Characteristics of Obstetric and Iatrogenic Urogenital Fistulas in Burkina Faso: A Cross-Sectional Study.
To compare the sociodemographic, clinical, and therapeutic characteristics of obstetric urogenital fistulas (OF) and iatrogenic urogenital fistulas (IF) treated in seven centers in Burkina Faso. Material and Methods. We carried out a cross-sectional study over a seven years' period (January 1, 2010 to December 31, 2016). We considered as iatrogenic all urogenital fistulas (UGF) occurred after elective caesarean section, gynecologic surgery (hysterectomy, myomectomy, and prolapse repair), or induced abortion. UGF following vaginal delivery after prolonged labor without obstetric maneuvers or caesarean section were considered as obstetric. UGF caused by other mechanisms (emergency caesarian section, congenital, and traumatic) were excluded from this study. The statistical analysis was carried out using version 14 of the STATA software. A logistic regression model was used to compare the two groups. 310 cases of UGF were included. IF accounted for 25.8% (n = 80) versus 74.2% (n = 230) for OF. The median age was 35 years for IF and 35.38 years for OF. The vesicovaginal fistulas were predominant (74.5%) in the two groups. All circumferential fistulas were found in the OF group. OF were frequently associated with residence in rural areas (OR = 1.8; CI = [1.05-3.1]), low level of education (OR = 5.4; CI = [2.3-12.9]), and a height under 158 cm (OR = 3.4 CI = [1.7-6.6]). Vaginal sclerosis was less common among IF (OR = 2.2; CI = [1-4.6]). The failure of surgical treatment after 3 months was more associated with OF (OR = 4.7; CI = [1.1-20.5]). OF were the most common, frequently affecting short women living in rural area and with low level of schooling. Fistulas were also more severe in the OF group. IF gave better results after surgical repair.


[Therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma: a Meta analysis].
To evaluate the therapeutic effect and safety of montelukast sodium combined with budesonide in children with cough variant asthma. The databases CNKI, Wanfang Data, VIP, PubMed, EMbase, and BioMed Central were searched for randomized controlled trials (RCTs) of montelukast sodium combined with budesonide in the treatment of children with cough variant asthma. Data extraction and quality assessment were performed for RCTs which met the inclusion criteria, and RevMan 5.3 software was used to perform quality assessment of the articles included and Meta analysis. A total of 11 RCTs involving 1 097 patients were included. The results of the Meta analysis showed that compared with the control group (inhalation of budesonide alone), the observation group (inhalation of montelukast sodium combined with budesonide) had significantly higher overall response rate and more improved pulmonary function parameters including forced expiratory volume in the first second, percentage of forced expiratory volume in the first second, and peak expiratory flow, as well as significantly lower recurrence rate (P<0.01). The incidence of adverse events showed no significant difference between the two groups. Inhalation of montelukast sodium combined with budesonide has a significant effect in children with cough variant asthma and does not increase the incidence of adverse events.


Isolation and molecular characterization of Banna virus from mosquitoes, Vietnam.
We isolated and characterized a Banna virus from mosquitoes in Vietnam; 5 strains were isolated from field-caught mosquitoes at various locations; Banna virus was previously isolated from encephalitis patients in Yunnan, China, in 1987. Together, these findings suggest widespread distribution of this virus throughout Southeast Asia.


Cost-effectiveness of mass dog rabies vaccination strategies to reduce human health burden in Flores Island, Indonesia.
The cost-effectiveness of different mass dog rabies vaccination strategies, defined as the costs per year of life lost (YLL) averted was evaluated for a period of 10 years by means of a dynamic simulation study for a typical village on Flores Island. In the base strategy (no dog vaccination and no post-exposure treatment (PET) of human bite cases), the model showed that the introduction of the virus by one infectious dog into an isolated village with 1500 inhabitants and 400 dogs resulted in 881 YLLs during a 10-year simulation period, which is equivalent to 30 human rabies cases. An annual dog vaccination campaign with a coverage of 70% using a short-acting vaccine saved 832 YLLs, while the cumulative costs for the public sector were US$3646 or US$4.38 per YLL averted. Switching to a long-acting vaccine, the annual vaccination strategies with a coverage of 50% (AV_156_50) or 70% (AV_156_70) reduced the baseline YLLs from 881 to respectively 78 and 26 YLLs with cumulative costs of US$3716 and US$2264 or US$4.63 and US$2.65 per YLL averted, respectively. In general, dog vaccination was more cost-effective than PET alone (US$2.65-4.63 per YLL averted versus US$23.29 per YLL averted). Although a combination of PET with AV_156_70 was less cost-effective compared to AV_156_70 alone, this strategy was able to prevent all human deaths due to rabies. A combination of PET with annual vaccination using a short-acting vaccine at a coverage of 50% was far from being cost-effective, suggesting that the currently applied rabies control in Flores Island is not an efficient investment in reducing human rabies burden. An increased investment in either an increase in the current coverage or in a switch from the short-acting vaccine to the long-acting vaccine type would certainly pay off.


Characterization of polymorphs of tranilast anhydrate and tranilast monohydrate when crystallized by two solvent change spherical crystallization techniques.
Spherically agglomerated crystals of tranilast (oral antiallergic agent) with improved availability in vitro, as well as improved micromeritic properties such as flowability and packability, were prepared by a novel spherical crystallization technique. The agglomerates of tranilast were found to be composed of new monohydrate I, II, or III, depending on the crystallization solvent and the procedure employed. With dehydration by heating, monohydrate I transformed to the stable alpha form directly. On the other hand, monohydrates II and III converted to the amorphous and beta forms, respectively, followed by further transformation to the alpha form at 110 and 150 degrees C, respectively. The amorphous and beta forms of agglomerates were easily prepared by storing the monohydrates under 0% RH at 30-40 degrees C. Monohydrate II and the amorphous form of the agglomerate with high surface energy could enhance the solubility and the dissolution rate of tranilast. A phase diagram of polymorphs of agglomerated tranilast was constructed to exhibit their interconversions under various humidities and temperatures.


Calcium-ATPase and insulin in adolescent offspring of essential hypertensive parents.
A number of abnormalities in calcium homeostasis have been reported in patients with essential hypertension. IN turn, insulin has been shown to influence the activity of the Ca(2+)-ATPase. We have previously shown that normotensive offspring of essential hypertensive individuals have an exaggerated insulin response to a glucose overload. Therefore, the aim of the present study was to evaluate basal and calmodulin-activated Ca(2+)-ATPase in red blood cells and its relationship to the insulin response during an intravenous glucose tolerance test in 27 normotensive adolescents with a family history of essential hypertension (F+) (mean age, 13.9 +/- 0.5 years) and in 10 control subjects matched for age and body mass index with no family history of hypertension (F-). The results (mean +/- SD) were as follows (mumol Pi/[mg protein/h]10(-1)): basal Ca(2+)-ATPase, 4.5 +/- 1.2 in F+ and 5.1 +/- 1.6 in F- (P = NS); calmodulin-activated Ca(2+)-ATPase, 13.6 +/- 3.9 in F+ and 16.2 +/- 1.7 in F- (P < .04). The insulin area under the curve after the glucose load was 3413 +/- 1674 microU/mL per hour in F+ and 2752 +/- 928 in F- (P = NS). Calmodulin-activated Ca(2+)-ATPase showed a negative correlation with the insulin area under the curve (r = -.59, P < .005) and cholesterol levels (r = -.38, P < .03). Urinary calcium excretion was 1.82 +/- 0.9 mmol/d in F+ and 2.47 +/- 0.9 mmol/d in F- (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


A step towards day case prostatectomy.
To compare laser prostatectomy, using both side-fire and contact lasers, with transurethral resection of the prostate (TURP) to identify the advantages and disadvantages of all three in the short-and long-term (1 year). Forty patients were randomized into one of four groups undergoing TURP, side-fire laser prostatectomy alone, side-fire with debridement and contact laser prostatectomy. Strict entry criteria ensured that no patients with malignancy were selected. The patients were reviewed after 3, 6 and 12 months. The duration of operation and length of hospital stay were significantly shorter in those undergoing laser side-fire treatment than those undergoing TURP. However, the early (3-month) symptom score was significantly worse in those treated by side-fire laser than in those treated by side-fire laser with debridement. After 1 year there was no significant difference in mean symptom score and mean urinary flow rate among the four groups. Laser prostatectomy offers the prospect of a shorter theatre and hospital stay and, by debriding the thermocoagulated tissue, the early irritative symptoms were reduced, with a significant improvement in symptom score after 3 months in patients with small prostates.


Bim Deletion Reduces Functional Deficits Following Ischemic Stroke in Association with Modulation of Apoptosis and Inflammation.
Cellular apoptosis is a key pathological mechanism contributing to neuronal death following ischemic stroke. The pro-apoptotic Bcl-2 family protein, Bim, is an important regulator of apoptosis. In this study we investigated the effect of Bim expression on post-stroke functional outcomes, brain injury and inflammatory mechanisms. Wild type (WT) and Bim-deficient mice underwent 1-h middle cerebral artery occlusion (MCAO) followed by 23 h of reperfusion. At 24-h post-stroke, we assessed functional deficit, infarct volume, immune cell death, as well as the number of infiltrating immune cells in the brain and circulating immune cells. Bim deficiency did not affect infarct volume (P > 0.05), but resulted in less motor impairment (~ threefold greater latency to fall in hanging grip strength test, P < 0.05) and a lower median clinical score than WT mice (P < 0.05). Additionally following MCAO, Bim-deficient mice exhibited fewer myeloid cells (particularly neutrophils) in the ischemic brain hemisphere and less apoptosis of CD3+ T cells in the spleen and thymus compared with WT (all P < 0.05). After MCAO, Bim-deficient mice also tended to have more M2-polarised macrophages in the brain than WT mice. In sham-operated mice, we found that Bim deficiency resulted in greater numbers of circulating total CD45+ leukocytes, Ly6Clo+ monocytes and CD3+ T cells, although MCAO did not affect the number of circulating cells at 24 h in either genotype. Our findings suggest that Bim deficiency modulates post-stroke outcomes, including reductions in motor impairment, brain inflammation and systemic post-stroke leukocyte apoptosis. Bim could therefore serve as a potential therapeutic target for stroke.


Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon.
We reviewed 21 patients with 22 ruptures of the extensor pollicis longus at a mean of 5.3 years after transfer of the extensor indicis proprius tendon. Of these, 19 with 21 transfers described the result as good, and two as fair. The mean deficit of extension between the operated and unoperated thumbs was 1.4 cm, and the mean flexion deficit 0.6 cm. Pressure gauge measurements showed that the strength of the transfer was 51% of that of the uninjured extensor. The two fair results had an extensor lag of over 1.5 cm. Independent extension of the index was maintained in all patients, none having a discernible lag, but the strength of index extension was reduced to 49% of that of the normal finger. There was no evidence of functional loss. Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon is a simple and reliable procedure with few complications. It gives satisfactory long-term extension of the thumb.


An analysis of 1986 drug procurement practices in hospitals within the United States.
The purpose of this study was to statistically answer a set of predefined objectives concerning pharmaceutical procurement. The key indicators were assumed to be cost per patient day and turnover rate. Of the 5,911 surveys mailed, 709 surveys were returned for a 12% response rate. The following statements were based on attempts to answer the six predetermined objectives. Pharmaceutical purchasing is controlled by pharmacy departments to the extent that comparisons to pharmaceutical purchasing by materials management departments was not possible. Prime vendor purchasing is the procurement method of choice. Competitive bidding through a group process is so popular that a valid comparison to nongroup bidding could not be accomplished with the results of this survey. Certain variables of group purchasing such as group age, contract adherence, and volume commitment, do not appear to be correlated to purchasing outcomes in this study. When comparing government to private hospitals, the private sector seems to have an advantage in managing turnover rates. Cost per patient day results were less conclusive. As single and multiple hospital systems were compared for purchasing outcomes, the results were not totally conclusive. Although, multiple hospital systems had a significantly higher turnover rate. Finally, a comparison based on the use, or lack of use, of prime vendor arrangements demonstrated interesting results. The duration of contract did not significantly affect the purchasing outcomes. Other hospital variables such as size, type, ownership, and organization, demonstrated notable trends. The importance of examining hospitals based on case mix and mission seems to be most important. Also, the ability to relate purchasing outcomes with formulary management strategies needs further study before conclusive statements can be adopted.


Palladium-catalyzed oxidative 6-exo-trig cyclization of 1,6-enynes: facile synthesis of bicyclo[4.1.0]heptan-5-ones.
We here describe a new palladium-catalyzed oxidative 6-exo-trig cyclization of 1,6-enynes at room temperature using tBuONO as an oxidant for the synthesis of 3-bicyclo[4.1.0]heptan-5-ones. This cascade strategy involves the hydration, cyclization and cyclopropanation sequence, and represents a new transition-metal-catalyzed oxidative cyclization of 1,6-enynes in a 6-exo-trig fashion.


The Federal Prisons' Mental Health Program 1930-1985.
This administrative history study examines the evolution of the Federal Bureau of Prisons Mental Health Program from an initial functional reliance on the medical model to expanded parameters of quasi-scientific behavioral and custodial administrative management of inmates.


Diabetes mellitus is equally frequent in chronic HCV and HBV infection.
To see the association of type 2 diabetes mellitus (Type 2 DM) in patients suffering from chronic HBV or HCV related liver disease. Patients were selected from the gastroenterology OPD of the medical research centre, diabetic controls from private diabetes clinic and healthy controls from the blood bank of the hospital. Patients with chronic liver disease had HBV, HCV tested using ELISA and blood sugar using a glucometer mostly as a 2 hour post prandial sample. Healthy controls had their sugar and ALT checked while donating blood and HBV, HCV were checked routinely. In diabetic controls, blood sample was taken as sera stored for HBV,HCV and ALT and later tested in batches. A random sugar of > or = 200 mg/dl was taken as diabetes. Of 400 patient with chronic liver disease 302 had HCV and 98 HBV infection. Diabetes was found in 24.5% HCV and 19.4% HBV related cases (not significant). Out of 410 healthy controls 18 were HCV and 17 HBV positive. Diabetes was found in only 1 (5.6%) HCV positive control and none of the HBV positive controls. Of 196 diabetics 10 (5.1%) were HCV positive and none HBV positive. Diabetes was more frequent in patients having liver cirrhosis than in those having chronic hepatitis (P < 0.01). Diabetes is equally frequent in both HBV and HCV related disease but is significantly more in those with chronic liver disease than in controls. The pancreatic damage secondary to extrahepatic viral replication appears to be the major cause but genetic factors also need to be explored.


Salt intake and plasma atrial natriuretic peptide and nitric oxide in hypertension.
In response to a high salt intake, salt-sensitive hypertensive individuals retain more sodium and manifest a rise in blood pressure greater than that in salt-resistant individuals. In this study, we tested whether salt sensitivity might be related at least in part to reduced secretion of atrial natriuretic peptide (ANP) or to abnormal nitric oxide production. We measured plasma ANP and NO2+NO3 in 7 normotensive individuals and 13 salt-sensitive and 14 salt-resistant blacks with essential hypertension under conditions of low (10 mEq/d) and high (250 mEq/d) salt intake. To evaluate possible racial differences in ANP secretion, we also measured plasma ANP in 6 salt-sensitive and 8 salt-resistant hypertensive whites during low and high salt intakes. Under low salt conditions, plasma ANP levels were not different in normotensive control subjects and salt-sensitive and salt-resistant hypertensive blacks. During high salt intake, plasma ANP levels did not change in control subjects and salt-resistant patients but decreased in salt-sensitive patients. ANP levels after high salt diet were lower (P < .01) in salt-sensitive than salt-resistant blacks. In hypertensive whites, high salt intake caused no significant change in plasma ANP. Under low salt conditions, plasma NO2+NO3 levels were higher (P < .05) in salt-sensitive (189 +/- 7.9 mumol/L) and salt-resistant (195 +/- 13.5 mumol/L) black patients than in control subjects (108 +/- 9.7 mumol/L). During high salt intake, plasma NO2+NO3 decreased significantly (P < .01) in both salt-sensitive (150 +/- 7.0 mumol/L) and salt-resistant (142 +/- 9.0 mumol/L) patients. These studies show that under conditions of high salt intake, salt-sensitive hypertensive blacks manifest a paradoxical decrease in ANP secretion. This abnormality may play a role in the reduced ability of these individuals to excrete a sodium load and in the sodium-induced rise in blood pressure. This study does not support the hypothesis that salt sensitivity depends on a deficit of nitric oxide production, but it suggests that high salt intake may alter the endothelium-dependent adaptation of peripheral resistance vessels.


Effects of substrates on biofilm formation observed by atomic force microscopy.
Formation of biofilm is known to be strongly dependent on substrates including topography, materials, and chemical treatment. In this study, a variety of substrates are tested for understanding biofilm formation. Sheets of aluminum, steel, rubber, and polypropylene have been used to examine their effects on formation of Pseudomonas aeruginosa biofilm. In particular, the morphological variation, transition, and adhesiveness of biofilm were investigated through local measurement by atomic force microscopy (AFM). Mechanism of removing biofilm from adhering to substrate is also analyzed, thus the understanding of the mechanism can be potentially useful to prevent the biofilm formation. The results reveal that formation of biofilm can remain on rough surface regardless of substrates in hot water, which may easily induce extra-polymeric substances detachment from bacterial surface. By probing using AFM, local force-distance characterization of extra-cellular materials extracted from the bacteria can exhibit the progress of the biofilm formation and functional complexities.


Clofibrate increases long-chain fatty acid oxidation by neonatal pigs.
Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonates. To increase efficiency of milk fat utilization by newborn pigs, the effect of clofibrate on in vivo and in vitro long-chain fatty acid (LCFA) oxidation was evaluated. Newborn male pigs were administered 5 mL of vehicle (2% Tween 80) with or without clofibrate (75 mg/kg body weight) once daily via i.g. gavage for 4 d. Total LCFA oxidative capacity was measured in respiration chambers after gastric infusion (n = 5 per treatment) with isoenergetic amounts of [1-(14)C]triglycerides (TGs), either oleic acid (18:1n-9) TG [3.02 mmol/kg body weight (BW)(0.75)] or erucic acid (22:1n-9) TG (2.46 mmol/kg BW(0.75)). Total expired (14)CO2 was collected and quantified at 20-min intervals over 24 h. Hepatic in vitro LCFA oxidation was determined simultaneously using [1-(14)C]oleic acid and erucic acid substrates. The in vivo 24-h accumulative [1-(14)C]TG oxidation (percentage of energy intake/kg BW(0.75)) tended to increase with clofibrate supplementation (P = 0.10), although there was no difference in the peak or mean utilization rate. The maximal extent of oleic acid TG oxidation was 1.6-fold that of erucic acid TG (P < 0.006). Hepatic in vitro LCFA oxidation increased 61% with clofibrate (P < 0.0008). The increase in mitochondria was 4-fold greater than in peroxisomes. The relative abundance of mRNA increased 2- to 3-fold for hepatic peroxisome proliferator-activated receptor α and its target genes (fatty acyl-coenzyme A oxidase and carnitine palmitoyltransferase) in the pigs that were administered clofibrate (P < 0.04). Clofibrate may improve in vivo LCFA oxidative utilization in neonatal pigs.


Immigrant fertility: an examination of social characteristics and assimilation.
"This study compares the fertility patterns of foreign-born and native-born women in Canada and examines whether [the] same set of social characteristics accounts for differential fertility among both the groups. The study also assesses the importance of social characteristics and assimilation on immigrant fertility behavior. Two generations of currently married/cohabiting women with spouse present are analyzed using multiple regressions. The results reveal similar effects on fertility of social characteristics for foreign-born and native-born, while in the case of younger generations the effects are stronger."


Comparison of Three-Class Attributes Sampling Plans and Variables Sampling Plans for Lot Acceptance Sampling in Food Microbiology.
Lot acceptance sampling is an established method of assessing the microbiological quality and safety of batches or consignments of food, but the choice between three-class attributes plans and variables plans is not always clear. Application of variables plans requires that the microorganism of concern be distributed normally, or log-normally. When such is not true, variables plans may place either the consumer or the producer at increased risk. Validation of normality is therefore essential when using variables plans. However, with small numbers of sample units as are typically analyzed in microbiological testing of food, statistical tests are unlikely to detect non-normality. Three-class attributes plans do not require strong distributional assumptions for correct application, and as well they have several practical and operational advantages over variables plans. Moreover, three-class attributes plans assess lot quality in a fashion fundamentally different from variables plans, and this difference precludes the usual statistical comparisons based on relative discriminatory ability. We conclude that when selecting acceptance sampling plans for microbiological testing of food, whether the plans be for regulatory, port-of-entry or in-plant purposes, three-class plans are generally preferable to variables plans.


Improving the aqueous solubility of triclosan by solubilization, complexation, and in situ salt formation.
Triclosan, an antimicrobial, although widely incorporated into many skin care products, toothpastes, and liquid soaps, presents formulation difficulties because it is practically insoluble in water. The objective of this study was to improve the aqueous solubility of triclosan through solubilization, complexation, and salt formation. The solubility of triclosan in distilled water and in phosphate buffers (pH 7.4) was determined at 30 degrees C. The order of solubilizing performance of the solubilizers was: N-methylglucamine> or =L-arginine>sodium lauryl sulfate>beta-cyclodextrin> or =hydroxypropyl-beta-cyclodextrin>ethanolamine>sodium benzoate>sodium methyl 4-hydroxybenzoate>triethanolamine> or =diethanolamine. These solubilizers increased the solubility of triclosan from 80- to 6000-fold. Micellar solubilization and the formation of either salts or complexes are postulated as possible mechanisms for the increase in the solubility of triclosan by the surfactant sodium lauryl sulphate, the cyclic sugar derivatives beta-cyclodextrin and 2-hydropropyl-beta-cyclodextrin, the amino acid L-arginine, and the amino sugar alcohol N-methylglucamine. Furthermore, although the bacteriostatic efficacy of triclosan was significantly increased when solubilized with N-methylglucamine, L-arginine, and ethanolamine, increased solubilization did not increase the effectiveness of triclosan for all solubilizers tested.


Proteomic profiling in Drosophila reveals potential Dube3a regulation of the actin cytoskeleton and neuronal homeostasis.
The molecular defects associated with Angelman syndrome (AS) and 15q duplication autism are directly correlated to expression levels of the E3 ubiquitin ligase protein UBE3A. Here we used Drosophila melanogaster to screen for the targets of this ubiquitin ligase under conditions of both decreased (as in AS) or increased (as in dup(15)) levels of the fly Dube3a or human UBE3A proteins. Using liquid phase isoelectric focusing of proteins from whole fly head extracts we identified a total of 50 proteins that show changes in protein, and in some cases transcriptional levels, when Dube3a fluctuates. We analyzed head extracts from cytoplasmic, nuclear and membrane fractions for Dube3a regulated proteins. Our results indicate that Dube3a is involved in the regulation of cellular functions related to ATP synthesis/metabolism, actin cytoskeletal integrity, both catabolism and carbohydrate metabolism as well as nervous system development and function. Sixty-two percent of the proteins were >50% identical to homologous human proteins and 8 have previously be shown to be ubiquitinated in the fly nervous system. Eight proteins may be regulated by Dube3a at the transcript level through the transcriptional co-activation function of Dube3a. We investigated one autism-associated protein, ATPα, and found that it can be ubiquitinated in a Dube3a dependent manner. We also found that Dube3a mutants have significantly less filamentous actin than wild type larvae consistent with the identification of actin targets regulated by Dube3a. The identification of UBE3A targets is the first step in unraveling the molecular etiology of AS and duplication 15q autism.


Safety aspects and pharmacokinetics of inhaled aerosolized gadolinium.
This study evaluated the pharmacokinetics and potential toxicity of inhaled aerosolized gadopentetate dimeglumine. The pharmacokinetics were evaluated with in vitro relaxometry of the lungs, blood, urine, and liver before and for up to 36 hours after a 5-minute inhalation of aerosolized gadopentetate dimeglumine (0.25 mol/L). For assessment of potential toxicity, hemodynamic variables were monitored during and for 10 minutes after inhalation. Extravascular lung water was measured before and after exposure. Finally, the potential for tissue damage was evaluated histologically. Pulmonary clearance of aerosolized gadopentetate dimeglumine was monoexponential with a half-time of 2.16 hours. Aerosolized gadopentetate dimeglumine was excreted through the kidneys, as shown by the decrease in urinary T1. Renal elimination was completed by 30 hours. No acute hemodynamic effect, histologic change, or induction of edema was demonstrated. This study shows that inhalation of aerosolized gadopentetate dimeglumine is well tolerated in rats and favors the further evaluation of this administration route, including clinical trials.


Cataract occurrence with antipsychotic drugs.
Chlorpromazine and several other phenothiazine neuroleptic drugs appear to induce cataract formation. However, the newer generation of antipsychotic agents has shown no evidence of an etiologic relationship with cataract occurrence. Research did reveal cataract occurrence in dogs who received quetiapine, which prompted concern despite there being no known causal link between quetiapine and lens opacities in humans. Nevertheless, quetiapine's manufacturer issued formal recommendations for ophthalmological follow-up examinations with the use of this drug. Infrequent occurrences of cataract development have been documented in people taking olanzapine but, again, without established causative association; a similar situation is seen with ziprasidone. Periodic ocular examinations of the lens are suggested for patients prescribed long-term treatment with phenothiazines or quetiapine.


Genome-wide analysis of mRNAs, lncRNAs, and circRNAs during intramuscular adipogenesis in Chinese Guizhou Congjiang pigs.
Intramuscular fat content is an important determinant of meat quality, and preadipocyte differentiation plays a critical role in intramuscular fat deposition in pigs. However, many types of RNA differentiation, including messenger RNA (mRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) remain unreported despite their crucial roles in regulating adipogenesis. Chinese Guizhou Congjiang pigs are raised in the Guizhou province of China for their high-quality meat. Therefore, it is important for breeders to explore the mechanisms of proliferation and differentiation of intramuscular adipocytes from the longissimus dorsi muscle of these pigs. In the present study, a transcriptome analysis of intramuscular preadipocytes from Chinese Guizhou Congjiang pigs, including analyses of mRNAs, lncRNAs, and circRNAs at days 0 (D0), 4 (D4), and 8 (D8) was performed. A total of 1,538, 639, and 445 differentially expressed (DE) mRNAs, 479, 192, and 126 DE lncRNAs, and 360, 439, and 304 DE circRNAs were detected between D4 and D0, D8 and D0, and D8 and D4, respectively. Functional analyses identified many significantly enriched RNAs related to lipid deposition, cell differentiation, metabolism processes, and obesity-related diseases, biological processes, and pathways. We identified two lncRNAs (TCONS_00012086 and TCONS_00007245) closely related to fat deposition according to their target genes and tissue expression profiles. Subcellular distribution analysis using quantitative real-time PCR (qRT-PCR) revealed that both TCONS_00012086 and TCONS_00007245 are cytoplasmic lncRNAs. These data provide a genome-wide resource for mRNAs, lncRNAs, and circRNAs potentially involved in Chinese Guizhou Congjiang pig fat metabolism, thus improving our understanding of their function in adipogenesis.


Fully Cationized Gold Clusters: Synthesis of Au25(SR+)18.
Although many thiolate-protected Au clusters with different numbers of Au atoms and a variety of thiolate ligands have been synthesized, to date there has been no report of a fully cationized Au cluster protected with cationic thiolates. Herein, we report the synthesis of the first member of a new series of thiolate-protected Au cluster molecules: a fully cationized Au25(SR+)18 cluster.


Regulation of the flavin redox potential by flavin-binding antibodies.
Single-chain Fv antibody fragments binding different flavin forms [10-(5'-carboxybutyl-)flavin (Fl[ox]) and 10-(5'-carboxybutyl)-1,5-dihydroflavin (Fl[red])] have been generated from an antibody phage-display library to study how a protein environment regulates the redox potential, starting from a protein other than a natural flavoprotein. These 'flavobodies' are characterized by time-resolved and steady-state fluorescence spectroscopy, by competitive ELISA methods (mapping of the antigen-binding site), and by molecular modelling. The three-dimensional models of the antigen-binding sites are consistent with the experimental results. Binding of anti-Fl(red) 5 to flavin increases the redox potential, mainly due to an Arg residue interacting with the flavin N1. Thus anti-Fl(red) 5 shows an 'oxidase-like' redox-potential behaviour, confirming the idea that positively charged residues in the vicinity of N1 increase the redox potential. The results obtained with anti-Fl(ox), which do not resemble a natural flavoprotein, show that when the pyrimidine-like nucleus of the flavin is not involved in binding, the redox potential is not significantly affected. These results are in contrast to those obtained with chicken riboflavin-binding protein.


Coronary angioplasty and Rotablator atherectomy trial (CARAT): immediate and late results of a prospective multicenter randomized trial.
Mechanical rotational atherectomy with the Rotablator is widely used for percutaneous coronary revascularization, but the ideal debulking strategy remains unknown. The purpose of this study was to compare the immediate and late results after Rotablator using two treatment strategies: Large burrs (burr/artery ratio of >0.7) to achieve maximal debulking (lesion debulking strategy) or small burrs (burr/artery ratio < or = 0.7) to modify lesion compliance (lesion modification strategy). Two hundred twenty-two patients at six centers were prospectively enrolled in this study and randomly assigned to large (n = 104 patients with 118 lesions) or small (n = 118 patients with 136 lesions) burrs. The primary endpoint was final diameter stenosis at the end of the procedure, and secondary endpoints included inhospital angiographic and clinical complications, and target lesion revascularization at 6 months. Baseline demographic and angiographic characteristics were similar. There were no differences in procedural success, the extent of immediate lumen enlargement, inhospital ischemic complications, or late target vessel revascularization. However, compared with small burrs, patients randomized to large burrs were more likely to experience serious angiographic complications (5.1% vs. 12.7%, P < 0.05) immediately after atherectomy. This study suggests that a routine lesion modification strategy employing small burrs (burr/artery ratio < or = 0.7) achieves similar immediate lumen enlargement and late target vessel revascularization compared with a more aggressive debulking strategy (burr/artery ratio >0.7), but with fewer angiographic complications.


Fourier transform infrared studies of secondary structure and orientation of pulmonary surfactant SP-C and its effect on the dynamic surface properties of phospholipids.
SP-C, a highly hydrophobic, 3.7-kDa protein constituent of lung surfactant, has been isolated from bovine lung lavage, purified, and reconstituted into binary lipid mixtures of 1,2-dipalmitoyl-phosphatidylcholine (DPPC) and 1,2-dipalmitoylphosphatidylglycerol (DPPG). Fourier transform infrared (FT-IR) spectroscopy has been applied to examine SP-C secondary structure, the average orientation of alpha-helical segments relative to the bilayer normal in membrane films, and the effect of protein on the thermotropic properties of the phospholipid acyl chains. In addition, dynamic surface measurements were made on phospholipid films at the A/W interface in the presence and absence of SP-C. SP-C (0.5 mol %) was found to possess about 60% alpha-helical secondary structure in lipid vesicles. Higher levels (1.5 mol %) of SP-C resulted in a slight increase of beta-forms, possibly resulting from protein aggregation. The helical segments exhibited an average angle of orientation of about 24 degrees with respect to the bilayer normal, suggesting a trans-bilayer orientation of the peptide. The observation that 70% of the peptide bond hydrogens are hard to exchange in D2O further reflects the hydrophobic nature of the molecule. SP-C produced little effect on the thermotropic properties of the binary lipid mixture, as measured from acyl chain C-H and C-D stretching frequencies. However, the presence of 1 mol % protein markedly reduced the viscance and increased the elasticity of surface films suggesting a mechanism by which SP-C facilitates the spreading of phospholipids on an aqueous surface. The possible physiological consequences of these observations are discussed.


Parasitic Helminths in Wild Boars (Sus scrofa) in Mazandaran Province, Northern Iran.
Wild boars (Sus scrofa) are distributed worldwide and found in many parts of Iran. Although S. scrofa is reservoirs for many parasites, there is little data on helminthic prevalence in them. We aimed to survey the status of helminthic infections in S. scrofa in the Mazandaran Province of northern Iran. Twenty-one wild boars were captured and examined for helminth infection during Dec 2012-Mar 2014. Adult worms such as Macracanthorhynchus hirudinaceus were identified by helminth size and shape, and the arrangement of the proboscis hooks. The sedimentation and flotation techniques were used to detect parasite eggs and larvae in faecal samples. Muscle samples were also surveyed for Trichinella larvae by artificial digestion method. Of the 21 samples, 13 (61.9%) were infected with one or more helminth species. Seven helminth types were identified in the alimentary track, comprising 5 nematodes, 1 trematode, and 1 acanthocephalan, with prevalence rates of Macracanthorhynchus hirudinaceus (57.14%), Globocephalus spp. (33.33%), Trichuris suis (19.04), Gongylonema pulchrum (14.28%), Fasciola hepatica (14.28%), Dioctophyma renale (4.76%), and Ascaris suum (4.76%). Wild boars might be involved in transmitting zoonotic parasites to humans. The abundance of these animals near human habitation creates favorable conditions for infection. So the risk of parasitic helminth diseases increases in other animals and humans.


[Long-term effects of Dendrolimus superans Bulter disturbance on forest landscape in Huzhong Forest Bureau of Great xing' an Mountains: a simulation study].
A spatially explicit landscape model LANDIS was applied to simulate the long-term effects of Dendrolimus superans Bulter disturbance on the forest landscape in Huzhong Forest Bureau of Great Xing' an Mountains. The statistical software pakage APACK was used to calculate the distribution area of D. superans and representative tree species, the aggregation index reflecting the spatial pattern, and the average area of forest patchs. The dynamics of forest landscape in the study region was simulated under two scenarios, i.e., with and without D. superans disturbance for 300 years (from 1990 to 2290). In the region, the distribution area of D. superans showed a trend of increased first and decreased then. Under D. superans disturbance scenario, the distribution area and the average patch size of Larix gmelinii in 0-150 years and the aggregation index of L. gmelinii in 0-190 years, the distribution area and the average patch size of Betula platyphylla and its aggregation index in 80-190 years, as well as the distribution area, average patch size, and aggregation index of Pinus sylvestris var. mongolica were lower or slightly lower than those under no disturbance scenario. D. superans disturbance led to the fragmentation of forest landscape to some extent.


Psoriasis arthropathy and HLA-B51: report of 5 cases.
Psoriasis arthropathy (PsA) is a chronic inflammatory arthropathy characterized by the association of arthritis with psoriasis. Although the precise mechanisms of PsA still remain obscure, several genetic and environmental factors have been suggested to play important roles. HLA-B51 has been strongly associated with Behçet's disease; however, its association with PsA has not been documented. We describe herein five Japanese patients (4 males and 1 female) with PsA and positive for HLA-B51. The clinical forms defined by Moll and Wright revealed that the polyarticular pattern was noted in two cases, and oligoarticular, distal, and spondyloarthropathy patterns were noted in one case each. Positive rheumatoid factor was detected in one patient, and antinuclear antibody in two patients. The other HLA subclasses were A2 and A31 in 3 cases, respectively. HLA-B51 was detected in 5 out of 17 patients with PsA examined in our department; in contrast, HLA-B51 was not detected in 17 patients with psoriasis vulgaris. Our observations suggest that HLA-B51 may play a role in the pathogenesis of PsA in the Japanese population.


Update on non-viral delivery methods for cancer therapy: possibilities of a drug delivery system with anticancer activities beyond delivery as a new therapeutic tool.
Cancer is the most formidable human disease. Owing to the heterogeneity of cancer, a single-treatment modality is insufficient for the complete elimination of cancer cells. Therapeutic strategies from various aspects are needed for cancer therapy. These therapeutic agents should be carefully selected to enhance multiple therapeutic pathways. Non-viral delivery methods have been utilized to enhance the tumor-selective delivery of therapeutic molecules, including proteins, synthetic oligonucleotides, small compounds and genes. As non-viral delivery methods, liposomes and polymer-based delivery materials to target tumors mainly by systemic delivery, physical methods including electroporation, sonoporation, and so on, to locally inject therapeutic molecules, and virosomes to use the viral infectious machinery for the delivery of therapeutic molecules are summarized. This article aims to provide an overview of the characteristic properties of each non-viral vector. It will be beneficial to utilize appropriately the vector for cancer treatment. Efficient and minimally invasive vectors are generally considered to be the ideal drug delivery system (DDS). However, against cancer, DDS equipped with antitumor activities may be a therapeutic choice. By combining therapeutic molecules with DDS having antitumor activities, enhancement of the multiple therapeutic pathways may be achieved.


Organizational factors associated with decreased mortality among Veterans Affairs patients with an ICU stay.
In-hospital mortality rates associated with an ICU stay are high and vary widely among units. This variation may be related to organizational factors such as staffing patterns, ICU structure, and care processes. We aimed to identify organizational factors associated with variation in in-hospital mortality for patients with an ICU stay. This was a retrospective observational cross-sectional study using administrative data from 34 093 patients from 171 ICUs in 119 Veterans Health Administration hospitals. Staffing and patient data came from Veterans Health Administration national databases. ICU characteristics came from a survey in 2004 of ICUs within the Veterans Health Administration. We conducted multilevel multivariable estimation with patient-, unit-, and hospital-level data. The primary outcome was in-hospital mortality. Of 34 093 patients, 2141 (6.3%)died in the hospital. At the patient level, risk of complications and having a medical diagnosis were significantly associated with a higher risk of mortality. At the unit level, having an interface with the electronic medical record was significantly associated with a lower risk of mortality. The finding that electronic medical records integrated with ICU information systems are associated with lower in-hospital mortality adds support to existing evidence on organizational characteristics associated with in-hospital mortality among ICU patients.


[Quality control of liver diagnosis in newly admitted patients].
The evaluation of pathological clinical findings or abnormal laboratory tests in the liver was prospectively investigated. Pathological findings were used for diagnosis or differential diagnosis in only 40% of 102 patients investigated. Further investigations, mainly laboratory tests, resulted in definitive diagnosis only in 20%. The yield of pathological results when routinely ordering liver-specific tests is not more than 20%. Fewer, but perhaps more invasive, investigations would lower costs and improve the diagnostic yield.


The Curated Food System: A Limiting Aspirational Vision of What Constitutes "Good" Food.
In an effort to elucidate an aspirational vision for the food system and explore whether the characteristics of such a system inadvertently set unattainable standards for low-wealth rural communities, we applied discourse analysis to the following qualitative datasets: (1) interviews with food experts and advocates, (2) scholarly and grey literature, (3) industry websites, and (4) email exchanges between food advocates. The analysis revealed eight aspirational food system discourses: production, distribution, and infrastructure; healthy, organic, local food; behavioral health and education; sustainability; finance and investment; hunger relief; demand-side preferences; romanticized, community led transformations. Study findings reveal that of eight discourses, only three encompass the experiences of low-wealth rural residents. This aspirational food system may aggravate the lack of autonomy and powerlessness already experienced by low-wealth rural groups, perpetuate a sense of failure by groups who will be unable to reach the aspirational food vision, silence discourses that might question those that play a role in the inequitable distribution of income while sanctioning discourses that focus on personal or community solutions, and leave out other policy-based solutions that address issues located within the food system. Further research might explore how to draw attention to silenced discourses on the needs and preferences of low-wealth rural populations to ensure that the policies and programs promoted by food system experts mitigate poor diets caused by food insecurity. Further research is needed to inform policies and programs to mitigate food insecurity in low-wealth rural populations.


First report of leaf blight disease of Livistona chinensis caused by Alternaria alternata in Pakistan.
Livistona chinensis (Jacq.) is also known as fan palm and is commonly grown in the subtropical region of the world. This plant is widely cultivated in Asia for ornamental purpose and also used in Chinese medicines (Li et al. 2019). In May 2021, severe leaf blight was observed on L. chinensis leaves in ornamental plant nurseries, located at Pattoki (30°59'41.5"N 73°48'43.8"E) District Kasur, Punjab province, Pakistan. The disease incidence was up to 50% and the initial symptoms appeared as chlorotic brown spots on the upper portion of leaves. Later, the spots expanded and changed into elliptical lesions on the leaves. The lesions with dark brown margins coalesced to cause extensive tissue necrosis of leaves and exhibited blight (Figure 1). Two to three leaves were taken from each infected plant. Infected leaves of each sample of L. chinensis were excised into small pieces (3-4 mm) with the help of sterilized scissor and surface disinfected with 1% NaClO for 20s and rinsed 3 times with sterilized distilled water. To isolate the potential causal organism, these pieces were plated on Potato Dextrose Agar (PDA) medium and incubated at 28 °C with 70 % relative humidity for 7 days. Purified cultures were obtained through single spore culture on PDA. All obtained isolates were preserved in 30% glycerol at -80°C. The fungal colony colour was olive to dark greenish and dark brown to black on the reverse side. The conidia (n=36 per isolate) were greenish to brown in colour, ellipsoid to obclavate, ovoid, irregular and measured an average range from 10.9 to 30.7 µm long x 6.3 to 12.5 µm wide with 2 to 5 transverse and 0 to 3 longitudinal septa (Figure 2). The genomic DNA was extracted from all isolates (n=40) and multi-locus sequence analysis approach was used for molecular identification. The Internal Transcribed Spacers (ITS) region, Alt a1 major allergen (ALT) gene, glyceraldehyde-3-phosphate dehydrogenase (GPD), actin (ACT) gene and histone 3 genes were amplified using ITS1/4 (White et al. 1990), Alt-4for/Alt-4rev (Lawrence et al. 2013), GPD1/GPD2 (Guerber et al. 2003), ACT512F/ACT783R (Carbone and Kohn, 1999) and H3-1a/H3-1b (Luan et al. 2007). Based on morphological and molecular characteristics, all isolates were identified as Alternaria alternata. The sequences of the representative isolate APLB-3 were submitted in the GenBank with the accession numbers (ITS: MZ663802), (ALT: MZ666883), (ACT: MZ666885), (GPD: MZ666884), and (Histone3: MZ666886) showing 100% similarity with ITS accession MK968038, ALT accession MN702781, ACT accession MT318253, GPD accession MT524743 and histone 3 accession MH824369. For pathogenicity test, potted L. chinensis plants (n=9) leaves were pin-pricked with sterilized needle (Bajwa et al. 2010) and inoculated with spore suspensions (107 spore/ml) of APLB-3 (1ml/leaf) to confirm Koch's postulates. After 14 days, the inoculated leaves showed chlorotic brown spots and leaf blight symptoms similar to those observed on infected plants in nurseries. The plants grown as the control group (n=9) were sprayed with sterilized distilled water and had no symptoms (Figure 3). The experiment was performed three times. The fungal pathogen was re-isolated from the artificial inoculated leaf tissues and identified as A. alternata based on morphological and molecular characterization. To our knowledge, this is the first record of A. alternata causing leaf blight disease of L. chinensis in Pakistan. This disease may potentially decrease the value of ornamental plants in Pakistan under favourable conditions and proper management strategies should be applied.


Diagnostic Value and Safety of Emergency Single-Balloon Enteroscopy for Obscure Gastrointestinal Bleeding.
This study assesses the diagnostic performance of emergency single-balloon enteroscopy (SBE) for obscure gastrointestinal bleeding (OGIB) under general anesthesia versus conscious sedation. The data of 102 OGIB in-patients from June 2015 to June 2018 were retrospectively analyzed. The diagnosis and detection rates and adverse events were calculated overall and in relation to age, gender, type of operation and anesthesia, bleeding type, different times of examination, and SBE route. All statistical analyses were performed using SPSS 24.0, and the diagnosis and detection rates were compared using the Chi-square test. Among the 102 patients, 66 patients had positive findings, while 11 patients had suspected positive findings, and the diagnosis and detection rates were 64.7% and 75.5%, respectively. Ulcers (19.6%) and tumors (16.7%) were the most common causes of OGIB. There were no statistical differences in diagnosis and detection rates between the ages of ≥60 and <60 and between different genders. Patients with emergency SBE had higher diagnosis and detection rates (68.6% vs. 35.3%, P = 0.023; 80.0% vs. 47.1%, P = 0.016, respectively), when compared with nonemergency SBE patients. The diagnosis rate at 24 hours was higher than that at 2-7 days and one week (88.0% vs. 61.5%, P = 0.030; 88.0% vs. 53.8%, P = 0.007). For overt bleeding, the difference in diagnosis rates at 24 hours, 2-7 days, and one week was statistically significant (100.0% vs. 57.1%, P = 0.006; 100.0% vs. 57.1%, P = 0.006). For occult bleeding, the pairwise comparison revealed no statistical difference. Patients with general anesthesia had a higher detection rate, when compared to patients with conscious sedation (87.9% vs. 63.9%, P = 0.004). In addition, adverse events under general anesthesia were lower, when compared to adverse events under conscious sedation (28.8% vs. 69.4%, P = 0.020). There was no significant difference in adverse events at the different time points (P > 0.05). Emergency SBE under general anesthesia achieves higher diagnosis and detection rates, and fewer adverse events under conscious sedation, when compared to nonemergency SBE, regardless of the route. For patients with overt bleeding, it is easier to find lesions by emergency SBE within 24 hours.


HGF/R-spondin1 rescues liver dysfunction through the induction of Lgr5+ liver stem cells.
Induction of endogenous adult stem cells by administering soluble molecules provides an advantageous approach for tissue damage repair, which could be a clinically applicable and cost-effective alternative to transplantation of embryonic or pluripotent stem cell-derived tissues for the treatment of acute organ failures. Here, we show that HGF/Rspo1 induce liver stem cells and rescue liver dysfunction. Carbon tetrachloride treatment promotes both fibrosis and Lgr5+ liver stem cell proliferation, whereas Lgr5 knockdown worsens fibrosis. Injection of HGF in combination with Rspo1 increases the number of Lgr5+ liver stem cells and improves liver function by attenuating fibrosis. We observe Lgr5+ liver stem cells in human liver fibrosis tissues, and once they are isolated, these cells are able to form organoids, and treatment with HGF/Rspo1 promotes their expansion. We suggest that Lgr5+ liver stem cells represent a valuable target for liver damage treatment, and that HGF/Rspo1 can be used to promote liver stem cell expansion.


The absence of B cells disrupts splenic and myocardial Treg homeostasis in coxsackievirus B3-induced myocarditis.
Although B cells are essential for humoral immunity and show noteworthy immunomodulatory activity through antibody-independent functions, the role of B cells in regulating Treg cell responses remains controversial. Tregs (CD4+CD25+Foxp3+) are considered to play an immunoprotective role in viral myocarditis (VMC) by controlling autoimmune effector T cells. Here, we proved that B-cell knockout can not only lead to significant reductions in Tregs in the spleen, blood, and heart of VMC mice but also decrease the activation and immune function of splenic Tregs, which was reversed by adoptive transfer of B cells; the transcription levels of TGF-β and Foxp3 in the myocardium were also significantly reduced. B-cell depletion by anti-CD20 impaired the anti-inflammatory function of splenic Tregs and the homeostasis of myocardial Tregs population. Moreover, B cells can convert CD4+CD25- T cells into Foxp3+ and Foxp3-, two functionally suppressive Treg subgroups. Although the reduction in myocardial inflammation in BKO mice indicates that B cells may play a proinflammatory role, the beneficial side of B cells cannot be ignored, that is, to control autoimmunity by maintaining Treg numbers. The results observed in the animal model of VMC highlight the potential harm of rituximab in the nonselective depletion of B cells in clinical applications.


Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy.
This study describes the safety and immunogenicity of a liposome-based vaccine injected into human subjects. Thirty healthy adult male volunteers were immunized with a liposome-encapsulated recombinant protein (R32NS181) containing epitopes from the repeat region of the circumsporozoite protein of Plasmodium falciparum. This antigen had previously been found to be poorly immunogenic in humans when it was adsorbed with Al(OH)3. In the present study, R32NS181 was encapsulated in liposomes containing monophosphoryl lipid A that were subsequently adsorbed to Al(OH)3. Increasing doses of liposomes containing antigen and monophosphoryl lipid A were used, but the liposomes were always adsorbed to the same dose of Al(OH)3. R32-specific serum IgG antibody responses to liposome-encapsulated R32NS181 were much higher than levels attained previously in humans with R32NS181 adsorbed to Al(OH)3. Geometric mean specific IgG levels after three doses ranged from 14 to 33 micrograms/ml. Sera from volunteers receiving the two highest doses inhibited P. falciparum sporozoite invasion of cultured hepatoma cells by an average of 92%, a result that was again superior to previously reported vaccines. Moderate but acceptable transient local reactogenicity was noted at high doses of the vaccine formulation, but little or no systemic toxicity was seen despite liposomal monophosphoryl lipid A doses up to 2200 micrograms. We conclude that encapsulation of poorly immunogenic circumsporozoite protein repeat peptides in monophosphoryl lipid A-containing liposomes is a successful adjuvant strategy in humans for inducing high levels of specific antibody production.


The quest for high temperature flexible polymers.
A unique set of material properties is needed to meet the special requirements of the medical market. Flexible poly(vinyl chloride), which has occupied a pre-eminent position for nearly half a century, is increasingly being challenged by newer and more advanced polymer systems. Several propylene-based elastomers with low crystallinities are promising to be the dominant medical materials of the future. This article discusses one company's actual experiences in utilizing these new materials in medical applications.


The taming of immunohistochemistry: the new era of quality control.
The most critical factor for interpreting the results of immunohistochemistry is verification of antibody sensitivity and specificity. While some manufacturers supply material data sheets with this information, many do not. This paper describes a well-defined quality assurance program for testing immune reagents. This program can be used to provide commercial suppliers of antisera with analyses of their products destined for government licensure applications. This paper illustrates the protocol and explains the testing philosophy developed over the last eight years.


The role of lymph node status in cancer-specific survival and decision-making of postoperative radiotherapy in poorly differentiated thyroid cancer: a population-based study.
This study aimed to investigate the prognostic value of lymph node (LN) status for patients with poorly differentiated thyroid cancer (PDTC), and to develop a reliable nomogram to predict the 3-, 5- and 10-year cancer-specific survival (CSS) and assist the decision-making of postoperative radiotherapy (PORT). The Surveillance, Epidemiology, and End Results (SEER) database was utilized to screen eligible patients who were diagnosed between 2004 and 2016. The optimal values of age, metastatic lymph node ratio (LNR), and the number of metastatic lymph nodes (MLN) were determined and incorporated into the construction of a nomogram. The performance of the model was evaluated by generating a calibration curve and calculating the consistency index (C-index). Based on the nomogram, patients were classified into three risk cohorts. The prognostic efficacy of PORT was evaluated in each cohort. A total of 522 PDTC patients were included in this study. The LN status-associated parameters (MLN and LNR) were independent risk factors for CSS of PDTC patients. Based on MLN, LNR, and other clinical characteristics (age and T stage), an individualized nomogram was constructed that showed an acceptable predictive performance. Furthermore, we proposed a novel risk-classification system to stratify PDTC patients and to assess the prognostic efficacy of PORT. Only patients in high-risk cohort were found eligible to benefit from PORT. LN status is statistically associated with the prognosis of PDTC patients. In addition, the individualized nomogram may be a significant tool to assist the evaluation of patients' long-term prognosis and to guide the decision-making for PORT.


Quantitative characterization of a hardwood milled wood lignin by nuclear magnetic resonance spectroscopy.
The structure of Eucalyptus grandis milled wood lignin (MWL) was investigated by 2D 1H-13C HSQC, HMQC, and 1H-1H TOCSY correlation NMR techniques and by quantitative 13C NMR as well as by the permanganate oxidation degradation technique. The combination of 2D NMR and quantitative 13C NMR spectroscopy of nonacetylated and acetylated lignin preparations allowed reliable identification and calculation of the amount of different lignin structures. About 85% of side-chain moieties were estimated on the structural level. This information was substantiated by data on the quantity of various functional groups and interunit linkages as a whole. A modified method for calculation of the h:g:s ratio has been suggested and compared with previously suggested approaches. E. grandis MWL has been determined to have an h:g:s ratio of 2:36:62. The amounts of various phenolic/etherified noncondensed/condensed guaiacyl and syringyl moieties were approximately estimated. E. grandis MWL contained approximately 0.60/Ar of beta-O-4 moieties along with small amounts of other structural units such as pino/syringyresinol (0.03/Ar), phenylcoumaran (0.03/Ar), and spirodienone (0.05/Ar). The degree of condensation was estimated at approximately 21%; the main condensed structures are 4-O-5 moieties (approximately 0.09/Ar). The structure of E. grandis MWL was compared with those of other lignin preparations isolated from various hardwoods.


Major contribution of sarcoplasmic reticulum Ca(2+) depletion during long-lasting activation of skeletal muscle.
Depolarization of skeletal muscle fibers induces sarcoplasmic reticulum (SR) Ca(2+) release and contraction that progressively decline while depolarization is maintained. Voltage-dependent inactivation of SR Ca(2+) release channels and SR Ca(2+) depletion are the two processes proposed to explain the decline of SR Ca(2+) release during long-lasting depolarizations. However, the relative contribution of these processes, especially under physiological conditions of activation, is not clearly established. Using Fura-2 and Fluo-5N to monitor cytosolic and SR Ca(2+) changes, respectively, in voltage-controlled mouse muscle fibers, we show that 2-min conditioning depolarizations reduce voltage-activated cytosolic Ca(2+) signals with a V1/2 of -53 mV but also induce SR Ca(2+) depletion that decreased the releasable pool of Ca(2+) with the same voltage sensitivity. In contrast, measurement of SR Ca(2+) changes indicated that SR Ca(2+) release channels were inactivated after SR had been depleted and in response to much higher depolarizations with a V1/2 of -13 mV. In response to trains of action potentials, cytosolic Ca(2+) signals decayed with time, whereas SR Ca(2+) changes remained stable over 1-min stimulation, demonstrating that SR Ca(2+) depletion is exclusively responsible for the decline of SR Ca(2+) release under physiological conditions of excitation. These results suggest that previous studies using steady-state inactivation protocols to investigate the voltage dependence of Ca(2+) release inactivation in fact probed the voltage dependence of SR Ca(2+) depletion, and that SR Ca(2+) depletion is the only process that leads to Ca(2+) release decline during continuous stimulation of skeletal muscle.


[Early detection of diabetes in pregnancy--a factor for reducing perinatal mortality and morbidity].
At present the main problem in gestational diabetes (GDM) is that only less than 10% of the pregnant diabetics could be diagnosed and accordingly treated. Analysing 101 cases of pregnant diabetics we refer to the incidence of peripartal and perinatal complications. The treatment with insulin was necessary to be applied on 70 of the patients (69.3%) in order to achieve normal glucose levels (between 3.3 and 6.6 mmol/l). If the metabolic complications are determined and treated in a later phase of pregnancy, there is a higher rate of complications (toxemias 29.7%, premature labor 21.8%, caesarean section 23.8%, perinatal mortality 2.9%, congenital anomalies 5.9% and the likelihood of large for gestational age babies 32.7%). Improvement of such results, which can be obtained in optimally treated insulin - dependent pregnants, is possible only by more early determination of all carbohydrate tolerance disturbances in pregnancy. This proposed diabetic screening is generally required in any pregnant woman with a history diabetes, obesity greater than or equal to 20%, age greater than or equal to 30 years and glucosuria. A gestational diabetes is to be considered into consideration if in a 50 g-oral-glucose-tolerance-test (50 g - OGTT) 2 values exceed normal limits (fasting level 5.55 mmol/l, 60 minutes level 8.88 mmol/l and 120 minutes level 7.22 mmol/l). Further observation of these patients has to be continued centrally.


Mutant gene phenotypes mediated by a Drosophila melanogaster retrotransposon require sequences homologous to mammalian enhancers.
We have analyzed the molecular structure of phenotypic revertants of gypsy-induced mutations to understand the molecular mechanisms by which this retrotransposon causes mutant phenotypes in Drosophila melanogaster. The independent partial revertants analyzed are caused by the insertion of different transposons into the same region of gypsy. One partial revertant of the yellow allele y2 arose as a consequence of the insertion of the jockey mobile element into gypsy sequences, whereas a second incomplete revertant is due to the insertion of the hobo transposon. In addition, a previously isolated partial revertant of the Hairy-wing allele Hw1 resulted from the integration of the BS transposable element into the same gypsy sequences. The region affected by the insertion of the three transposons contains 12 copies of a repeated motif that shows striking homology to mammalian transcriptional enhancers. Our results suggest that these sequences, which might be involved in the transcriptional control of the gypsy element, are also responsible for the induction of mutant phenotypes by this retrotransposon.


Biochemical and PMF MALDI-TOF analyses of two novel papain-like plant proteinases.
Two cysteine endopeptidases from latex of Araujia angustifolia (araujiain aI and araujiain aIII) were purified and characterized by means of conventional and proteomics techniques (MALDI-TOF). N-terminal sequences showed a high percentage of identity with cysteine proteinases belonging to the papain family. The peptide mass fingerprint analysis demonstrated a close homology among both proteinases.


Patents, genomics, research, and diagnostics.
Two kinds of currently available genomic patents may significantly interfere with medical research: (1) patents such as those on specific single nucleotide polymorphisms (SNPs), which may include claims that control the inference of phenotypic characteristics from specific genotypes, and (2) patents on computer-based genomic information, databases, or manipulation procedures. These will create more serious encumbrances than will patents on expressed sequence tags (ESTs). Two approaches should be considered vis-à-vis these genomic patents: (1) Reconsideration and redefinition of the recent extensions of patentable subject matter into more and more intangible areas. This could be pursued by legislation or by test litigation to seek Supreme Court reversal of certain of the decisions of the Court of Appeals for the Federal Circuit (CAFC). (2) A narrow legislative exemption protecting the ability to use SNPs and phenotypic-genotypic relationships in medical research, including contexts in which medical research and clinical practice are substantially intertwined.


Optimization of whole-genome sequencing of Plasmodium falciparum from low-density dried blood spot samples.
Whole-genome sequencing (WGS) is becoming increasingly useful to study the biology, epidemiology, and ecology of malaria parasites. Despite ease of sampling, DNA extracted from dried blood spots (DBS) has a high ratio of human DNA compared to parasite DNA, which poses a challenge for downstream genetic analyses. The effects of multiple methods for DNA extraction, digestion of methylated DNA, and amplification were evaluated on the quality and fidelity of WGS data recovered from DBS. Low parasite density mock DBS samples were created, extracted either with Tween-Chelex or QIAamp, treated with or without McrBC, and amplified with one of three different amplification techniques (two sWGA primer sets and one rWGA). Extraction conditions were evaluated on performance of sequencing depth, percentiles of coverage, and expected SNP concordance. At 100 parasites/μL, Chelex-Tween-McrBC samples had higher coverage (5 × depth = 93% genome) than QIAamp extracted samples (5 × depth = 76% genome). The two evaluated sWGA primer sets showed minor differences in overall genome coverage and SNP concordance, with a newly proposed combination of 20 primers showing a modest improvement in coverage over those previously published. Overall, Tween-Chelex extracted samples that were treated with McrBC digestion and are amplified using 6A10AD sWGA conditions had minimal dropout rate, higher percentages of coverage at higher depth, and more accurate SNP concordance than QiaAMP extracted samples. These findings extend the results of previously reported methods, making whole genome sequencing accessible to a larger number of low density samples that are commonly encountered in cross-sectional surveys.


Slit-Robo GTPase-activating proteins are differentially expressed in murine dorsal root ganglia: modulation by peripheral nerve injury.
The Slit-Robo GTPase-activating proteins (srGAPs) play an important role in neurite outgrowth and axon guidance; however, little is known about its role in nerve regeneration after injury. Here, we studied the expression of srGAPs in mouse dorsal root ganglia (DRG) following sciatic nerve transection (SNT) using morphometric and immunohistochemical techniques. Reverse transcriptase polymerase chain reaction and Western blot analysis indicated that srGAP1 and srGAP3, but not srGAP2, were expressed in normal adult DRG. Following unilateral SNT, elevated mRNA and protein levels of srGAP1 and srGAP3 were detected in the ipsilateral relative to contralateral L(3-4) DRGs from day 3 to day 14. Immunohistochemical results showed that srGAP1 and srGAP3 were largely expressed in subpopulations of DRG neurons in naïve DRGs. However, after SNT, srGAP3 in neurons was significantly increased in the ipsilateral relative to contralateral DRGs, which peaked at day 7 to day 14. Interestingly, DRG neurons with strong srGAP3 labeling also coexpressed Robo2 after peripheral nerve injury. These results suggest that srGAPs are differentially expressed in murine DRG and srGAP3 are the predominant form. Moreover, srGAP3 may participate in Slit-Robo signaling in response to peripheral nerve injury or the course of nerve regeneration.


The calcium deficiency hypothesis of hypertension.
The proposed role of maintenance of calcium homeostasis in the prevention and nonpharmacologic treatment of hypertension has prompted controversial interpretations of the data on which the proposal is based. To provide a more current perspective, we summarize the epidemiologic data, results of clinical studies of calcium metabolism in humans with hypertension, effects of controlled interventions of calcium supplementation in humans, and findings from laboratory studies intended to elucidate possible mechanisms. Data from the epidemiologic and clinical trials support a protective role for calcium in regulating arterial pressure. A potentially important relationship between the "calcium hypothesis" and "salt-sensitivity" may provide further insights into the mechanisms involved. Results of experiments in vascular physiology indicate that dietary calcium's effect in lowering blood pressure is mediated in part through direct action on the vasculature.


Human mutational constraint as a tool to understand biology of rare and emerging bone marrow failure syndromes.
Inherited bone marrow failure (IBMF) syndromes are rare blood disorders characterized by hematopoietic cell dysfunction and predisposition to hematologic malignancies. Despite advances in the understanding of molecular pathogenesis of these heterogeneous diseases, genetic variant interpretation, genotype-phenotype correlation, and outcome prognostication remain difficult. As new IBMF and other myelodysplastic syndrome (MDS) predisposition genes continue to be discovered (frequently in small kindred studies), there is an increasing need for a systematic framework to evaluate penetrance and prevalence of mutations in genes associated with IBMF phenotypes. To address this need, we analyzed population-based genomic data from >125 000 individuals in the Genome Aggregation Database for loss-of-function (LoF) variants in 100 genes associated with IBMF. LoF variants in genes associated with IBMF/MDS were present in 0.426% of individuals. Heterozygous LoF variants in genes in which haploinsufficiency is associated with IBMF/MDS were identified in 0.422% of the population; homozygous LoF variants associated with autosomal recessive IBMF/MDS diseases were identified in only .004% of the cohort. Using age distribution of LoF variants and 2 measures of mutational constraint, LOEUF ("loss-of-function observed/expected upper bound fraction") and pLI ("probability of being loss-of-function intolerance"), we evaluated the pathogenicity, tolerance, and age-related penetrance of LoF mutations in specific genes associated with IBMF syndromes. This analysis led to insights into rare IBMF diseases, including syndromes associated with DHX34, MDM4, RAD51, SRP54, and WIPF1. Our results provide an important population-based framework for the interpretation of LoF variant pathogenicity in rare and emerging IBMF syndromes.


Respiratory function decline and DNA mutation in mitochondria, oxidative stress and altered gene expression during aging.
Aging is a biological process that is characterized by the gradual loss of physiological function and increases in the susceptibility to disease of an individual. During the aging process, a wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) has been observed in somatic tissues of humans and animals. This is associated with the decline in mitochondrial respiratory function; excess production of the reactive oxygen species (ROS); increase in the oxidative damage to mtDNA, lipids and proteins in mitochondria; accumulation of point mutations and large-scale deletions of mtDNA; and altered expression of genes involved in intermediary metabolism. It has been demonstrated that the ROS may cause oxidative damage and mutations of mtDNA and alterations of the expression of several clusters of genes in aging tissues and senescent cells. We found that intracellular levels of hydrogen peroxide (H2O2) and oxidative damage to DNA in the tissue cells and skin fibroblasts of old donors were higher than those of young donors. In H2O2-induced senescent skin fibroblasts, we observed an increase in the protein expression and activity levels of manganese-dependent superoxide dismutase and a concurrent decrease in the activity of cytochrome c oxidase and the rate of oxygen consumption. Moreover, the mRNA and protein expression levels of pyruvate dehydrogenase (PDH) were decreased but those of PDH kinase and lactate dehydrogenase were increased in senescent skin fibroblasts. The changes in the expression of these enzymes suggest a metabolic shift from mitochondrial respiration to glycolysis as a major supply of ATP in aging human cells. On the other hand, recent studies on mitochondrial mutant mice, which carry a proofreading deficient subunit of DNA polymerase gamma, revealed that mtDNA mutations accumulated in somatic tissues in the mice that displayed prominent features of aging. Taken together, we suggest that the respiratory function decline and increase in the production of the ROS in mitochondria, accumulation of mtDNA mutation and oxidative damage, and altered expression of a few clusters of genes that culminated in the metabolic shift from mitochondrial respiration to glycolysis for major supply of ATP were key contributory factors in the aging process in the human and animals.


Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.
Osteonecrosis of the femoral head (ONFH) involves necrosis of bone and bone marrow of the femoral head caused by ischemia with unknown etiology. Previous genetic studies on ONFH failed to produce consistent results, presumably because ONFH has various causes with different genetic backgrounds and the underlying diseases confounded the associations. Steroid-associated ONFH (S-ONFH) accounts for one-half of all ONFH, and systemic lupus erythematosus (SLE) is a representative disease underlying S-ONFH. We performed a genome-wide association study (GWAS) to identify genetic risk factors for S-ONFH in patients with SLE. We conducted a two-staged GWAS on 636 SLE patients with S-ONFH and 95 588 non-SLE controls. Among the novel loci identified, we determined S-ONFH-specific loci by comparing allele frequencies between SLE patients without S-ONFH and non-SLE controls. We also used Korean datasets comprising 148 S-ONFH cases and 37 015 controls to assess overall significance. We evaluated the functional annotations of significant variants by in silico analyses. The Japanese GWAS identified 4 significant loci together with 12 known SLE susceptibility loci. The four significant variants showed comparable effect sizes on S-ONFH compared with SLE controls and non-SLE controls. Three of the four loci, MIR4293/MIR1265 [odds ratio (OR) = 1.99, P-value = 1.1 × 10-9)], TRIM49/NAALAD2 (OR = 1.65, P-value = 4.8 × 10-8) and MYO16 (OR = 3.91, P-value = 4.9 × 10-10), showed significant associations in the meta-analysis with Korean datasets. Bioinformatics analyses identified MIR4293, NAALAD2 and MYO16 as candidate causal genes. MIR4293 regulates a PPARG-related adipogenesis pathway relevant to S-ONFH. We identified three novel susceptibility loci for S-ONFH in SLE.


Expression of tumor-associated carbohydrate antigens correlates with hepatic metastasis of pancreatic cancer: clinical and experimental studies.
This study was designed to detect an useful indicator to prognose postoperative hepatic metastases of pancreatic cancer. We analyzed clinical and histological data in thirty patients. Of the ten items analyzed, only preoperative serum CA 19-9 level was indicative of postoperative hepatic metastases. When the patients were classified into two groups in regard to the CA 19-9 level making a boundary at 50 U/ml, the group of CA 19-9 level equal to, or over, 50 U/ml possessed a significantly higher frequency of the hepatic metastases. With a design based on these clinical results, we experimentally studied a correlation between expression of three carbohydrate antigens (CA 19-9, DUPAN-2 and Span-1) and incidence of blood-borne hepatic metastases in nude mice by using six human pancreatic, cancer cell lines. These antigens were immunocytochemically detectable in four cell lines (SUIT-2, AsPC-1, HPAF and Capan-2) and were undetectable in two cell lines (MIA PaCa-2 and BxPC-3). All of the former cell lines formed metastatic lesions in the liver. In contrast, the latter two did not cause hepatic metastases at all. Moreover, these antigens were expressed more intensely in the metastatic foci than in the primary transplanted tumor lesion in the spleen. There is a positive correlation between expression of the carbohydrate antigens and metastatic potential of pancreatic cancer.


Management of Multidrug-Resistant Infections in Cirrhosis.
The World Health Organization describes antimicrobial resistance as one of the biggest threats to global health, food security, and development with indiscriminate use of antimicrobials globally driving the emergence of multidrug-resistant bacteria, resistant to 60% of antimicrobials in some countries. Infections with multidrug-resistant organisms (MDROs) have increased in recent decades in patients with cirrhosis, who are frequently prescribed antibiotics, regularly undergo invasive procedures such as large volume paracentesis, and have recurrent hospitalizations, posing a particular risk in this already immunocompromised cohort of patients. In this review, we explore mechanisms underlying this vulnerability to MDRO infection; the effect of bacterial infections on disease course in cirrhosis; prevalence of MDROs in patients with cirrhosis; outcomes following MDRO infection; fungal infections; antibiotics and their efficacy; and management of MDRO infections in terms of detection, antimicrobial and nonantimicrobial treatments, prophylaxis, antibiotic stewardship, the gut microbiome, and technological interventions.


Multi-level total en bloc spondylectomy for solitary lumbar metastasis of myxoid liposarcoma.
This article reports a case of solitary lumbar metastasis of myxoid liposarcoma treated by multi-level total en bloc spondylectomy. Myxoid liposarcoma has a predisposition to initial metastasis at an extrapulmonary site including bone. However a bone scan and FDG-PET, which are generally used for a whole-body screening of metastasis, are not sensitive to bone metastasis from myxoid liposarcoma. These situations make it difficult to achieve curative resection of a bone metastasis, especially in the spine. The patient was a 54-year-old man who had an intralesional excision of soft tissue tumor in the right thigh. He had an additional expansive excision due to the histological diagnosis of myxoid liposarcoma at the initial surgery. Four years postoperatively, L3 metastasis expanding to the adjacent vertebrae was detected using magnetic resonance imaging. Plain radiographs and computed tomography showed no evidence of the tumor involving the lumbar spine. A bone scan was false-negative although FDG-PET showed mild uptake. There was no other metastasis on the further examination. Multi-level total en bloc spondylectomy was performed using a combined posterior-anterior approach. The lumbar nerves were dissected and preserved. The vertebral bodies of L2, 3 and the upper half of L4, which had been invaded by the tumor, were removed en bloc using an anterolateral extraperitoneal approach. He had no local recurrence or further metastasis until he died of ischemic cardiac disease 14 months postoperatively.


Volumetric bone mineral density in normal subjects, aged 5-27 years.
Concerns have been raised regarding the validity of using areal bone mineral density (aBMD) as a substitute for the true volumetric bone mineral density (vBMD) in the pediatric population. We studied 209 normal subjects (109 males), aged 5-27 yr, to examine the influence of age, gender and growth on vBMD. The femoral neck, midthird of the femoral shaft, and the four lumbar vertebral bodies (L1-L4) were studied. Using data on bone width and height obtained by dual energy x-ray absorptiometry, bone volume was calculated with the assumption that all three sites are cylinders. In contrast to aBMD, vBMD of the femoral neck bore no relationship to age or weight in both sexes, but was significantly related to height in females (r2 = 0.07; P = 0.01). Similarly, vBMD of the femoral shaft (vFBMD) did not change with age or height in either sex. In females, a significant inverse relationship was seen between vFBMD and weight (r2 = 0.14; P = 0.001). Male subjects had higher vFBMD than females (mean +/- SD, 0.73 +/- 0.11 vs. 0.70 +/- 0.12; P = 0.047), but no sex difference was seen in vBMD of the femoral neck. Conversely, vBMD of L1-L4 remained age and growth dependent, although the strength of the relationship was weaker than that for aBMD (data not shown). In conclusion, the vBMD of the femoral neck and shaft is independent of age and is less dependent on growth variables in children and young adults than is aBMD. These observations offer a different perspective from our previous concepts of aBMD.


Online Three Dimensional Liquid Chromatography/Mass Spectrometry Method for the Separation of Complex Samples.
In this work, a novel online three dimensional liquid chromatography (3D-LC) system was first developed by effectively coupling of preseparation and comprehensive 2D-LC using a stop-flow interface, aiming at improving the separation of complex samples. The sample was separated into two or several fractions through the first dimensional separation, and then each fraction was transferred in an orderly way into the following comprehensive 2D-LC part for further analysis. More optimal conditions could be operated in the second and third dimensions according to the properties of each fraction. Thus, the resolution of the 3D-LC system was substantially improved. Analysis of soybean extract was taken as a proof-of-principle to demonstrate the powerful separation of the established 3D-LC system. The amide column was selected as the first dimension column. Weakly polar metabolites (such as lipids, aglycones, etc.) and polar metabolites (such as glycosides, etc.) were separated into different fractions. Fluorophenyl and C18 columns were used in the second and third dimensions of the 3D-LC system for further separation, respectively. There were 83 flavonoids characterized in the soybean extract, including many difficult to separate isomers and low-abundance flavonoids; in total, they were nearly 30% more than those identified in the comparative comprehensive 2D-LC approach. In conclusion, this 3D-LC system is flexible in construction and applicable to complex sample analysis.


Ectophosphatase activity in the triple-negative breast cancer cell line MDA-MB-231.
Breast cancer is one of the most common cancers in the female population worldwide, and its development is thought to be associated with genetic mutations that lead to uncontrolled and accelerated growth of breast cells. This abnormal behavior requires extra energy, and indeed, tumor cells display a rewired energy metabolism compared to normal breast cells. Inorganic phosphate (Pi) is a glycolytic substrate of glyceraldehyde-3-phosphate dehydrogenase and has an important role in cancer cell proliferation. For cells to obtain Pi, ectoenzymes in the plasma membrane with their catalytic site facing the extracellular environment can hydrolyze phosphorylated molecules, and this is an initial and possibly limiting step for the uptake of Pi by carriers that behave as adjuvants in the process of energy harvesting and thus partially contributes to tumor energy requirements. In this study, the activity of an ectophosphatase in MDA-MB-231 cells was biochemically characterized, and the results showed that the activity of this enzyme was higher in the acidic pH range and that the enzyme had a Km = 4.5 ± 0.5 mM para-nitrophenylphosphate and a Vmax = 2280 ± 158 nM × h-1 × mg protein-1 . In addition, classical acid phosphatase inhibitors, including sodium orthovanadate, decreased enzymatic activity. Sodium orthovanadate was able to inhibit ectophosphatase activity while also inhibiting cell proliferation, adhesion, and migration, which are important processes in tumor progression, especially in metastatic breast cancer MDA-MB-231 cells that have higher ectophosphatase activity than MCF-7 and MCF-10 breast cells.


Inhibition of Poly-(ADP-Ribose) Polymerase Protects the Kidney in a Canine Model of Endotoxic Shock.
Poly-(ADP-ribose) polymerases (PARPs), a super family of enzymes, play important roles in preserving genomic integrity, regulating transcriptions, protecting telomeres and determining cell fate. PARP overactivation leads to metabolic disorder and cell injury via depletion of energy substance. However, it is still unclear whether PARP overactivation happens during acute kidney injury (AKI) caused by endotoxic shock (ES). Here, we built a canine model of lipopolysaccharide-induced ES to explore the role of PARP during the development AKI. We also used an intravenous injection of 3-aminobenzamide (3-AB) to further explore whether PARP inhibition rescues the kidney from injury. Cell fate and energy metabolism were detected to explore the underlying mechanisms. As a result, Western blot and immunohistochemistry assays showed PARP overactivation in the very early phase of ES. Through PARP inhibition by 3-AB, we observed significant improvement of systemic hemodynamics, renal hemodynamics, renal oxygen metabolism and renal tubular cell apoptosis. These findings indicated that overactivation of PARP plays an important role in septic AKI. Inhibition of PARP overactivation may protect renal function against hemodynamic disorder, renal metabolism disturbance and renal cell apoptosis during endotoxic AKI.


A simple calculation for the buildup and decay of radon progeny.
A Markov chain in conjunction with an electronic spreadsheet is used to generate the buildup and decay patterns of radon progeny in a procedure involving only multiplication and addition. Markov chains are highly suitable for calculations of this type. Because the Markov matrix may not be readily available, and because some health physicists may not be familiar with this procedure, we give the values of a Markov matrix and demonstrate how it can be used to produce a Markov chain describing the buildup and decay of radon progeny.


Dissertations into Practice: 10 years on, 40 articles later.
Frances Johnson, Regular Feature Editor, looks back on the first 10 years of student projects published in Dissertations into Practice. Forty articles later, she notes that the value of these short features, then as now, is in recognising the potential of student research to a wider audience and the implications of their research on practice.


Gender differences in horizontal strabismus: Systematic review and meta-analysis shows no difference in prevalence, but gender bias towards females in the clinic.
Strabismus is a misalignment of the visual axis that affects 2-3% of the population and can lead to loss of binocular vision. It is currently controversial whether there is a gender difference in the most common form of visual misalignment: horizontal strabismus. Some studies claimed that more females than males have an outward deviation (exotropia), while others concluded that there is no significant gender difference. No previous work has systematically explored gender differences in horizontal strabismus or has compared the results of population-based studies with those of clinic-based studies. We conducted a systematic review and meta-analysis of studies reporting the prevalence of horizontal strabismus. We included 73 population-based studies and compared their disclosed gender population with that in 141 comparable clinical-based studies. We analysed the data according to gender, strabismus type (esotropia, exotropia), and geographic region/ethnicity. Summary statistics showed a nearly identical prevalence of horizontal strabismus (2.558% for males, 2.582% for females), esotropia (1.386% males vs. 1.377% females), and of exotropia (1.035% males vs. 1.043% females). Meta-analysis results showed that these differences between males and females were not statistically significant (odds ratio (OR) = 1.01; 95% confidence interval (CI) = 0.97-1.10), but that females were significantly more frequent (by 7.50%) in clinic-based studies than males, with 5.00% more females for esotropia, and 12.20% more females for exotropia when adjusted for the population's sex ratio. The extent of the female gender bias differed between geographic regions/societies, with Asians having the lowest bias towards females and Latin American countries having the strongest bias. Males and females have the same prevalence of horizontal strabismus, including exotropia. Females with strabismus seek health care or are brought to clinics significantly more often than males. This is an example of gender bias in health care in favour of females rather than males, apparently because parents - erroneously fearing only cosmetic consequences - are more concerned about strabismus in their daughters than their sons. Societal attitudes towards females, as well as economic factors (insurance status), appear to be relevant factors that determine the magnitude of the gender bias in horizontal strabismus.


In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding.
Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = approximately 3.5; chocolate pudding, pH = approximately 5.5-6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and 19.961 (0.668) mg/capsule for the comparator not exposed to food, the sample exposed to applesauce, and the sample exposed to apple juice, respectively. However, exposure to chocolate pudding altered the integrity of the pellet's enteric coating (mean [SD] potency results, 17.780 [1.605] mg/capsule). Results of impurities testing suggested that none of the test foods caused significant degradation of the drug product. Mean dissolution results found that after 2 hours in 0.1 N HCl, < or = 1% of duloxetine was released from the comparator and pellets exposed to applesauce and apple juice. However, the mean dissolution profile of the sample exposed to pudding reported near-total release (90%) after 2 hours in 0.1 N HCl during the gastric challenge portion of the dissolution test. Results from this study found that the enteric coating of duloxetine pellets mixed with applesauce or apple juice was not negatively affected. The pellets were stable at room temperature for < or = 2 hours and should quantitatively allow delivery of the full capsule dose, provided that the pellet integrity is maintained (ie, not crushed, chewed, or otherwise broken). Therefore, mixing duloxetine pellets with applesauce or apple juice appears to be an acceptable vehicle for administration. However, exposing the pellets to chocolate pudding damaged the pellets' enteric coating, suggesting that pudding may be an unacceptable vehicle for administration.


AcuFocus Corneal Inlay to Correct Presbyopia Using Femto-LASIK. One Year Results of a Prospective Cohort Study.
To evaluate the safety and efficacy of the AcuFocus small aperture corneal inlay (KAMRA) for the correction of presbyopia using femto-LASIK. This is a prospective, non-randomised cohort study including 50 presbyopic patients with hyperopia, emmetropia or mild myopia. The intracorneal inlay was implanted in the non-dominant eye using a VisuMax femtosecond laser (Zeiss 500 kHz) to create a superior-hinged flap. The inlay was centred over the visual axis. Minimum postoperative follow-up was performed for a period of 12 months. Fifty intracorneal inlays were implanted. At one year follow-up, the median uncorrected near visual acuity significantly improved from Jaeger (J)8 to J2 (p < 0.001). 94 % of patients could read J3 or better. The median uncorrected distance visual acuity also improved from 20/32 to 20/22 (p < 0.001). 92 % of patients could see 20/32 or better. One implant had to be recentred at four weeks follow-up. One implant was removed six months after implantation due to insufficient uncorrected near and distance visual acuity as well as slight corneal haze, which resolved four weeks later under topical treatment with fluorometholone eye drops, without any loss of best corrected distance visual acuity. No other complications occurred during the postoperative follow-up period. AutoFocus Corneal Inlay (ACI), also known as KAMRA, can provide a safe, effective and, most importantly, reversible treatment for presbyopia in hyperopic, myopic and emmetropic patients.


Decreased central opioid activity in premenstrual syndrome: luteinizing hormone response to naloxone.
To evaluate central opioid activity in women with prospectively documented premenstrual syndrome (PMS) and control women in the mid- and late luteal phases of the menstrual cycle. Blood was collected every 15 minutes 1 hour before (0800) and 2 hours after treatment (0900-1100). The treatment was administered in a randomized fashion and consisted of naloxone 1 or 4 mg or placebo, and blood was assayed for luteinizing hormone (LH). Baseline estradiol, progesterone, and prolactin were measured at 0800 and 0900 hours. There was a significant increase in LH area under the curve and mean LH in response to naloxone in the midluteal phase in the control (P < .001). The PMS subjects did not display a significant increase in LH concentration in response to naloxone in the midluteal phase. There were no significant LH responses to naloxone in either group in the late luteal phase. There were no significant differences in estradiol, progesterone, or prolactin concentrations or estrogen to progesterone ratios between groups. Control women have an enhanced central opioid tone during the midluteal phase that diminishes and becomes minimal in the late luteal phase of the menstrual cycle. In contrast, women with PMS have a loss of central opioid tone during the midluteal phase as indicated by the loss of LH response to naloxone. This attenuated central opioid tone in women with PMS as compared with asymptomatic control women may play a role in the pathophysiology of PMS.