetric voxel volume of 1 mm(3). Sex, income, triglycerides, total cholesterol, and fasting glucose did not differ between groups, but obese adolescents had significantly lower HDL, higher LDL, and higher fasting insulin levels than lean adolescents. Intracranial vault volume did not differ between groups, but obese adolescents had smaller intracranial vault-adjusted brain parenchymal volumes. Obese adolescents had 4 clusters (>100 contiguous voxels) of T1 relaxation that were significantly different (P < .005) from those in lean adolescents. Three of these clusters had longer T1s in obese adolescents (in the orbitofrontal and parietal regions), and 1 cluster had shorter T1s, compared with lean adolescents. Our results suggest that obesity may have a significant impact on brain development, especially in the frontal and parietal lobes. It is unclear if these changes persist into adulthood or whether they indicate that obese subjects follow a different developmental trajectory during adolescence.


Factors influencing time-location patterns and their impact on estimates of exposure: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).
We assessed time-location patterns and the role of individual- and residential-level characteristics on these patterns within the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) cohort and also investigated the impact of individual-level time-location patterns on individual-level estimates of exposure to outdoor air pollution. Reported time-location patterns varied significantly by demographic factors such as age, gender, race/ethnicity, income, education, and employment status. On average, Chinese participants reported spending significantly more time indoors and less time outdoors and in transit than White, Black, or Hispanic participants. Using a tiered linear regression approach, we predicted time indoors at home and total time indoors. Our model, developed using forward-selection procedures, explained 43% of the variability in time spent indoors at home, and incorporated demographic, health, lifestyle, and built environment factors. Time-weighted air pollution predictions calculated using recommended time indoors from USEPA overestimated exposures as compared with predictions made with MESA Air participant-specific information. These data fill an important gap in the literature by describing the impact of individual and residential characteristics on time-location patterns and by demonstrating the impact of population-specific data on exposure estimates.


Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults.
Naltrexone/bupropion ER (Contrave): newly approved treatment option for chronic weight management in obese adults.


Phenol biodegradation by plant growth promoting bacterium, S. odorifera: kinetic modeling and process optimization.
One of the main organic pollutants that could result from industrial products and chemical transformations is phenol. In the current study, the kinetics of Serratia odorifera, which was isolated from arable soil, was studied by growing it on broth minimal medium spiked with phenol as only carbon source and energy. The newly isolated plant growth-promoting bacterium (PGPB), S. odorifera, was used for the first time for phenol biodegradation. The growth kinetics parameters (phenol-dependent) including maximum specific growth rate (μmax), half-saturation coefficient (Ks), and the Haldane's growth kinetics inhibition coefficient (Ki), were tested via Haldane inhibition model and resulted on the 0.469 (h -1), 26.6 (mgL-1), and 292 (mgL-1), respectively. The sum of squared error (SSR) of 4.89 × 10-3 was fitted to the experimental data by Haldane equation. The results of phenol biodegradation were fitted into the modified Gombertz model. The increase of phenol concentrations led to increases in both the rate of phenol biodegradation and lagging time. The optimal phenol biodegradation and bacterial growth obtained by S. odorifera, were at 28 °C incubation temperature and a pH of 7.0. The pathway of phenol biodegradation by S. odorifera was proposed in the current study to provide a new insight into synchronization of phenol biodegradation and plant growth-promoting bacteria. This may play an important role in remediation of phenol-contaminated soil besides promoting the plant growth, thus lessening the plant stress.


Epileptic activity can induce both long-lasting potentiation and long-lasting depression.
Epileptic seizures are associated with massive changes of intracellular ion concentrations which could cause persistent changes in efficacy of afferent excitation. Such alterations were investigated in the CA1 area of hippocampal slices using the acute high potassium model of epilepsy which allows rapid wash of the epileptogenic solution. Field potentials elicited by stimulation of Schaffer collaterals were recorded in stratum pyramidale and stratum radiatum. The experiments revealed that long-lasting potentiation as well as long-lasting depression of field potentials could result from superfusion with high potassium. These changes were NMDA-dependent, but did not depend on the discharge type (interictal vs. ictal) of the slice. It is concluded that epileptic activity cannot only lead to an enhancement of responses to afferent excitation, but also to a long-lasting depression. This depression could represent a self-protective mechanism of the brain which may also be involved in post-ictal depression of cerebral activity.


Secretion of beta-amyloid precursor protein involves multiple cleavage sites.
A major histopathological feature of Alzheimer's disease is deposits of a approximately 4-kDa beta-amyloid peptide derived by proteolytic processing from a precursor, the beta-amyloid precursor protein (beta-APP). Proteolytic cleavage of beta-APP within the approximately 4-kDa beta-amyloid domain permits the secretion of the amino-terminal portion of beta-APP while concomitantly producing a membrane bound approximately 9-kDa carboxyl-terminal fragment. We have characterized the proteolytic cleavage site for beta-APP secretion by amino acid sequence analysis of the approximately 9-kDa beta-APP carboxyl-terminal cleavage product produced by recombinant and native expression systems. Recombinant beta-APP was generated by a vaccinia virus expression system in CV-1 monkey fibroblasts; endogenous beta-APP was obtained using a fibroblast line derived from an individual with Down's syndrome. The sequences of both unlabeled and metabolically radiolabeled approximately 9-kDa fragment from CV-1 cells reveal that the major (60%) secretory cleavage site is after Lys16 of the beta-amyloid domain as reported previously; however, an additional cleavage site is seen after Phe19 (40%). Radiosequence analysis of the carboxyl-terminal fragment purified from Down's syndrome fibroblasts indicates cleavage sites after Phe19, Glu22, and Gly25 and not after Lys16. CV-1 cells expressing beta-APP mutants lacking 4 and 6 amino acids adjacent to Lys16 yielded approximately 9-kDa fragments with two identical cleavage sites, neither of which occurred after the retained Lys16 but were after Glu11 and His13. These data suggest that secretion of beta-APP involves multiple proteinases and that the composition of these proteinases may vary within different cell backgrounds.


Correction to "2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4".
[This corrects the article DOI: 10.1021/acsmedchemlett.7b00485.].


Interaction between thyroxine and tricyclic antidepressant drugs on cardiac neurotransmitter receptors.
The effect of chronic administration of desmethylimipramine (DMI) and iprindole on cardiac neurotransmitter receptors was studied. In addition, the influence of these drugs on the action of thyroxine (T4) on myocardial receptors was investigated. Administration of iprindole (10 mg/kg i.p., twice daily for 11 days) markedly increased the number of beta- adrenergic receptors in the heart and significantly reduced the affinity of these receptors for (-)[3H]dihydroalprenolol ([3H]DHA). Injection of T4 (500 mg/rat i.m., for 5 days) concomitantly with iprindole resulted in a lower beta-adrenergic receptor density that with iprindole treatment alone, but significantly higher than that measured in control rats. Affinity of the receptors for (-)[3H]quinuclidinyl benzilate ([3H]QNB) in heart membrane preparations of animals pretreated with T4 alone or with T4 plus iprindole was not different from control. Neither pretreatment with DMI nor with iprindole affected the density of cholinergic muscarinic receptors in the heart or their affinity for [3H]QNB. The decrease in cardiac cholinergic receptors induced by administration of T4 was not prevented by simultaneous injections of DMI. Combined administration of iprindole and T4 caused a reduction in the affinity of myocardial cholinergic muscarinic receptors, but restored the number of these receptors to normal. The results demonstrate distinct differences between DMI and iprindole in their effects on cardiac neurotransmitter receptors and in the influence of these drugs on the actions of T4 on receptors in the heart.


Increased depressive and anxiety symptoms in non-heterosexual individuals: Moderation by childhood factors using a twin design.
Evidence indicates that minority stress does not sufficiently explain mental health disparities in non-heterosexual compared to heterosexual individuals. We investigated alternative mechanisms whereby childhood factors (childhood gender nonconformity, early-life adversities and parent-child interactions) moderate the relationships between sexual orientation and depressive and anxiety symptoms. The sample comprised twin pairs from the Finnish Genetics of Sexuality and Aggression cohort (n = 3166 individuals, mean age = 37.5 ± 2.93 years). Twin analyses using structural equation modelling was performed in OpenMx. Specifically, we tested whether childhood factors differentially moderated the underlying genetic and environmental influences on the relationships between sexual orientation, and depressive and anxiety symptoms. The associations between non-heterosexuality, and depressive and anxiety symptoms (r = 0.09, 0.10 respectively) were significantly influenced by both genetic and environmental factors. The genetic influences explaining the relationships of sexual orientation with depressive and anxiety symptoms were maximal at high levels of childhood gender nonconformity (βA = 0.09 and 0.11 respectively) whereas the individual-specific environmental influences on these relationships were maximal at lower levels of childhood gender nonconformity (βE = -0.10). Childhood factors were assessed retrospectively in a cross-sectional design. Childhood gender nonconformity is associated with increased genetic and decreased individual-specific environmental influences on mental health among non-heterosexual individuals. Childhood gender nonconformity may, thus, enhance genetic risk and non-genetic protective processes for depressive and anxiety symptoms among non-heterosexual individuals.


Cell chirality regulates coherent angular motion on small circular substrates.
Collective cell migration occurs in a wide range of physiological and pathological processes, such as wound healing and tumor metastasis. Experiments showed that many types of cells confined in circular islands can perform coherent angular rotation, yet the underlying mechanisms remain unclear. Here we propose a biomechanical model, including the membrane, microtubules, and nucleus, to study the spatiotemporal evolutions of small cell clusters in confined space. We show that cells can spontaneously transfer from "radial pattern" to "chiral pattern" due to fluctuations. For a pair of cells with identical chiral orientation, the cluster rotates in the opposite direction of the chiral orientation, and the fluctuations can reverse the cluster's rotational direction. Interestingly, during the persistent rotation, each cell rotates around its own centroid while it is revolving around the island center and shows a constant side to the island center, as tidal locking in astronomy. Furthermore, for a few more cells, coherent angular rotation also appears, and the emergence of a central cell can accelerate the cluster rotation. These findings shed light on collective cell migration in life processes and help to understand the spatiotemporal dynamics of active matter.


The left atrial function is transiently impaired in Tako-tsubo cardiomyopathy and associated to in-hospital complications: a prospective study using two-dimensional strain.
Tako-tsubo cardiomyopathy (TTC) is characterized by the presence of transient left ventricular (LV) dysfunction. Whether left atrial (LA) function is also impaired in this setting is unclear. To assess prospectively LA peak systolic longitudinal strain (LAS) by two-dimensional strain at the acute phase of TTC and after recovery and its association with in-hospital complications. 40 patients with typical TTC (mean age 79.5 ± 10 years) underwent transthoracic-Doppler echocardiography at the acute phase and at follow-up (32 ± 18 days later), including the measurement of the LAS (mean of maximal strain from the 4-2 chamber views). A control group of 15 patients (75 ± 7 years, 13 women) without overt cardiovascular disease served as a comparative group. In-hospital complication was a composite of death, heart failure, cardiogenic shock, LV thrombus, and sustained ventricular arrhythmia. In the TTC group, LAS improved significantly between the two examinations from 15 ± 5.5% to 27 ± 8% (p < 0.01) whereas LA volume did not change (p = NS). In the control group LAS was 30 ± 4% (p < 0.01 vs. TTC acute phase, p = NS vs. TTC follow-up). In TTC, at the acute phase LAS was independently correlated to LV global longitudinal strain (LVGLS), and after recovery to E/e', and the change of LAS was independently correlated to the change of the LVGLS (all, p < 0.01). Furthermore LAS was independently correlated to in-hospital complications (p < 0.01). LA function (reservoir) is transiently impaired in TTC and associated to in-hospital complications. Furthermore, the improvement of LAS parallel the dynamic improvement of LVGLS suggests that TTC induces a transient global left heart dysfunction.


Organizational issues in health informatics: a model approach.
In this paper, we present a model that describes the stages of the implementation of an information system in a health care organization. The model offers no explanation of the implementation process but rather describes in a cyclic order the domains that are relevant when implementing a system. The model offers thus an opportunity to identify gaps in our knowledge and understanding of implementation processes and provides also the conceptual basis for a higher education course of health informatics that is focusing on organizational change and the pivotal role of information and communication technology.


Epidemiology of the lymphomas in the United Kingdom: recent developments.
A discussion of the difficulties associated with classification of the lymphomas, particularly by subtype, precedes the descriptive epidemiology of the disease. Recent data collected in the United Kingdom and Yorkshire are presented to illustrate demographic features and variations in lymphoma incidence, both in relation to certain time periods and geographical distribution. Lymphoma aetiology is addressed in the light of current epidemiological approaches, using as an example data from a Yorkshire based case-control study. Three broad areas of aetiological significance--genetics, viruses and immunity--form the bases for presenting descriptions of known or suspected aetiological factors associated with Hodgkin's disease and non-Hodgkin's lymphoma. The final overview points the way to relevant future research.


Physiopathological variations in the mechanical properties of skin.
An evaluation of the rheological properties of skin is provided by measuring "in situ" the ability of skin to withstand vertical forces of extension. In physiological conditions the biomechanical parameters are reproducible and related to age, sex, skin thickness and the microarchitecture of the connective tissue studied by scanning electron microscopy. These observations shed some light on the structure-function relationship of the fibrous framework of the connective tissue. Variation in the biomechanical parameters can be used to substantiate clinical diagnosis and to monitor the evolution and the therapy of various diseases of the connective tissue.


Hypoxia, hypoxia-inducible gene 2 (HIG2)/HILPDA, and intracellular lipolysis in cancer.
Tumor tissues are chronically exposed to hypoxia owing to aberrant vascularity. Hypoxia induces metabolic alterations in cancer, thereby promoting aggressive malignancy and metastasis. While previous efforts largely focused on adaptive responses in glucose and glutamine metabolism, recent studies have begun to yield important insight into the hypoxic regulation of lipid metabolic reprogramming in cancer. Emerging evidence points to lipid droplet (LD) accumulation as a hallmark of hypoxic cancer cells. One critical underlying mechanism involves the inhibition of adipose triglyceride lipase (ATGL)-mediated intracellular lipolysis by a small protein encoded by hypoxia-inducible gene 2 (HIG2), also known as hypoxia inducible lipid droplet associated (HILPDA). In this review we summarize and discuss recent key findings on hypoxia-dependent regulation of metabolic adaptations especially lipolysis in cancer. We also pose several questions and hypotheses pertaining to the metabolic impact of lipolytic regulation in cancer under hypoxia and during hypoxia-reoxygenation transition.


Multiphoton microscopy providing pathological-level quantification of myocardial fibrosis in transplanted human heart.
Multiphoton microscopy (MPM), a high-resolution laser scanning technique, has been shown to provide detailed real-time information on fibrosis assessment in animal models. But the value of MPM in human histology, especially in heart tissue, has not been fully explored. We aimed to evaluate the association between myocardial fibrosis measured by MPM and that measured by histological staining in the transplanted human heart. One hundred and twenty samples of heart tissue were obtained from 20 patients consisting of 10 dilated cardiomyopathies (DCM) and 10 ischemic cardiomyopathies (ICM). MPM and picrosirius red staining were performed to quantify collagen volume fraction (CVF) in explanted hearts postoperatively. Cardiomyocyte and myocardial fibrosis could be clearly visualized by MPM. Although patients with ICM had significantly greater MPM-derived CVF than patients with DCM (25.33 ± 12.65 % vs. 19.82 ± 8.62 %, p = 0.006), there was a substantial overlap of CVF values between them. MPM-derived CVF was comparable to that derived from picrosirius red staining based on all samples (22.58 ± 11.13% vs. 21.19 ± 11.79%, p = 0.348), as well as in DCM samples and ICM samples. MPM-derived CVF was correlated strongly with the magnitude of staining-derived CVF in both all samples and DCM samples and ICM samples (r = 0.972, r = 0.963, r = 0.973, respectively; all p < 0.001). Intra- and inter-observer reproducibility for MPM-derived CVF and staining-derived CVF were 0.995, 0.989, 0.995, and 0.985, respectively. Our data demonstrated that MPM can provide a pathological-level assessment of myocardial microstructure in transplanted human heart.


Hyaluronan and layilin mediate loss of airway epithelial barrier function induced by cigarette smoke by decreasing E-cadherin.
Cigarette smoke (CigS) exposure is associated with increased bronchial epithelial permeability and impaired barrier function. Primary cultures of normal human bronchial epithelial cells exposed to CigS exhibit decreased E-cadherin expression and reduced transepithelial electrical resistance. These effects were mediated by hyaluronan (HA) because inhibition of its synthesis with 4-methylumbelliferone prevented these effects, and exposure to HA fragments of <70 kDa mimicked these effects. We show that the HA receptor layilin is expressed apically in human airway epithelium and that cells infected with lentivirus expressing layilin siRNAs were protected against increased permeability triggered by both CigS and HA. We identified RhoA/Rho-associated protein kinase (ROCK) as the signaling effectors downstream layilin. We conclude that HA fragments generated by CigS bind to layilin and signal through Rho/ROCK to inhibit the E-cadherin gene and protein expression, leading to a loss of epithelial cell-cell contact. These studies suggest that HA functions as a master switch protecting or disrupting the epithelial barrier in its high versus low molecular weight form and that its depolymerization is a first and necessary step triggering the inflammatory response to CigS.


Ultrasound in Diagnosis of Magnet Dislocation of Cochlear Implants: A Retrospective Study in Patients With Surgical Magnet Repositioning and Preinterventional Ultrasound Examination.
To investigate whether ultrasound is a reliable diagnostic tool to identify magnet dislocation in patients with cochlear implant. Retrospective analysis. A tertiary referral medical center. Patients with cochlear implant who presented with the suspicion of magnet dislocation between January 1, 2009 and July 31, 2019. Preinterventional ultrasound with subsequent surgical magnet repositioning. Accuracy of ultrasound in detecting magnet dislocation; intraoperative extent of magnet dislocation. Out of the 28 included patients (n = 28 magnets, 36% ♀; 51.6 years [±19.0 yr]) the diagnosis by the preoperative ultrasound was confirmed intraoperatively in 25 patients (89%). In two cases (7%), tissue swelling impeded the determination of the magnet by the preoperative ultrasound. In one case, ultrasound misdiagnosed the magnet as not dislocated. During revision surgery, all 28 magnets were repositioned successfully revealing a predominant partial dislocation (86%) compared with complete magnet dislocation (14%). In CI-patients undergoing 1.5 Tesla MRI, partial magnet dislocation occurs much more frequently than complete magnet dislocation. The clinical suspicion of a dislocated cochlear implant magnet can be accurately confirmed by preoperative ultrasound. Thus, preoperative diagnostic ultrasound can be advocated as the diagnostic tool of first choice.


Temporal stability and detection sensitivity of the dry swab-based diagnosis of SARS-CoV-2.
The rapid spread and evolution of various strains of SARS-CoV-2, the virus responsible for COVID-19, continues to challenge the disease controlling measures globally. Alarming concern is, the number of second wave infections surpassed the first wave and the onset of severe symptoms manifesting rapidly. In this scenario, testing of maximum population in less time and minimum cost with existing diagnostic amenities is the only possible way to control the spread of the virus. The previously described RNA extraction-free methods using dry swab have been shown to be advantageous in these critical times by different studies. In this work, we show the temporal stability and performance of the dry swab viral detection method at two different temperatures. Contrived dry swabs holding serially diluted SARS-CoV-2 strains A2a and A3i at 25°C (room temperature; RT) and 4°C were subjected to direct RT-PCR and compared with standard VTM-RNA based method. The results clearly indicate that dry swab method of RNA detection is as efficient as VTM-RNA-based method in both strains, when checked for up to 72 h. The lesser CT values of dry swab samples in comparison to that of the VTM-RNA samples suggest better sensitivity of the method within 48 h of time. The results collectively suggest that dry swab samples are stable at RT for 24 h and the detection of SARS-CoV-2 RNA by RT-PCR do not show variance from VTM-RNA. This extraction free, direct RT-PCR method holds phenomenal standing in the present life-threatening circumstances due to SARS-CoV-2.


Clinical spectrum of allergic and pseudoallergic drug reactions.
Among the many types of adverse effects of drugs, allergic reactions constitute a very significant minority, with respect to both their frequency and sometimes serious consequences. To keep the term "drug allergy" meaningful, it should be limited to those adverse drug reactions that are based on immune mechanisms or that can reasonably be presumed to have this basis. Pseudoallergic drug reactions, which will also be considered in this issue, have similar clinical manifestations and some common pathogenetic mechanisms, but the initiating event does not appear to involve a reaction between the drug or a drug metabolite and specific antibodies. Clinically, drug allergy is commonly observed in nonatopic as well as atopic people. Innumerable drugs have been reported to produce these types of reactions, but in many instances drug metabolites may be the actual culprits. Clinical manifestations of drug allergy also are legion. Unfortunately, essentially none of these is unique or specific for drug allergy, but it is important for clinicians to think of this very treatable condition along with other diagnostic possibilities. It is convenient and helpful to classify allergic reactions to drugs according to Gell and Coombs' four main types of hypersensitivity processes, but in many instances more than one mechanism may be involved, just as immune responses to most antigens generally are complex. Type I reactions are generally immunoglobulin (Ig) E-mediated, and clinical manifestations include urticaria, angioedema, respiratory symptoms, and anaphylaxis. Pseudoallergic reactions of the latter type are called anaphylactoid.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of single- and tri-frequency ultrasound on self-assembly and characterizations of bionic dynamic rat stomach digestion of pepsin-soluble collagen from chicken leg skin.
Chicken feet, aplenty by-products in the chicken industry, are rich in collagen and contain abundant amino acids so that it can be used as an important source for the collagen market. Pepsin-soluble collagen (PSC) was extracted from chicken leg skin and explored the effects of single- and tri-frequency ultrasound on the self-assembly and vitro digestion characteristics. By the diverging and tri-frequency ultrasound reactor, PSC was treated with 20 kHz/270w (C20H5m), 40 kHz/270w (C40H5m), 60 kHz/270w (C60H5m), 20/40/60 kHz/90w × 3 (CtH5m) for 5 min. Results showed that ultrasound could accelerate the process of collagen self-assembly, and 60 kHz/270w was the fastest. Microfiber diameters of C60H5m were 65-89 nm, which was significantly lower than the control without ultrasound (80-161 nm). The digestion results indicated polypeptides with relative molecular weights founded in the range 200-5000 Da were exceeded 85%. The final digested product had the highest content of oligopeptide, consistent rheological properties, and elastic behavior. The cavitation and mechanical of ultrasound have effects on the self-assembly process and collagen gel structure and digestion characteristics, which is of great significance for the development of the chicken industry and collagen market.


Spleen stiffness can predict liver decompensation and survival in patients with cirrhosis.
Liver stiffness measurement (LSM) has been predicting liver decompensation and survival in cirrhotics. The aim of our study was to investigate if spleen stiffness measurement (SSM) by 2D shear-wave elastography could predict better the probability of decompensation and mortality, compared with LSM and other parameters. Consecutive cirrhotic patients were recruited between 1/2017 and 12/2021. LSM and SSM were performed at baseline and epidemiological, clinical, and laboratory data were collected. Clinical events were recorded every 3 months. Totally, 177 patients were followed for a mean period of 31 ± 18 months. In Cox regression analysis, only SSM was independently associated with the probability of decompensation (HR: 1.063, 95% CI: 1.009-1.120; P = 0.021), offering an AUROC of 0.710 (P = 0.003) for predicting 1-year liver decompensation (NPV: 81.1% for the cut-off point of 37 kPa). The occurrence of death/liver transplantation was independently associated only with higher SSM (HR: 1.043; 95% CI:1.003-1.084; P = 0.034). The AUROC of SSM for predicting 1-year death/liver transplantation was 0.72 (P = 0.006) (NPV: 95% for the cut-off of 38.8 kPa). The performance of SSM to predict the 1-year death/liver transplantation increased in high-risk patients (CTP: B/C plus MELD >10 plus LSM > 20 kPa), giving an AUROC of 0.80 (P < 0.001). Only 1/26 high-risk patients with SSM < 38.8 kPa died during the first year of follow-up (NPV: 96.4%). SSM was the only factor independently associated with the probability of decompensation and occurrence of death, showing better diagnostic accuracy for the prediction of 1-year decompensation or death compared with LSM and MELD score.


Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization and apoptosis.
Rasagiline, a neuroprotective inhibitor of type B monoamine oxidase, prevented PK111195-induced apoptosis in SH-SY5Y cells through inhibition of mitochondrial apoptosis signaling (J Neural Transm 120:1539-1551, 2013, J Neural Transm 122:1399-1407, 2015). This paper presents that PK11195 induced superoxide flashes, the transit production burst, mediated by cyclosporine A-sensitive membrane permeability transition. Rasagiline prevented superoxide flashes, calcium efflux, and cell death by PK11195. Regulation of the initial pore formation at the inner mitochondrial membrane was confirmed as the decisive mechanism of neuroprotection by rasagiline.


Dimensional overlap between time and space.
Several pieces of evidence suggest that our mental representations of time and space are linked. However, the extent of this linkage between the two domains has not yet been assessed. We present the results of two experiments that draw on the predictions of the dimensional overlap model (Kornblum, Hasbroucq, & Osman, Psychological Review 97:253-270, 1990). The stimulus and response sets in these reaction time experiments were related to either time or space. The obtained stimulus-response congruency effects were of about the same size for identical stimulus-response sets (time-time or space-space) and for different stimulus-response sets (time-space or space-time). These results support the view that our representations of time and space are strongly linked.


[Congenital hyperinsulinism revealed by sudden infant death].
We report the case of a girl of 5 and a half months admitted for discomfort and consciousness loss at home and supported on sudden infant death protocol. Workup was negative. Autopsy showed only signs of asphyxia. Microscopic examination of the pancreas showed hypertrophic beta cells of Langerhans islets, explaining death linked to severe hypoglycemia by inappropriate insulin hypersecretion. This observation highlights the importance of the management of sudden infant unexpected death according to the protocol of the National Health Authority, which includes an autopsy with complete sampling, which in this case resulted in a diagnosis of unknown disease the lifetime of the child.


Modulation of Central Carbon Metabolism by Acetylation of Isocitrate Lyase in Mycobacterium tuberculosis.
Several enzymes involved in central carbon metabolism such as isocitrate lyase and phosphoenolpyruvate carboxykinase are key determinants of pathogenesis of Mycobacterium tuberculosis (M. tb). In this study, we found that lysine acetylation plays an important role in the modulation of central carbon metabolism in M. tb. Mutant of M. tb defective in sirtuin deacetylase exhibited improved growth in fatty acid-containing media. Global analysis of lysine acetylome of M. tb identified three acetylated lysine residues (K322, K331, and K392) of isocitrate lyase (ICL1). Using a genetically encoding system, we demonstrated that acetylation of K392 increased the enzyme activity of ICL1, whereas acetylation of K322 decreased its activity. Antibodies that specifically recognized acetyllysine at 392 and 322 of ICL1 were used to monitor the levels of ICL1 acetylation in M. tb cultures. The physiological significance of ICL1 acetylation was demonstrated by the observation that M. tb altered the levels of acetylated K392 in response to changes of carbon sources, and that acetylation of K392 affected the abundance of ICL1 protein. Our study has uncovered another regulatory mechanism of ICL1.


Comparison between 308-nm excimer light alone versus 308-nm excimer light and platelet-rich plasma in the treatment for localized vitiligo.
Monochromatic excimer light (MEL) is a safe and effective treatment for localized stable vitiligo. Previous reports of the combination of platelet-rich plasma (PRP) with narrowband ultraviolet B (NB-UVB) or excimer laser yielded conflicting results. This prospective, self-controlled, randomized, comparative study aimed to assess whether the addition of PRP to MEL therapy would be of an additive benefit in the treatment for localized stable vitiligo. Patients/Methods The current study included 36 patients with at least 2 more or less symmetrical patches of localized stable vitiligo (72 patches). For each patient, each of the 2 vitiligo patches was randomly assigned to receive either MEL therapy (twice weekly) with bi-weekly intradermal PRP (group A) or MEL therapy alone (group B) for a maximum of 4 months or till complete repigmentation. The degree of repigmentation was categorized as absent (0%), poor (1-25%), moderate (26-50%), good (51-75%), or excellent (>75%). Patients were asked about their level of satisfaction (not satisfied at all, partially satisfied, satisfied, or completely satisfied). Side effects were recorded, and follow-up for 3 months was done. No statistically significant difference was observed between the 2 groups regarding the degree of repigmentation, the patients' level of satisfaction, and the frequency of side effects (p = 0.504, 0.490, and 0.912, respectively). At the end of the follow-up period, recurrence was observed in only 3 patients. The current study showed no statistically significant difference between using MEL alone or with intradermal PRP in the treatment for localized stable vitiligo.


Historical releases of mercury to air, land, and water from coal combustion.
Coal combustion is one of the largest contemporary sources of anthropogenic mercury (Hg). It releases geologically sequestered Hg to the atmosphere, and fly ash can contaminate terrestrial and aquatic systems. We estimate that coal combustion has released a cumulative total of 38.0 (14.8-98.9, 80% C.I.) Gg (gigagrams, 109g or thousand tonnes) of Hg to air, land, and water up to the year 2010, most of which (97%) has occurred since 1850. The rate of release has grown by two orders of magnitude from 0.01Ggyr-1 in 1850 to 1Ggyr-1 in 2010. Geographically, Asia and Europe each account for 32% of cumulative releases and an additional 18% is from North America. About 26.3 (10.2-68.3) Gg, 71% of the total, were directly emitted to the atmosphere, mostly from the industrial (45%) and power generation (36%) sectors, while the remainder was disposed of to land and water bodies. While Europe and North America were the major contributing regions until 1950, Asia has surpassed both in recent decades. By 2010, Asia was responsible for 69% of the total releases of Hg from coal combustion to the environment. Control technologies installed on major emitting sources capture mainly particulate and divalent Hg, and therefore the fraction of elemental Hg in emissions from coal combustion has increased over time from 0.46 in 1850 to 0.61 in 2010. About 11.8 (4.6-30.6) Gg of Hg, 31% of the total, have been transferred to land and water bodies through the disposal or utilization of Hg-containing combustion waste and collected fly ash/FGD waste; approximately 8.8Gg of this Hg have simply been discarded to waste piles or ash ponds or rivers.


A laboratory exercise in somesthesis that is expeditious, inexpensive, and suitable for large classes.
A teaching laboratory is described that demonstrates two principles of the somatosensory system: 1) the "spot-like" nature of skin sensitivity and 2) tactile acuity. This laboratory has been used for a large medical school class (140-160 students). One reason for the success of this laboratory is the ability to provide a sufficient number of stimulating apparatuses. The two-point discrimination device used to measure tactile acuity can be made easily and cheaply. In addition, two other demonstrations are described that are suitable for smaller classes or that students can do on their own. Although this lab was designed for medical students, the content makes it suitable for undergraduate or high school students.


Cardiovascular risk factors in a French-Canadian population: resolution of genetic and familial environmental effects on blood pressure by using extensive information on environmental correlates.
Genetic and environmental influences on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MBP) were examined in 371 French-Canadian families by using path analysis. Familial environment was estimated with environmental indices constructed from as many as 14 (of a pool of more than 100) correlates of blood pressure (BP). Approximately 20% of the variance in BP can be accounted for by the composite index, and the types of variables and the direction of their effects vary as a function of age and of the multivariate context. Path analysis of the family data suggests that genetic heritability is relatively high in children (from 0.49 for SBP to 0.56 for MBP) but much smaller in adults (from 0.08 for DBP to 0.18 for SBP). The proportion of variability explained by familial environment is estimated to be the same in children and adults and is much higher than reported to date (from 0.30 for SBP to 0.42 for DBP). In addition, sibships share significant nontransmitted environmental effects, and there is no evidence to suggest specific maternal effects in the aggregation of BP. Two unique findings emerge from this study. First, unlike in most earlier studies, we were able to arrive at the same parsimonious model for each of the BP variables. Second, the familial environment accounts for a substantial proportion of the variability in BP, which has been considerably underestimated in earlier studies.


A comparison of three cell types as potential candidates for intervertebral disc therapy: annulus fibrosus cells, chondrocytes, and bone marrow derived cells.
Candidate cell types for disc cell transplantation therapy include anulus fibrosus (AF) cells, chondrocytes, and bone marrow derived cells (BMDCs). We compared the disc matrix production in these three types of cells, before and after stimulation with rhBMP-2. There is no study extant that compares these three cell types to determine the best candidate for the disc cell therapy. AF cells, chondrocytes, and BMDCs (iliac crest and femur) were isolated and grown in monolayer. They were treated for 3 days with rhBMP-2. After 3 days, proteoglycan (sGAG) content in the media was quantified. The results were normalized by cell numbers. The mRNA expression of aggrecan, type I collagen, and type II collagen was measured using real-time PCR. Each cell type was also cultured in chamber slides and immunostained for aggrecan, type I collagen, and type II collagen after 3 days of treatment with rhBMP-2. (1) Without rhBMP-2 the chondrocytes produced more proteoglycan (sGAG) as compared to the other two cell types (AF cells and BMDCs). After stimulation with rhBMP-2 the chondrocytes produce even more proteoglycan than the other two cell types. (2) As compared to the other two cell types, in terms of mRNA expression, the chondrocytes expressed more aggrecan, type I collagen, and type II collagen before stimulation with rhBMP-2. After rhBMP-2 stimulation, the chondrocytes expressed even more aggrecan, type I collagen, and type II collagen in proportion to the concentration of rhBMP-2. For the BMDCs there were no changes in type I and II collagen. (3) rhBMP-2 stimulation produced increases in the protein levels of aggrecan, type I and II collagen in all three types of cells. On balance, according to these results, it would seem that chondrocytes are the best candidate for the disc cell therapy.


Detection of volatile mutagens in creosote and coal tar.
Creosote and coal tar were examined for the presence of volatile mutagens by use of the so-called "taped plate assay". Application of this method, recently published by Distlerath et al., reveals that vapour escaping from creosote and coal tar at 37 degrees C was able to revert the Salmonella typhimurium strains TA98 and TA100 in the presence of S9 mix. The simplicity of this method makes it useful for routine screening of industrial fluids or solid products for the presence of volatile mutagens.


Inducing effect of testosterone on the hepatic reduction of zearalenone in the female prepubertal rat.
The prepubertal responsiveness of 3α-hydroxysteroid dehydrogenase and zeara-lenone-reducing activity to either a large subcutaneous dose of testosterone or dietary zearalenone was investigated in female rats. Testosterone induced both the activity of the 3α-hydroxysteroid dehydrogenase, with androsterone as substrate, and zearalenone reduction to α- and (β-zearalenol. Zearalenone had no effect on the activity of 3α-hydroxysteroid dehydrogenase, but had a slight inducing effect on the zearalenone reduction to β-zearalenol. Both testosterone and zearalenone had a growth-promoting effect on uterus.


MiR-484 promotes non-small-cell lung cancer (NSCLC) progression through inhibiting Apaf-1 associated with the suppression of apoptosis.
Increasing studies have indicated that the dysregulated microRNAs (miRNAs) are associated with tumorigenesis, development and even the poor prognosis of a variety of tumors, including the non-small-cell lung cancer (NSCLC). Here in our study, we found that miRNA-484 was expressed highly in NSCLC clinical tumor samples in comparison to the matched adjacent tissues. In addition, high and low expression of miRNA-484 was observed in NSCLC cell lines and lung normal cells, respectively. Furthermore, the capability of migration and proliferation changed accompanied with the altered expression of miR-484 in NSCLC. Apoptotic protease activating factor-1 (APAF-1), frequently down-regulated in a number of types of cancer, was found to be reduced in NSCLC tissue samples or NSCLC cell lines along with high expression of miR-484, which were inversely expressed in Apaf-1 over-expressed tissues or cells. Moreover, miR-484 triggered the migration and proliferation, and simultaneously reduced the cleavage of poly (ADP-ribose) polymerase-2 (PARP-2) and Caspase-3 of A549 cells, which could be suppressed by the improvement of Apaf-1. And the inhibition of Apaf-1 could reverse the function caused by miR-484 in A549 cells, suggesting that Apaf-1 was targeted by miR-484 directly and it could be acted as a potential therapeutic target against NSCLC. In conclusion, the reductive Apaf-1 regulated by miR-484 accelerated the NSCLC cell progression associated with the inhibition of apoptosis via down-regulating Caspase-3 and PARP cleavage.


Long-lasting enhancement of metabotropic excitatory amino acid receptor-mediated polyphosphoinositide hydrolysis in the amygdala/pyriform cortex of deep prepiriform cortical kindled rats.
We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA) receptor may be associated with the long-lasting seizure susceptibility of kindling. The present study further examined PPI hydrolysis induced by trans-ACPD, a selective agonist of the metabotropic EAA receptor, as well as by IBO in brain slices of rats kindled from the deep prepiriform cortex (DPC). IBO-stimulated accumulation of [3H]inositol monophosphate ([3H]InsP) was significantly increased in the AM/PC by 162 (P less than 0.0001), 130 (P less than 0.005) and 81% (P less than 0.03) at 24 h, 7 days and 28 days, respectively, after the last kindled seizure, whereas it was increased significantly only at 24 h after the last seizure in the HIPP and did not change at any time in the limbic forebrain (LFB). The IBO-stimulated accumulation of [3H]InsP was significantly increased by 55% (P less than 0.01) in the AM/PC of partially kindled rats reaching an average stage of 3.7, but not in the AM/PC of those remaining at stage 1, 7 days after the last kindled seizure. Trans-ACPD-stimulated PPI hydrolysis was significantly increased in the AM/PC of DPC-kindled rats by 65 (P less than 0.05) and 45% (P less than 0.005) at 7 and 28 days, respectively, after the last kindled seizure. Cis-ACPD-stimulated PPI hydrolysis was also significantly increased in the AM/PC of DPC-kindled rats by 45 (P less than 0.03) and 30% (P less than 0.04) at 7 and 28 days, respectively, after the last seizure. There was no increase in trans-ACPD- or cis-ACPD-stimulated PPI hydrolysis in the HIPP or LFB. These results further confirm our previous studies showing that the metabotropic EAA receptor-stimulated PPI hydrolysis exhibited a long-lasting increase in the AM/PC irrespective of the primary stimulation site for kindling.


Lives saved by public health restrictions over the Victorian COVID-19 Delta variant epidemic wave, Aug-Nov 2021.
Prior to mid-2021, Australia's approach to COVID-19 was to eliminate community transmission. However, between August-November 2021, the state of Victoria, Australia, experienced an outbreak of the Delta variant that continued to grow despite extensive lockdowns and public health measures in place. While these public health restrictions were ultimately unable to stop community transmission, they likely had a major impact reducing transmission and adverse health outcomes relative to voluntary risk-mitigation only (e.g., in response to rising cases and deaths, some people may avoid crowded settings, hospitality, retail, social occasions, or indoor settings). This study aims to estimate the impact of the August-November 2021 enforced public health restrictions in Victoria, compared to voluntary risk-mitigation only. An agent-based model was calibrated to Victorian epidemiological, health and behavioural data from 1 August to 30 November 2021, as well as policies that were implemented over that period. Two counter-factual scenarios were run for the same period with (a) no restrictions in place; or (b) voluntary risk-mitigation only, based on behaviour measured over the December-January Omicron BA.1 epidemic wave when restrictions were not in place. Over August-November 2021, the baseline model scenario resulted in 97,000 (91,000-102,000) diagnoses, 9100 (8500-9700) hospital admissions, and 480 (430-530) deaths. Without any restrictions in place, there were 3,228,000 (3,200,000-3,253,000) diagnoses, 375,100 (370,200-380,900) hospital admissions, and 16,700 (16,000-17,500) deaths. With voluntary risk-mitigation equal to those observed during the Omicron BA.1 epidemic wave, there were 1,507,000 (1,469,000-1,549,000) diagnoses, 130,300 (124,500-136,000) hospital admissions, and 5500 (5000-6100) deaths. Public health restrictions implemented in Victoria over August-November 2021 are likely to have averted more than 120,000 hospitalizations and 5000 deaths relative to voluntary risk-mitigation only. During a COVID-19 epidemic wave voluntary behaviour change can reduce transmission substantially, but not to the same extent as enforced restrictions.


[Procedure in severe ischemia of the extremities in patients with obliterating arterial diseases].
The authors' experience with the treatment of 134 patients enabled them to formulate indications for sympathectomy, reconstructive operations and primary amputations.


Evolutionary implication of human endogenous retrovirus HERV-H family.
The human endogenous retrovirus (HERV-H) family is most abundant and widely distributed in the human genome, with about 100-1,000 full-length or deleted elements and a similar number of solitary, long-terminal repeats. The HERV-H env ORF has been characterized in humans and in the course of primate evolution, indicating the increased possibility of biological roles in humans. Using the polymerase chain reaction approach with a human monochromosomal DNA panel, 70 env fragments belonging to the HERV-H family from chromosomes 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, X, and Y were identified and analyzed. They showed 82-99% sequence similarity to that of HERV-H (accession no. AF108843). We also identified other HERV-H env fragments in the DDBJ/EMBL/GenBank databases. The total of 120 fragments was evolutionarily analyzed. Phylogenetic analysis suggests that the HERV-H env family is divided into one major and two minor groups. The HERV-H members have been actively proliferated and evolved by intra-chromosomal spread during hominid radiation.


[Hemispheric laterality and early childhood autism. A case study of the etiologic and nosologic problem of the autistic syndrome in childhood].
Most studies on childhood autism emphasize a left hemispheric disturbance. In the presented case a primary right (and only secondary left) hemispheric dysfunction seems to be obvious. This seems to be true also for other reports in the literature. Supported by the hypermasculine aspect of our patient a pathological intrauterine testosterone level is suggested to be responsible for the observed altered cerebral asymmetry and consecutive hemispheric dysfunction. The advantage of such neuropsychologic findings and hypothesis should stimulate further studies on autism and other psychiatric disturbances.


Gonococcal meningitis and ventriculitis in the presence of a ventriculoperitoneal shunt.
This report describes a young woman with a ventriculoperitoneal shunt who developed gonococcal meningitis and ventriculitis. Her infection responded to treatment with antimicrobial agents without removal of the shunt.


Does Zoledronic Acid Improve Appendicular Lean Mass in Older Women with Osteoporosis? A Sub-Analysis of a Randomized Clinical Trial.
Coexistence of osteoporosis and sarcopenia (osteosarcopenia), is associated with increased risk for fractures, falls, and mortality. Although there are multiple medications for management of osteoporosis, there are no approved pharmacotherapy for sarcopenia. We examined the effect of zoledronic acid on muscle mass indices including ALM (Appendicular Lean Mass) and ALM/Height2 in a cohort of older women with osteoporosis who were residents of Long-Term Care Communities (LTCCs). A secondary analysis of a 2-year double-blind, randomized, placebo-controlled clinical trial. Residents of LTCCs. Sixty-two postmenopausal women with osteoporosis. Participants either received 5 mg infusion of zoledronic acid or placebo, once at the start of the study. Participant's ALM/Height2, ALM, total hip BMD (Bone Mineral Density) and spine BMD were measured in 6, 12 and 24 months. On average, participants were 86.7 years old and had a BMI of 27.4 kg/m2. There was no significant difference in change from baseline (mean ± SE) between the treatment group and the placebo group in ALM/Height2: (-0.15 vs -0.02, p = 0.541) and (-0.17 vs 0.001, p = 0.315) and (-0.29 vs -0.19, p = 0.646) or ALM: (-0.38 vs -0.09, p = 0.455) and (-0.45 vs -0.005, p = 0.216) and (-0.70 vs -0.48, p = 0.553) at 6, 12, and 24 months respectively. In addition, after adjusting for a possible confounding, the ALM/Height2 or ALM did not have significant improvements from baseline at 6 months, 12 months, and 24 months either in the treatment group or in the placebo group. However, there were significant improvements in the BMD at the total hip and the spine in the treatment group compared with the placebo group at all three time points. Among older women residing in LTCCs, a single dose of zoledronic acid did not increase ALM/Height2 and ALM, despite improving the BMD at the total hip and the spine at the 2-year follow-up.


An algorithm for predicting proton nuclear magnetic resonance deshielding over a carbon-carbon double bond.
Hydrogen nuclei located over a carbon-carbon double bond in a strong magnetic field experience NMR shielding effects that result from the magnetic anisotropy of the nearby double bond and various other intramolecular shielding effects. We have used GIAO, a subroutine in Gaussian 98, to calculate isotropic shielding values and to predict the proton NMR shielding increment for a simple model system: methane held in various orientations, positions, and distances over ethene. The average proton NMR shielding increments of several orientations of methane have been plotted versus the Cartesian coordinates of the methane protons relative to the center of ethene. A single empirical equation for predicting the NMR shielding experienced by protons over a carbon-carbon double bond has been developed from these data. The predictive capability of this equation has been validated by comparing the shielding increments for several alkenes calculated using our equation to the experimentally observed shielding increments. This equation predicts the NMR shielding effects more accurately than previous models that were based on fewer geometries of methane over ethene. In fact, deshielding is predicted by this equation for protons over the center and within about 3 A of a carbon-carbon double bond. This result is in sharp contrast to predictions made by the long-held McConnell "shielding cone" model found in nearly every textbook on NMR, but is consistent with experimental observations. The algorithm for predicting the (de)shielding increment for a proton over an alkene can be used in a spreadsheet on a PC or incorporated into software that estimates chemical shifts using additive substituent constants or a database of structures. In either application its use can substantially improve the accuracy of the estimated chemical shift of a proton in the vicinity of a carbon-carbon double bond, and thus assist in spectral assignments and in correct structure determination.


Biological and molecular characterization of H13N2 influenza type A viruses isolated from turkeys and surface water.
The pathogenicity potential of two H13N2 influenza viruses, one isolated from turkeys and the other isolated from surface water, was evaluated in turkeys, chickens, and mallard ducks (Anas platyrhynchos) after intracranial and oculonasal inoculation. Both isolates replicated in turkey poults, causing depressed weight gain, morbidity and mortality; both also caused histopathological lesions, such as mild to severe pancreatitis, hepatitis, and nephritis in turkeys. These isolates replicated in mallard ducklings but not in chickens. There was depressed weight gain in ducklings given the H13N2 isolate from water. Neither isolate caused morbidity or mortality in ducklings or chicks after inoculation.


Effect of a weight loss intervention on anthropometric measures and metabolic risk factors in pre- versus postmenopausal women.
The present study examines changes in body weight, fat mass, metabolic and hormonal parameters in overweight and obese pre- and postmenopausal women who participated in a weight loss intervention. Seventy-two subjects were included in the analysis of this single arm study (premenopausal: 22 women, age 43.7 +/- 6.4 years, BMI 31.0 +/- 2.4 kg/m2; postmenopausal: 50 women, age 58.2 +/- 5.1 years, BMI 32.9 +/- 3.7 kg/m2). Weight reduction was achieved by the use of a meal replacement and fat-reduced diet. In addition, from week 6 to 24 participants attended a guided exercise program. Body composition was analyzed with the Bod Pod(R). Blood pressures were taken at every visit and blood was collected at baseline and closeout of the study to evaluate lipids, insulin, cortisol and leptin levels. BMI, fat mass, waist circumference, systolic blood pressure, triglycerides, glucose, leptin and cortisol were higher in the postmenopausal women at baseline. Both groups achieved a substantial and comparable weight loss (pre- vs. postmenopausal: 6.7 +/- 4.9 vs 6.7 +/- 4.4 kg; n.s.). However, in contrast to premenopausal women, weight loss in postmenopausal women was exclusively due to a reduction of fat mass (-5.3 +/- 5.1 vs -6.6 +/- 4.1 kg; p < 0.01). In premenopausal women 21% of weight loss was attributed to a reduction in lean body mass. Blood pressure, triglycerides, HDL-cholesterol, and glucose improved significantly only in postmenopausal women whereas total cholesterol and LDL-cholesterol were lowered significantly in both groups. Both groups showed comparable weight loss and in postmenopausal women weight loss was associated with a pronounced improvement in metabolic risk factors thereby reducing the prevalence of metabolic syndrome.


Results of a phase II study of lenalidomide and rituximab for refractory/relapsed chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is an incurable disease in need of new therapeutic strategies. The immunomodulatory agent, lenalidomide, has shown activity as salvage therapy for CLL. In this phase II trial, we combined lenalidomide with rituximab in 25 patients (range, 41-79) with refractory/relapsed CLL. Lenalidomide was administered orally on escalating doses, with cycle 1 doses of 2.5mg daily on days 1-7, 5mg on days 8-14, and 10mg on days 15-21 followed by 7days off. On cycle 2 and beyond, lenalidomide was administered at 20mg daily on days 1-21. Rituximab was administered at 375mg/m(2) intravenously on a weekly basis for the first cycle starting on day 15 for 4 doses, with each cycle being 28days. Treatment was continued until disease progression or toxicity. Overall response rate was 45.8% on intent-to-treat and 61.1% in evaluable patients (all partial responses). Median time to treatment failure was 14.3 months for evaluable patients, and median overall survival was not reached. The most common grade 3/4 toxicity was neutropenia (72% of patients). The most common nonhematologic toxicity was infection (29% of patients). Lenalidomide combined with rituximab showed activity in heavily treated refractory CLL with an acceptable toxicity profile.


The impact of malignant disease on facial nerve function after parotidectomy.
Studies of immediate postoperative facial nerve function following parotidectomy focus on benign disease. The purpose of the study was to compare facial nerve function with regard to benign or malignant disease in patients undergoing superficial parotidectomy. Retrospective cohort study of consecutive patients undergoing parotidectomy between 1995 to 2002. House-Brackmann (HB) grade was recorded or assigned at the first postoperative visit. For patients with HB grade of III or greater, final resolution of facial nerve function was recorded. A chi2 analysis for independence was conducted between patients with HB grade of II or less and those with HB grade of III or greater and final pathological finding (benign vs. malignant disease). Mean and median times to resolution were determined for patients with HB grade of III or greater. Times to resolution for benign and malignant disease for those with HB grade of III or greater were compared (Kaplan-Meier method). Sixty-seven patients with benign disease and 52 with malignant disease were included. Ninety-four percent of patients with benign disease had HB grade of II or less at first postoperative visit (mean period, 11.6 d) compared with 76.9% of patients with malignant disease (mean period, 12.4 d). A chi2 analysis found this difference significant (chi2 = 7.36, P =.0067). Time to resolution for HB grade of III or greater was 253.8 days (+/-168.2 d) with median time of 229.5 days for benign disease and 182.4 days (+/-134.6 d) with median time of 138 days for malignant disease. Kaplan-Meier comparison found no significant differences in time to final resolution (P =.83). Three patients in the group with malignant disease had unresolved dysfunction (one patient for >2 y). Patients with benign disease have a greater chance of having HB grade of II or less immediately following surgery; however, whether the disease is benign or malignant, long-term final facial nerve function is the same.


Metabolic effects of alterations in meal frequency in hypercholesterolaemic individuals.
It has been suggested that the metabolic consequences of a given diet may depend in part on the frequency with which meals are eaten. To investigate the effects of meal frequency on plasma lipid metabolism, 16 free-living hypercholesterolaemic men and women consumed their usual diet as 3 or 9 meals/day in random order for 4 weeks. Dietary macronutrient intake and body weight remained similar on the 2 regimens. Fasting plasma lipids were measured after 2, 3 and 4 weeks on each regimen and there were no significant differences in the fasting concentrations of plasma total, LDL, and HDL cholesterol, triglycerides, apolipoprotein A-I and B and the ratio of total: LDL and LDL:HDL cholesterol (HDL-C) on the two diets. The mean (+/- S.D.) fasting total cholesterol was 6.73 +/- 0.74 and 6.81 +/- 0.88 mmol/l on 3 and 9 meals/day, respectively and LDL-C was 4.77 +/- 0.66 and 4.87 +/- 0.78 mmol/l, respectively. There was also no significant variation in the response of plasma triglycerides or serum insulin to a high fat meal following a 3 week adaptation to regimens of 3 and 9 meals/day. Finally the 24 h urinary output of C-peptide was similar on each diet. The consumption of isoenergetic diets as 3 and 9 meals/day did not influence fasting plasma lipid levels, C-peptide excretion or the plasma triglyceride response to a high fat meal of a group of free living hypercholesterolaemic subjects.


Caveat emptor: The accuracy of claims data in appendicitis research.
International Classification of Disease, ninth/tenth revision codes are used to identify patients with appendicitis and classify severity of disease for research and hospital reimbursement. We sought to determine accuracy of International Classification of Disease, ninth/tenth revision codes in classifying appendicitis as uncomplicated versus complicated (defined as perforated, necrotic, or abscess) compared with the clinical gold standard: surgeon characterization of the appendix in the operative report. Retrospective review of operative reports and discharge International Classification of Disease, ninth/tenth revision codes for patients ≥18 years old who underwent noninterval, nonincidental appendectomy between January 2012 and December 2019 at a tertiary referral center. Sensitivity, specificity, and positive predictive value were calculated for International Classification of Disease, ninth/tenth revision codes to classify appendicitis accurately as complicated compared with surgeon description. ICD-9/10 codes and surgeon description were categorized into complicated/uncomplicated based on the American Association for the Surgery of Trauma grading system. In the study, 1,495 patients with acute appendicitis underwent appendectomy. Per surgeon description, 200 (13%) were complicated and 1,295 (87%) uncomplicated. Compared with surgeon description, discharge International Classification of Disease, ninth/tenth revision codes did not accurately identify complicated appendicitis: sensitivity = 0.68, positive predictive value = 0.77. As a sensitivity analysis, the cohort was stratified by public versus private payers, and the results did not change. International Classification of Disease, ninth/tenth revision codes do not accurately identify surgeon-described complicated appendicitis. Nearly one-third of the cases of complicated appendicitis were coded as uncomplicated. Such misclassification negatively impacts reimbursement for complicated appendicitis care and could lead to misleading results in research and quality improvement activities that rely on these codes.


Expression, purification, and functional analysis of an antigen-targeting fusion protein composed of CD40 ligand and the C-terminal fragment of ovalbumin.
Delivering antigen via molecules specifically targeting receptors on the surface of antigen-presenting cells is a strategy to improve immune responses. In this study, an antigen-targeting fusion protein (OVA-CD40LS) composed of the C-terminal fragment of ovalbumin and the extracellular domain of mouse CD40 ligand was constructed by genetic fusion. The OVA-CD40LS and the control OVA (rOVA) genes were cloned in Escherichia coli and over-expressed as insoluble proteins. The rOVA protein was purified from the insoluble fraction of E. coli cell lysate by nickel affinity chromatography and refolded by step-wise dialysis to give a yield of 11.8 mg/L of culture. The OVA-CD40LS was purified by a 'two-round' nickel affinity and on-column protein-refolding chromatography. The yield was 528 μg/L of culture. The purified OVA-CD40LS, but not the rOVA, was able to simulate the production of pro-inflammatory cytokines and up-regulate cell surface marker proteins in mouse bone marrow-derived dendritic cells. The purified OVA-CD40LS elicited a robust immune response when injected submucosally in the oral cavity of mice. Collectively, the results indicate that the OVA-CD40LS fusion protein was biologically active, functioning as an antigen-targeting protein.


Growth of Cyanobacteria: Optimization for Increased Carbohydrate Content.
Growths of Lyngbya limnetica and Oscillatoria obscura were investigated at varying pH, light intensity, temperature, and trace element concentration with a view to optimize these parameters for obtaining the maximum carbohydrate content. The maximum growth for both strains was obtained at pH 9.0 and temperature 20 ± 3 °C using a light intensity of 68.0 μmol m-2 s-1 with continuous shaking. Growth under the nitrogen starvation condition affected the carbohydrate content more compared to the phosphorus starvation, and maximum concentrations were found as 0.660 and 0.621 g/g of dry biomass for L. limnetica and O. obscura, respectively. Under the optimized nitrogen-rich conditions, the specific growth rates for the two strains were found to be 0.187 and 0.215 day-1, respectively. The two-stage growth studies under nitrogen-rich (stage I) followed by nitrogen starvation (stage II) conditions were performed, and maximum biomass and carbohydrate productivity were found as 0.088 and 0.423 g L-1 day-1 for L. limnetica. This is the first ever attempt to evaluate and optimize various parameters affecting the growth of cyanobacterial biomass of L. limnetica and O. obscura as well as their carbohydrate contents.


The whistleblower stages model in British National Health Service Inquiries.
This article applies the whistleblowing stages model to whistleblowing journeys as seen in British National Health Service (NHS) Inquiries. It provides a qualitative analysis of Inquiry Reports since 2001, using Interpretive Content Analysis to allocate material to stages. It is found that the Inquiry Reports show a wide variety of reporting mechanisms, but that most persons initially report internally. It seems to confirm recent suggestions that WB is often not a "one off" or simple and linear process, but a protracted process. While the simple stages model may be appropriate for individual "whistle-blowing incident" by a single whistleblower, it needs to be revised for the protracted process of raising concerns in a variety of ways by different people as shown in the Inquiry Reports. The evidence is confined to the publicly available material that was presented in the Inquiry Reports. It provides a template to apply to cases of whistleblowing, and provides some baseline material. This paper is one of the first to explore the whistleblowing stages model using qualitative material to one setting over time.


Measles or Not Measles? That Is the Question!
We present a diagnostically challenging case of a patient who presented with fever and rash during a measles outbreak. The diagnosis was complicated by the interpretation of the results of serological tests, which resulted in implementation of major preventive measures in the hospital. The patient was later confirmed to have murine typhus.


Right ventricular thrombus and pulmonary emboli in a patient with emphysema: an echocardiographic and Doppler documentation.
Pulmonary hypertension is a known complication of chronic obstructive pulmonary disease (COPD). A worsening dyspnea in a patient with COPD is usually a sequela of the pulmonary disease. However, it may be due to pulmonary embolism, a complication which is difficult to diagnose in such patients. We present a patient with COPD in whom two-dimensional and Doppler echocardiography confirmed the diagnosis of pulmonary emboli by documenting right ventricular thrombus and pulmonary hypertension. This case report emphasizes the usefulness of these noninvasive cardiac imaging techniques in the detection and evaluation of pulmonary embolism in patients with COPD.


The development of humoral and cellular immune response in pregnant rabbits after infection with Toxoplasma gondii and their influence on foetal infections.
Both humoral and cellular immune response during experimental toxoplasmosis of rabbits were studied in different stages of pregnancy. The application of different schemes of immunization made possible to detect immunological phenomena in particular stage of development depending on foetus evolution. The research conducted so far, has demonstrated no significant protective influence of humoral as well as cellular resistance to foetus infection of mothers acute infection.


Essential rosemary oil enrichment of minimally processed potatoes by vacuum-impregnation.
Vacuum impregnation (VI) has been recognized as a promising tool for the introduction of solutes into the internal structure of some porous food products. The enrichment of minimally processed potatoes with aromatic compounds could represent an interesting method for product innovation. This study was aimed at applying VI with rosemary essential oil on a minimally processed potato product in order to obtain an innovative fresh-cut potato product, and to evaluate its influence on the physico-chemical, sensorial and microbiological properties of potato sticks during refrigerated storage and after frying. A pressure of 60 mbar was applied for 30 min followed by a relaxation time at atmospheric pressure of 30 min to potato sticks immersed in rosemary oil solutions in concentration between 0 and 12%. Prepared samples were packed and stored at 4 °C for 14 days. Analytical determinations were carried out on the fresh and fried product. The weight gain of potatoes promoted by VI was in the range of 6-14%, depending on the concentration of rosemary essential oil. The rosemary essential oil concentration gradients of impregnated potato sticks were detected by GC analysis and sensorial test, evidencing their persistency during storage and after frying. The treatment seemed to improve microbiological stability, not affecting the texture, moisture, but slightly deteriorating the product color. Results obtained in the present study confirm the potentiality of VI for fresh products innovation.


Trends in conventional cardiovascular risk factors and myocardial infarction subtypes among young Chinese men with a first acute myocardial infarction.
There is limited data on the characteristics of conventional risk factors (RFs) in young Chinese men hospitalized with a first acute myocardial infarction (AMI). We analyzed the trends in and prevalence of cardiovascular RFs and subtypes of MI during the first AMI in young Chinese men. A total of 2739 men aged 18-44 years hospitalized for a first AMI were identified from 2007 to 2017. The overall prevalence of RFs and their respective temporal trends and subtypes of AMI were evaluated. The most prevalent conditions were smoking, followed by hypertension and then obesity. Patients aged <35 years had a much higher prevalence of hypercholesterolemia and obesity. Compared with a similar reference population in the United States, young Chinese men had a higher prevalence of smoking and dyslipidemia, but a lower prevalence of obesity, hypertension, and diabetes. The prevalence of hypertension increased from 2007 through 2017 (p trend <.001), whereas smoking decreased gradually. AMI frequently presented as ST-segment elevation MI (STEMI) (77.5%). Cluster of conventional RFs (3 RFs, odds ratio [OR]: 1.69, 95% confidence interval [CI]: 1.11-2.57; ≥4 RFs, OR: 2.50, 95% CI: 1.55-4.03] and multivessel disease (OR = 1.32, 95% CI: 1.08-1.60) increased the risk of non-STEMI (NSTEMI). Conventional RFs were highly prevalent in young Chinese men who were hospitalized for first AMI events, and the temporal trends varied different between China and US populations. Multivessel disease and cluster of conventional RFs are closely related to NSTEMI. Optimized preventive strategies among young adults are warranted.