Levels in the interpretive optimisation of selectivity in high-performance liquid chromatography: a magical mystery tour.
Interpretive approaches for selectivity optimisation, which are those supported by retention models, are able to exploit efficiently the capabilities of the chromatographic system. The resolution of a mixture is usually faced in a first trial by looking for a unique experimental condition, able to resolve all compounds in the sample. If this is not possible, the problem can be outlined with less ambitious aims, focusing on only some compounds. In an extreme case, a single analyte can be individually optimised. Current strategies that give answer to the different goals pursued in the analysis, which are classified as total, partial and specific, are reviewed. Optimisation oriented to deconvolution, useful in case of partial coelution, and robust measurements of resolution, are also outlined. The steps recognised in any chromatographic optimisation procedure, and some fundamentals and tools used in optimisation approaches for isocratic and gradient elution are commented to explain different strategies. Examples of increasing complexity are supplied to explain the problematic arose, and the convenience in applying a certain methodology. Details on the mathematical treatment for each particular optimisation strategy are also given.


Sites in the third intracellular loop of the alpha 2A-adrenergic receptor confer short term agonist-promoted desensitization. Evidence for a receptor kinase-mediated mechanism.
To investigate the mechanisms of agonist-promoted desensitization of the alpha 2-adrenergic receptor (alpha 2AR), the human alpha 2AAR and a mutated form of the receptor were expressed in CHW cells. After cells were exposed to epinephrine for 30 min, the ability of the wild type alpha 2AAR to mediate inhibition of forskolin-stimulated adenylyl cyclase was depressed by approximately 78%. To assess the role of receptor phosphorylation during desensitization, cells were incubated with 32Pi, exposed to agonist, and alpha 2AAR purified by immunoprecipitation with a fusion protein antibody. Agonist-promoted desensitization was found to be accompanied by phosphorylation of the alpha 2AAR in vivo. The beta-adrenergic receptor kinase (beta ARK) is known to phosphorylate purified alpha 2AAR in vitro. We found that heparin, a beta ARK inhibitor, ablated short term agonist-induced desensitization of alpha 2AAR, while such desensitization was unaffected by inhibition of protein kinase A. To further assess the role of beta ARK, we constructed a mutated alpha 2AAR which has a portion of the third intracellular loop containing 9 serines and threonines (potential phosphorylation sites) deleted. This mutated alpha 2AAR failed to undergo short term agonist-induced desensitization. Agonist promoted in vivo phosphorylation of this mutated receptor was reduced by 90%, consistent with the notion that receptor phosphorylation at sites in the third intracellular loop plays a critical role in alpha 2AAR desensitization. After 24 h of agonist exposure, an even more profound desensitization of alpha 2AAR occurred, which was not accompanied by a decrease in receptor expression. Rather, long term agonist-induced desensitization was found to be due in part to a decrease in the amount of cellular Gi, which was not dependent on receptor third loop phosphorylation sites.


Carob pulp preparation rich in insoluble fibre lowers total and LDL cholesterol in hypercholesterolemic patients.
Recently, insoluble fibre from carob pulp has been found to affect blood lipids in animals in a similar manner as soluble dietary fibre. To investigate whether a carob pulp preparation containing high amounts of insoluble fibre has a beneficial effect on serum cholesterol in humans. Volunteers (n = 58) with hypercholesterolemia were recruited to participate in a randomised, double- blind, placebo-controlled and parallel arm clinical study with a 6 week intervention phase. All participants consumed daily both, bread (two servings) and a fruitbar (one serving) either with (n = 29) or without (n = 29) a total amount of 15 g/d of a carob pulp preparation (carob fibre). Serum concentrations of total, LDL and HDL cholesterol and triglycerides were assessed at baseline and after week 4 and 6. The consumption of carob fibre reduced LDL cholesterol by 10.5 +/- 2.2% (p = 0.010). The LDL:HDL cholesterol ratio was marginally decreased by 7.9 +/- 2.2 % in the carob fibre group compared to the placebo group (p = 0.058). Carob fibre consumption also lowered triglycerides in females by 11.3 +/- 4.5% (p = 0.030). Lipid lowering effects were more pronounced in females than in males. Daily consumption of food products enriched with carob fibre shows beneficial effects on human blood lipid profile and may be effective in prevention and treatment of hypercholesterolemia.


Regulation of O6-methylguanine-DNA methyltransferase levels in rat liver and kidney.
It was found that rat kidney contains a protein similar to that previously described in rat liver which catalyzes the transfer of the methyl group from O6-methylguanine in DNA to a protein-bound cysteine residue. The amount of the renal O6-methylguanine-DNA methyltransferase was increased up to 2.5-fold during renal hypertrophy in response to unilateral nephrectomy or treatment with folic acid. These results indicate that the protein in kidney resembles that in rat liver which is known to be increased in response to a variety of hepatotoxins or to partial hepatectomy. The liver O6-methylguanine-DNA methyltransferase was reduced by hypophysectomy or thyroidectomy and could be increased by treatment with growth hormone or thyroxine. The level in the liver was considerably lower than the adult value in 1-day-old rats and increased to adult values by 14 to 21 days. At no time was the amount in the neonatal rat liver higher than in the adult, indicating that liver cell proliferation alone is not obligatorily coupled with an elevated methyltransferase level. The high sensitivity of neonatal rats to liver carcinogenesis by dimethylnitrosamine may be related to the high rate of cell proliferation and the lower capacity to repair O6-methylguanine.


Seed credit model in Uganda": Participation and empowerment dynamics among smallholder women and men farmers.
Seed is life and can be a source of empowerment and disempowerment for women and men farmers. In this study, to close the gender gaps in seed, the Community Enterprises Development Organization, the Alliance of Bioversity and CIAT and the National Agricultural Research Organization developed a seed credit model available to men and women belonging to farmer groups. A mixed method was used to collect information from two districts in central Uganda on how the seed credit model reconstructed access, use, control and resulting benefits. Results showed that the provision of the seed credit model was considered a blessing even though it had many nuances. As a result of the seed credit model, we saw increased productivity in women's fields, increased income and decision making over income incurred from the sale of their crops. Their social status has been enhanced, and they now occupy a place of respect in their communities and households, where they can make decisions and get assets like houses and land. While it increased productivity, income and enhanced food and nutrition security needs of the family, it also changed power dynamics within the household as women become more empowered. To maintain power relations, men limited women's access to fertile land and family labor, which defined the quantity of seed gotten from the seed credit model. Women's participation and involvement in the seed credit model decreased over time as they were expected to pay their spouses' seed loans. Men's participation decreased because they were no longer entrusted with seed loans as their payment rate was very low. As we reap positive benefits, we have to ensure we don't 'do harm' when empowering our beneficiaries.


[Incidental renal adenocarcinoma: study on 54 cases].
Between 1974 and 1992, both inclusive, 204 renal adenocarcinomas were treated in the Urology Unit of the '12 de Octubre' Hospital, of which 54 (26.4%) were diagnosed by chance. The relative frequency of these renal tumours has experienced a highly significant progressive increase, from 0 in the 1974-1978 interval, to 13.04% in 1978-1980, 14.7% between 1981-1983, 20.68% in 1984-1986, 37.84% in 1987-1990, to reach over the last three-year period of 1990-1992 the remarkable figure of 41.93%. There has been no differences regarding incidence by sex (50% males and 50% females). Mean age at presentation is 61.5 years, ranging from 23 to 78 years. The suspected pathological cause most frequently leading to carry out the study where renal carcinoma is accidentally diagnosed are gastrointestinal disorders (50% of cases). The most frequently used imaging diagnostic technique is ultrasound (50% cases), emphasising the gradual increase in the number of cases diagnosed by ultrasound or CAT during the course of the study. Carcinomas accidentally diagnosed by CAT are those with less volume in our series. Regarding tumour characteristics, it should be pointed out a higher occurrence in the right kidney (64.8%) and a most frequent location in the upper renal pole (48%). Mean tumoral volume was 126 cc, although that value has gradually dropped, so that now the mean volume of accidental tumours treated over the last 5 is being 91 cc. Most cases present low staging at the time of diagnosis, 81% being pT2 N0 M0. Current overall survival is 89% of all cases followed-up.


Proteases as probes of mitochondrial monoamine oxidase topography in situ.
Selective inactivation of the multiple forms of mitochondrial monoamine oxidase (MAO) by proteases in intact and hypotonically disrupted rat liver mitochondria has been used to examine the question of differential membrane orientations of the A and B enzymes. Proteases used as probes included trypsin, beta-chymotrypsin, and the extracellular protease of Staphylococcus aureus, chosen for their different amino acid specificities. With all three proteases, no changes in the relative rates of MAO-A and MAO-B inactivation were observed after disruption of the mitochondria. Trypsin and beta-chymotrypsin gave much faster rates of MAO-A inactivation in both intact and disrupted mitochondria. The selective effect of trypsin on MAO-A was also confirmed in human placental mitochondria, which possess only A-type activity. The effectiveness of hypotonicity in disrupting the outer membrane of the mitochondria was shown by rapid protease inactivation of an intermembrane space marker enzyme, adenylate kinase (EC 220.127.116.11). Contrary to some recent reports in the literature, these findings strongly suggest that the MAO-A and MAO-B multiple-form catalytic activities do not reside on opposite faces of the membrane.


Median raphe cyst: A clinically challenging diagnosis.
Median raphe cyst is an uncommon developmental anomaly that can develop anywhere along the midline of the external genitals. Only a few hundred cases have been published in the English literature and the lack of awareness of this entity can lead to confusion and misdiagnosis. We report here a case of median raphe cyst located in the midline of the anterior scrotum of a 35- year-old man. Clinically, the patient presented with a scrotal mass increasing substantially in size over two days associated with tenderness, skin erythema, and scrotal pain. Radiologic interpretation of a sonogram and computed tomography scan suggested a thrombosed vessel. The patient was diagnosed with septic thrombophlebitis associated with overlying cellulitis. Despite conservative therapy with antibiotics, the patient developed pyrexia, tachycardia, and leukocytosis prompting surgical excision of the lesion. Histopathologic examination revealed an infected median raphe cyst. The cyst wall was lined by a stratified epithelium that included numerous Alcian blue positive goblet cells. The epithelial cells showed reactive changes with infiltration by numerous neutrophils. Our objective is to bring attention to and thereby facilitate the diagnosis of this unusual entity.


NMR structure of the bovine prion protein.
The NMR structures of the recombinant 217-residue polypeptide chain of the mature bovine prion protein, bPrP(23-230), and a C-terminal fragment, bPrP(121-230), include a globular domain extending from residue 125 to residue 227, a short flexible chain end of residues 228-230, and an N-terminal flexibly disordered "tail" comprising 108 residues for the intact protein and 4 residues for bPrP(121-230), respectively. The globular domain contains three alpha-helices comprising the residues 144-154, 173-194, and 200-226, and a short antiparallel beta-sheet comprising the residues 128-131 and 161-164. The best-defined parts of the globular domain are the central portions of the helices 2 and 3, which are linked by the only disulfide bond in bPrP. Significantly increased disorder and mobility is observed for helix 1, the loop 166-172 leading from the beta-strand 2 to helix 2, the end of helix 2 and the following loop, and the last turn of helix 3. Although there are characteristic local differences relative to the conformations of the murine and Syrian hamster prion proteins, the bPrP structure is essentially identical to that of the human prion protein. On the other hand, there are differences between bovine and human PrP in the surface distribution of electrostatic charges, which then appears to be the principal structural feature of the "healthy" PrP form that might affect the stringency of the species barrier for transmission of prion diseases between humans and cattle.


Induction of dopa (3,4-dihydroxyphenylalanine) decarboxylase in blowfly integument by ecdysone. A demonstration of synthesis of the enzyme de novo.
The activity of the enzyme dopa (3,4-dihydroxyphenylalanine) decarboxylase, present in the epidermis cells of blowfly larvae, increases during the late third instar under the influence of the steroid hormone, ecdysone. By using the double-labelling technique and immune precipitation with univalent antibody to dopa decarboxylase, we demonstrated that the increase in enzyme activity was due to a stimulation of synthesis of enzyme molecules de novo. In this respect, the action of ecdysone is similar to the action of other steroid hormones.


Effect of Endosperm Type and Storage Length of Whole Plant Corn Silage on Nitrogen Fraction, Fermentation Products, Zein Profile and Starch Digestibility.
Zeins are commercially important proteins found in corn endosperms. The objective of this study was to evaluate the effect of altering zeins levels in corn inbreds lines carrying endosperm mutations with differential allelic dosage and analyze its impact on the composition, nutritive value, and starch digestibility of whole plant corn silage (WPCS) at 5 storage length. Three inbred lines carrying 3 different endosperm modifiers [opaque-2 (o2), floury-2 (fl2) and soft endosperm-1(h1)] were pollinated with 2 pollen sources to form pairs of near isogenic lines with either 2 or 3 doses of the mutant allele for each endosperm modifier. The experiment was designed as a split-plot design with 3 replications. Pollinated genotype was the main plot factor and storage length was the sub-plot level factor. Agronomic precautions were taken to mimic hybrid WPCS to the extent possible. Samples were collected at approximately 30% dry matter (DM) using a forage harvester and ensiled in heat-sealed plastic bags for 0, 30, 60, 120 and 240 d. Thus, the experiment consisted of 30 treatments (6 genotypes x storage lengths) and 90 ensiling units (3 replications per treatment). Measurements included nutrient analysis including crude protein, soluble crude protein, amylase-treated neutral detergent fiber, acid detergent fiber, lignin, starch, fermentation end products, zeins concentration, and in vitro starch digestibility (ivSD). The nutritional profile of the inbred-based silage samples was similar to hybrids values reported in literature. Significant differences were found in fresh (unfermented) sample kernels for endosperm vitreousness and zein profiles between and within isogenic pairs. The o2 homozygous (3 doses of mutant allele) had the highest reduction in vitreousness level (74.5 to 38%) and zein concentration (6.2 to 4.7% of DM) compared with the heterozygous counterpart (2 doses of mutant allele). All genotypes showed significant reduction of total zeins and α-zeins during progressive storage length. In vitro starch digestibility increased with storage length and had significant effect of genotype and storage length but not for genotype by storage length interaction, which suggest that the storage period did not attenuate the difference in ivSD between near isogenic pairs caused by zeins in WPCS. Both total zeins and α-zeins showed a strong negative correlation with ivSD which agrees with the general hypothesis that the degradation of zeins increases ruminal starch degradability. Homozygous o2 was the only mutant with significantly higher ivSD compared with the heterozygous version which suggest that, if all other conditions remain constant in a WPCS systems, substantial reductions in endosperm's α-zeins are required to significantly improve ivSD in the silo.


[Some aspects of correction of nasal tip congenital deformities].
The paper reviews both short- and lon-termed results of conventional methods for the correction of nasal tip congenital deformities: Converse for broad tip correction, Armstrong for long tip and Burian for protruding tip. The revealed disadvantages of the abovementioned methods are summarized. Treatment efficiency proved to be higher when classifying nasal tip deformities in monodeformities and combined ones. This allows more precise analyzing of deformity compounds and provides better short- and long-termed results.


Acute toxicity of chlorpyrifos and carbosulfan to glochidia of the freshwater mussel Hyriopsis bialata Simpson, 1900.
The acute toxicity of carbosulfan and chlorpyrifos in formulated pesticides to glochidia (larvae) of the freshwater mussel (Hyriopsis bialata Simpson, 1900) was evaluated under static conditions in moderately hard dechlorinated tap water. Measured pesticide concentrations were 26 to 34% lower than nominal concentrations; therefore, all results are expressed in terms of measured active ingredient. Carbosulfan was relatively non-toxic to the mussel larvae with median effective concentrations (EC50) of carbosulfan at 24 and 48 h greater than 0.10 mg/L. The EC50s of chlorpyrifos at 24 and 48 h were 0.083 and 0.078 mg/L, respectively (measured concentrations). The 48-h EC50 of a combined exposure to a mixture of chlorpyrifos and carbosulfan at a constant ratio of 2.9:1 was 0.0142:0.049 mg CP:CB/L. In a separate experiment, the effect of water hardness on carbosulfan, chlorpyrifos, or a combined exposure was assessed using glochidia exposed to either soft, moderately hard, or hard reconstituted water. There was no effect of water hardness on the survival of glochidia after 24- or 48-h exposure to carbosulfan. The chlorpyrifos 48-h EC50s in soft water, moderately hard water, and hard water were 0.18, 0.11, and 0.16 mg/L, respectively. The data indicate that the lowest water hardness resulted in the highest survival of glochidia, whereas an increase to moderate water hardness resulted in significantly decreased survival of glochidia (F = 15.5, P < 0.05). The EC50s of a combined exposure at 48 h in soft water, moderately hard water, and hard water were 0.124:0.044, 0.132:0.047, and 0.064:0.022 mg CP:CB/L, respectively. The data indicate that the combined toxicity was lowest at low and moderate water hardness, whereas an increase to high water hardness resulted in a significantly decreased survival of glochidia. After 48 h, the toxicity of the combined chlorpyrifos and carbosulfan exposure in soft and hard water was greater than that of chlorpyrifos alone.


Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease.
Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.


Iodine Content of Wild and Farmed Seafood and Its Estimated Contribution to UK Dietary Iodine Intake.
Iodine is an important nutrient for human health and development, with seafood widely acknowledged as a rich source. Demand from the increasing global population has resulted in the availability of a wider range of wild and farmed seafood. Increased aquaculture production, however, has resulted in changes to feed ingredients that affect the nutritional quality of the final product. The present study assessed the iodine contents of wild and farmed seafood available to UK consumers and evaluated its contribution to current dietary iodine intake. Ninety-five seafood types, encompassing marine and freshwater fish and shellfish, of wild and farmed origins, were purchased from UK retailers and analysed. Iodine contents ranged from 427.4 ± 316.1 to 3.0 ± 1.6 µg·100 g-1 flesh wet weight (mean ± SD) in haddock (Melanogrammus aeglefinus) and common carp (Cyprinus carpio), respectively, being in the order shellfish > marine fish > freshwater fish, with crustaceans, whitefish (Gadiformes) and bivalves contributing the greatest levels. Overall, wild fish tended to exhibit higher iodine concentrations than farmed fish, with the exception of non-fed aquaculture species (bivalves). However, no significant differences were observed between wild and farmed Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss), and turbot (Psetta maxima). In contrast, farmed European seabass (Dicentrarchus labrax) and seabream (Sparus aurata) presented lower, and Atlantic halibut (Hippoglossus hippoglossus) higher, iodine levels than their wild counterparts, most likely due to the type and inclusion level of feed ingredients used. By following UK dietary guidelines for fish consumption, a portion of the highest oily (Atlantic mackerel, Scomber scombrus) and lean (haddock) fish species would provide two-thirds of the weekly recommended iodine intake (980 µg). In contrast, actual iodine intake from seafood consumption is estimated at only 9.4-18.0% of the UK reference nutrient intake (140 µg·day-1) across different age groups and genders, with females obtaining less than their male equivalents.


A Molecular-Splicing Strategy for Constructing a Near-Infrared Fluorescent Probe for UDP-Glucuronosyltransferase 1A1.
UDP-glucuronosyltransferase 1A1 (UGT1A1) is a vital metabolic enzyme responsible for the clearance of endogenous substances and drugs. Hitherto, the development of fluorescent probes for UGTs was severely restricted due to the poor isoform selectivity and on-off or blue-shifted fluorescence response. Herein, we established a novel "molecular-splicing" strategy to construct a highly selective near-infrared (NIR) fluorescent probe, HHC, for UGT1A1, which exhibited a NIR signal at 720 nm after UGT1A1 metabolism. HHC was then successfully used for the real-time imaging of endogenous UGT1A1 in living cells and animals and to monitor the bile excretion function. In summary, an isoform-specific NIR fluorescent probe has been developed for monitoring UGT1A1 activity in living systems, high-throughput screening of novel UGT1A1 inhibitors and visual evaluation of bile excretion function.


Phylogeography of the Angolan black and white colobus monkey, Colobus angolesnsis palliatus, in Kenya and Tanzania.
Little is known about genetic variation in the 6-8 subspecies of Colobus angolensis, currently distinguished by pelage differences. We present a comparative genetic analysis of one of these subspecies, C. a. palliatus, in Kenya and Tanzania that assesses evolutionary relationships and patterns of mitochondrial genetic diversity in 103 individuals across its geographic range. Fecal samples from approximately 156 individuals were collected in four localities: (1) Diani Forest, Kenya; (2) Shimoni, Kenya; (3) Udzungwa Mountains National Park, Eastern Arc Mountains, Tanzania; and (4) Mount Rungwe, Southern Highlands, Tanzania. These samples represent at least six groups, with 5-15 samples from each. Comparative sequence analysis of a 1,795 base pair mtDNA fragment revealed 19 unique haplotypes in four populations. Phylogenetic analyses suggest that sampled Kenyan haplotypes are paraphyletic, with one Kenyan haplotype basal to all other sampled haplotypes. Analysis of molecular variance (AMOVA) suggests high levels of genetic variation among populations (Phi(ST) 0.72, P<0.001). Genetic data are concordant with a subspecies level differentiation between C. a. palliatus populations in Kenya and those in Central and southern Tanzania, as earlier suggested based on pelage differences. This study highlights the evolutionary distinctiveness of Kenyan populations of C. a. palliatus relative to Tanzanian populations. Although C. a. palliatus habitat in Tanzania is currently better protected than in Kenya, our results suggest Kenyan and Tanzanian populations should be considered distinct units, and the protection of C. a. palliatus habitat in Kenya, as well as habitat connectivity between Kenyan populations, should be prioritized for conservation and management.


Dramatic decline of northern bat Eptesicus nilssonii in Sweden over 30 years.
We monitored northern bat Eptesicus nilssonii (Keyserling & Blasius, 1839) acoustically along a 27 km road transect at weekly intervals in 1988, 1989 and 1990, and again in 2016 and 2017. The methodology of data collection and the transect were the same throughout, except that the insect-attracting mercury-vapour street-lights along parts of the road were replaced by sodium lights between the two survey periods. Counts along sections of the transect with and without street-lights were analysed separately. The frequency of bat encounters in unlit sections showed an average decline of 3.0% per year, corresponding to a reduction of 59% between 1988 and 2017. Sections with street-lights showed an 85% decline over the same period (6.3% per year). The decline represents a real reduction in the abundance of bats rather than an artefact of changed distribution of bats away from roads. Our study conforms with another long-term survey of the same species on the Baltic island of Gotland. Our results agree with predictions based on climate change models. They also indicate that the decline was caused directly by the disuse of the insect-attracting mercury-vapour street-lights, which may have resulted in lower availability of preferred prey (moths). In the 1980s, E. nilssonii was considered the most common bat in Sweden, but the subsequent decline would rather qualify it for vulnerable or endangered status in the national Red List of Threatened Species.


Correlation between lung and plasma angiotensin converting enzyme and the hypotensive effect of captopril in conscious rabbits.
We measured both pulmonary and plasma angiotensin converting enzyme (ACE) activity in conscious rabbits before and for 6 days after administration of captopril (2 mg/kg i.v.). Pulmonary ACE activity was measured by means of modified indicator-dilution techniques after bolus injection of [3H]benzoyl-phenyl-alanyl-alanyl-proline ( BPAP , synthetic substrate for ACE). Plasma ACE activity was also determined radiometrically with [3H] BPAP as substrate. In addition, we measured the systemic pressor response to i.v. bolus dose of angiotensin I both before and after captopril. Twenty-four hours after captopril, pulmonary metabolism of BPAP had decreased from control of 73 +/- 5 to 8 +/- 2%; even 6 days after drug treatment there was still evidence of inhibition. In contrast, plasma ACE activity was significantly (P less than .05) reduced within 15 min of treatment (to 20% of control levels) but recovered within 24 hr. The time course of changes in the pressor response to angiotensin I, after captopril, resembled that of plasma ACE activity. Mean systemic arterial blood pressure was 81 +/- 4 torr at control and reached its nadir at 24 hr (64 +/- 2 torr; P less than .05); thereafter a gradual recovery ensued, similar in time course to that of pulmonary ACE. These data suggest that inhibition of plasma ACE and also the pressor response to angiotensin I are unrelated temporally to the hypotensive effects of captopril.


The Price of Artificial Intelligence.
Whilst general artificial intelligence (AI) is yet to appear, today's narrow AI is already good enough to transform much of healthcare over the next two decades. There is much discussion of the potential benefits of AI in healthcare and this paper reviews the cost that may need to be paid for these benefits, including changes in the way healthcare is practiced, patients are engaged, medical records are created, and work is reimbursed. Whilst AI will be applied to classic pattern recognition tasks like diagnosis or treatment recommendation, it is likely to be as disruptive to clinical work as it is to care delivery. Digital scribe systems that use AI to automatically create electronic health records promise great efficiency for clinicians but may lead to potentially very different types of clinical records and workflows. In disciplines like radiology, AI is likely to see image interpretation become an automated process with diminishing human engagement. Primary care is also being disrupted by AI-enabled services that automate triage, along with services such as telemedical consultations. This altered future may necessarily see an economic change where clinicians are increasingly reimbursed for value, and AI is reimbursed at a much lower cost for volume. AI is likely to be associated with some of the biggest changes we will see in healthcare in our lifetime. To fully engage with this change brings promise of the greatest reward. To not engage is to pay the highest price.


[The benefit of angiotensin converting enzyme inhibitor for geriatric syndrome in the elderly].
Angiotensin converting enzyme (ACE) inhibitor plays an important role not only as an antihypertensive drug but also for prevention of various complications related to geriatric syndrome. Pneumonia in the disabled elderly is mostly due to silent aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract. Aspiration is related to the dysfunction of dopaminergic neurons by cerebrovascular disease, resulting in impairments in both the swallowing and cough reflexes. ACE inhibitor can increase in the sensitivity of the cough reflex particularly in older post-menopausal women, and improvement of the swallowing reflex. In a 2-year follow-up study in stroke patients, patients who did not receive ACE inhibitors had a higher risk of mortality due to pneumonia than in stroke patients who were treated with ACE inhibitor. Moreover, the mortality of pneumonia was significantly lower in older hypertensive patients given ACE inhibitors than in those treated with other antihypertensive drugs. On the other hand, we found a new benefit of ACE inhibitor on the central nervous system. The mortality in Alzheimer's disease patients who received brain-penetrating ACE inhibitor was lower than in those who received other antihypertensive drugs. In a 1-year follow-up study, cognitive decline was lower in patients receiving brain-penetrating ACE inhibitors than in patients receiving a non-brain-penetrating ACE inhibitor or a calcium channel blocker. Brain-penetrating ACE inhibitors may slow cognitive decline in patients with mild to moderate Alzheimer's disease. ACE inhibitor might be effective for the disabled elderly, resulting in the prevention of aspiration pneumonia and Alzheimer's disease for the elderly.


Astrocyte-derived hepcidin aggravates neuronal iron accumulation after subarachnoid hemorrhage by decreasing neuronal ferroportin1.
Iron accumulation is one of the most essential pathological events after subarachnoid hemorrhage (SAH). Ferroportin1 (FPN1) is the only transmembrane protein responsible for exporting iron. Hepcidin, as the major regulator of FPN1, is responsible for its degradation. Our study investigated how the interaction between FPN1 and hepcidin contributes to iron accumulation after SAH. We found that iron accumulation aggravated after SAH, along with decreased FPN1 in neurons and increased hepcidin in astrocytes. After knocking down hepcidin in astrocytes, the neuronal FPN1 significantly elevated, thus attenuating iron accumulation. After SAH, p-Smad1/5 and Smad4 tended to translocate into the nucleus. Moreover, Smad4 combined more fragments of the promoter region of Hamp after OxyHb stimulation. By knocking down Smad1/5 or Smad4 in astrocytes, FPN1 level restored and iron overload attenuated, leading to alleviated neuronal cell death and improved neurological function. However, the protective role disappeared after recombinant hepcidin administration. Therefore, our study suggests that owing to the nuclear translocation of transcription factors p-Smad1/5 and Smad4, astrocyte-derived hepcidin increased significantly after SAH, leading to a decreased level of neuronal FPN1, aggravation of iron accumulation, and worse neurological outcome.


[Health anxiety - increased knowledge and treatment options].
Patients with hypochondriasis are preoccupied with the fear or belief that they have a serious, undiagnosed disease. This concern derives from misinterpretations of benign physical sensations, and persists despite appropriate reassurance to the contrary. They have, on average, disproportionately high rates of visits to physicians, specialty consultations, laboratory tests, and surgical procedures, as well as high health care costs. Despite this extensive medical attention, they find their care unsatisfactory, which is understandable, as convincing alternative explanations to their ailments are repeatedly delayed. Physicians, in turn, may feel discouraged and frustrated in relation to these individuals where their best efforts to help often prove ineffective or are even rejected. Recent scientific studies have shown that cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRI) are effective treatment options for health anxiety as demonstrated in clinical trials.


Failure to Participate in Sports: An Evaluation of Preparticipation Physicals in a Local School District.
To determine the incidence of the documentation of athlete failure of preparticipation sports physicals. This was a retrospective observational study that involved review of preparticipation examination physical form documentation from multiple clinicians for all student athletes who participated in athletics during the 2018 to 2019 academic year at Galveston Independent School District (GISD). We collected the reasons for failure to pass the preparticipation physical examination. Of the approximately 800 student athlete forms reviewed, 183 forms indicated individual athletes failed the visual acuity or cardiovascular portions of the preparticipation physical examination. Athlete failures of the preparticipation physical examination may cause delays in sports participation, and time and monetary costs to students and their parents. Inconsistences in guidelines used to clear athletes as well as variation in form completion impacts whether athletes reportedly failed or passed the examination. Mass participation screening becomes a safety net for communities for athletes who may not have primary care providers to encourage follow-up with a regular clinician for previously undiagnosed medical issues and standardizing guideline use and form completion across clinicians who do these exams may improve numbers of athletes who are cleared to play sports. Focusing on preventable and addressable preparticipation examination failures may help clinicians who perform these exams, while also establishing a safety net for previously undiagnosed medical conditions. Instituting yearly vision checks, addressing cardiovascular issues, and encouraging yearly follow-up with primary care clinicians can more readily address physical and mental health issues and will provide more comprehensive care to student athletes.


Organisational efforts to improve quality while reducing healthcare disparities: the case of breast cancer screening among Arab women in Israel.
(1) To improve quality and equity by increasing utilisation of mammography screening among Israeli Arab women. (2) To explore effectiveness of designing interventions with a combined top-down and bottom-up approach. Retrospective study at two periods of time: 2004--intervention's preliminary stages; 2005--intervention's implementation. Maccabi Healthcare Services (MHS), an Israeli health plan serving 1.7 million members at study period; 7% of them are Arabs by 139 branches, 13 of which serve Arabs exclusively. MACRO-ORGANISATIONAL INTERVENTION (TOP DOWN): Development of a computerised Mammography Promotion System, phone contacts with non-respondents and intraorganisational reporting of screening rates. INTENSIVE INTERVENTION (BOTTOM UP): A local analysis of barriers to care and implementation of tailored solutions. This intervention was initiated and documented in three Arab branches, with spillover to the entire Arab sector. MEASURE DEFINITION: Biennial breast cancer (BC) screening of eligible women. Improvement measures Changes in BC screening rates in Arabs and comparisons with overall MHS BC screening rates for 2004 and 2005. In 2005, average BC screening rates in Arab branches increased from 26.7% to 46.2% (73% improvement), while overall MHS screening rates increased from 49.0% to 63.1% (29% improvement). Analysis of the relative differences between 2004 and 2005 BC screening rates indicated statistically significant differences (p<0.006) in rates between the Arab and other branches. These results did not change after adjustment for branch size, region and branch average age. Combined top-down interventions and bottom-up initiatives are effective for formulating programmes to reduce inequality.


Histological and physical analysis of bone neoformation by osteogenesis distraction: A preliminary report.
Osteogenesis distraction (OD) is a mainstream technique in maxillofacial surgical reconstruction with varied applications. OD technique employs a distractor with the aim to get new bone in the site of interest. Osseous maturation time is necessary before the device can be removed and few patients' complaint of related discomfort, especially when these devices are external, and induces superficial infections, paresthesia, hypertrophic scars and social relationship difficulties. The use of Low Level Laser Therapy (LLLT) has been proved beneficial to soft tissue and osseous repairs. 12 rabbits were randomly divided in to two groups. In all animals, distractor was placed and one group was exposed to LLLT while the other group served as control. After consolidation, animals were sacrificed, the new bone formed were subjected to investigations including histomorphometric, physical analysis and tomographical analysis. Statistical analyses were performed using SPSS software. Newly formed bone was significantly different between the groups. The physical properties of the neobone were comparatively better when the animals were exposed to LLLT with varying statistical significance. The results obtained with smaller sample size in this study need to be interpreted with care. The results of this preliminary pilot study encourage the use of LLLT during healing period. However the histological, tomographical and physical findings need to be ascertained using a larger sample size to study the bio-stimulatory effects with laser therapy from basics to clinical relevance on wound and bone healing.


A Honeycomb-like Co@N-C Composite for Ultrahigh Sulfur Loading Li-S Batteries.
Because of the high theoretical capacity of 1675 mAh g-1 and high energy density of 2600 Wh kg-1, respectively, lithium-sulfur batteries are attracting intense interest. However, it remains an enormous challenge to realize high utilizations and loadings of sulfur in cathodes for the practical applications of Li-S batteries. Herein, we design a quasi-2D Co@N-C composite with honeycomb architecture as a multifunctional sulfur host via a simple sacrificial templates method. The cellular flake with large surface area and honeycomb architecture can encapsulate much more sulfur, leading to high sulfur content (HSC) composites, and by stacking these HSC flakes, a high sulfur loading (HSL) electrode can be realized due to their high layer bulk density. Compared to our previous work in multifunctional Co-N-C composites, the cellular Co@N-C composite displays a distinct enhancement in the sulfur content, sulfur loading, cycle stability, and rate performance. Benefiting from the cellular morphology, a composite with an HSC of 93.6 wt % and an electrode with an HSL of 7.5 mg cm-2 can be obtained simultaneously, which exhibited excellent rate performance up to 10 C (3.6 mg cm-2) and great cycling stability.


The biology of IL-12: coordinating innate and adaptive immune responses.
Cytokines play critical roles in regulating all aspects of immune responses, including lymphoid development, homeostasis, differentiation, tolerance and memory. Interleukin (IL)-12 is especially important because its expression during infection regulates innate responses and determines the type and duration of adaptive immune response. IL-12 induces interferon-gamma (IFN-gamma) production by NK, T cells, dendritic cells (DC), and macrophages. IL-12 also promotes the differentiation of naïve CD4+ T cells into T helper 1 (Th1) cells that produce IFN-gamma and aid in cell-mediated immunity. As IL-12 is induced by microbial products and regulates the development of adaptive immune cells, IL-12 plays a central role in coordinating innate and adaptive immunity. IL-12 and the recently identified cytokines, IL-23 and IL-27, define a family of related cytokines that induce IFN-gamma production and promote T cell expansion and proliferation.


Internal Medicine residents use heuristics to estimate disease probability.
Training in Bayesian reasoning may have limited impact on accuracy of probability estimates. In this study, our goal was to explore whether residents previously exposed to Bayesian reasoning use heuristics rather than Bayesian reasoning to estimate disease probabilities. We predicted that if residents use heuristics then post-test probability estimates would be increased by non-discriminating clinical features or a high anchor for a target condition. We randomized 55 Internal Medicine residents to different versions of four clinical vignettes and asked them to estimate probabilities of target conditions. We manipulated the clinical data for each vignette to be consistent with either 1) using a representative heuristic, by adding non-discriminating prototypical clinical features of the target condition, or 2) using anchoring with adjustment heuristic, by providing a high or low anchor for the target condition. When presented with additional non-discriminating data the odds of diagnosing the target condition were increased (odds ratio (OR) 2.83, 95% confidence interval [1.30, 6.15], p = 0.009). Similarly, the odds of diagnosing the target condition were increased when a high anchor preceded the vignette (OR 2.04, [1.09, 3.81], p = 0.025). Our findings suggest that despite previous exposure to the use of Bayesian reasoning, residents use heuristics, such as the representative heuristic and anchoring with adjustment, to estimate probabilities. Potential reasons for attribute substitution include the relative cognitive ease of heuristics vs. Bayesian reasoning or perhaps residents in their clinical practice use gist traces rather than precise probability estimates when diagnosing.


Biosynthesis of 7,8-diaminopelargonic acid, a biotin intermediate, from 7-keto-8-aminopelargonic acid and S-adenosyl-L-methionine.
Resting cells of Escherichia coli strain D302(bioD302) can synthesize 7,8-diaminopelargonic acid from 7-keto-8-aminopelargonic acid. The product of this aminotransferase reaction has been identified by paper chromatography and electrophoresis. Glucose enhances the vitamer yield twofold. Of the 19 amino acids tested as amino donors, only methionine proved to be significantly stimulatory. In cell-free extracts, however, methionine was completely inactive unless both adenosine triphosphate (ATP) and Mg(2+) were present. S-Adenosyl-l-methionine (SAM) was about 10 times more effective than methionine, ATP, and Mg(2+). The optimal conditions for the reaction were determined, and substrate inhibition was found for 7-keto-8-aminopelargonic acid. It has been possible to eliminate certain impurities as amino donors in the commercial preparation of SAM and those that may arise in enzymatic reactions in which SAM is a substrate. The direct participation of SAM in the aminotransferase reaction seems a likely possibility.


Bidirectional tick transport by migratory birds of the African-Western Palearctic flyway over Turkish Thrace: observation of the current situation and future projection.
This study was carried out at a vital stopover site of migrating birds in the Turkish Thrace, European part of Turkey, on the Mediterranean/Black Sea Flyway. Ticks were collected from the birds captured in the four migration periods, i.e., autumn 2020, spring 2021, autumn 2021, and spring 2022, and identified morphologically. Throughout the study, 10,651 birds from 77 species were examined, and 671 belonging to 34 species were found infested. The infestation prevalence in total birds and the mean number of ticks per infested bird were 6.3% and 3.8 (range: 1-142), respectively. A total of 2573 ticks were collected with the following species distribution and numbers: Ixodes spp. 70 larvae, I. frontalis 1829 larvae, 337 nymphs, and 30 adults, I. acuminatus 16 nymphs and 42 adults, I. ricinus 39 larvae, 141 nymphs, and one adult, Hyalomma spp. seven larvae and 60 nymphs, and Haemaphysalis sp. one larva. Prevalence, intensity, and species distribution of the ticks in birds varied depending on the month, season, year, and species-specific migration phenology of the birds. The results show that precise determination of the tick-borne risk associated with migratory birds for a particular region necessarily requires long-term and comprehensive studies and indicates that anthropogenic climate change and habitat degradation can significantly differentiate the risk by influencing the migration phenology in birds and by making new regions suitable for the establishment of different ticks.


Improving the selection and development of influenza vaccine viruses - Report of a WHO informal consultation on improving influenza vaccine virus selection, Hong Kong SAR, China, 18-20 November 2015.
Since 2010 the WHO has held a series of informal consultations to explore ways of improving the currently highly complex and time-pressured influenza vaccine virus selection and development process. In November 2015 experts from around the world met to review the current status of efforts in this field. Discussion topics included strengthening influenza surveillance activities to increase the availability of candidate vaccine viruses and improve the extent, timeliness and quality of surveillance data. Consideration was also given to the development and potential application of newer laboratory assays to better characterize candidate vaccine viruses, the potential importance of antibodies directed against influenza virus neuraminidase, and the role of vaccine effectiveness studies. Advances in next generation sequencing and whole genome sequencing of influenza viruses were also discussed, along with associated developments in synthetic genomics technologies, evolutionary analysis and predictive mathematical modelling. Discussions were also held on the late emergence of an antigenic variant influenza A(H3N2) virus in mid-2014 that could not be incorporated in time into the 2014-15 northern hemisphere vaccine. There was broad recognition that given the current highly constrained influenza vaccine development and production timeline it would remain impossible to incorporate any variant virus which emerged significantly long after the relevant WHO biannual influenza vaccine composition meetings. Discussions were also held on the development of pandemic and broadly protective vaccines, and on associated regulatory and manufacturing requirements and constraints. With increasing awareness of the health and economic burdens caused by seasonal influenza, the ever-present threat posed by zoonotic influenza viruses, and the significant impact of the 2014-15 northern hemisphere seasonal influenza vaccine mismatch, this consultation provided a very timely opportunity to share developments and exchange views. In all areas, a renewed and strengthened emphasis was placed on developing concrete and measurable actions and identifying the key stakeholders responsible for their implementation.


Geomorphology and habitat diversity in the Pantanal.
The present study deals with the inter-relations in the relief which forms the Bacia do Alto Rio Paraguay (BAP) in mid-west Brazil. The overall aim is to discuss the relationship between relief forms and the biodiversity of the Pantanal. The BAP is a natural environmental system with contrasts in two of the compartments on which it is formed: the plateau, the most elevated compartment, highly transformed by human activities, and the plain which forms the Pantanal, which is more preserved and less transformed in relation to productive activities. The analysis was performed based on publications with a geomorphologic focus, examining the different relief units of the BAP and the dynamics of the revealing processes of landscape change which the Pantanal has undergone since the end of the Pleistocene.


Genetic analysis identifies the missing parchment of New Zealand's founding document, the Treaty of Waitangi.
Genetic analyses provide a powerful tool with which to identify the biological components of historical objects. Te Tiriti o Waitangi | The Treaty of Waitangi is New Zealand's founding document, intended to be a partnership between the indigenous Māori and the British Crown. Here we focus on an archived piece of blank parchment that has been proposed to be the missing portion of the lower parchment of the Waitangi Sheet of the Treaty. However, its physical dimensions and characteristics are not consistent with this hypothesis. We perform genetic analyses on the parchment membranes of the Treaty, plus the blank piece of parchment. We find that all three parchments were made from ewes and that the blank parchment is highly likely to be a portion cut from the lower membrane of the Waitangi Sheet because they share identical whole mitochondrial genomes, including an unusual heteroplasmic site. We suggest that the differences in size and characteristics between the two pieces of parchment may have resulted from the Treaty's exposure to water in the early 20th century and the subsequent repair work, light exposure during exhibition or the later conservation treatments in the 1970s and 80s. The blank piece of parchment will be valuable for comparison tests to study the effects of earlier treatments and to monitor the effects of long-term display on the Treaty.


[Fibromuscular dysplasia of the brachial artery--2 case reports and review of the literature].
Yet being an uncommon disease in general, the manifestation of the fibromuscular dysplasia (FMD) in the upper extremities is exceedingly rare. Two patients with FMD of the brachial artery are presented and the literature concerned is reviewed. In this location the formation of microthrombi with subsequent embolization into the periphery instead of progressive vessel stenosis seems to be the leading pathophysiological principle. Therapeutic options are discussed.


The management of primary open angle glaucoma.
Glaucoma is one of the commonest causes of blindness in the world. In the UK, about 7% of people over the age of 75 years have primary open angle glaucoma, the most common type of glaucoma and the cause of visual impairment in about 13% of those registered blind. Early detection and treatment can usually prevent blindness. However, half of all patients with primary open angle glaucoma in the UK do not present until vision has begun to deteriorate. Here we consider ways of improving detection and management.


Surgical leg rotation: cortical neuroplasticity assessed through brain mapping using transcranial magnetic stimulation.
Rotationplasty (Borggreve-Van Nes operation) is a rare limb salvage procedure, most often applied to children presenting with sarcoma of the distal femur. In type A1 operation, the distal thigh is removed and the proximal tibia is axially rotated by 180°, remodeled, grafted onto the femoral stump, and then prosthetized. The neurovascular bundle is spared. The rotated ankle then works as a knee. The foot plantar and dorsal flexors act as knee extensors and flexors, respectively. Functional results may be excellent. Cortical neuroplasticity was studied in three men (30-31 years) who were operated on the left lower limb at ages between 7 and 11 years and were fully autonomous with a custom-made prosthesis, as well as in three age-sex matched controls. The scalp stimulation coordinates, matching the patients' brain MRI spots, were digitized through a 'neuronavigation' optoelectronic system, in order to guide the transcranial magnetic stimulation coil, thus ensuring spatial precision during the procedure. Through transcranial magnetic stimulation driven by neuronavigation, the cortical representations of the contralateral soleus and vastus medialis muscles were studied in terms of amplitude of motor evoked potentials (MEPs) and centering and width of the cortical areas from which the potentials could be evoked. Map centering on either hemisphere did not differ substantially across muscles and participants. In the operated patients, MEP amplitudes, the area from which MEPs could be evoked, and their product (volume) were larger for the muscles of the unaffected side compared with both the rotated soleus muscle (average effect size 0.75) and the muscles of healthy controls (average effect size 0.89). In controls, right-left differences showed an effect size of 0.38. In no case did the comparisons reach statistical significance (P>0.25). Nevertheless, the results seem consistent with cortical plasticity reflecting strengthening of the unaffected leg and a combination of cross-education and skill training of the rotated leg.


Diosgenin effectively suppresses skin inflammation induced by phthalic anhydride in IL-4/Luc/CNS-1 transgenic mice.
To quantitatively evaluate the therapeutic effects of diosgenin (DG) and investigate the role of IL-4 on skin inflammation, alterations in luciferase-derived signal and general phenotype biomarkers were measured in IL-4/Luc/CNS-1 transgenic mice with phthalic anhydride (PA)-induced skin inflammation after treatment with DG for 4 weeks. High levels of luciferase-derived signal detected in the abdominal region and submandibular lymph node (SL) of the PA treated group was significantly decreased by 67-88% in the PA + DG cotreated group. Furthermore, the weight of the lymph node and spleen, IgE concentration, epidermis thickness, and number of infiltrated mast cells were lower in the PA + DG treated group than the PA + Vehicle treated group. Moreover, expression of IL-6 and vascular endothelial growth factor (VEGF) also decreased in the PA + DG cotreated group. These results suggest that PA-induced skin inflammation could be successfully suppressed by DG treatment in IL-4/Luc/CNS-1 Tg mice through attenuation of IL-4 and IL-6 expression, as well as decreased IgE concentration and mast cells infiltration.


Influence of CoQ10 on autonomic nervous activity and energy metabolism during exercise in healthy subjects.
CoQ10 has come to be widely used as a dietary supplement, and daily intake of it has increased in recent years. CoQ10 is produced in all living organisms and is an essential coenzyme for energy synthesis in the mitochondria and an important scavenger of reactive oxygen species. This is a randomized, double-blind, placebo-controlled experiment to examine the acute effects of a single dose of CoQ10 on the autonomic nervous system (ANS) by using power spectral analysis of HRV and energy metabolism at rest and during low intensity exercise in healthy subjects. Eleven nonsmoking healthy male students (age: 26+/-1 y) volunteered to participate in this experiment. CM5 lead ECG and gas exchange parameters were recorded 5 min before, and 30 min and 60 min after the oral administration of CoQ10 or a placebo. Following this, the subjects exercised using a stationary cycle ergometer for 10 min at 60 rpm with an intensity of 30% of heart rate reserve. During the exercise, the ECG and gas exchange parameters were recorded continuously. There were no significant differences in heart rate between the CoQ10 and placebo trials at rest or during exercise. With regard to the integrated values of the spectrum, there were no significant differences in the HF power representing parasympathetic activity or LF power representing both sympathetic and parasympathetic nervous activities between the trials at any timepoint. However, during the exercise, HF power and LF power in the CoQ10 trial showed a tendency to increase compared with the placebo trial (p<0.1). Total power representing the over-all ANS activity was significantly increased in the CoQ10 trial during exercise, which implied that autonomic nervous activity was augmented by CoQ10 (p<0.05). CoQ10 also induced enhanced lipid oxidation as shown by the significantly lower respiratory gas exchange ratio (R) and increased fat oxidation during exercise. The results shed some light upon the relationship between the autonomic nervous activity and energy metabolism. These results suggested that CoQ10 may increase fat oxidation with augmented autonomic nervous activity during low intensity exercise.


Characteristics and Quality Appraisal of the Economic Evaluations Done in Ethiopia: A Systematic Review.
Health economic evaluation identifies, measures, values, and compares alternative strategies to efficiently allocate scarce resources. The validity, methodological quality, and generalizability of economic evaluations must be assessed, as poorly designed studies can lead to incorrect conclusions. Therefore, this study aimed to evaluate the quality and characteristics of published economic evaluations done in Ethiopia, using the Quality of Health Economics Studies (QHES) and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) instruments. Various electronic databases were searched using different keywords. We included only original studies conducted in Ethiopia that evaluated the cost and consequences of at least two health interventions. Abstracts, treatment guidelines, reviews, expert opinions, and studies that included other countries were excluded. Two reviewers independently evaluated each study using the QHES and CHEERS instruments and any disagreements were then resolved by a third reviewer. The study included 21 studies published between 2002 and 2021. HIV was the most frequently evaluated medical condition, examined in four (19.06%) of the 21 studies. Seventeen of the studies (80.95%) compared healthcare services or programs, while the other four examined pharmaceutical products. Cost-utility analysis was the economic evaluation technique used in 14 studies (66.67%). Of the studies that disclosed their funding sources, foreign institutions were involved in funding 71.43% of them. Disability-adjusted life-year (DALY) was an outcome metric used in nine (42.86%) studies. The average QHES score of the studies was 82%. Fourteen studies had QHES scores of ≥75% and two had scores of <50%. The studies evaluated using the CHEERS instrument ranged in quality from 42.9% to 92.9%, with an average of 78.23%. Our study revealed that Ethiopia lacks health economic evaluations, particularly on non-communicable diseases. This indicates that the economic evaluation of healthcare interventions in Ethiopia is still in its early stages. Additionally, Ethiopian institutions have played a very limited role in funding research, highlighting the importance of active participation from local institutions.


Heterogeneous patterns of CEBPalpha mutation status in the progression of myelodysplastic syndrome and chronic myelomonocytic leukemia to acute myelogenous leukemia.
We aimed to assess the role of CEBPalpha mutations in the progression of myelodysplastic syndrome (MDS) to acute myelogenous leukemia (AML) and their cooperating mutations. Mutational analysis of CEBPalpha with direct sequencing for each PCR product was done on matched bone marrow samples obtained from 50 adult patients with MDS at diagnosis and at AML transformation. Cloning analysis was used to determine the allelic distribution. CEBPalpha mutations were identified in four patients at diagnosis of MDS, including one with refractory anemia with excess blasts and three with chronic myelomonocytic leukemia. At AML transformation, three patients retained the identical mutant clones as their initial diagnosis, three acquired the mutations, and one lost CEBPalpha mutation when she gained FLT3/ITD mutation. Together, seven patients had CEBPalpha mutations throughout the disease course; four patients had NH(2)-terminal mutations resulting in a frameshift and truncation of the protein, three of them had two different mutations either on the same alleles or on different alleles, two had missense mutations, and one had a deletion in the basic region leucine zipper domain. Except for one with coexistence of N-ras mutation, no sample harbored cooperating mutations with FLT3 or N-ras genes. CEBPalpha mutations had no influence on the time to AML progression or overall survival. Our results show that CEBPalpha mutations play a role in a subset of patients with MDS, especially in chronic myelomonocytic leukemia. The mutation status was heterogeneous, exhibiting identical clone, clonal change, or clonal evolution during the progression to AML.


The Cedar Project: mortality among young Indigenous people who use drugs in British Columbia.
Young Indigenous people, particularly those involved in the child welfare system, those entrenched in substance use and those living with HIV or hepatitis C, are dying prematurely. We report mortality rates among young Indigenous people who use drugs in British Columbia and explore predictors of mortality over time. We analyzed data collected every 6 months between 2003 and 2014 by the Cedar Project, a prospective cohort study involving young Indigenous people who use illicit drugs in Vancouver and Prince George, BC. We calculated age-standardized mortality ratios using Indigenous and Canadian reference populations. We identified predictors of mortality using time-dependent Cox proportional hazard regression. Among 610 participants, 40 died between 2003 and 2014, yielding a mortality rate of 670 per 100 000 person-years. Young Indigenous people who used drugs were 12.9 (95% confidence interval [CI] 9.2-17.5) times more likely to die than all Canadians the same age and were 7.8 (95% CI 5.6-10.6) times more likely to die than Indigenous people with Status in BC. Young women and those using drugs by injection were most affected. The leading causes of death were overdose (n = 15 [38%]), illness (n = 11 [28%]) and suicide (n = 5 [12%]). Predictors of mortality included having hepatitis C at baseline (adjusted hazard ratio [HR] 2.76, 95% CI 1.47-5.16), previous attempted suicide (adjusted HR 1.88, 95% CI 1.01-3.50) and recent overdose (adjusted HR 2.85, 95% CI 1.00-8.09). Young Indigenous people using drugs in BC are dying at an alarming rate, particularly young women and those using injection drugs. These deaths likely reflect complex intersections of historical and present-day injustices, substance use and barriers to care.


Genetic basis for a rare floral mutant in an Andean species of Solanaceae.
White forms of typically pigmented flowers are one of the most common polymorphisms in flowering plants. Although the range of genetic changes that give rise to white phenotypes is well known from model systems, few studies have identified causative mutations in natural populations. Here we combine genetic studies, in vitro enzyme assays, and biochemical analyses to identify the mechanism underlying the loss of anthocyanin pigment production in the naturally occurring white-flowered morph of Iochroma calycinum (Solanaceae). Comparison of anthocyanin gene sequences revealed a putative loss-of-function mutation, an 11 amino-acid deletion in dihydroflavonol 4-reductase (DFR), in the white morph. Functional assays of Dfr alleles from blue and white morphs demonstrated that this deletion results in a loss of enzymatic activity, indicating that the deletion could be solely responsible for the lack of pigment production. Consistent with this hypothesis, quantitative PCR showed no significant differences in expression of anthocyanin genes between the morphs. Also, thin layer chromatography confirmed that the white morph continues to accumulate compounds upstream of the DFR enzyme. Collectively, these experiments indicate that the structural mutation at Dfr underlies the rare white flower morph of I. calycinum. This study is one of only a few examples where a flower color polymorphism is due to a loss-of-function mutation in the coding region of an anthocyanin enzyme. The rarity of such mutations in nature suggests that negative consequences prevent fixation across populations.


From resistance to attraction: a different approach to change.
How can physician executives interested in promoting change be more effective at the task? This article explores how to create an attraction towards change, as opposed to viewing change as overcoming resistance. Learning to recognize naturally occurring change, identify attractors, explore the rationality of others' points of view, and reduce risk are clear and constructive insights from research and emerging systems science. Other ideas to consider are: Understand the issues of those you wish to change, create changes that are "exothermic," produce system changes, accept responsibility, learn from failed efforts, and focus on building relationships of trust.


Paragonimiasis in Japan: a twelve-year retrospective case review (2001-2012).
Paragonimiasis, or lung fluke infection, is a food-borne parasitic disease caused by infection with trematodes belonging to the genus Paragonimus. Although paragonimiasis was once considered successfully controlled in the 1970s, new cases began to emerge in the late 1980s. To apprehend the current-day situation of the re-emergent cases of paragonimiasis in Japan, we conducted a retrospective review of 443 patients who were referred to our laboratory and diagnosed as having paragonimiasis during 2001-2012. Patients were diagnosed as having paragonimiasis based primarily on immunodiagnostic methods in addition to clinical, laboratory, and radiographic findings. Patient data were extracted from consultation sheets from attending physicians and were analyzed. Majority of the patients were residents of Kyushu Island. However, a substantial number of cases were also from other parts of Japan. Immigrants (mostly from China, Thailand, and Korea) accounted for a quarter of the cases. Native Japanese contracted paragonimiasis by consuming wild boar meat or freshwater crabs, whereas immigrants contracted the infection almost exclusively by consumption of freshwater crabs. Eosinophilia and elevated serum IgE levels were found in around 80% of the patients. Parasite egg detection was documented only in 11.7% of the cases, showing the reliance on serological tests for diagnosing paragonimiasis in current clinical practice. Paragonimiasis remains a public health issue in Japan, and the situation should be closely monitored.


Health disparities experienced by Hispanics--United States.
In the 2000 census, 35.3 million persons in the United States and 3.8 million persons in the Commonwealth of Puerto Rico identified themselves as Hispanic (i.e., Hispanic, Spanish, or Latino; of all races). Hispanics constituted 12.5% of the U.S. population in the 50 states; by subpopulation, they identified as Mexican (7.3%), Puerto Rican (1.2%), Cuban (0.4%), and other Hispanic (3.6%). For certain health conditions, Hispanics bear a disproportionate burden of disease, injury, death, and disability when compared with non-Hispanic whites, the largest racial/ethnic population in the United States. The leading causes of death among Hispanics vary from those for non-Hispanic whites. This week's MMWR is the second in a series focusing on racial/ethnic health disparities; eliminating these disparities will require culturally appropriate public health initiatives, community support, and equitable access to quality health care.


[Neurogenic pulmonary edema. Pathogenesis, clinical picture and therapy].
Neurogenic pulmonary edema (NPE) is a rare but always life-threatening complication in patients with central nervous system lesions. NPE is evident if patients shortly after cerebral lesions suddenly develop pulmonary edema and other causes of the symptoms, such as aspiration of gastric content, congestive heart failure and direct toxic exposure, are ruled out. The current body of literature, partially obtained by computer-guided search (Winspirs) regarding epidemiology, pathophysiology and therapy of NPE was reviewed. Additionally, the case of a patient who developed a sudden pulmonary edema after an episode of tonic-clonic seizures is analyzed. We first provide information about history, definition, incidence and mortality of NPE. Second, a case report of a postictal NPE is presented to illustrate the clinical picture of NPE, and the applied therapeutic strategies are discussed. Third, recent pathophysiologic concepts about symptoms and possible therapeutic principles are reviewed. Fourth, a rational therapeutic plan for the prehospital emergency therapy of NPE is outlined. The different etiologies all have one characteristic feature: an acute emergency which causes increased intracerebral pressure (ICP). NPE is known in patients after cerebral trauma, intracranial hemorrhage, stroke, intracranial tumor or seizures. The incidence is estimated at around 1% after cerebral trauma, at 71% after cerebral hemorrhage and at 2% after seizures. Mortality is appraised to lie between 60 and 100%, independent of etiology. There is a definite pathophysiologic sequence leading to NPE: a central nervous system lesion causes a sudden increase in ICP which triggers an upregulation of sympathetic signal transduction to assure brain perfusion. Increased tonus of venous and arterial vessels and of myocardial function are the immediate consequences. However, if systemic vascular resistance (SVR) increases excessively, left ventricular failure and finally pulmonary edema (NPE) may result. Additionally, the protein-rich edema fluid points to an increased endothelial permeability within the pulmonary circuit. This is thought to be caused by the acute pressure increase and by neurohumoral mechanisms, possibly similar to those described for the systemic inflammatory response syndrome (SIRS). The most important central nervous system structures involved in NPE are the medulla oblongata and the hypothalamus. NPE is always a life-threatening symptom after increased ICP, where immediate therapeutic interventions are imperative. A rational therapeutic approach needs to be focused on decreasing ICP as primary goal. Additionally, attempts should be made to optimize body oxygenation, decrease pre- and afterload and increase myocardial contractility. Postictal patients suspicious for incipient ventilation problems must be admitted to hospital for further evaluation.


Comparing the Efficiencies of Third Molar Surgeries With and Without a Dentist Anesthesiologist.
Two different anesthesia models were compared in terms of surgical duration, safer outcomes, and economic implications. Third molar surgeries performed with and without a separate dentist anesthesiologist were evaluated by a retrospective data analysis of the surgical operative times. For more difficult surgeries, substantially shorter operative times were observed with the dentist anesthesiologist model, leading to a more favorable surgical outcome. An example calculation is presented to demonstrate economic advantages of scheduling the participation of a dentist anesthesiologist for more difficult surgeries.


Assessing Residents' Veteran-Centered Care Skills in the Clinical Setting.
Despite their placement in Veterans Health Administration centers nationwide, residents' training and assessment in veteran-centered care is variable and often insufficient. We assessed residents' ability to recognize and address mental health issues that affect US military veterans. Two unannounced standardized patient (SP) cases were used to assess internal medicine residents' veteran-centered care skills from September 2014 to March 2016. Residents were assessed on 7 domains: military history taking, communication skills, assessment skills, mental health screening, triage, and professionalism, using a 36-item checklist. After each encounter, residents completed a questionnaire to assess their ability to recognize knowledge deficits. Residents' mean scores were compared across training levels, between the 2 cases, and by SP gender. We conducted analysis of variance (ANOVA) tests to analyze mean performance differences across training levels and descriptive statistics to analyze self-assessment questionnaire results. Ninety-eight residents from 2 internal medicine programs completed the encounter and 53 completed the self-assessment questionnaire. Residents performed best on professionalism (0.92 ± 0.20, percentage of the maximal score) and triage (0.87 ± 0.17), and they scored lowest on posttraumatic stress disorder (0.52 ± 0.30) and military sexual trauma (0.33 ± 0.39). Few residents reported that they sought out training to enhance their knowledge and skills in the provision of services and support to military and veteran groups beyond their core curriculum. This study suggests that additional education and assessment in veteran-centered care may be needed, particularly in the areas of posttraumatic stress disorder and military sexual trauma.


Enhanced repair effect of toll-like receptor 4 activation on neurotmesis: assessment using MR neurography.
Alternative use of molecular approaches is promising for improving nerve regeneration in surgical repair of neurotmesis. The purpose of this study was to determine the role of MR imaging in assessment of the enhanced nerve regeneration with toll-like receptor 4 signaling activation in surgical repair of neurotmesis. Forty-eight healthy rats in which the sciatic nerve was surgically transected followed by immediate surgical coaptation received intraperitoneal injection of toll-like receptor 4 agonist lipopolysaccharide (n = 24, study group) or phosphate buffered saline (n = 24, control group) until postoperative day 7. Sequential T2 measurements and gadofluorine M-enhanced MR imaging and sciatic functional index were obtained over an 8-week follow-up period, with histologic assessments performed at regular intervals. T2 relaxation times and gadofluorine enhancement of the distal nerve stumps were measured and compared between nerves treated with lipopolysaccharide and those treated with phosphate buffered saline. Nerves treated with lipopolysaccharide injection achieved better functional recovery and showed more prominent gadofluorine enhancement and prolonged T2 values during the degenerative phase compared with nerves treated with phosphate buffered saline. T2 values in nerves treated with lipopolysaccharide showed a more rapid return to baseline level than did gadofluorine enhancement. Histology exhibited more macrophage recruitment, faster myelin debris clearance, and more pronounced nerve regeneration in nerves treated with toll-like receptor 4 activation. The enhanced nerve repair with toll-like receptor 4 activation in surgical repair of neurotmesis can be monitored by using gadofluorine M-enhanced MR imaging and T2 relaxation time measurements. T2 relaxation time seems more sensitive than gadofluorine M-enhanced MR imaging for detecting such improved nerve regeneration.


An autosomal genomic screen for dementia in an extended Amish family.
Apolipoprotein E (APOE) is the only universally confirmed susceptibility gene for late-onset Alzheimer disease (LOAD), although many loci are believed to modulate LOAD risk. The genetic homogeneity of isolated populations, such as the Amish, potentially provide increased power to identify LOAD susceptibility genes. Population homogeneity in these special populations may reduce the total number of susceptibility genes contributing to the complex disorder, thereby increasing the ability to identify any one susceptibility gene. Dementia in the Amish is clinically indistinguishable from LOAD in the general population. Previous studies in the Amish demonstrated a significantly decreased frequency of the APOE-4 susceptibility allele, but significant familial clustering of dementia [M.A. Pericak-Vance, C.C. Johnson, J.B. Rimmler, A.M. Saunders, L.C. Robinson, E.G. D'Hondt, C.E. Jackson, J.L. Haines, Alzheimer's disease and apolipoprotein E-4 allele in an Amish population, Ann. Neurol. 39 (1996) 700-704]. These data suggested that a genetic etiology independent of APOE may underlie the dementia observed in this population. In the present analysis, we focused on a large, multiplex, inbred Amish family (24 sampled individuals; 10 of whom are affected). We completed a genomic screen to identify novel LOAD loci (n=316 genetic markers), using both model-dependent "affecteds-only" analysis (dominant and recessive) and model-independent affected relative pair analysis. Interesting results (lod>1.5 or p<0.01) were obtained for markers on eight chromosomes (2q, 5q, 6q, 7p, 8p, 8q, 11p, 18p, 18q, and 19q). The highest overall score was a multipoint lod score of 3.1 on chromosome 11p. Most regions we identified were not previously detected by genomic screens of outbred populations and may represent population-specific susceptibilities to LOAD. These loci are currently under further investigation in a study of LOAD including additional Amish families.


Toward Omics-Scale Quantitative Mass Spectrometry Imaging of Lipids in Brain Tissue Using a Multiclass Internal Standard Mixture.
Mass spectrometry imaging (MSI) has accelerated our understanding of lipid metabolism and spatial distribution in tissues and cells. However, few MSI studies have approached lipid imaging quantitatively and those that have focused on a single lipid class. We overcome this limitation by using a multiclass internal standard (IS) mixture sprayed homogeneously over the tissue surface with concentrations that reflect those of endogenous lipids. This enabled quantitative MSI (Q-MSI) of 13 lipid classes and subclasses representing almost 200 sum-composition lipid species using both MALDI (negative ion mode) and MALDI-2 (positive ion mode) and pixel-wise normalization of each lipid species in a manner analogous to that widely used in shotgun lipidomics. The Q-MSI approach covered 3 orders of magnitude in dynamic range (lipid concentrations reported in pmol/mm2) and revealed subtle changes in distribution compared to data without normalization. The robustness of the method was evaluated by repeating experiments in two laboratories using both timsTOF and Orbitrap mass spectrometers with an ∼4-fold difference in mass resolution power. There was a strong overall correlation in the Q-MSI results obtained by using the two approaches. Outliers were mostly rationalized by isobaric interferences or the higher sensitivity of one instrument for a particular lipid species. These data provide insight into how the mass resolving power can affect Q-MSI data. This approach opens up the possibility of performing large-scale Q-MSI studies across numerous lipid classes and subclasses and revealing how absolute lipid concentrations vary throughout and between biological tissues.


Quantitative Trait Loci Mapping Identified Candidate Genes Involved in Plant Height Regulation in Rice.
Rice plant height is an agricultural trait closely related to biomass, lodging tolerance, and yield. Identifying quantitative trait loci (QTL) regions related to plant height regulation and developing strategies to screen potential candidate genes can improve agricultural traits in rice. In this study, a double haploid population (CNDH), derived by crossing 'Cheongcheong' and 'Nagdong' individuals, was used, and a genetic map was constructed with 222 single-sequence repeat markers. In the RM3482-RM212 region on chromosome 1, qPh1, qPh1-1, qPh1-3, qPh1-5, and qPh1-6 were identified for five consecutive years. The phenotypic variance explained ranged from 9.3% to 13.1%, and the LOD score ranged between 3.6 and 17.6. OsPHq1, a candidate gene related to plant height regulation, was screened in RM3482-RM212. OsPHq1 is an ortholog of gibberellin 20 oxidase 2, and its haplotype was distinguished by nine SNPs. Plants were divided into two groups based on their height, and tall and short plants were distinguished and clustered according to the expression level of OsPHq1. QTLs and candidate genes related to plant height regulation, and thus, biomass regulation, were screened and identified in this study, but the molecular mechanism of the regulation remains poorly known. The information obtained in this study will help develop molecular markers for marker-assisted selection and breeding through rice plant height control.


[Chromosome structure, histones and gene activity in Drosophila].
The problem to be reviewed in this study concerns the mechanism of regulation of gene activity relied on the structural changes of the chromatin. The role of histones in the regulation of transcription is discussed on the basis of the results obtained by the authors and literature data. In particular, the results are presented of the investigations of decrease of the histone amount in the cell nucleus using the deficiency of histone structural genes. This leads both to the increase of the X-chromosome template activity and the inhibition of variegated position effect. The latter is also inhibited by feeding of larvae with T2-DNA. It is supposed that the chromatin structure is a mechanism of epigenetic changes and the gene inactivation due to the position effect inherited in cell lineages in an example of such epigenetic changes.


Subcutaneous Lumbar Spine Index (SLSI) as a Risk Factor for Surgical Site Infection After Lumbar Fusion Surgery: A Retrospective Matched Case-Control Study.
A retrospective matched case-control study. This study aims to investigate the value of Subcutaneous Lumbar Spine Index (SLSI) as a predictor of early surgical site infection (SSI) after lumbar intervertebral fusion surgery. A retrospective case-control study was performed on patients who underwent transforaminal lumbar interbody fusion (TLIF) from January 1, 2014 to December 31, 2019 in a single institution. Cases were defined as those who developed early SSI according to the US Center for Disease Control and Prevention criteria, and controls were matched from those patients without early SSI using the following matched criteria: gender, age, time of surgery and diabetes. Subcutaneous fat thickness (SFT) and SLSI were measured on preoperative MRI mid-sagittal T2 weighted images. A total of 3615 patients who underwent TLIF were enrolled in this study. Thirty-three patients were included in early SSI, and sixty-six patients were selected as matched controls. Univariate analysis indicated that fusion levels (P = .007), operation time (P = .022), obesity (P = .013), SFT (P = .002) and SLSI (P = .001) were significantly associated with early SSI. Multiple logistic regression analysis revealed that multilevel fusion levels (P = .021), obesity (P = .035), a large SFT (P = .026) and a high SLSI (P = .012) were independent risk factors. Body mass index (BMI) and SLSI were moderately correlated (r2 = .55). ROC curve demonstrated that SLSI was more sensitive than SFT to predict the early SSI. SLSI is a novel radiological risk factor for early SSI development and is a better indicator than SFT to predict early SSI risk after lumbar intervertebral fusion.


Childhood chronic inflammatory demyelinating neuropathies: clinical course and long-term follow-up.
Chronic inflammatory demyelinating neuropathy (CIDP) is a rare disease in childhood. We reviewed the clinical characteristics, response to therapy, and long-term prognosis in 13 children (1.5 to 16 years of age) diagnosed with CIDP at Washington University Medical Center, St. Louis, and the Royal Children's Hospital, Melbourne, Australia, between 1979 and 1994. The most common presenting symptom (in 11/13 [85%]) was lower extremity weakness associated with difficulty in walking. Preceding events within 1 months of onset, mostly intercurrent infections or vaccinations, occurred in seven children (54%). The disease was monophasic in three children (23%). One relapse occurred in four (30%) and multiple relapses in six (46%). All patients had at least short-term response to steroids. Three children (23%) recovered completely during the first year. Ten children (77%) had residual weakness after an average follow-up of 6 years. There seems to be two populations of children with CIDP. One subgroup, with a favorable prognosis, progressed to peak disability over less than 3 months; these children often have a monophasic course with complete resolution of symptoms and signs and withdrawal from all medications by 1 year after onset. A second subgroup progressed for 3 months or longer; these children all required substantial does of prednisone for prolonged periods and had considerable long-term morbidity with persistent weakness.


Identification and characterization of the two-enzyme system catalyzing oxidation of EDTA in the EDTA-degrading bacterial strain DSM 9103.
In a gram-negative isolate (DSM 9103) able to grow with EDTA as the sole source of carbon, nitrogen, and energy, the first two steps of the catabolic pathway for EDTA were elucidated. They consisted of the sequential oxidative removal of two acetyl groups, resulting in the formation of glyoxylate. An enzyme complex that catalyzes the removal of two acetyl groups was purified and characterized. In the reaction, ethylenediaminetriacetate (ED3A) was formed as an intermediate and N,N'-ethylenediaminediacetate was the end product. The enzyme complex consisted of two components: component A' (cA'), most likely a monooxygenase, which catalyzes the cleavage of EDTA and ED3A while consuming oxygen and reduced flavin mononucleotide (FMN)-H2, and component B' (cB'), an NADH2:FMN oxidoreductase that provides FMNH2 for cA'. cB' could be replaced by other NADH2:FMN oxidoreductases such as component B of the nitrilotriacetate monooxygenase or the NADH2:FMN oxidoreductase from Photobacterium fischeri. The EDTA-oxidizing enzyme complex accepted EDTA as a substrate only when it was complexed with Mg2+, Zn2+, Mn2+, Co2+, or Cu2+. Moreover, the enzyme complex catalyzed the removal of acetyl groups from several other aminopolycarboxylic acids that possess three or more acetyl groups.


[Effect of lisinopril on cardiac parameters and mortality after myocardial infarction in rats].
To analyse the effect of early (< 24h) administration of lisinopril on ventricular remodeling and mortality after myocardial infarction (MI) in rats. Wistar rats weighing 200-250 g were submitted to ligation of the left coronary artery (LCA) and divided into three groups: SHAM (S, n = 9); infarcted and lisinopril (20mg/kg/day) treated rats (L, n = 38); infarcted and non-treated animals (NT, n = 24). Three months later, the cardiac function was studied in isolated heart preparation according to the Langendorff technique. Starling curves were constructed using fluid injection in the left ventricular balloon, which permitted to alter the diastolic pressure range from 0 to 30mmHg by means of pressure increments of 5mmHg. Body weight (BW), right ventricular weight (RVW), and RVW/BW were also determined. Three months after the surgery, the comparative mortality rate among groups was: S = 0; L = 34.4% and NT = 54.4% (p > 0.05, for L vs NT). In infarctions < 40% of the left ventricle (LV), the RVW/BW relation was S = L < NT (p < 0.05); the left ventricular systolic pressure was S > L > NT (p < 0.05). In infarctions > 40% of LV, the RVW/BW relation was S < L = NT (p < 0.05). For the Starling curves, the results were S > L > NT (p < 0.05). In our model lisinopril did not interfere with post-infarction mortality of rats, although decreasing the mortality risk in 49%, in the treated group. The drug also altered the remodeling process, preventing hypertrophy and systolic disfunction after MI, mainly in infarctions < 40% of LV.


A Systematic Literature Review of Factors Affecting the Timing of Menarche: The Potential for Climate Change to Impact Women's Health.
Menarche is the first occurrence of a woman's menstruation, an event that symbolizes reproductive capacity and the transition from childhood into womanhood. The global average age for menarche is 12 years and this has been declining in recent years. Many factors that affect the timing menarche in girls could be affected by climate change. A systematic literature review was performed regarding the timing of menarche and four publication databases were interrogated: EMBASE, SCOPUS, PubMed, and Cochrane Reviews. Themes were identified from 112 articles and related to environmental causes of perturbations in menarche (either early or late), disease causes and consequences of perturbations, and social causes and consequences. Research from climatology was incorporated to describe how climate change events, including increased hurricanes, avalanches/mudslides/landslides, and extreme weather events could alter the age of menarche by disrupting food availability or via increased toxin/pollutant release. Overall, our review revealed that these perturbations in the timing of menarche are likely to increase the disease burden for women in four key areas: mental health, fertility-related conditions, cardiovascular disease, and bone health. In summary, the climate does have the potential to impact women's health through perturbation in the timing of menarche and this, in turn, will affect women's risk of disease in future.


Modified citrus pectin (MCP) increases the prostate-specific antigen doubling time in men with prostate cancer: a phase II pilot study.
This trial investigated the tolerability and effect of modified citrus pectin (Pecta-Sol) in 13 men with prostate cancer and biochemical prostate-specific antigen (PSA) failure after localized treatment, that is, radical prostatectomy, radiation, or cryosurgery. A total of 13 men were evaluated for tolerability and 10 for efficacy. Changes in the prostate-specific antigen doubling time (PSADT) of the 10 men were the primary end point in the study. We found that the PSADT increased (P-value<0.05) in seven (70%) of 10 men after taking MCP for 12 months compared to before taking MCP. This study suggests that MCP may lengthen the PSADT in men with recurrent prostate cancer.


Energetic recovery in porcine grafts by minimally invasive liver oxygenation.
Gaseous insufflation of oxygen via the venous vascular system has proven to be an effective tool for preventing anoxic tissue injury after extended time periods of ischemic liver preservation. Most experimental studies so far have been undertaken in rat models and include a series of pinpricks into postsinusoidal venules as an outlet for the insufflated gas. Here, we describe a simplified technique for minimally invasive liver oxygenation in porcine grafts, representing a hassle-free access to organ oxygenation without vascular lesions. We retrieved livers from Landrace pigs and cold-stored them in histidine-tryptophan-ketoglutarate solution. Subsequent to 18 h preservation, we treated some livers for an additional 2 h with gaseous oxygen, insufflated via silicone tubing inserted into the suprahepatic caval vein. Gas pressure was limited to 18 mm Hg. We occluded the infrahepatic caval vein with a bulldog clamp. Gas bubbles left the graft via the portal vein. We assessed liver integrity by energetic tissue status and by controlled in vitro reperfusion with autologous blood. Magnetic resonance imaging demonstrated homogeneous gas distribution in the persufflated tissue without major shunting. Biochemical analyses revealed effective and homogeneous restoration of energetic homeostasis in the ischemic graft before reperfusion. Sinusoidal endothelial clearance of hyaluronic acid was significantly improved upon reperfusion, as was hepatic arterial flow. Parenchymal enzyme loss was concordantly mitigated after minimally invasive liver oxygenation. Our results indicate that gaseous oxygen persufflation of the porcine liver is possible without tissue trauma, and significantly enhances post-preservation recovery of the graft.


Quantitative and qualitative evaluations of brief interventions to change excessive drinking, smoking and stress in the police force.
To evaluate the effects of a brief intervention to reduce excessive drinking, smoking and stress among police. (1) Controlled intervention trial with pre and post-intervention assessment approximately 8 months apart; (2) focus group identification of relevant factors). Assessment was carried out of 954 NSW (Australia) police at 19 stations within two matched districts in the Sydney metropolitan area. Five focus groups were carried out with 43 randomly selected police from the matched districts. Weekly alcohol consumption and binge drinking, smoking and symptoms of stress were measured by a self-administered Health and Fitness Questionnaire. Recorded responses to set questions provided qualitative data. Participation was high (89%) at both quantitative assessments. Alcohol consumptions, particularly among men, was high at both baseline and follow-up assessments, although comparisons between groups across occasions showed no significant intervention effects. Excessive drinkers and those reporting moderate to severe stress levels reported more sick leave days (p < 0.05, p < 0.05). A significant increase in awareness of alcohol policies in the work-place showed in both experimental and control groups over time (p < 0.01). The percentage of smokers declined significantly in both intervention and control groups. Overall, women had significantly more symptoms of stress than men. Only 20% of police thought they would seek advice from work-place staff about alcohol consumption, 14% for smoking and 61% for stress. In the qualitative study, employees generally distrusted their organization's involvement in health unless work performance was affected. Seeking professional assistance for life-style issues was viewed as a sign of weakness. Alcohol use was seen as a way of obtaining information or group membership, self-medication and socializing. The brief interventions did not produce significant improvements in three life-style factors beyond positive trends in alcohol consumption among women and general reductions in smoking among both study groups. Combining quantitative and qualitative approaches helped identify interactive individual and organizational factors which influence behavioural and cultural norms.


Observation of a Burstein-Moss shift in rhenium-doped MoS2 nanoparticles.
We investigated the optical properties of rhenium-doped MoS2 nanoparticles and compared our findings with the pristine and bulk analogues. Our measurements reveal that confinement softens the exciton positions and reduces spin-orbit coupling, whereas doping has the opposite effect. We model the carrier-induced exciton blue shift in terms of the Burstein-Moss effect. These findings are important for understanding doping and finite length scale effects in low-dimensional nanoscale materials.