Influences of crude extract of tea leaves, Camellia sinensis, on streptozotocin diabetic male albino mice.
Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. The aim of the present study was to investigate the hypoglycemic activity of the crude tea leaves extract on streptozotocin (STZ)-induced diabetic mice. The average body weight of animals with diabetes and their percentage changes of body weight gain after 15 and 30 days were significantly lower than that of the normal control mice. In diabetic mice, supplementation with tea leaves extract decreased the loss of body weight. After 15 and 30 days, significant increases in the levels of serum glucose, triglycerides, cholesterol, creatinine, urea, uric acid, glutamic pyruvic acid transaminase (GPT) and glutamic oxaloacetic acid transaminase (GOT) were noted in STZ-diabetic mice fed with normal diet. Also, the values of total protein in this group were statistically declined after 15 and 30 days. The levels of serum glucose and GPT were significantly elevated after 15 and 30 days in diabetic mice supplemented with tea leaves extract. Moreover, the level of serum GOT was notably increased after 30 days. Insignificant alterations were observed in the levels of serum triglycerides, cholesterol, total protein, creatinine, urea and uric acid in diabetic mice supplemented with tea leaves extract. Thus, the present results have shown that tea leaves extract has the antihyperglycemic, antihyperlipidemic, and antihyperproteinemic effects and consequently may alleviate liver and kidney damage associated with STZ-induced diabetes in mice.


Signaling Systems in Oral Bacteria.
The supra- and subgingival plaque biofilm communities of plaque are composed of hundreds of different microbes. These communities are spatially and temporally structured, largely due to cell-cell communications that coordinate synergistic interactions, and intracellular signaling systems to sense changes in the surrounding environment. Homeostasis is maintained through metabolic communication, mutualistic cross-feeding, and cross-respiration. These nutritional symbioses can reciprocally influence the local microenvironments by altering the pH and by detoxifying oxidative compounds. Signal transduction mechanisms include two-component systems, tyrosine phosphorelays, quorum sensing systems, and cyclic nucleotide secondary messengers. Signaling converges on transcriptional programs and can result in synergistic or antagonistic interbacterial interactions that sculpt community development. The sum of all these interactions can be a well-organized polymicrobial community that remains in homeostasis with the host, or a dysbiotic community that provokes pathogenic responses in the host.


Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.
Acupuncture can alleviate depression-like behaviors. However, the neural mechanisms behind the anti-depressive effect remain unknown. Perineuronal net (PNN) abnormalities have been reported in multiple psychiatric disorders. This study investigated the modulation and neural mechanism of PNNs in the anti-depressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points. A rat depression model was induced by chronic unpredicted mild stress (CUMS). The results revealed that CUMS, applied for four weeks, specifically reduces PNNs around parvalbumin (PV). In addition, EA and fluoxetine treatments reverse the decrease in PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons in the medial prefrontal cortex (mPFC) after CUMS. Furthermore, EA treatment can reverse the decrease in the protein expression of PNN components (aggrecan and brevican) in the mPFC caused by stress. After EA treatment, the decreased expression of GAD67, GLuA1, and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. PNN degradation in mPFC brain areas potentially interferes with the anti-depressant benefits of EA in rats with depression induced by CUMS. EA treatment did not increase PNNs+ cell density and the ratio of PV and PNN double-positive cells to PV+ neurons after PNNs degradation in the mPFC brain region of rats. This finding indicated that the mechanism of acupuncture's anti-depressant effect may be based on reversing the CUMS-induced decline in PNN expression, the functional impairment of γ-aminobutyric acid (GABA) neurons, and the regulation of excitatory synaptic proteins expression.


Detection of esophageal motor disorders by radionuclide transit studies. A reappraisal.
Radionuclide measurement of esophageal transit has been proposed as a screening test for esophageal motor dysfunction. In this study we evaluated the radionuclide esophageal transit test in 49 consecutive patients undergoing esophageal manometry for esophageal motor disorders. Esophageal transit was assessed using a 10-ml water bolus labeled with 250 microCi technetium-99m sulfur colloid. In preliminary studies in 14 healthy controls, mean transit time was 9.6 +/- 2.1 (SD) sec. Prolonged transit (greater than 15 sec) was observed in two of 28 swallow sequences in the control subjects. Transit times were prolonged in all patients with achalasia or diffuse esophageal spasm, and in five of seven patients with nonspecific abnormalities of peristaltic progression. The test was abnormal in only three of seven patients with high-amplitude peristalsis (nutcracker esophagus) and in none of three patients with hypertensive lower esophageal sphincter. Additionally, prolonged transit was seen in two of 18 patients with normal manometry. We conclude that the radionuclide transit test using a liquid bolus successfully identifies motor disorders characterized by defective peristaltic progression but not disorders in which peristalsis is intact. A major limiting factor appears to be the small number of swallow sequences tested. The test may not, therefore, be accurate enough to consider adopting as a sensitive and noninvasive screening test in the evaluation of patients with suspected esophageal motor disorders.


How long can culturable bacteria and total DNA persist in environmental waters? The role of sunlight and solid particles.
In this work, sunlight inactivation of two indicator bacteria in freshwater, with and without solid particles, was studied and the persistence of culturable cells and total DNA was compared. Environmental water was used to prepare two matrices, with and without solid particles, which were spiked with Escherichia coli and Enterococcus faecalis. These matrices were used to prepare microcosm bags that were placed in two containers: one exposed to sunlight and the other in the dark. During one month, samples were removed from each container and detection was done by membrane filter technique and real-time PCR. Kinetic parameters were calculated to assess sunlight effect. Indicator bacteria without solid particles exposed to sunlight suffered an immediate decay (<4h) compared with the ones which were shielded from them. In addition, the survival of both bacteria with solid particles varied depending on the situation analyzed (T99 from 3 up to 60days), being always culturable E. coli more persistent than E. faecalis. On the other side, E. faecalis DNA persisted much longer than culturable cells (T99>40h in the dark with particles). In this case active cells were more prone to sunlight than total DNA and the protective effect of solid particles was also observed. Results highlight that the effects caused by the parameters which describe the behavior of culturable microorganisms and total DNA in water are different and must be included in simulation models but without forgetting that these parameters will also depend on bacterial properties, sensitizers, composition, type, and uses of the aquatic environment under assessment.


Postoperative regression of retroperitoneal fibrosis in patients with inflammatory abdominal aortic aneurysms: evaluation with spiral computed tomography.
Partial or total regression of aortic and retroperitonel fibrosis after surgery has been reported in combination with inflammatory abdominal aortic aneurysm (AAA). In this report, we consider the most recent 21 patients with inflammatory AAA consecutively operated on at our institution. The group was composed of 19 men and 2 women, with a mean age of 66 years. In addition to preoperative CT angiographic study, abdominal ultrasound and aortoiliac angiography were also performed. There were no perioperative deaths. The perioperative morbidity rate was 9.5%. In 20 cases (95.2%), the aortic wall was subjected to histological examination with calculation of an inflammatory index. Each patient was reexamined with spiral CT angiography after surgery; postoperative results were assessed in terms of changes in maximal fibrotic-mantle thickness observed on follow-up spiral CT angiograms, expressed both in millimeters and percentage of change. Regression was analyzed for possible correlation with preoperative severity of fibrotic reaction, time of the postoperative exam, inflammatory index, and changes in the fibrotic process involving the adjacent structures. The results show that postoperative improvement was significantly more marked in cases characterized by higher preoperative inflammatory indices in the aneurysmal wall; the time course of regression was highly variable; but on the whole, improvement was more substantial during the early months after surgery, with significant slowing after the second or third year.


Molecular characterization of an inhibitor of apoptosis in the Egyptian armyworm, Spodoptera littoralis, and midgut cell death during metamorphosis.
The cDNA corresponding to an inhibitor of apoptosis (IAP) from the Egyptian armyworm, Spodoptera littoralis, was cloned by RT-PCR. Sequence analysis showed that the IAP of S. littoralis (SlIAP) contains two baculoviral IAP repeat (BIR) motifs, followed by a RING finger, an organization which is very similar to that of other lepidopteran IAPs. SlIAP mRNA was detected in ovary, testis, salivary gland, fat body, epidermis, brain and midgut of S. littoralis. During the last larval instar, prepupal and pupal stages, brain mRNA levels remained approximately constant, whereas those of midgut showed a large peak centred in the prepupal stage. Midgut morphology changed during metamorphosis from a semi-transparent, cylindrical structure in last instar larvae to a brownish globular mass in pupae. TUNEL assays, LysoTracker staining and caspase-3 immunohistochemistry, indicated that programmed cell death in midgut starts actively at the onset of pupation process, coinciding with the dramatic decrease of SlIAP mRNA levels observed at the same time.


Estimates of clinically useful measures in competing risks survival analysis.
Competing risks occur frequently in follow-up clinical studies. To assess treatment or covariate effects, measures of clinical impact based on crude cumulative incidence should be considered, such as relative risks or the absolute risk reduction. In this work, transformation models through suitable link functions provide a straightforward approach to obtain point and interval estimates of such measures. An extension of the Klein and Andersen proposal, based on pseudo-values, is considered. Non-additive effects were tested by interactions between baseline (spline function on time) and covariates. The methods are applied to the evaluation of the impact of axillary lymph node nanometastases on metastatic relapse of breast cancer patients. Further, a literature data set on prostate cancer was used for illustration.


A multivariate analysis of prognostic factors in management of pineal tumor.
A multivariate analysis of prognostic factors of treatment outcome of pineal tumor. From February 1979 to June 1987, 25 patients with primary pineal tumors were treated in our department. Patients were treated with either AECL Co-60 unit or 10 MV linear accelerator to the primary tumor with an adequate margin or to the whole brain (median dose of 36 Gy) with or without a cone-down boost of 10 to 20 Gy. Craniospinal irradiation was performed in two patients with positive CSF cytology. Minimum follow-up was 40 months. Patients were further stratified according to tumor type. Group I consisted of seven patients with pineal germinoma. Group II included nine patients with nongerminoma, and Group III represented nine patients treated without a histological verification but clinical diagnosis. The relapse-free survival (RFS) of Group I patients was 100% and 86% at 2 and 5 years, respectively. Relapse-free survival was 55% and 21% at 2 and 5 years, respectively, for Group II patients. Six of 9 patients in Group II died of disease due to either local recurrence or tumor seeding. Eight of 9 patients in Group III remain no evidence of disease, and RFS was 89% at 2 and 5 years. Multivariate analysis revealed that tumor histology is the only significant prognosticator. Age, gender, type of surgical procedure, RT field, and tumor dose were not. Cox's regression model also failed to demonstrate a significant correlation of tumor seeding with the type of surgery. The type of tumors in the pineal region dictates the treatment outcome. Definitive radiation therapy is effective in controlling germinoma, whereas a more aggressive approach is needed to improve local control for nongerminoma. For a localized pineal lesion, we advocate that treatment can be tailored to the primary tumor with adequate margins. However, for locally advanced tumors whole brain or craniospinal irradiation should be considered. No definitive correlation between type of surgery and the probability of tumor seeding was identified.


Olfactory disorders in coronavirus disease 2019 patients: a systematic literature review.
Recent scientific literature has widely described a possible major role of smell dysfunction as a specific symptom of coronavirus disease 2019. This systematic review may provide a more holistic approach to current knowledge of the disease. A systematic review was completed using Embase, PubMed and Web of Science databases that considered original articles focused on olfactory evaluation in coronavirus disease 2019 patients, published between March and May 2020, in English language. From the 483 research papers initially identified, 32 original studies were selected, comprising a total of 17 306 subjects with a laboratory confirmed diagnosis of coronavirus disease 2019. Individual study sample sizes ranged from 6 to 6452 patients. This comprehensive analysis confirmed that olfactory disorders represent an important clinical feature in coronavirus disease 2019, with a prevalence of 11-100 per cent in included patients, although there was heterogeneity in terms of assessment tools and population selection criteria. The results indicate that an accurate clinical evaluation should be carried out using structured questionnaires and tests with olfactory substances.


Psychological considerations for chronic orofacial pain.
This article presents an overview of psychologic and behavioral issues related to chronic orofacial pains. Clinicians are first introduced to the role that biobehavioral issues play in the onset and maintenance of orofacial pains. Specific foundational principles for the development of successful biobehavioral interventions are then presented and examples of successful biobehavioral treatment programs for orofacial pains are described. Positive outcomes in chronic orofacial pain management often require a multidimensional approach to treatment because of the complexity of dysfunctions. The principles and procedures outlined in this article can guide the development of effective biobehavioral management approaches for orofacial pain conditions.


Keratolenticuloplasty: arcuate keratotomy for cataract surgery and astigmatism.
Cataract surgery has evolved into a procedure in which pre-existing refractive errors can be corrected simultaneously to improve uncorrected visual acuity following surgery. This paper describes keratolenticuloplasty, a new technique of clear corneal arcuate keratotomy for cataract surgery that corrects pre-existing astigmatic errors at the time of cataract extraction. This technique uses topical anesthesia, a single pair of arcuate corneal incisions placed on the steepest axis of astigmatism, one-step capsulorhexis, hydrodissection, intercapsular phacoemulsification, and injection of an elastic intraocular lens within the capsular bag. The technique has been used in over 1,000 patients with follow-up of 24 months. Uncorrected visual acuity of 20/40 or better with no associated complications was achieved in 96% of patients.


The effect of anaesthesia on the inhibition of pentagastrin-evoked gastric acid secretion induced by atropine in the rat.
1. In the anaesthetized, vagally intact rat, with a perfused gastric lumen, atropine produced a maximum inhibition of 60% of maximal pentagastrin-evoked gastric acid secretion. Sub-maximal pentagastrin-stimulated secretion was also inhibited by atropine.2. In the anaesthetized, vagotomized rat, with a perfused gastric lumen, atropine had no inhibitory effect on maximal pentagastrin-evoked gastric acid secretion.3. In the conscious fistula rat, atropine totally abolished both the basal gastric acid secretion and the maximal gastric acid secretion evoked by pentagastrin. In the anaesthetized chronic fistula rat, doses of atropine up to 1.6 mg.kg(-1) administered subcutaneously produced a maximum inhibition of 70% of maximal pentagastrin-evoked gastric acid secretion. Vagotomy did not affect the response to atropine.4. In the conscious Heidenhain pouch rat, doses of atropine up to 1.6 mg.kg(-1) administered subcutaneously produced a maximum inhibition of 70.9% of maximal pentagastrin-evoked gastric acid secretion. Both anaesthesia and vagotomy, alone or in combination, did not affect the response to atropine.


Assessment of micro-polarity anisotropy as a function of surfactant packing in sodium dodecyl sulphonate-hexane reverse micelles.
The micro-polarity anisotropy behaviour across the aqueous phase of a SDS (sodium dodecyl sulphonate)-hexane reverse micelle (RM) relies on the SDS packing in the oil-water interfacial self-assembled surfactant structure of the RM.


Effect of Microencapsulation on Chemical Composition and Antimicrobial, Antioxidant and Cytotoxic Properties of Lemongrass (Cymbopogon flexuosus) Essential Oil.
Lemongrass (Cymbopogon flexuosus) essential oil exhibits antimicrobial and antioxidant properties due to the presence of α-citral and β-citral. Essential oils are susceptible to volatilization and oxidation when applied to food matrices. Therefore, a barrier is needed to protect this material. The present study aims to produce microparticles containing lemongrass essential oil, with gum arabic and maltodextrin using spray drying technology. Lemongrass essential oil was extracted by the hydrodistillation method and later microencapsulated with different wall materials. Free and microencapsulated lemongrass essential oil was evaluated for the cytotoxic activity (using Artemia salina as test sample), chemical composition (GC-MS), encapsulation efficiency, antioxidant activity (DPPH, ABTS and FRAP), antimicrobial activity and minimum inhibitory concentration. The lethal concentration (LC50) of lemongrass essential oil in the cytotoxic test was 8.43 μg/mL against Artemia salina; a high activity that can be associated with the presence of α-citral (~33%) and β-citral (~21%) in the samples, since these were the main compounds with bioactive properties. The highest value of microencapsulation efficiency (88.11%) was obtained when only gum arabic was used as wall material. In general, the microparticles showed satisfactory antioxidant activity (expressed as Trolox equivalents, between 348.66 and 2042.30 µmol/100 g) and bactericidal effect in vitro against Gram-positive and Gram-negative microorganisms. In conclusion, the microencapsulated lemongrass essential oil is a promising functional additive in the food and pharmaceutical industries. This study shows that microparticles containing lemongrass essential oil can be prepared using gum arabic and maltodextrin as wall materials by spray drying, resulting in high microencapsulation efficiency. The drying process maintained the antimicrobial and antioxidant properties of the essential oil. Therefore, the microencapsulated lemongrass essential oil is considered a natural, functional and promising additive in the food industry. Its antimicrobial action can increase the shelf life of fresh and semi-fresh products such as cheese, yogurts and meat products. In addition, its antioxidant action can delay the lipid and protein oxidation in food products.


Oxygen and bile acid content in the azygos blood. Clues to the azygos derivation in patients with portal hypertension.
In patients with cirrhosis, elevation of azygos blood flow has been attributed on indirect grounds to cephalad portosystemic collaterals. To gather more information on the origin of the azygos blood, we studied the oxygen and bile acid content of the azygos and mixed venous blood in patients with portal hypertension. Azygos oxygen saturation was 59.6 +/- 6.0% in 8 controls, and significantly higher in 35 patients with cirrhosis (76.7 +/- 7.6%; P less than 0.01) as well as in 6 patients with noncirrhotic portal hypertension (84.0 +/- 8.2%; P less than 0.01). High oxygen saturation, however, was not correlated to azygos blood flow in patients with cirrhosis. In cirrhotic patients, total bile acid concentrations were 28.1 +/- 20.4 mumol/l in the pulmonary artery and 25.9 +/- 17.6 mumol/l in the azygos vein, giving an azygos to mixed venous ratio of 0.95 +/- 0.18. These results provide new evidence that elevated azygos blood flow in patients with portal hypertension is derived from the portal system, and perhaps predominantly from the splenic territory.


Brain sizes, surfaces, and neuronal sizes of the cortex cerebri: a stereological investigation of man and his variability and a comparison with some mammals (primates, whales, marsupials, insectivores, and one elephant).
This study deals with the stereological estimation of macroscopic sizes of brain and cortex, i.e., volume, surface, and folding, and of microscopic neuronal sizes, i.e., density, mean size, size distribution, and number of neurons. The results show that the degree of variability in man amounts to about 15%. A decrease in volume of the different gray structures can be observed in man after the age of 65 years. The surface, folding index, and length of convolution do not alter with aging. The comparison with mammals of various sizes allows the conclusion that there is a high correlation to brain size for nearly all macroscopic values. Man and elephant, however, have a cortical surface which is, in comparison with whales, relatively small. In contrast, whales have very small cortices compared with man. At the cytoarchitectonic level, the neuronal density has a correlation to brain size. Contrary to other mammals, the primates and man have a high fraction of small granular neurons, especially in layer 4. The assumption that the number of cortical neurons beneath a given surface area of cortex is the same in all mammals cannot be verified, especially in those with large brains. The allometric connection between brain size and parameters is not valid for all measurements (e.g., thickness of cortex, mean size of neurons, perikaryal size distribution, and glial density). Yet some other measurements are well correlated.


Characterization of seven new HLA alleles from the Henan and Gansu Provinces of China.
Four new class I and three class II alleles have been found in Chinese individuals.


Complete sequence and characterization of the Ectropis oblique mitochondrial genome and its phylogenetic implications.
In the present study, we sequenced the entire mitochondrial genome (mitogenome) of Ectropis oblique using PCR amplification and sequencing methods The entire mitogenome is 15,356bp long, including 13 protein coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and A+T rich element. The base composition and gene arrangement are identical to those of other lepidopterans. Of these 37 genes, twenty three are resided on heavy strand, while fourteen located on light strand. The newly sequenced mitogenome displayed a biased Adenine/thymine 84.94% usage versus guanine/cytosine. The AT skewness is 0.030 and the GC skewness is -0.180. Twelve out of 13 PCGs initiated with canonical start codon (ATN), while cox1 started with CGA. The A+T rich element of E. oblique is 363bp long and contains of many features common to lepidopteran insects, including the 'ATAGA' motif, a 22bp poly (T) stretch and a microsatellite-like (AT)8 element upstream of trnM. Further, this mitogenome comprises 15 intergenic spacer and overlapping regions. Phylogenetic analyses showed that E. oblique belongs to Geometridae, and that the monophyly of Lepidoptera superfamilies is well supported.


Processing complex graphemes in handwriting production.
Recent studies on handwriting production and neuropsychological data have suggested that orthographic representations are multilevel structures that encode information on letter identity and order, but also on intermediate-grained processing units such as syllables and morphemes. This study on handwriting production examined whether orthographic representations also include a graphemic-processing level. French adults wrote words containing an embedded one-, two-, or three-letter grapheme (e.g., a in clavier, ai in prairie, ain in plainte) on a digitizer. The results for letter duration revealed that the timing of movement processing depends on grapheme length (e.g., the duration of a for one-letter graphemes was shorter than that for two-letter graphemes, which, in turn, was shorter than that for three-letter graphemes). Two- and three-letter graphemes start to be processed before we start to write them. The results therefore revealed that orthographic representations also encode information on grapheme complexity.


Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development.
Cortical map formation requires the accurate targeting, synaptogenesis, elaboration and refinement of thalamocortical afferents. Here we demonstrate the role of Ca2+/calmodulin-activated type-I adenylyl cyclase (AC1) in regulating the strength of thalamocortical synapses through modulation of AMPA receptor (AMPAR) trafficking using barrelless mice, a mutant without AC1 activity or cortical 'barrel' maps. Barrelless synapses are stuck in an immature state that contains few functional AMPARs that are rarely silent (NMDAR-only). Long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical synapses require postsynaptic protein kinase A (PKA) activity and are difficult to induce in barrelless mice, probably due to an inability to properly regulate synaptic AMPAR trafficking. Consistent with this, both the extent of PKA phosphorylation on AMPAR subunit GluR1 and the expression of surface GluR1 are reduced in barrelless neurons. These results suggest that activity-dependent mechanisms operate through an AC1/PKA signaling pathway to target some synapses for consolidation and others for elimination during barrel map formation.


Arterial baroreceptor control of peripheral vascular resistance in experimental heart failure.
Heart failure is known to impair arterial baroreceptor control of heart rate. To determine if baroreceptor control of peripheral vascular resistance is also impaired, heart rate and hind limb vascular responses to phenylephrine and nitroglycerin administration were compared in control dogs and in dogs with heart failure produced by chronic rapid ventricular pacing. Baroreflex control of the heart rate was depressed in the dogs with heart failure, as evidenced by a reduced slope of the blood pressure-to-heart rate relationship (controls: -2.5 +/- 0.3 beats/mm Hg versus heart failure: -1.5 +/- 0.2 beats/mm Hg [(p less than 0.04)]). Arterial blood pressure in the dogs with heart failure was also reduced (controls: 90 +/- 3 mm Hg versus heart failure: 75 +/- 3 mm Hg [(p less than 0.01)]). Nevertheless, dogs with heart failure exhibited normal slopes of the blood pressure versus hind limb vascular resistance relationship (controls: -2.4 +/- 0.4 units/mm Hg versus heart failure: -2.9 +/- 0.5 units/mm Hg [(p = NS)]), consistent with preserved baroreflex control of the peripheral vasculature. These data suggest that heart failure impairs arterial baroreflex control of heart rate and lowers the baroreflex pressure operating range but does not alter baroreflex control of peripheral resistance.


Age-specific incidence rates for cytogenetically-defined subtypes of acute myeloid leukaemia.
It is generally considered that most cancers arise following the accumulation of several genetic events and that as a consequence its incidence increases with age. We report a cytogenetic subgroup of acute myeloid leukaemia whose incidence is independent of age. This observation indicates that acute myeloid leukaemia can develop via multiple pathways, and underlines the importance of cytogenetics in understanding this disease.


Assessing the impact of long-term changes in climate and atmospheric deposition on a shallow alpine lake from southeast Tibet.
Regional warming and atmospheric nitrogen deposition have been widely recorded to impact remote catchments and alpine lakes; however, their independent roles and interactions have rarely been identified. Here, we combined down-core analyses of sedimentary mercury (Hg) and aluminum (Al) with multiple proxies (i.e. nitrogen stable isotope, chlorophyll a pigments, diatoms) for a radiometrically-dated sediment core of an alpine lake in southeast Tibet to track the atmospheric deposition of pollutants, and to examine possible effects of climate and catchment forcing over the past three centuries. The sediment data revealed that airborne deposition of Hg was recorded from the ~1860s, with an accelerating increase in anthropogenic Hg flux since the ~1960s. A synchronous decrease in reconstructed lake-water TOC indicated that acid deposition may have affected lake-water carbon concentrations and impaired catchment export of decomposed organic matter (OM). A moderate depletion of bulk sediment δ15N started from the ~1820s, but was followed by an enriching trend after the ~1970s. This positive shift of δ15N was associated with elevated sediment OM and decreased catchment runoff of clastic materials (as inferred by Al). Sediment OM content displayed an accelerating increase from the ~1960s, with an increased input of autochthonous sources (i.e. lower bulk sediment C:N ratios), such as algae (as inferred by sedimentary chlorophyll a pigments). Meanwhile, climate warming and decreased lake-water TOC enhanced the production of algae, which was characterized by a more enriched δ15N signal than that of allochthonous OM. Furthermore, atmospheric acid deposition was significantly related to diatom assemblage changes, with an increase in acidophilous taxa. Our sediment evidence revealed the dominating impact of climate and catchment processes on lake-water chemistry and algal shifts in the context of atmospheric nitrogen deposition, and highlighted an increasing link of external forcing with in-lake processes in enriching sediment δ15N signal over the last few decades.


Corticosteroids in patients undergoing cardiac surgery: A meta-analysis of 12,559 patients.
Corticosteroids can attenuate the inflammatory response to cardiopulmonary bypass, but their benefits on clinical outcomes are unclear. We conducted a meta-analysis to evaluate whether corticosteroid therapy affects outcomes in patients undergoing cardiac surgery. We searched PubMed, Embase, EBSCO and Cochrane databases from 1 January 2010 to 14 March 2022 for randomized controlled trials (RCTs) that assessed corticosteroid versus non- corticosteroid therapy in patients undergoing cardiac surgery. The primary outcome was in-hospital mortality. Secondary outcomes were renal failure, infection, delirium, intensive care unit (ICU) and hospital stay. Four RCTs including 12,559 patients (6265 randomized to corticosteroid therapy and 6294 to non-corticosteroid therapy) were included. One-hundred and 92 of 6265 patients (3.1%) randomized to the corticosteroid group versus 221 of 6294 patients (3.5%) randomized to the non-corticosteroid group experienced death during hospitalization. Compared the control group, corticosteroid therapy did not significantly reduce in-hospital mortality, with an RR of 0.87 (0.72-1.06), p = .16. There was no difference in the incidence of infection (RR 0.78 (0.56-1.10), p = .16), delirium during hospitalization (RR 1.01 (0.90-1.14), p = .85), or the length of hospital stay (MD -0.13 (-0.32 to 0.05), p = .17). However, corticosteroid therapy significantly reduced the risk of renal failure ( RR 0.82 (0.67-0.99), p = .04), and the length of ICU stay (MD -0.41 (-0.65 to -0.17), p < .01). Corticosteroids did not significantly reduce the rates of in-hospital mortality, infection, or delirium, but reduce the incidence of renal failure and the length of ICU stay.


Performance discrepancies on the California Verbal Learning Test: Second Edition (CVLT-II) after traumatic brain injury.
One hundred fourteen patients with traumatic brain injury (TBI), selected from a 5-year series of consecutive rehabilitation referrals, completed the California Verbal Learning Test -- Second Edition (CVLT-II) within 1 year after injury. Various performance contrasts (i.e., proactive interference, retroactive interference, rapid forgetting, and retrieval problems) were evaluated. Initial analyses revealed higher rates of rapid forgetting in the TBI group as compared to the standardization sample. Follow-up analyses between those patients with and without unusual degrees of rapid forgetting did not reveal any significant differences between these groups on demographic or neurological variables (p>0.10 for all variables). It is concluded that performance discrepancies on the CVLT-II should never be used in isolation to determine the presence or absence of acquired cerebral or memory impairment. However, regardless of the cause, such discrepancies may still be relevant for clinical treatment recommendations.


Phosphatase Wip1 is essential for the maturation and homeostasis of medullary thymic epithelial cells in mice.
Thymic epithelial cells (TECs) are a key cell type in the thymic microenvironment essential for T cell development. However, intrinsic molecular mechanisms controlling TEC differentiation and activities are poorly defined. In this study, we found that deficiency of p53-induced phosphatase 1 (Wip1) in mice selectively caused severe medullary TEC (mTEC) maturation defects in an intrinsic manner. Wip1 knockout (KO) mice had decreased mature epithelial cell adhesion molecule⁺Ulex europaeus agglutinin-1 (UEA-1)⁺mTECs, including UEA-1⁺MHC class II(high), UEA-1⁺CD80⁺, UEA-1⁺CD40⁺, and UEA-1⁺Aire⁺ cells, but not decreased numbers of cortical epithelial cell adhesion molecule⁺BP-1⁺ TECs, in the postnatal stage but not in the fetal stage. Wip1-deficient mTECs express fewer tissue-restricted Ags and UEA-1⁺involucrin⁺ terminal-differentiated cells. Animal models, including grafting fetal Wip1-deficient thymic tissue into T cell-deficient nude mice and reconstitution of lethally irradiated Wip1KO mouse recipients with wild-type bone marrow cells, also showed the impaired mTEC components in Wip1KO thymi, indicating the intrinsic regulatory role of Wip1 in mTEC maturation. Furthermore, thymus regeneration was significantly less efficient in adult Wip1KO mice than in wild-type mice after cyclophosphamide treatment. Wip1 deficiency resulted in elevated p38 MAPK activity in mTECs. Activated p38 MAPK has the ability to suppress CD40 expression on mTECs. Wip1-deficient thymi displayed poor response to CD40L in the fetal thymus organ culture system. Thus, Wip1 positively controls mTEC maturation, homeostasis, and regeneration through limiting the p38 MAPK pathway.


In situ deposition of MOF-74(Cu) nanosheet arrays onto carbon cloth to fabricate a sensitive and selective electrocatalytic biosensor and its application for the determination of glucose in human serum.
A new electrocatalytic biosensor (MOF-74(Cu) NS-CC) based on the in situ deposition of MOF-74(Cu) nanosheet on carbon cloth via a bottom-up synthetic approach in a glass tube was developed. The electrocatalytic activity of the deposited MOF-74(Cu) NS was demonstrated in the oxidation of glucose to gluconate under alkaline conditions. The results revealed that the proposed method of in situ formation of MOF-74(Cu) NS onto a carbon cloth surface in a multi-layer solution is capable to generate a stable MOF-74(Cu) NS-CC electrode with excellent sensing performance. When the as-synthesized MOF-74(Cu) NS-CC was applied directly as the working electrode for glucose sensing, it showed much higher conductivity and redox activity than MOF-74(Cu) NS-GCE. With the potential applied at 0.55 V (vs. Ag/AgCl), this new electrocatalytic biosensor exhibits an excellent linear relationship between current density and concentration of glucose. Moreover, a wide linear range of detection (1.0 to 1000 μM) was observed. The limit of detection was found to be 0.41 μM (S/N = 3). The response sensitivity is 3.35 mA mM-1 cm-2 when the concentration of glucose is in the range 1-100 μM and 3.81 mA mM-1 cm-2 for the 100-1000 μM concentration range. This study provides a low-cost, easy to prepare, and reproducible methodology for the synthesis of highly redox-active nanomaterials based on the in situ formation of two-dimensional MOF-74(Cu) NS for the development of new electrocatalytic biosensors. Graphical abstract.


Simulated assessment of light transport through ischaemic skin flaps.
Currently, free flaps and pedicled flaps are assessed for reperfusion in postoperative care using colour, capillary refill, temperature, texture, and Doppler signal (if available). While these techniques are effective, they are prone to error due to their qualitative nature. In this research, different wavelengths of light were used to quantify the response of ischaemic tissue. The assessment provides indicators that are key to developing a point-of-care diagnostic device that is capable of observing reduced perfusion quantitatively. Detailed optical models of the layers of the skin were set up and appropriate optical properties assigned, with due consideration of melanin and haemoglobin concentration. A total of 24 models of healthy, perfused and perfusion-deprived tissue were used to assess the responses when illuminated with visible and near-infrared wavelengths of light. In addition to detailed fluence maps of photon propagation, a simple mathematical model is proposed to assess the differential propagation of photons in tissue; the optical reperfusion factor (ORF). The results show clear advantages of using light at longer wavelengths (red, near-infrared) and the inferences drawn from the simulations hold significant clinical relevance. The simulated scenarios and results consolidate the belief in a multi-wavelength, point-of-care diagnostic device, and inform its design to quantify blood flow in transplanted tissue. The modelling approach is applicable beyond the current research and can be used to investigate other medical conditions in the skin that can be mathematically represented. Through these, additional inferences and approaches to other point-of-care devices can be realised.


Expression, purification and characterisation of recombinant Escherichia coli derived chicken interleukin-12.
Zoonotic viruses, such as H5N1 Avian Influenza, pose major threats to both animals and humans, and with this in mind there is a need for the development of new anti-viral strategies. The cytokine interleukin-12 (IL-12) is known to play a pivotal regulatory role in the anti-viral response due to its role in the induction of the key anti-viral cytokine IFN-gamma. Therefore, strategies which provide a means for the production of therapeutic quantities of IL-12 may be of major benefit. Here we describe the development of biologically active Escherichia coli (E. coli) derived chicken IL-12 (ChIL-12). The single chain ChIL-12 gene was cloned into the pET32b expression vector, transformed into the BL-21 E. coli strain and expression induced with IPTG. Over expressed protein was solubilised with zwittergent detergent and isolated utilising Nickel ion affinity chromatography. Biological activity was determined as ChIL-12 stimulated proliferation of pre-treated T-cells in vitro. This study is the first example of a biologically active E. coli derived IL-12 from a non-mammalian vertebrate subsequently providing a means for testing the anti-viral therapeutic potential of ChIL-12 in an in vivo model.


Efficacy of the fluorescent dyes Fast Blue, Fluoro-Gold, and Diamidino Yellow for retrograde tracing to dorsal root ganglia after subcutaneous injection.
The present study was designed to investigate the efficacy of the fluorescent dyes Fast Blue (FB), Fluoro-Gold (FG), and Diamidino Yellow (DY) for retrograde tracing of lumbar dorsal root ganglia after their subcutaneous injection into different hindlimb digits. Injections of equal volumes (0.5 microl) of 51% FB or 2% FG resulted in similar mean numbers of sensory neurones labelled by each tracer. Injection of equal volumes (0.5 microl) of FB or FG in a single digit followed 10 days later by a second injection of the same volume of 5% DY into the same digit resulted in similar mean numbers of labelled sensory neurones for each of the three tracers. Furthermore, on average, 75% of all the FB-labelled cells and 74% of all FG-labelled cells also contained DY. Repeating the same experiment with an increased volume of DY (1.5 microl) resulted in an increase in the mean number of double-labelled profiles to 82 and 84% for FB and FG, respectively. The results show that FB, FG and DY label similar numbers of cutaneous afferents and that a high level of double labelling may be obtained after sequential injections in digits. These properties make them suitable candidates in investigations where a combination of tracers with similar labelling efficacies is needed.


Cardiovascular autonomic function in multiple sclerosis.
The autonomic nervous function of the cardiovascular system was investigated by non-invasive methods in 30 multiple sclerosis patients between 20 and 50 years of age. The results were compared to those of 30 healthy controls in the same age group. Minor abnormalities of parasympathetic and sympathetic function occurred. Heart rate variation at deep breathing was reduced and more than half of the patients had abnormal responses during an orthostatic procedure, mainly as an increased rise in heart rate. Decreased rise in blood pressure at sustained handgrip was also demonstrated. The abnormalities correlated poorly with other clinical signs and symptoms in the patients.


Development of a novel cell-based assay to monitor the transactivation activity of the HSV-1 protein ICP0.
The herpes simplex virus type 1 (HSV-1) immediate-early phosphoprotein infected cell protein 0 (ICP0) is a potent transcriptional activator of viral genes and is required for efficient viral replication and reactivation from latency. However, it is largely unknown what role specific cellular factors play in the transactivator function of ICP0. With the long-term goal of identifying these factors, we developed a cell-based assay in a 96-well format to measure this activity of ICP0. We designed a system using a set of HSV-1 GFP reporter viruses in which the expression of GFP is potently induced by ICP0 in cell culture. The initial feasibility of this system was confirmed over a 24-h period by fluorescence microscopy. We adapted this assay to a 96-well plate format, quantifying GFP expression with a fluorescence scanner. Our results indicate that the cell-based assay we developed is a valid and effective method for examining the transactivating activity of ICP0. This assay can be used to identify cellular factors that regulate the transactivating activity of ICP0.


Prevalence of khat chewers among primary health clinic attenders in Kenya.
In a rural district hospital in Kenya, the authors screened 100 randomly selected outpatients for khat (miraa) chewing. A surprisingly high number of them admitted chewing khat leaves. The implications of this finding and the controversy about whether or not khat is a harmful drug are discussed.


Estimation of the rate of partial inbreeding.
Estimates are given for the rate of partial inbreeding when a maternal homozygous genotype and her progeny are known. Also considered are estimates for X-linked genes (or haplo-diploid organisms), situations in which there is more than one type of inbreeding, inbreeding in previous generations, variation in male allelic frequencies, and null alleles. These procedures could be used in animals as well as plants although the size of the progeny array must be fairly large.


How Often Are Antibiotic-Resistant Bacteria Said to "Evolve" in the News?
Media plays an important role in informing the general public about scientific ideas. We examine whether the word "evolve," sometimes considered controversial by the general public, is frequently used in the popular press. Specifically, we ask how often articles discussing antibiotic resistance use the word "evolve" (or its lexemes) as opposed to alternative terms such as "emerge" or "develop." We chose the topic of antibiotic resistance because it is a medically important issue; bacterial evolution is a central player in human morbidity and mortality. We focused on the most widely-distributed newspapers written in English in the United States, United Kingdom, Canada, India, and Australia. We examined all articles that focused primarily on the evolution of antibiotic resistance, were published in 2014 or earlier, and were accessible in online archives, for a total of 1639 articles. The total years examined per newspaper ranged from 5 to 37 years with a median of 27 years, and the overall range was 1978-2014. We quantified how many articles included the term "evolve" and analyzed how this varied with newspaper, country, and time. We found that an overall rate of 18% of articles used the term "evolve" but with significant variation among countries. Newspapers in the United Kingdom had the highest rate (24%), more than double of those in India (9%), the country with the lowest rate. These frequencies were lower than those found in scientific papers from both evolutionary journals and biomedical journals. There were no statistically significant changes in frequency and no trends when "evolve" usage was compared against variables such as newspaper circulation, liberal/conservative bias, time, and state evolution acceptance in U.S. newspapers. This study highlights the globally low usage of the word "evolve" in the popular press. We suggest this low usage may affect public understanding and acceptance of evolutionary concepts.


[Intensive preoperative gamma teletherapy combined with endogenous interferon induction in the treatment of stomach cancer].
The authors analyze results of combined treatment of 72 patients using preoperative intensive gamma teletherapy. Increase of 4-year survival was observed only in patients showing no regional metastases and equalled 18.7%. The authors worked out a method of preoperative radiation treatment against the background of induction of endogenous interferon by curantyl. The course of radiation therapy was carried out in association with a 2-3 times increase of the interferon levels in the blood and was accompanied by a reduction of the immunodepressive effect of gamma teletherapy on the body.


Expression Partitioning of Duplicate Genes at Single Cell Resolution in Arabidopsis Roots.
Gene duplication is a key evolutionary phenomenon, prevalent in all organisms but particularly so in plants, where whole genome duplication (WGD; polyploidy) is a major force in genome evolution. Much effort has been expended in attempting to understand the evolution of duplicate genes, addressing such questions as why some paralog pairs rapidly return to single copy status whereas, in other pairs, both paralogs are retained and may diverge in expression pattern or function. The effect of a gene - its site of expression and thus the initial locus of its function - occurs at the level of a cell comprising a single cell type at a given state of the cell's development. Using Arabidopsis thaliana single cell transcriptomic data we categorized patterns of expression for 11,470 duplicate gene pairs across 36 cell clusters comprising nine cell types and their developmental states. Among these 11,470 pairs, 10,187 (88.8%) had at least one copy expressed in at least one of the 36 cell clusters. Pairs produced by WGD more often had both paralogs expressed in root cells than did pairs produced by small scale duplications. Three quarters of gene pairs expressed in the 36 cell clusters (7,608/10,187) showed extreme expression bias in at least one cluster, including 352 cases of reciprocal bias, a pattern consistent with expression subfunctionalization. More than twice as many pairs showed reciprocal expression bias between cell states than between cell types or between roots and leaves. A group of 33 gene pairs with reciprocal expression bias showed evidence of concerted divergence of gene networks in stele vs. epidermis. Pairs with both paralogs expressed without bias were less likely to have paralogs with divergent mutant phenotypes; such bias-free pairs showed evidence of preservation by maintenance of dosage balance. Overall, we found considerable evidence of shifts in gene expression following duplication, including in >80% of pairs encoding 7,653 genes expressed ubiquitously in all root cell types and states for which we inferred the polarity of change.


Four methods in diagnosing protozoal parasites in stool.
Stool examination by 4 different methods showed that zinc sulphate floatation technique was more or less the best.


Normal body mass index (BMI) can rule out metabolic syndrome: An Israeli cohort study.
The aim of the study was to assess whether body mass index (BMI) can be used as a simple and reliable survey test for metabolic syndrome.The study is an observational cohort study among patients who visited the Rambam Periodic Examinations Institute (RPEI). We analyzed the correlation between obesity indices and presence of metabolic syndrome. We identified the ideal value of BMI for identification of patients at risk for metabolic syndrome. We also described the correlation between different BMI values and its negative predictive value (NPV) for metabolic syndrome.During the study years, 23,993 patients visited the RPEI, and 12.5% of them fulfilled the criteria for metabolic syndrome. Women with metabolic syndrome had higher proportion of obesity, when compared with men (89.9% vs 52.6%; P < .0001). Normal BMI had very high NPV to rule out metabolic syndrome among men and women (98% and 96%, respectively). Using receiver-operating characteristic curve, we found BMI 27 to be the ideal value for identification of metabolic syndrome for the entire cohort (area under the curve [AUC] 0.767, 95% confidence interval [CI] 0.758-0.775, P < .0001), for men (AUC 0.726, 95% CI 0.715-0.738, P < .0001), and for women (AUC 0.843, 95% CI 0.831-0.855, P < .0001). BMI below 30 provided NPV of 91.1% to rule out metabolic syndrome.The BMI as single survey measurement of obesity offers high NPV for metabolic syndrome and can be used by physician and patients for this purpose.


A Comparison of Proliferative Capacity of Reticular and Erosive Variants of Oral Lichen Planus by Argyrophilic Nucleolar Organizer Regions Method.
Oral lichen planus (OLP), an immune mediated disorder, has been recognized since 1869 and is presented as any one of the six variants. Reticular and erosive are the most frequently encountered. Its proliferative capacity can give some information regarding its progression. We adopted the argyrophilic nucleolar organizer regions (AgNORs) method because of its simplicity to use and dependable results. We evaluated AgNORs in basal, suprabasal, and squamous cell layers. We also compared these three layers within two variants, reticular, and erosive. Thirty clinically diagnosed patients of OLP were included in the study. Reticular and erosive variants were included in our study. This was followed by hematoxylin and eosin staining and later by the AgNOR method. The mean number of AgNORs per nucleus was calculated. Thirteen males and 17 females were the gender distribution. Twenty-three (76.67%) had reticular pattern and seven (23.33%) had erosive pattern. The basal cell layer had the highest mean AgNOR compared to suprabasal and squamous layers. Even among, erosive and reticular variants, the former had higher mean AgNOR counts. Our results suggest that the inflammatory infiltrate close to the epithelial cells can alter the proliferation index for the pattern of protein synthesis of these cells. Moreover, the high proliferative index in OLP can be related to a specific immunologic response. We conclude that AgNOR can be used as a proliferative marker in earlier lesions to detect the severity.


Instability of (CTG)n•(CAG)n trinucleotide repeats and DNA synthesis.
Expansion of (CTG)n•(CAG)n trinucleotide repeat (TNR) microsatellite sequences is the cause of more than a dozen human neurodegenerative diseases. (CTG)n and (CAG)n repeats form imperfectly base paired hairpins that tend to expand in vivo in a length-dependent manner. Yeast, mouse and human models confirm that (CTG)n•(CAG)n instability increases with repeat number, and implicate both DNA replication and DNA damage response mechanisms in (CTG)n•(CAG)n TNR expansion and contraction. Mutation and knockdown models that abrogate the expression of individual genes might also mask more subtle, cumulative effects of multiple additional pathways on (CTG)n•(CAG)n instability in whole animals. The identification of second site genetic modifiers may help to explain the variability of (CTG)n•(CAG)n TNR instability patterns between tissues and individuals, and offer opportunities for prognosis and treatment.


Sustainable Food Production and Nutraceutical Applications from Qatar Desert Chlorella sp. (Chlorophyceae).
Microalgae isolated from the Qatari desert was identified as thermotolerant, with a rich metabolite profile that is appropriate for use as food and health supplements. In this research, a species of Chlorella, QUCCCM3, from the Qatar University Culture Collection of Cyanobacteria and Microalgae, was investigated for its growth characteristics and metabolite compositions for use as potential feedstock for food production. The strain was cultivated at 30, 35, and 40 °C, covering the annual average low and high temperatures in Qatar. The highest growth rates were recorded for cultures at 30 °C with 0.64 ± 0.04 day-1, followed by a growth rate of 0.54 ± 0.06 day-1 at 40 °C, indicating its thermotolerance ability. The biomass exhibited a high protein content (43 ± 2.3%), with existence of lysine (4.13%) as an essential amino acid, and docosahexaenoic acid, linoleic acid, and alpha-linolenic acid as important omega fatty acids present. On the other hand, Chlorella sp. QUCCCM3 also exhibited a high capacity for scavenging free radicals with an antiproliferative effect against chronic myeloid leukemia K562 cancer cells. The results indicate that Chlorella sp. QUCCCM3 is a promising candidate that can be produced year-round, in the Qatar environment, for commercial applications such as feed and nutraceutical supplements.


Developing multicomponent edible films based on chitosan, hybrid of essential oils, and nanofibers: Study on physicochemical and antibacterial properties.
Plastic waste is one of the major threats to the environment, and an urgent need to replace synthetic plastics with sustainable materials is progressively growing. Herein, sustainable films based on chitosan, Satureja, and Thyme essential oils (EOs), and chitosan nanofibers (NF) were developed for the first time. To this end, 1% (w/w) of EOs and 2 wt% of NF were incorporated into the chitosan solution. Despite the very similar chemical structure of carvacrol and thymol, which are the major constituents of Satureja and Thyme EOs, respectively, they imposed notably different effects on the physicochemical properties of chitosan films. Thyme EO was more efficient at establishing hydrogen bonds with chitosan. The disruptive effect of EOs on the crystalline network of chitosan was demonstrated through X-ray diffraction analysis. Satureja and Thyme EOs decreased and increased the barrier property of the chitosan films against water vapor, respectively. However, the barrier property was greatly improved in the presence of chitosan nanofibers. Satureja EO exhibited a more efficient antibacterial property against E. coli rather than Thyme EO. The fruits and vegetables, coated by the chitosan/EO/NF system, were less perished as compared with the control and chitosan-coated samples indicating the promising potential of the developed system to be used as edible and sustainable films and coatings due to their enhanced antibacterial and barrier properties.


Suboptimal Level of Bone-Forming Cells in Advanced Cirrhosis are Associated with Hepatic Osteodystrophy.
Bone loss is common in advanced cirrhosis, although the precise mechanisms underlying bone loss in cirrhosis are unknown. We studied the profile and functionality of bone-forming cells and bone-building proteins in bone marrow (BM) of individuals with cirrhosis (n = 61) and individuals without cirrhosis as normal controls (n = 50). We also performed dual energy X-ray absorptiometry for clinical correlation. BM mesenchymal cells (MSCs) were analyzed for colony-forming units-fibroblasts and their osteogenic (fibronectin-1 [FN1], insulin-like growth factor binding protein 3 [IGFBP3], collagen type 1 alpha 1 chain [COL1A1], runt-related transcription factor 2 [RUNX2], and alkaline phosphatase, liver [ALPL]) and adipogenic ( adiponectin, C1Q, and collagen domain containing [ADIPOQ], peroxisome proliferator-activated receptor gamma [PPARγ], and fatty acid binding protein 4 [FABP4]) potentials. Colony-forming units-fibroblasts were lower in patients with cirrhosis (P = 0.002) than in controls. Cirrhotic BM-MSCs showed >2-fold decrease in osteogenic markers. Compared to controls, patients with cirrhosis showed fewer osteocytes (P = 0.05), osteoblasts, chondroblasts, osteocalcin-positive (osteocalcin+) area, clusters of differentiation (CD)169+ macrophages (P < 0.001, each), and nestin+ MSCs (P = 0.001); this was more apparent in Child-Turcotte-Pugh (CTP) class C than A (P < 0.001). Multivariate logistic regression showed low nestin+ MSCs (P = 0.004) as a predictor of bone loss. Bone-resolving osteoclasts were comparable among CTP groups, but >2-fold decreased anti-osteoclastic and increased pro-osteoclastic factors were noted in patients with CTP C compared to CTP A. Bone-building proteins (osteocalcin [P = 0.008], osteonectin [P < 0.001], and bone morphogenic protein 2 [P = 0.001]) were decreased while anti-bone repair factors (fibroblast growth factor 23 [P = 0.015] and dipeptidyl peptidase 4 [P < 0.001]) were increased in BM and peripheral blood; this was more apparent in advanced cirrhosis. The dual energy X-ray absorptiometry scan T score significantly correlated with the population of osteoblasts, osteocytes, MSCs, and CD169+ macrophages. Conclusion: Osteoprogenitor cells are substantially reduced in patients with cirrhosis and more so in advanced disease. Additionally, increased anti-bone repair proteins enhance the ineffective bone repair and development of osteoporosis in cirrhosis. Hepatology Communications 2018;0:0-0).


Capgras syndrome-a biochemical marker?
Two cased of Capgras syndrome are reported in which platelet monoamine oxidase (MAO) activity is singificantly less than that of 24 psychiatric controls and 39 nonpsychiatric controls. This is the first report of a consistent biochemical abnormality associated with the Capgras phenomenon. Additional evidence is discussed which suggests that psychiatric patients with Capgras syndrome may belong to a discrete group of behavioral disorders characterized by reduced platelet MAO activity.


The hippocampo-cortical loop: spatio-temporal learning and goal-oriented planning in navigation.
We present a neural network model where the spatial and temporal components of a task are merged and learned in the hippocampus as chains of associations between sensory events. The prefrontal cortex integrates this information to build a cognitive map representing the environment. The cognitive map can be used after latent learning to select optimal actions to fulfill the goals of the animal. A simulation of the architecture is made and applied to learning and solving tasks that involve both spatial and temporal knowledge. We show how this model can be used to solve the continuous place navigation task, where a rat has to navigate to an unmarked goal and wait for 2 seconds without moving to receive a reward. The results emphasize the role of the hippocampus for both spatial and timing prediction, and the prefrontal cortex in the learning of goals related to the task.


Acanthamoeba and fungal keratitis in a woman with a history of Intacs corneal implants.
To report a case of corneal perforation secondary to Acanthamoeba and fungal keratitis in a patient with a history of Intacs corneal implants. The patient's history, clinical presentation, and pathologic analysis were reviewed. A 56-year-old woman with keratoconus was referred to the university eye center for a corneal perforation secondary to a chronic corneal ulcer initially diagnosed as herpes simplex keratitis. The patient had Intacs inserted in the same eye 14 months earlier, but had them removed approximately 1 month before her visit. After emergency keratoplasty, the patient's corneal tissue was sent for histopathologic examination, which showed an Acanthamoeba and fungal coinfection. Atypical sources of keratitis should be considered in patients with a chronic corneal ulcer and a history of Intacs corneal implants.


The stabilizing effect of various implants on the torn acromioclavicular joint. A biomechanical study.
A biomechanical in vitro test was performed to determine the stabilizing effect of various implants for the surgical treatment of the torn acromioclavicular joint. In a specially designed testing device, plastic and cadaver specimens of the shoulder girdle were stressed in various ways. Different dislocations between the acromion and the clavicle and between the clavicle and the coracoid were determined, as well as the stiffness of the implants. A convenient stabilizing effect combined with less rigid fixation to secure the newly treated AC joint was provided by K-wire fixation with cerclage. Interfering shear and bending stresses could be avoided with this method, while the other implants showed various disadvantages. From a biomechanical point of view, a carbon-fiber ligament replacement provides sufficient stability in cases of chronic acromioclavicular separation.


Effects of hydrothermal treatment on the pyrolysis behavior of Chinese fan palm.
The effect of hydrothermal treatment (HTT) on Chinese fan palm pyrolysis was investigated. It indicated that HTT could effectively remove a large portion of alkali/alkaline earth metals and disrupt the chemical structure to a certain extent. HTT delayed the initial decomposition temperature but accelerated the pyrolysis process completely. HTT also increased the relative contents of both sugars and hydrocarbons in pyrolysis. At 210°C, HTT had the most significant promotion effect on the sugars formation with the relative content of 30.58%. While, The relative content of phenols, acids, furans, aldehydes, esters and CO2 decreased more or less after HTT. With increasing pyrolysis temperature, the relative content of most groups of chemicals except hydrocarbons decreased. Response contours were analyzed to find the optimal reaction conditions for generating acids, phenols, sugars and hydrocarbons, respectively. The results indicated both pyrolysis temperature and HTT temperature had distinct influence on relative contents of products.


Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials.
Variability in neurodegenerative disease progression poses great challenges for the evaluation of potential treatments. Identifying the persons who will experience significant progression in the short term is key for the implementation of trials with smaller sample sizes. We apply here disease course mapping to forecast biomarker progression for individual carriers of the pathological CAG repeat expansions responsible for Huntington disease. We used data from two longitudinal studies (TRACK-HD and TRACK-ON) to synchronize temporal progression of 15 clinical and imaging biomarkers from 290 participants with Huntington disease. We used then the resulting HD COURSE MAP to forecast clinical endpoints from the baseline data of 11,510 participants from ENROLL-HD, an external validation cohort. We used such forecasts to select participants at risk for progression and compute the power of trials for such an enriched population. HD COURSE MAP forecasts biomarkers 5 years after the baseline measures with a maximum mean absolute error of 10 points for the total motor score and 2.15 for the total functional capacity. This allowed reducing sample sizes in trial up to 50% including participants with a higher risk for progression ensuring a more homogeneous group of participants.


Reverse the curse--the role of deubiquitination in cell cycle control.
Reversible protein ubiquitination is a crucial mechanism regulating the progression through the eukaryotic cell cycle. Ubiquitin-dependent signaling is terminated by specific deubiquitinating enzymes (DUBs), which now are known to be integral components of the core cell cycle machinery and cell cycle checkpoints. The importance of DUBs for cell cycle control is underscored by their frequent misregulation in cancer. Here, we discuss the role of deubiquitinating enzymes in controlling proliferation.


An exterior and interior leaded dust deposition survey in New York City: results of a 2-year study.
Environmental concentrations of leaded dust were monitored by weekly sample collection of interior and exterior settled dust that had accumulated due to atmospheric deposition. The weekly deposition amounts were measured and the cumulative rates of lead in dust that deposited on a weekly basis over 2 year's time were determined. The sampling analysis revealed that the median values of leaded dust for the interior plate (adjacent to the open window), unsheltered exterior plate, and the sheltered exterior plate were 4.8, 14.2, and 32.3 microg/feet2/week, respectively. The data supports the existence of a continuous source of deposited leaded dust in interior and exterior locations within New York City. Additional data from a control plate (interior plate with the window closed) demonstrate that the source of the interior lead deposition was from exterior (environmental) sources. Because of the ubiquitous nature of lead in our environment and the toxic threat of lead to the cognitive health of children, this data provides a framework for the understanding of environmental exposure to lead and its potential for continuing accumulation within an urban environment.


tert-Butyl hydroperoxide-induced radical production in rat liver mitochondria.
When rat liver mitochondria are treated with tert-butyl hydroperoxide (TBHP) in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), electron paramagnetic resonance (EPR) signals are detected attributable to spin adducts resulting from the trapping of methyl, tert-butoxyl, and tert-butylperoxyl radicals. The addition of respiratory substrate results in a 3- to 7.5-fold increase in the signal intensity of the DMPO/methyl adduct, no change in the signal intensity of the DMPO/tert-butoxyl adduct, and complete loss of the DMPO/tert-butylperoxyl adduct signal. The magnitude of increase of methyl radical production in the presence of respiratory substrate is related to the respiratory control ratio (RCR) of the mitochondrial preparation. In the presence of antimycin A, which blocks electron flow between cytochromes b and c1, no stimulation of methyl radical production is detected with respiratory substrate. Stimulation of methyl radical production by the addition of respiratory substrate is detected in cytochrome c-depleted mitochondria. A similar increase in methyl radical production is detected when ferrous cytochrome c is treated with TBHP in the presence of DMPO (as compared to when ferricytochrome c is used). These results indicate that TBHP is reduced directly by either cytochrome c1, cytochrome c, or by both of these electron transport chain components in mitochondria undergoing state 4 respiration.


Mutation Profiling Indicates High Grade Prostatic Intraepithelial Neoplasia as Distant Precursors of Adjacent Invasive Prostatic Adenocarcinoma.
High Grade Prostatic Intraepithelial Neoplasia (HGPIN) is the putative precursor lesion to prostatic adenocarcinoma (PCa), but the precise relationship between HGPIN and PCa remains unclear. We performed a molecular case study in which we studied mutation profiles of six tumor-associated HGPIN lesions in a single case of TMPRSS2:ERG fusion positive Gleason score 7 PCa that we had previously mapped for somatic mutations in adjacent Gleason patterns 3 and 4 foci, using microdissection and targeted deep-sequencing. A total of 32 tumor-specific mutated sites were successfully amplified and sequenced, including 25 truncal mutations and 7 mutations that were specific to either the Gleason pattern 3 or pattern 4 foci. All six HGPIN foci shared the same tumor-specific TMPRSS2:ERG fusion breakpoint, establishing that they were all clonally related to the adjacent invasive tumor. Among the 32 gene targets mutated in the invasive tumor, only mutation of the OR2AP1 gene, a truncal mutation, was found in a single focus of HGPIN. The remaining gene targets that were successfully sequenced were wild-type in all other HGPIN foci. This study demonstrates the feasibility of targeted mutation profiling of HGPIN lesions, which will be important to understand PCa tumorigenesis. The results in this case, showing a remarkable absence of truncal mutations in HGPIN lesions bearing the tumor-specific ERG fusion, indicate HGPIN lesions may be relatively stable genetically and argue against a stepwise clonal evolution model of HGPIN to PCa. Prostate 76:1227-1236, 2016. © 2016 Wiley Periodicals, Inc.


Persistence of Ia antigen and antigen-presenting activity by cultured human monocytes.
Human peripheral blood monocytes cultured in vitro on plastic for up to 28 days supported the proliferation of antigen-specific, HLA-restricted T-cell blasts as well as freshly isolated blood mononuclear cells. Seventy-three percent of adhered monocytes were Ia antigen-positive by immunofluorescence when the cultures were initiated, this proportion fell to 70 +/- 13% after 28 days. The antigen-presenting function of cultured monocytes was inhibited by monoclonal anti-Ia antibody as compared with freshly isolated mononuclear cells. These results indicate that human monocytes retain their antigen-presenting function during maturation to macrophages in vitro.


Polymer-coated hollow-fiber microextraction of estrogens in water samples with analysis by gas chromatography-mass spectrometry.
A novel sorbent, dihydroxylated polymethylmethacrylate (DHPMM), coated on hollow-fiber membrane, is used for the polymer-coated hollow-fiber microextraction of trace amounts of natural and synthetic estrogens, such as diethylstilbestrol, estrone, 17beta-estradiol and 17alpha-ethynylestradiol, in aqueous samples. In this procedure, estrogens were extracted using the functionalized polar DHPMM polymer with derivatization using N-methyl-N-(trimethylsilyl)trifluoroacetamide followed by gas chromatography-mass spectrometric analysis. The detection limits for estrogens in aqueous sample were between 0.03 and 0.8 ng l(-1) and the calibration curves were linear over the concentration range 0.05-10 microgl(-1) and had correlation coefficients of >0.994. The relative standard deviations (RSDs) were <15% (n = 3). This simple, accurate, sensitive and selective analytical method is applicable to the determination of trace amounts of estrogens in reservoir and potable water samples.


Three-dimensional simulations of the scoliosis derotation maneuver with Cotrel-Dubousset instrumentation.
The derotation maneuver using Cotrel-Dubousset instrumentation (CDI) is intended to correct the counterdirectional transverse plane rotations of the spine and of the vertebrae in thoracic scoliosis. This was simulated in a finite element model of an idealized thoracic scoliosis with an initial 65 degrees scoliosis angle and 0 degree kyphosis angle. After 90 degrees of rod rotation the apical vertebra derotated 50 degrees towards the sagittal plane but the apical vertebra axial rotation worsened by 8 degrees. The scoliosis angle corrected to 29 degrees and a 54 degrees kyphosis was created. If the initial rod curvature was reduced by 9 degrees, the model predicted only small changes in spinal curvature resulting from the forces required to connect the vertebrae to the hooks. Decreased kyphosis and scoliosis curvatures but increased vertebra axial rotation were produced by the derotation maneuver. The increase in apical vertebra axial rotation was reversed by modifying the representation of the motion segments by repositioning their effective axes 30 mm posteriorly.


A parameterized model for mean urinary inflow rate and its preliminary application in radiotherapy for cervical cancer.
Forty-nine patients with stage IIb cervical cancer were included to investigate the changes in bladder volume in response to different approaches to maintaining consistent bladder filling. The impacts of age (P age), water consumption (P wat ), and body mass index (BMI, P bmi ) on the mean urinary inflow rate (v tot ) were analysed. The bladder volume (BV) increased linearly over time. A large variation in v tot among individuals was observed, ranging from 0.19 to 5.13 ml/min. The v tot was correlated with P age (R = -0.53, p = 0.01) and P wat (R = 0.84, p = 0.00), and no correlation between v tot and P bmi was found (p > 0.05). Therefore, v tot could be parameterized using two methods: multivariable linear regression and iterative fitting. There was no statistically significant difference between the two methods. The model accuracy was successfully assessed with several validation tests for patients with good compliance (79.2% of all patients), and the proportion of radiotherapy (RT) fractions with zero wait time (one ultrasound (US) scan) increased from 6.5% to 41.2%. The optimal US scanning number and RT time could be provided using this model. This adaptive RT approach could reduce patient discomfort caused by holding onto urine and reduce technician labour as well as cost.


Serum calcification propensity and its association with biochemical parameters and bone mineral density in hemodialysis patients.
T50 is a novel serum-based marker that assesses the propensity for calcification in serum. A shorter T50 indicates a greater propensity to calcify and has been associated with cardiovascular disease and mortality among patients with chronic kidney disease. The factors associated with T50 and the correlation between T50 and bone mineral density (BMD) are unknown in hemodialysis (HD) patients. This cross-sectional study included 184 patients undergoing HD. Individuals were grouped into tertiles of T50 to compare the demographic and disease indicators of the tertiles. Linear regression was used to evaluate the association between T50 and hip and spinal BMD in a multivariate model. Mineral and inflammatory parameters, including serum phosphate (r = -0.156, p = 0.04), albumin (r = 0.289, p < 0.001), and high-sensitivity C-reactive protein (r = -0.224, p = 0.003) levels, were associated with T50. We found a weak association between T50 and BMD in the total hip area in the unadjusted model (β = 0.030, p = 0.04) but did not find a statistically significant association with the total hip (β = 0.017, p = 0.12), femoral neck (β = -0.001, p = 0.96), or spinal BMD (β = 0.019, p = 0.33) in multivariable-adjusted models. T50 was moderately associated with mineral and inflammatory parameters but did not conclusively establish an association with BMD in HD patients. Broad-scale future studies should determine whether T50 can provide insights into BMD beyond traditional risk factors in this population.


Randomized trial of pacemaker and lead system for safe scanning at 1.5 Tesla.
Magnetic resonance imaging (MRI) of pacemakers is a relative contraindication because of the risks to the patient from potentially hazardous interactions between the MRI and the pacemaker system. Chest scans (ie, cardiac magnetic resonance scans) are of particular importance and higher risk. The previously Food and Drug Administration-approved magnetic resonance conditional system includes positioning restrictions, limiting the powerful utility of MRI. To confirm the safety and effectiveness of a pacemaker system designed for safe whole body MRI without MRI scan positioning restrictions. Primary eligibility criteria included standard dual-chamber pacing indications. Patients (n = 263) were randomized in a 2:1 ratio to undergo 16 chest and head scans at 1.5 T between 9 and 12 weeks postimplant (n = 177) or to not undergo MRI (n = 86) post-implant. Evaluation of the pacemaker system occurred immediately before, during (monitoring), and after MRI, 1-week post-MRI, and 1-month post-MRI, and similarly for controls. Primary end points measured the MRI-related complication-free rate for safety and compared pacing capture threshold between MRI and control subjects for effectiveness. There were no MRI-related complications during or after MRI in subjects undergoing MRI (n = 148). Differences in pacing capture threshold values from pre-MRI to 1-month post-MRI were minimal and similar between the MRI and control groups. This randomized trial demonstrates that the Advisa MRI pulse generator and CapSureFix MRI 5086MRI lead system is safe and effective in the 1.5 T MRI environment without positioning restrictions for MRI scans or limitations of body parts scanned.


Dynamic expression of nine QTLs for tiller number detected with single segment substitution lines in rice.
Nine single segment substitution lines (SSSLs) in rice, which contain quantitative trait loci (QTLs) for tiller number on substituted segments detected in previous studies, were selected as materials to analyse dynamic expression of the QTLs in this study. These SSSLs and their recipient parent, Hua-jing-xian 74 (HJX74), were grown in four different environments and were measured for tiller number at nine different growth stages. An indirect methodology was applied in QTL mapping through analyzing multi-environment phenotypic data. Dynamics of three types of effects (including total effect, main effect, and QE interaction effect) of QTLs was released. It was shown that nine QTLs exhibited statistically significant effects only at certain stages. Effects of a QTL, although insignificant at certain stages, displayed dynamic change with the growth of rice plants. Two common features of nine QTLs were detected, one is no expression within 7 days after transplanting, and the other is opposite expression existed during the whole growth period. Nine QTLs largely focused on expression in certain stages, and accordingly were suggested to partition into three types, expression in prophase, both in prophase and in anaphase, and evenly during the whole stage. It may be reasonable explanation that dynamics of main effects of QTLs are likely due to gene expression selectly at certain times, while dynamics of QE interaction effects of QTLs might attribute to the subrogation of environmental factors. Examination of the association between QE interaction effect and specified environmental factors across stages may provide useful information on how an environmental factor regulates QTL expression.


Variants in HNRNPH1 are associated with high myopia in humans and ocular coloboma in zebrafish.
High myopia is one of the most common causes for blindness due to its associated complications. Genetic factor has been considered as the major cause for early-onset high myopia (eoHM), but exact genetic defects for most eoHM are yet to be identified. Through multi-step bioinformatics analysis of our in-house whole exome sequencing dataset from 6397 individuals, variants from 928 probands with eoHM were further compared with those from in-house controls as well as gnomAD database. The results showed that loss-of-function (LoF) variants in a novel gene HNRNPH1 were identified in two of 928 probands with eoHM but in none of 5469 probands with other eye conditions (p = 0.02). LoF variants in HNRNPH1 were extremely rare and intolerant, while two LoF variants in 928 eoHM were statistically higher than their frequency in gnomAD (p = 5.98 × 10-4 ). These two LoF variants, c.2dup/p.(M1?) and c.121dup/p.(Q41Pfs*20), were absent from existing database. Variants in HNRNPH1 have not been associated with any inherited eye disease before. Expression of HNRNPH1 was enriched in ganglion cell layer and inner nuclear layer in humans. Knockdown of hnrnph1 in zebrafish resulted in ocular coloboma. All these suggest that HNRNPH1 is potential contribution to eoHM when mutated.


Methyl 4-(5-meth-oxy-1H-indol-3-yl)benzoate.
In the title compound, C(17)H(15)NO(3), the dihedral angle between the benzene ring and the indole ring system is 22.5 (3)°. In the crystal, mol-ecules are linked by N-H⋯π and C-H⋯O inter-actions.


Community-based exposure estimate for hydrogen sulfide.
Indoor and outdoor air pollution monitoring may indicate potential human exposure to air contaminants. Individual and population exposures to air contaminants depend upon many factors including time spent outdoors and indoors, permeability of housing structures, and mobility within a community. In this report, we illustrate an approach for using long-term air monitoring to establish patterns or changes of environmental exposures, improve validity and representativeness of data, and prevent exposure misclassification. Long-term air monitoring for hydrogen sulfide (H2S) at 14 Dakota City, Nebraska, residences identified differences in area-wide concentration levels, geographic locations, and seasonal exposures. Air data for 1999 indicated that Dakota City residents were repeatedly exposed, both indoors and outdoors, to moderate levels (>or=90 parts per billion [ppb]) of H2S. Using GIS modeling and kriging, we produced a geographic gradient of exposure estimate or map for ambient H2S. These findings formed the basis for designing two health investigations for this community.


Recent Applications of Azo Dyes: A Paradigm Shift from Medicinal Chemistry to Biomedical Sciences.
Azo molecules possess the characteristic azo bond (-N=N-) and are considered fascinating motifs in organic chemistry. Since the last century, these brightly colored compounds have been widely employed as dyes across several industries in applications for printing, food, paper, cosmetics, lasers, electronics, optics, material sciences, etc. The discovery of Prontosil, an antibacterial drug, propelled azo compounds into the limelight in the field of medicinal chemistry. Subsequent discoveries including Phenazopyridine, Basalazide, and Sulfasalazine enabled azo compounds to occupy a significant role in the drug market. Furthermore, azo compounds have been employed as antibacterial, antimalarial, antifungal, antioxidant, as well as antiviral agents. The metabolic degradation of many azo dyes can induce liver problems if ingested, posing a safety concern and limiting their application as azo dyes in medicinal chemistry. However, azo dyes remain particularly significant for applications in cancer chemotherapy. Recently, a paradigm shift has been observed in the use of azo dyes: from medicinal chemistry to biomedical sciences. The latter benefits from azo dye application are related to imaging, drug delivery, photo-pharmacology and photo switching. Herein, we have compiled and discussed recent works on azo dye compounds obtained so far, focusing on their medicinal importance and future prospects.


Vole population cycles: A case for kin-selection?
Kin-selection, as evidenced by aggression between individuals with a low coefficient of relation, may be a significant contributing factor in vole population cycles. Demographic and behavioral studies support this idea.


Long Intergenic Non-Coding RNA LINC00885 Promotes Tumorigenesis of Cervical Cancer by Upregulating MACC1 Expression Through Serving as a Competitive Endogenous RNA for microRNA-432-5p [Retraction].
[This retracts the article DOI: 10.2147/CMAR.S291778.].


Changes in pairwise functional connectivity associated with changes in cognitive performance in cognitively normal older individuals: A two-year observational study.
Neurobiological substrates of cognitive decline in cognitively normal older individuals have been investigated by resting-state functional magnetic resonance imaging, but little is known about the relationship between longitudinal changes in the whole brain. In this study, we examined two-year changes in functional connectivity among 80 gray matter areas and investigated the relationship to two-year changes in cognitive performance. A cross-validated permutation variable importance measure was applied to select features related to a change in cognitive performance. Age-corrected changes in eleven pairs of functional connections were selected as important features, all related to brain areas that belong to the default mode network. A linear regression model with cross-validation demonstrated a mean correlation coefficient of 0.55 between measured and predicted changes in the cognitive composite score. These results suggest that intra- and inter-network connections in the default mode network are associated with cognitive changes over two years among cognitively normal individuals.


Characteristics of Cerebrovascular Injury in the Hyperacute Phase After Induced Severe Subarachnoid Hemorrhage.
Although there have been several investigations regarding acute brain injury after subarachnoid hemorrhage (SAH), the pathological conditions of severe SAH are unclear. In this study, we pursued the characteristics of cerebrovascular injury in the hyperacute phase after experimentally induced severe SAH. Twenty-three male Sprague-Dawley rats were subjected to sham or SAH operation using the endovascular perforation method and were evaluated for brain edema, blood-brain barrier (BBB) permeability, and arterial endothelial cell injury at 5 min after SAH (experiment 1). Next, animals were examined for functional and morphological changes of cerebral artery for 30 min after an acetazolamide injection administered 5 min after SAH (experiment 2). In experiment 1, while cerebral blood flow (CBF) was reduced, brain edema was not observed in SAH-operated rats. BBB permeability detected by immunoglobulin G extravasation was observed in the optic tract and was accompanied by the upregulation of phosphorylated extracellular signal-regulated kinase (ERK)-positive astrocytes. In addition, the number of phosphorylated ERK-positive endothelial cell in the distal middle cerebral artery (MCA) was significantly increased by SAH. In experiment 2, CBF in non-lethal SAH rats was reduced, and no response to acetazolamide was detected. Conversely, CBF in lethal SAH increased due to acetazolamide, although the value of CBF was low. Furthermore, there was significant narrowing of the MCA in SAH-operated rats. The findings suggest that the optic tract and the cerebral artery are the most vulnerable areas regarding cerebrovascular injury in a hyperacute phase after severe SAH and that they are associated with fatal outcomes.


Pre- and postnatal inflammatory mechanisms in chronic lung disease of preterm infants.
Epidemiological data suggest a strong association between chorioamnionitis and the development of chronic lung disease in preterm infants. Increased concentrations of proinflammatory cytokines present in the amniotic fluid and the systemic fetal circulation seem to be important mediators in the early inflammatory response by recruiting and activating inflammatory cells and by inducing pathways of lung injury. As a consequence vascular cell adhesion molecules are upregulated and a marked infiltration of neutrophils and macrophages as well as an increased expression of interleukin-8 mRNA in the bronchoalveolar epithelium and in the interstitial tissue takes place. These antenatal events may prime the lungs such that various injurious factors in the postnatal period provoke an excessive inflammatory response: oxygen toxicity, mechanical ventilation, inappropriate resuscitation, pulmonary and systemic infections, persistent ductus arteriosus. Besides proinflammatory cytokines, toxic oxygen radicals, lipid mediators and potent proteases may be responsible for acute and chronic lung injury. In general, an imbalance between pro- and anti-inflammatory factors can be considered as a hallmark of lung injury, and may considerably affect normal alveolarisation and pulmonary vascular development by inducing growth arrest of the immature lung.


An investigation into the compartmentalization of the sporulation transcription factor sigmaE in Bacillus subtilis.
Sporulation in Bacillus subtilis involves the formation of a polar septum, which divides the sporangium into a mother cell and a forespore. The sigmaE factor, which is encoded within the spoIIG operon, is a cell-specific regulatory protein that directs gene transcription in the mother cell. SigmaE is synthesized as an inactive proprotein pro-sigmaE, which is converted to the mature factor by the putative processing enzyme SpoIIGA. Processing of pro-sigmaE does not commence until after asymmetric division when sigmaE is largely confined to the mother cell. Processing depends on the signalling protein SpoIIR, which delays proteolysis until after polar septation, but the mechanism by which sigmaE is confined to the mother cell is not understood. Previous work favoured a model in which pro-sigmaE localizes to the mother cell face of the polar septum, such that sigmaE would be selectively released into mother cell cytoplasm. Based on the use of green fluorescent protein (GFP) fusions, we now report that pro-sigmaE is distributed approximately uniformly along all membrane surfaces and is not confined to the mother- cell face of the septum. Rather, our results are consistent with a model in which preferential and persistent transcription of the spoIIG operon in the mother cell and degradation of sigmaE in the forespore contribute to the selective accumulation of sigmaE in the mother cell. Persistent transcription of spoIIG after polar septation also contributes to the proper timing of pro-sigmaE processing.


Perceptions of a Teleophthalmology Screening Program for Diabetic Retinopathy in Adults With Type 1 and Type 2 Diabetes in Urban Primary Care Settings.
Teleophthalmology has improved diabetic retinopathy screening, and should be expanded in urban areas, where most unscreened individuals reside. In this study we explored facilitators and barriers of teleophthalmology in primary care settings in Toronto, Canada. Semistructured interviews were conducted with 7 health-care providers and 7 individuals with diabetes to explore their perspectives of teleophthalmology in urban primary care settings. Interview data were analyzed using interpretive thematic analysis to generate themes. Six themes were identified. Facilitators included patient-centred implementation, access to teleophthalmology at primary care sites and patients' trust in their providers' recommendations. Barriers included patients' lack of understanding of diabetic retinopathy and the health-care system, providers' lack of interest and the need to streamline administrative processes. Although teleophthalmology was well-received by patients, there was limited interest from primary care providers. Strategies for increasing uptake include increasing primary care providers' awareness of teleophthalmology's value in urban centres, improving administrative processes and centralizing patient recruitment.


YAP1 silencing attenuated lung injury/fibrosis but worsened diaphragmatic function by regulating oxidative stress and inflammation response in mice.
Oxidative stress is a crucial mechanism in the pathophysiology of lung injury/fibrosis and diaphragmatic dysfunction. Yes-associated protein 1 (YAP1) is a key oxidative stress response regulator. However, how lung injury/fibrosis and the subsequent YAP1 silencing treatment affect diaphragmatic function remains largely uncharacterized. In this study, mice models of acute lipopolysaccharide (LPS) and paraquat exposure were used to establish acute lung injury and chronic pulmonary fibrosis. AT2 and C2C12 cells were co-cultured under LPS and paraquat challenge. YAP1 was interfered with shRNA given in vivo and verteporfin administration in vitro. Pulmonary histology, contractile properties, and cross-sectional areas (CSAs) of the diaphragm and gastrocnemius were evaluated. Histological and biochemical analyses were performed for targeted biomarker determination. We found that LPS and paraquat caused significant lung injury/fibrosis and significantly reduced the diaphragmatic-specific force and CSAs compared with the control. YAP1 silencing alleviated inflammatory cell infiltration or collagen deposition in the lungs yet worsened the already impaired diaphragmatic function by increasing inflammatory cytokines (IL-6 and TNF-α), mitochondrial reactive oxidative species (ROS) emission, protein degradation (Murf-1, atrogin-1, and calpain), and decreasing antioxidant capabilities (superoxide dismutase 2 and glutathione peroxidase). No significant improvements were observed in diaphragmatic function by transient YAP1 knockdown in the gastrocnemius. In vitro, LPS- or paraquat-caused cytotoxicity in AT2 cells was mostly alleviated by verteporfin in a concentration that was 20-fold higher than that in C2C12 cells (20 and 1 μg/mL, respectively). Finally, 0.5 μg/mL of verteporfin significantly ameliorated hydrogen peroxide-induced proteolytic activity and antioxidant enzyme suppression in C2C12 cells, whereas 2 μg/mL of verteporfin deteriorated the same. Collectively, lung injury/fibrosis adversely affects the diaphragm. YAP1 inhibition alleviates lung injury/fibrosis but worsens diaphragmatic function potentially by enhancing inflammatory cytokines and ROS-mediated protein degradation. This disparity might be attributed to differences in susceptibility to YAP1 inhibition between muscles and the lungs.


Metabolic engineering of thermophilic Bacillus licheniformis for chiral pure D-2,3-butanediol production.
2,3-Butanediol is an important compound that can be used in many areas, especially as a platform chemical and liquid fuel. But traditional 2,3-butanediol producing microorganisms, such as Klebsiella pneumonia and K. xoytoca, are pathogens and they can only ferment sugars at 37°C. Here, we reported a newly developed Bacillus licheniformis. A protoplast transformation system was developed and optimized for this organism. With this transformation method, a marker-less gene deletion protocol was successfully used to knock out the ldh gene of B. licheniformis BL1 and BL3. BL1 was isolated earlier from soil for lactate production and it was further evolved to BL3 for xylose utilization. Combined with pH and aeration control, ldh mutant BL5 and BL8 can efficiently ferment glucose and xylose to D-(-) 2,3-butanediol at 50°C, pH 5.0. For glucose and xylose, the specific 2,3-butanediol productivities are 29.4 and 26.1 mM/h, respectively. The yield is 0.73 mol/mol for BL8 in xylose and 0.9 mol/mol for BL5 and BL8 in glucose. The D-(-) 2,3-butanediol optical purity is more than 98%. As far as we know, this is the first reported high temperature butanediol producer to match the simultaneous saccharification and fermentation conditions. Therefore, it has potential to further lower butanediol producing cost with low cost lignocellulosic biomass in the near future.


The contractile phenotype of peritubular smooth muscle cells is locally controlled: possible implications in male fertility.
The contractile activity of peritubular tissue is responsible for the propulsion of spermatozoa along the lumen of seminiferous tubules toward the hilum of the testis. This function is performed by specialized contractile cells [peritubular smooth muscle cells (PSMC)] in response to the locally produced agonist, endothelin (ET). Here, we review current information on the complex ET-mediated control of peritubular contractility. In addition, we report new data demonstrating that the relaxant peptide adrenomedullin is produced by Sertoli cells and interferes with ET-mediated contraction of PSMC. Given the relevance of the seminiferous tubule sperm output for male fertility, the detailed definition of the mechanisms controlling peritubular contractility could contribute in different ways to novel therapeutic opportunities and provide potential targets for contraceptive strategies.


Optimized design of an antireflection coating for textured silicon solar cells.
The short-circuit current density of a solar cell is used as a merit function to optimize solar cell antireflection coating designs. J(sc)/J(max) ratios reach 99%, even with a 10-nm-thick passivation layer.


Combined retrocaval ureter and retroperitoneal fibrosis: report of a case.
The first case of a simultaneous retrocaval ureter and retroperitoneal fibrosis of the right ureter is presented. The diagnosis was made roentgenographically on the basis of the S-shaped course of the proximal right ureter and medial deviation of the tapered and obstructed mid ureteral segment. This was confirmed by exploration of the right ureter and retroperitoneal biopsy. The surgical treatment of this unusual entity is described.