Cloning of the cta operon from alkaliphilic Bacillus firmus OF4 and characterization of the pH-regulated cytochrome caa3 oxidase it encodes.
We have cloned and sequenced the DNA of alkaliphilic Bacillus firmus OF4 encompassing the cta operon that encodes a pH-regulated cytochrome caa3 oxidase. The gene organization is identical with that of the homologous Bacillus subtilis caa3 oxidase locus (van der Oost, J., von Wachenfeld, C., Hederstedt, L. & Saraste, M. (1991) Mol. Microbiol. 5, 2063-2072). The deduced amino acid sequences of the four putative structural subunits (CtaC-F) indicate substantial similarity to caa3-type oxidases from other Bacillus species and to other members of the family of mitochondrial-type aa3 oxidases. A marked paucity of basic residues was noted in the cytochrome c-containing domain of CtaC, which faces the highly alkaline external milieu. We have also purified the enzyme as a three-subunit complex, with possible trace amounts of a fourth subunit. N-terminal sequence analysis of the two largest subunits confirmed them to be encoded by the cloned cta genes. An additional, minor caa3 component with distinctive chromatographic properties was noted during purification. Analysis of mRNA with a ctaD probe revealed an abundant 4-kilobase message of the right size to encode CtaC-F. The cellular content of this message varied with growth pH. Cells grown at pH 10.5 contained 2 to 2.5 times more message than those grown at pH 7.5, in good correspondence with the relative amounts of caa3 oxidase found in the cells. The ctaB gene, immediately upstream from the ctaC-F genes, was found to be transcribed onto a low abundance 5-kilobase message, which is likely also to encode CtaC-F. Levels of this message were not affected by growth pH.


Forensic discrimination of photocopy and printer toners II. Discriminant analysis applied to infrared reflection-absorption spectroscopy.
Copy toner samples were analyzed using reflection-absorption infrared microscopy (R-A IR). The grouping of copy toners into distinguishable classes achieved by visual comparison and computer-assisted spectral matching was compared to that achieved by multivariate discriminant analysis. For a data set containing spectra of 430 copy toners, 90% (388/430) of the spectra were initially correctly grouped into the classifications previously established by spectral matching. Three groups of samples that did not classify well contained too few samples to allow reliable classification. Samples from two other pairs of groups were similar and often misclassified. Closer examination of spectra from these groups revealed discriminating features that could be used in separate discriminant analyses to improve classification. For one pair of groups, the classification accuracy improved to 91% (81/89) and 97% (28/29), for the two groups, respectively. The other pair of groups were completely distinguishable from one another. With these additional tests, multivariate discriminant analysis correctly classified 96% of the 430 R-A IR toner spectra into the toner groups found previously by spectral matching.


Genotypes of glutathione S-transferase M1 and N-acetyltransferase 2 in Japanese patients with gastric cancer.
BACKGROUND: Genetic polymorphisms of some metabolizing enzymes, such as glutathione S-transferase M1 ( GSTM1) and N-acetyltransferase 2 ( NAT2), have recently been shown to affect individual susceptibility to various types of cancers. However, the link between the GSTM1 polymorphism and gastric cancer is controversial and there are few studies focusing on the relation between a combination of the two enzyme genotypes and gastric cancer risk.METHODS: Genotypes of GSTM1 and NAT2 were determined by polymerase chain reaction (PCR) or restriction fragment length polymorphism (RFLP) following PCR in 147 Japanese patients with gastric cancer and 112 autopsied Japanese patients without stomach, lung, urinary bladder, or colon cancer.RESULTS: The frequency of the GSTM1 null genotype was significantly increased in the cancer patients (91 individuals; 61.9%) compared with the controls (55 individuals; 49.1%) ( P < 0.05; odds ratio, 1.68). The incidence of patients with the homozygously wild genotype of NAT2 (rapid acetylator) was slightly lower in the cancer group (59 individuals; 40.1%) than in the control group (58 individuals; 51.8%). The proportion of patients with both the GSTM1 gene and homozygously wild genotype of NAT2 was significantly smaller in the cancer group (19 individuals; 12.9%) than in the control group (29 individuals; 25.9%) ( P < 0.05). In addition, in a comparison of four subgroups of gastric cancer which were classified by both the genotype of GSTM1 and the predicted phenotype of NAT2, the number of subjects in the subgroup " GSTM1+/rapid" was significantly smaller than the expected numbers of the other three subgroups ( P < 0.05).CONCLUSION: It is suggested that a combination of GSTM1 and NAT2 decreases the risk of gastric cancer in Japanese patients.


Effects of the dopamine D3 receptor ligand 7-OH-DPAT on male rat ejaculatory behavior.
As previously shown, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) produces a marked and highly characteristic facilitation of male rat ejaculatory behavior, and this effect is not sensitive to dopamine (DA) receptor antagonists of the D1 or D2 receptor families. The structural congener 7-OH-DPAT, primarily characterized as a DA D3 receptor selective ligand, produced a facilitation of male rat ejaculatory behavior, as evidenced by a dose-dependent decrease in the number of intromissions preceding ejaculation and in time to ejaculation. These effects could be antagonized by pretreatment with the DA D2/D3 receptor antagonist, raclopride. Thus, 7-OH-DPAT-induced effects on male rat ejaculatory behavior can be pharmacologically differentiated from effects produced by 8-OH-DPAT.


Duration and intensity of physical activity and disability among European elderly men.
To investigate the relationship between duration and intensity of physical activity and disability 10 years later, and to investigate the possible effect of selective mortality. Longitudinal data of 560 men aged 70?-?89 years, without disability at baseline from the Finland, Italy and The Netherlands Elderly (FINE) Study was used. Physical activity in 1990 was based on activities like walking, bicycling and gardening. Disability severity (three categories) in 1990 and 2000 was based on instrumental activities, mobility and basic activities of daily living. Men in the highest tertile of total physical activity had a lower risk of disability than men in the lowest tertile (odds ratio (OR) 0.46; 95% confidence interval (CI): 0.26-0.84). This was due to duration of physical activity (OR highest tertile 0.42; 95% CI: 0.23-0.78 compared to the lowest tertile). Intensity of physical activity was not associated with disability. Addition of deceased men as fourth category leaded to weaker associations between physical activity and disability (OR highest tertile 0.67; 95% CI: 0.44-1.02). Even in old age among relatively healthy men, a physically active lifestyle was inversely related to disability. To prevent disability duration of physical activity seems to be more important than intensity.


Benign scrotal tumors masquerading as expanding varicoceles.
Vascular lesions of the scrotum though most often varicoceles, can occasionally represent either benign or malignant tumors containing vascular elements. Two pediatric patients presenting with vascular scrotal masses resembling varicoceles are reported. Histologic interpretation of the operative specimens demonstrated benign tumors of the scrotum. Hemangiomas, hamartomas, or mesenchymal tumors should be especially suspect in the presence of any vascular right scrotal lesion. Because of the infrequency of prepubertal varicoceles, any vascular lesion of the scrotum in this age group should undergo biopsy before simple excision is performed to rule out the presence of malignancy. Early excision of benign mesenchymal tumors is especially important if, as some believe, they eventually dedifferentiate to more malignant tumors later in the lifetime of an individual.


Effects of online social media on improving mothers' behaviors towards preventing their children's otitis media based on the PRECED model: a randomized educational intervention trial.
Otitis media is one of the most common diseases in children, especially those under 2 years of age. This study aimed to investigate the effect of educational intervention based on the PRECEDE model on mothers' preventive behaviors of middle ear infections in infants. This study was conducted as an educational randomized controlled trial on 88 mothers with infants referred to health centers in Arak, Iran. Sampling from September 2021 to February 2022 selected trough stratified random sampling who were assigned to two groups of experimental = 44 and control = 44. The data collection tool was a reliable and valid questionnaire that included demographic information, constructs of PRECEDE model regarding otitis media, and preventive behaviors. The experimental group received 4 training sessions (each session 60 min) through WhatsApp social network. Information was collected through an online questionnaire before and 3 months after the educational intervention from both groups. Data analysis was also performed with SPSS version 23. Before the educational intervention there was no significant difference between the experimental and control groups in the otitis media preventive behaviors and structures of PRECEDE model (p > 0.05). After the educational intervention, in the experimental group the average score of knowledge from 0.49 to 0.81, attitude from 4.01 to 4.58, enabling factors from 0.72 to 0.85, reinforcing factors from 3.31 to 3.91 and behavior from 3.25 to 3.66 increased significantly (p < 0.001). PRECEDE-based education with controlling, monitoring and follow-up during the program was effective in promoting the preventive behaviors of otitis media. Therefore, due to the side effects of otitis media, especially in vulnerable periods such as childhood, it is recommended that trainings based on this model be carried out in other health care centers and clinics in order to maintain children health. This trial has been registered at the Iranian Registry of Clinical Trials, IRCT20210202050228N1. Prospectively registered at 2021-May-21, (2021/05/21) available at: URL: https://en.irct.ir/trial/54073 .


Cell death mechanisms of plant-derived anticancer drugs: beyond apoptosis.
Despite remarkable progress in the discovery and development of novel cancer therapeutics, cancer remains the second leading cause of death in the world. For many years, compounds derived from plants have been at the forefront as an important source of anticancer therapies and have played a vital role in the prevention and treatment of cancer because of their availability, and relatively low toxicity when compared with chemotherapy. More than 3000 plant species have been reported to treat cancer and about thirty plant-derived compounds have been isolated so far and have been tested in cancer clinical trials. The mechanisms of action of plant-derived anticancer drugs are numerous and most of them induce apoptotic cell death that may be intrinsic or extrinsic, and caspase and/or p53-dependent or independent mechanisms. Alternative modes of cell death by plant-derived anticancer drugs are emerging and include mainly autophagy, necrosis-like programmed cell death, mitotic catastrophe, and senescence leading to cell death. Considering that the non-apoptotic cell death mechanisms of plant-derived anticancer drugs are less reviewed than the apoptotic ones, this paper attempts to focus on such alternative cell death pathways for some representative anticancer plant natural compounds in clinical development. In particular, emphasis will be on some promising polyphenolics such as resveratrol, curcumin, and genistein; alkaloids namely berberine, noscapine, and colchicine; terpenoids such as parthenolide, triptolide, and betulinic acid; and the organosulfur compound sulforaphane. The understanding of non-apoptotic cell death mechanisms induced by these drugs would provide insights into the possibility of exploiting novel molecular pathways and targets of plant-derived compounds for future cancer therapeutics.


Minimally invasive surgical and miniscrew-assisted rapid palatal expansion (MISMARPE) in adult patients.
The purpose of this study was to evaluate maxillary expansion, operative time and pain associated with a new minimally invasive surgical technique to treat maxillary hypoplasia in adult patients. Consecutive patients were included and prospectively analyzed. The technique consists in miniscrew-assisted rapid palatal expansion (MARPE), minimally invasive approach to maxillary osteotomies, latency period and activation period until the desired expansion. The parameters evaluated included operative time, treatment-related pain by the visual analog scale (VAS), and transverse maxillary expansion. The Shapiro-Wilk test was used to assess the normality of data distribution. A paired t-test was used to compare the data between T0 (preoperative) and T1 (postoperative - end of activation). The significance level was set at 5%. Eleven patients were included. Mean operative time was 24.11 min (14.4-32 min) and overall postoperative VAS score was 2.81 (0-9). A comparative analysis showed significant increases in maxillary width at the skeletal, alveolar, and dental levels (p < 0.0001 for all), with a mean range of 1.8 (SD 0.3) mm to 4.7 (SD 0.5) mm. The present minimally invasive surgical MARPE (MISMARPE) technique appears to yield good skeletal outcomes with minimal trauma. It might have potential for clinical use, but larger comparative studies are needed to confirm the clinical relevance of the approach.


Interface modification effect between p-type a-SiC:H and ZnO:Al in p-i-n amorphous silicon solar cells.
Aluminum-doped zinc oxide (ZnO:Al) [AZO] is a good candidate to be used as a transparent conducting oxide [TCO]. For solar cells having a hydrogenated amorphous silicon carbide [a-SiC:H] or hydrogenated amorphous silicon [a-Si:H] window layer, the use of the AZO as TCO results in a deterioration of fill factor [FF], so fluorine-doped tin oxide (Sn02:F) [FTO] is usually preferred as a TCO. In this study, interface engineering is carried out at the AZO and p-type a-SiC:H interface to obtain a better solar cell performance without loss in the FF. The abrupt potential barrier at the interface of AZO and p-type a-SiC:H is made gradual by inserting a buffer layer. A few-nanometer-thick nanocrystalline silicon buffer layer between the AZO and a-SiC:H enhances the FF from 67% to 73% and the efficiency from 7.30% to 8.18%. Further improvements in the solar cell performance are expected through optimization of cell structures and doping levels.


Modelling the inhibition of sorbic and benzoic acids on a native yeast cocktail from table olives.
The single and combined effects, in a synthetic medium at selected pH values, of sorbic and benzoic acids on a yeast cocktail (Saccharomyces cerevisiae, Pichia anomala, Issatchenkia occidentalis, and Candida diddensiae, isolated from table olives) have been studied. Applying the checkerboard method the minimum inhibitory concentration (MIC) obtained for the respective individual preservatives (expressed as undissociated acid) were: sorbic acid, 5.94, 3.85 and 3.19 mM at pH of 4.5, 4.0, and 3.5, respectively; and benzoic acid, not detected (at total 20.5 mM), 10.40 and 6.83 mM, respectively, for the same pH levels. The estimated fractional inhibitory concentrations (FIC) indexes showed additive effects between inhibitors. Fractional area (fa), modelled by the (extended) Lambert and Lambert [2003. A model for the efficacy of combined inhibitors. J. Appl. Microbiol. 95, 734-743] equation (ELPM), also showed additives of both preservatives but different shapes in the dose-response curves; the individual MIC (as undissociated acid) deduced from this method were: 5.60, 3.31, and 3.26 mM for sorbic acid at pH of 4.5, 4.0, and 3.5, respectively; and 29.65 (extrapolated), 10.00, and 6.25 mM for benzoic acid at the same pH levels. Mixtures above the curves connecting the limits (MIC) at each pH were also inhibitory. There was agreement between MIC values from FIC and ELPM, although the last one provided further information on the inhibition behaviour. I. occidentalis was the most resistant yeast of the cocktail to sorbic and benzoic acids.


Long-term outcomes after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis for ulcerative colitis.
During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME. This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score. Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03). Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC.


Associations between dietary intake and breast milk dioxin levels in Tokyo, Japan.
The presence of dioxins in breast milk has gained much attention recently. However, in Japan the relationship between the consumption of different foods and the human breast milk dioxin concentrations is still unclear. Breast milk was taken from 240 mothers residing in Tokyo, Japan to measure and analyze the concentrations of polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar poly-chlorinated biphenyls contained in the fat. Individual milk samples were obtained from the mothers 30 days after delivery in 1999 and 2000. The data of the mothers' diets before pregnancy were collected by means of food frequency and amount estimation. Spearman correlation analysis and stepwise multiple linear regression were used to analyze the data. The concentrations of dioxins in breast milk were influenced mainly by the mother's age and history of breast-feeding. All the Spearman correlation coefficients were less than 0.20. Pork, roast ham, sausage, salt codfish and tempura had negative correlations with breast milk dioxins. History of breast-feeding and the mother's age should be considered and emphasized in this kind of analysis. The cause effect relationship between dietary intake and breast milk dioxin levels were still uncertain.


Insights on urinary NGAL obtained in a primary care setting.
A majority of patients developing acute kidney injury (AKI) receive medical care from their primary care physicians prior to the occurrence of conditions that predispose them to this complication. To characterize the uNGAL concentrations in primary care patients and to assess these concentrations with regard to different reference intervals, we conducted a multicenter, cross-sectional study with random selection of general practitioners (GP) from all GP offices in seven Swiss cantons. 1000 adults (566 females; mean age 57±17 years) were included. The median absolute uNGAL was 21 ng/L. Elevated uNGAL (>100 ng/L) together with normal kidney test results (eGFR and albuminuria) were found in 6.5% of all patients. Females had a significantly higher uNGAL than did males. Among a multitude of different clinical and laboratory variables, only age, gender, liver function parameters, WBC and CRP were significantly associated with uNGAL levels in a multivariate analysis. When examining the proposed KDIGO classification of chronic kidney disease, the uNGAL levels at the given eGFR stages changed with increasing albuminuria stages and vice versa. Age, gender, markers of inflammation and liver function, exert influences on uNGAL concentrations. A substantial proportion of patients exhibited normal kidney testing together with elevated uNGAL, potentially identifying patients with increased renal stress and at increased risk for the development of AKI.


Clinical Indications for Growth Hormone Therapy.
Growth hormone (GH) is an injectable medication originally used to replace the deficiency of the hormone, but has expanded to treating conditions that may reduce growth and adult height even when the body maintains endogenous GH production. In the United States, there are 8 Food and Drug Administration (FDA)-approved indications for pediatric GH therapy: GH deficiency, Prader-Willi Syndrome, small for gestational age (SGA) without catch-up growth, idiopathic short stature, Turner syndrome, SHOX gene haploinsufficiency, Noonan Syndrome, and chronic renal insufficiency. We characterize the growth patterns and effects of GH treatment in each of these indications. We also review patterns of growth that warrant referral to a pediatric endocrinologist, as well as safety updates. This review is intended to guide practitioners on the initial evaluation and management of patients with short stature, and the indications for GH therapy.


Design and construction of novel thrombin inhibitors featuring P3-P4 quaternary lactam dipeptide surrogates.
Potent serine protease inhibitor 1a featuring a hybrid P3-P4 quaternary lactam dipeptide surrogate was prepared based upon SAR and molecular modeling investigations and in order to further probe the S2/S3 thrombin and FXa subsites. An efficient and concise synthetic route to the key aminolactam intermediate 4 was developed. The design, synthesis, and biological activity of this target and its P3-P4 diastereomer 1b is presented.


Quality of life among health care workers in Arab countries 2 years after COVID-19 pandemic.
Assessment of the quality of life (QoL) among healthcare workers (HCWs) is vital for better healthcare and is an essential indicator for competent health service delivery. Since the coronavirus disease 2019 (COVID-19) pandemic strike, the frontline position of HCWs subjected them to tremendous mental and psychological burden with a high risk of virus acquisition. This study evaluated the QoL and its influencing factors among HCWs residing in the Arab countries. This was a cross-sectional study using a self-administered online questionnaire based on the World Health Organization QoL-BREF instrument with additional questions related to COVID-19. The study was conducted in three different languages (Arabic, English, and French) across 19 Arab countries between February 22 and March 24, 2022. A total of 3,170 HCWs were included in the survey. The majority were females (75.3%), aged 18-40 years (76.4%), urban residents (90.4%), married (54.5%), and were living in middle-income countries (72.0%). The mean scores of general health and general QoL were 3.7 ± 1.0 and 3.7 ± 0.9, respectively. Those who attained average physical, psychological, social, and environmental QoL were 40.8, 15.4, 26.2, and 22.3%, respectively. The income per capita and country income affected the mean scores of all QoL domains. Previous COVID-19 infection, having relatives who died of COVID-19, and being vaccinated against COVID-19 significantly affected the mean scores of different domains. A large proportion of the Arab HCWs evaluated in this study had an overall poor QoL. More attention should be directed to this vulnerable group to ensure their productivity and service provision.


The use of stroma-free hemoglobin solution for partial exchange transfusion in aortic resection in dogs.
Vascular surgery involves multiple transfusions with their concomitant hazards. At the start of each vascular procedure, 20 per cent of each patient's blood (approximately 1,000 of 5,600 ml) is removed and replaced with colloid and crystalloid and the withdrawn blood returned at the end of surgery. Theoretically, if 40 per cent of the blood volume (2,000+ ml) could be withdrawn, essentially no banked blood would be required for a major vascular procedure. Therefore, 40 per cent (900+ ml) of the blood volume of twenty greyhounds was withdrawn under anesthesia and replaced with stroma-free hemoglobin solution (SFHS). Abdominal aortic resection and graft replacement was performed, and any blood lost during the procedure was replaced with SFHS. After surgery the withdrawn blood was returned to the dog and excess volume removed with postoperative hemodilution diuresis. The study included a battery of twenty tests for monitoring during the procedure and at intervals from this project that in greyhounds 40 per cent or more of the blood volume may be removed and replaced with SFHS and major vascular surgery done without undue risk and with unaltered kidney function.


Switching the Cleavage Sites in Palladium on Carbon-Catalyzed Carbon-Carbon Bond Disconnection.
We have demonstrated a palladium on carbon-catalyzed approach to regioselectively alter the cleavage sites of the C-C bonds of cinnamaldehyde derivatives by a slight change in the reaction conditions in isopropanol under an O2 atmosphere. Styrene derivatives could be selectively formed by the addition of Na2CO3 in association with the dissociation of carbon monoxide, while benzaldehyde derivatives were generated by the addition of CuCl and morpholine instead of Na2CO3.


Improving hospital budgeting and accountability a best practice approach.
Best practices in setting and managing healthcare organization budgets include: Using comparative benchmarks. Setting accurate, high-performance department budgets. Establishing a culture of accountability. Managing expenses. Monitoring variances and requiring corrective action plans. Employing a balanced scorecard.


Cystic fibrosis in Latin America-Improving the awareness.
The burden of cystic fibrosis (CF) in Latin America is being increasingly recognized and is significant compared with other regions of the world. In this short communication, we assess the current situation in some Latin American countries and make suggestions for possible directions for future focus. We discuss the work that remains in deciphering how the various genetic, environmental and medical factors interact and influence outcomes in different ethnic groups. We also consider the need for consistency in both research and access to services across Latin America, including CF registries, neonatal screening programs, access to specialized CF healthcare practitioners, transition to adult clinics and treatment regimens. Progress in these areas is likely to build on the advances to date, and improve the lives of patients in Latin America who are affected by this debilitating and life-limiting disorder.


Effectiveness of γ-oryzanol in reducing neuromotor deficits, dopamine depletion and oxidative stress in a Drosophila melanogaster model of Parkinson's disease induced by rotenone.
The γ-orizanol present in rice bran oil contains a mix of steryl triterpenyl esters of ferulic acid, which is believed to be linked to its antioxidant potential. In this study we investigated the neuroprotective actions of γ-orizanol (ORY) against the toxicity induced by rotenone (ROT) in Drosophila melanogaster. The flies (both genders) aged between 1 and 5 days old were divided into four groups of 50 flies each: (1) control, (2) ORY 25 μM, (3) ROT 500 μM, (4) ORY 25 μM+ROT 500 μM. Flies were concomitantly exposed to a diet containing ROT and ORY for 7 days according to their respective groups. Survival and behavior analyses were carried out in vivo, and ex vivo analyses involved acetylcholinesterase activity (AChE), determination of dopaminergic levels, cellular viability and mitochondrial viability, activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reactive species levels (RS), lipid peroxidation (TBARS) and contents of total thiols and non-proteic thiols (NPSH). Our results show for the first time that ORY not only acts as an endogenous activator of the cellular antioxidant defenses, but it also ameliorates rotenone induced mortality, oxidative stress and mitochondrial dysfunction. Our salient findings regarded the restoration of cholinergic deficits, dopamine levels and improved motor function provided by ORY. These results demonstrate the neuroprotective potential of ORY and that this effect can be potentially due to its antioxidant action. In conclusion, the present results show that ORY is effective in reducing the ROT induced toxicity in D. melanogaster, which showed a neuroprotective action, possibly due to the presence of the antioxidant constituents such as the ferulic acid.


Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer.
In recent years, the proportion of patients with NSCLC diagnosed at an early stage has increased continuously. In this study, we analyzed samples and data collected from 119 samples from 67 early stage patients with NSCLC, including 52 pairs of tumor and adjacent non-neoplastic samples, and performed RNA-sequencing analysis with high sequencing depth. We found that immune-related genes were highly enriched among the differentially expressed genes and observed significantly higher inferred immune infiltration levels in adjacent non-neoplastic samples than in tumor samples. In survival analysis, the infiltration of certain immune cell types in tumor, but not adjacent non-neoplastic, samples were associated with overall patient survival, and excitingly, the differential infiltration between paired samples (tumor minus non-neoplastic) was more prognostic than expression in either non-neoplastic or tumor tissues. We also performed B cell receptor (BCR) and T cell receptor (TCR) repertoire analysis and observed more BCR/TCR clonotypes and increased BCR clonality in tumor than in non-neoplastic samples. Finally, we carefully quantified the fraction of the five histologic subtypes in our adenocarcinoma samples and found that higher histologic pattern complexity was associated with higher immune infiltration and low TCR clonality in the tumor-proximal regions. Our results indicated significantly differential immune characteristics between tumor and adjacent non-neoplastic samples and suggested that the two regions provided complementary prognostic values in early-stage NSCLCs.


Immunoblotting with monoclonal antibodies: loss of immunoreactivity with human immunoglobulins arises from polypeptide chain separation.
Immunoblotting has been used to study the antigen binding characteristics of 5 monoclonal antibodies (Mc/Abs) against human Ig (1 anti-kappa, 2 anti-gamma and 2 anti-delta chain. Of the 4 Mc/Abs only 1 (the anti-kappa chain Mc/Ab) reacted with its antigen when blotted from reducing SDS polyacrylamide gels. However, the 4 Mc/Abs which recognise immunoglobulin heavy chains were able to bind their antigens when blotted from native or non-reducing SDS gels. The lack of reactivity of the latter Mc/Abs in blots from reduced SDS gels may be attributed to the separation of Ig which occurs during electrophoresis after the -S-S- bonds are broken. It may be concluded that the conformation of Ig heavy chains is considerably altered when Ig molecules are disrupted and Ig chains separated, and several heavy chain determinants are lost during this process. Therefore determinants recognised by the anti-heavy chain Mc/Abs are most likely to be of the 'conformational' type whereas the anti-light chain Mc/Ab may well recognise a purely sequential determinant.


1,25-Dihydroxyvitamin D3 modulates the effects of interleukin 2 independent of IL-2 receptor binding.
Previous studies have shown that 1,25-dihydroxyvitamin D3 (calcitriol) is a macrophage-derived cytokine and a potent inhibitor of IL-2 and interferon-gamma (IFN-gamma) production and T lymphocyte proliferation. The growth inhibitory effect of calcitriol is only partially reversed by IL-2 addition, suggesting IL-2 independent effects. In this report we characterize the IL-2-independent effects of calcitriol on lymphocyte activation. Calcitriol inhibited cellular transition from early to late G1 (G1A-G1B transition) in both the absence and presence of IL-2. Exogenous IL-2 did not increase either IFN-gamma production or transferrin receptor (TfR) expression in the presence of calcitriol despite increases in cell entry into late G1 and proliferation. Calcitriol treatment reduced TfR expression by activated T lymphocytes independent of their location in the cell cycle, further suggesting its independence from IL-2-mediated events. Combinations of rIL-2 and rIL-4 did not reverse calcitriol-dependent inhibition of proliferation and TfR expression to any greater degree than rIL-2 alone. Northern blot analysis demonstrated the decrease in IFN-gamma and TfR mRNA accumulation with calcitriol treatment was unaffected by exogenous IL-2. In contrast, IL-2R mRNA and protein were increased by IL-2, with superinduction in the presence of calcitriol, demonstrating that the lack of effect on IFN-gamma and TfR was not due to IL-2 insensitivity. Moreover, equivalent numbers of high-affinity IL-2R were expressed by both control and calcitriol-treated T lymphoblasts. Thus, lectin-activated T lymphocyte responsiveness to IL-2, as measured by IL-2R expression and proliferation, can be partly to completely dissociated from IFN-gamma production and TfR expression in the presence of calcitriol. Finally, IL-2-induced proliferation of unstimulated mononuclear cells and purified T lymphocytes was inhibited by calcitriol. These data indicate that local production of calcitriol by activated macrophages is capable of regulating T lymphocyte activation not only through suppression of IL-2 production, but also through additional mechanism(s), that are mediated at a post-IL-2R level.


Endoscopic curettage and bone grafting of the enchondroma of the proximal phalanx of the great toe.
Enchondromas are the most commonly found benign tumors of the small bones of the foot, mainly involve the phalanges and metatarsals. They are usually asymptomatic, and are found as an incidental finding on routine X-rays. Surgical intervention is indicated in symptomatic lesions as well as larger lesions (greater than 3-4cm) even if these lesions are asymptomatic. Enchondroma most often can be adequately treated with intralesional curettage and bone grafting. A technique of endoscopic curettage and bone grafting of enchondroma of the proximal phalanx of the hallux is described. This has the advantage of minimally invasive surgery of better cosmesis, less surgical trauma and preservation of the cortical integrity.


Detection of feline immunodeficiency virus by a nested polymerase chain reaction.
A specific and sensitive polymerase chain reaction (PCR) procedure for the detection of feline immunodeficiency virus (FIV) in peripheral blood mononuclear cells (PBMC) was developed. PBMC from both blood samples and cultures were digested by proteinase K in a lysis buffer, and after heat inactivation of the proteinase, the resultant material was used in a two step amplification protocol using nested sets of primers. Two independent amplifications, from the gag and pol genes respectively, were performed in each tube. The PCR was positive for six of 14 samples from FIV seropositive adult cats, while all 36 samples from seronegative cats were negative. In comparison with an antigen-capturing ELISA procedure, the PCR detected FIV infection in PBMC cultures on average two days earlier.


The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature.
Human epidermal growth factor receptor-2 (HER2) is regarded as an important and promising target in the treatment of HER2-positive breast cancers. However, the correlation of clinicopathological characteristics and prognostic significance of HER2 overexpression in gastric cancer patients remains unclear. Our aim was to clarify this issue. Embase, PubMed, and the Cochrane Library were searched for relevant articles published up to May 2016. Outcomes of interest contained sex, age, tumor size, tumor site, tumor node metastasis (TNM) stage, distant metastasis, lymph node metastasis, Lauren's classification, differentiation grade, lymphovascular invasion, neural invasion, and multivariate analysis data for overall survival. A total of 41 studies of 17,494 gastric cancer patients were identified with HER2 test. HER2 positive rate was 19.07% (95% CI = 9.16, 28.98). There existed statistical significance between HER2 overexpression and patients' prognosis (RR = 1.47, 95% CI = 1.09, 1.98). Male patients (OR = 1.48, 95% CI = 1.34, 1.65), proximal tumors (OR = 1.25, 95% CI = 1.07, 1.47), intestinal-type tumors (OR = 3.37, 95% CI = 2.54, 4.47), advanced stage cancers (OR = 1.35, 95% CI = 1.10, 1.66), lymph node metastasis (OR = 1.26, 95% CI = 1.14, 1.41), well-differentiated cancers (OR = 1.79, 95% CI = 1.15, 2.76), and distant metastasis (OR = 1.91, 95% CI = 1.08, 3.38) were correlated with higher HER2 expression rates. However, no statistical differences existed in age, tumor size, lymphovascular invasion, or neural invasion. Subgroup analysis revealed that HER2 expression rates reported in articles from Asian (19.52%) countries were quantitatively higher than those from European (16.91%) areas. Results were consistent with those reports that define HER2 status according to trastuzumab for gastric cancer (ToGA) criteria. This study showed that HER2 overexpression was associated with poor prognosis in gastric cancer patients. HER2 positive rates may be associated with sex, tumor site, TNM staging system, distant metastasis, lymph node metastasis, Lauren's classification, and differentiation grade in gastric cancer patients. The HER2 expression rate in Asians may be higher than that in Europeans. This study offers a convenient way for doctors to select patients for relevant HER2 detection and following treatment.


Hormonal Receptor Expression in Endometrial Carcinoma: A Retrospective Immunohistochemical Study in a Nigerian Tertiary Hospital.
Endometrial carcinoma is the commonest genital tract malignancy in most developed nations, but it lags behind cervical carcinoma and ovarian cancers in most developing nations including Nigeria. Estrogen has been described as a promoter of endometrial carcinogenesis. The aim of this study was to demonstrate the frequency of estrogen receptor (ER) and progesterone receptor (PR) expressions of endometrial carcinoma and to correlate it with tumour grade. Cases of endometrial carcinoma diagnosed in the Department of Pathology over a 10-year period were reviewed retrospectively. The paraffin-embedded blocks were retrieved, and immunohistochemistry for ER and PR was performed on them. Haematoxylin and eosin (H&E) slides were reviewed, and tumours were graded by three independent pathologists. Data were analysed using SPSS version 22. The level of significance was set at P ≤ 0.05. There were 44 cases of endometrial carcinoma. ER and PR were positive in 29.5% and 18.2% of endometrial carcinoma, respectively. There was no significant association between ER (P = 0.361) and PR (P = 0.204) expressions and histological grade of the tumour. The most common histological grade was grade 3 with 70% of cases (36 cases), whereas 13 cases (26%) were grade 2 and only 2 cases (4%) were grade 1. The positive expressions of ER and PR in endometrial carcinoma suggest that steroid receptor studies may be of potential benefit in the management of some patients with endometrial carcinoma. Future studies employing larger sample size are therefore recommended.


On the connection between interannual variations of winter haze frequency over Beijing and different ENSO flavors.
This study investigated the connection between interannual variations in winter haze frequency over Beijing and different flavors of the El Niño-Southern Oscillation (ENSO). The results showed that the haze frequency was highest during eastern-Pacific (EP) El Niño winters and lowest during EP La Niña winters. No below-normal winter haze frequency years were observed during EP El Niño winters, and no above-normal years were observed during EP La Niña winters. However, the relationship between winter haze frequency and central-Pacific (CP) ENSO conditions was more complex, i.e., both above- and below-normal haze frequency years were equally probable during CP El Niño and CP La Niña winters, and the difference in the number of mean haze days associated with these flavors was exceptionally small. The nearly opposite atmospheric circulation patterns between EP El Niño and EP La Niña winters were responsible for the substantial difference in local winter haze frequency, as these patterns established favorable and unfavorable local meteorological conditions for haze formation, respectively. However, the diverse in situ haze frequency situations during CP El Niño and CP La Niña winters and the small relative differences between such winters could reflect the complexity of the CP ENSO's impacts on haze-related circulation anomalies. The results of this study may help improve winter haze frequency forecasts for Beijing through more accurate climatic predictions.


Taller Indian women are more successful at the marriage market.
Whereas being tall has consistently been found a favorable characteristic at the marriage market for men, much less is known about the association between stature and marital success among women. Taller women are healthier than shorter women, give birth more easily and their offspring are healthier. We therefore would expect them to be more successful at the marriage market. However, existing evidence is mixed. We study the association between women's height and the odds of being married, marrying young, experiencing a divorce, and becoming widowed, and the association between women's height and their husbands' educational attainment and occupational status. Data come from the Indian National Family Health Survey 2005-2006, a representative study among 124,385 women and 74,369 men in all Indian states. Effects of female height on being married, marrying young, divorce, widowhood, and husband's occupation were estimated using logistic regression models. Effects of female height on husband's education were estimated using OLS regression models. Woman's education and age were always taken into account. Where possible controls for husband's height, husband's education, and age at marriage were included. Positive effects of women's height on favorable marital outcomes were found. Taller than average women are more likely to marry, get higher educated husbands with better jobs and are less likely to marry at a very young age or to lose their husbands through divorce or premature death. Taller Indian women seem to be more successful at the marriage market.


Nonlinear modelisation of heavy metal removal from aqueous solution using Ulva lactuca algae.
After extensive analysis, Ulva lactuca dried algae, collected from the Monastir coastal zone, was proven to be successful as an adsorbent for the removal of certain inorganic pollutants. The main objective of this study was the nonlinear modeling of heavy metal removal from an aqueous solution, using a freely available and well analyzed biomaterial, as well as the evaluation of its efficacy on various metal ion sorptions. Although relatively low specific surface area, compared to more conventional adsorbents, the selected biomaterial displays very interesting retention capacities when used with aqueous inorganic pollutants. The pseudo, first and second-order kinetic models were used to investigate the kinetic retention mechanism. Assuming the nonlinear form, the results indicate that the retention mechanism is diffusion controlled. Concerning the heavy metal uptake capacity, it was found that the selected biomaterial has a retention capacity of 67 mg g(-1) of Ni(II), 112 mg g(-1) of Cu(II), 127 mg g(-1) of Cd(II) and 230 mg g(-1) of Pb(II).


A new proposal of CPR based on coronary perfusion pressure.
Closed chest massage and tracheal intubation are not enough. The 70% success rate promised by Kouwenhoven 31 years ago is not realised. Coronary perfusion pressure is the main goal. To achieve this a proposal of a combined new CPR is advocated which encompass the following items besides closed chest massage and tracheal intubation: (a) use of high dose methoxamine (instead of epinephrine), (b) use of continuous abdominal pressure (instead of intermittent pressure), (c) unloading the pump, which means no use of any intravenous fluids, and (d) intracardiac injection of medications until restarting of spontaneous circulation.


NiFe-coordinated zeolitic imidazolate framework derived trifunctional electrocatalyst for overall water-splitting and zinc-air batteries.
Developing high-efficient non-noble metal electrocatalysts toward oxygen reduction reaction (ORR), oxygen evolution reaction (OER), hydrogen evolution reaction (HER), water-splitting, and the zinc-air battery is essential but challenging. Zeolitic imidazole frameworks (ZIFs) are generally employed as ideal platforms for the design and fabrication of energy-related catalysts by exploiting their porous structure with high surface area and flexibility. This work presents the preparation of NiFe-bimetallic species decorated N-doped porous carbon composite (NiFe@NPC) through pyrolyzing the NiFe-coordinated ZIF precursor. The obtained NiFe@NPC shows a larger surface area and porous nanostructure comprising the active bimetallic species evenly distributed in the conductive carbon matrix. The nanocomposite demonstrates excellent trifunctional catalytic activity toward ORR, OER, and HER. For ORR, NiFe@NPC offers a half-wave potential value of 0.87 V, which is positively shifted by 30 mV relative to that of Pt/C in 1 M KOH. NiFe@NPC exhibits OER activity with superior overpotential, reaction kinetics, and durability to those of IrO2. It also demonstrates the desirable HER activity with a low overpotential of 150 mV at 10 mA/cm2 and excellent durability in an acidic electrolyte. Additionally, the water-splitting configuration and zinc-air battery assembled with NiFe@NPC catalyst reveal superior performance to noble-metal catalysts. Such excellent electrocatalytic performance can be attributed to the distinct chemical composition of evenly distributed bimetallic active sites on highly conductive carbon sheets, and the porous nanostructure with large surface area and fast mass transfer.


Irreconcilable conflict: the tobacco industry and the public health challenge of tobacco use.
Thomas Novotny reflects on new research by Stanton Glantz and colleagues and the implications of their findings for engaging the tobacco industry on tobacco product regulation.


A novel hybrid strategy for PM2.5 concentration analysis and prediction.
The analysis and prediction of air pollutants are of great significance in environmental research today since airborne pollution is a substantial threat, especially in urban agglomerations of China. To develop more effective warning systems and management advice, the authorities and city dwellers need more accurate forecasts of the air pollution. Most previous analysis systems were based on costly observation apparatus at fixed sites, forecasting models were usually built on observations within a certain range, and some observations contained biases. In this paper, a novel and effective framework, termed HML-AFNN, was successfully developed to analyse and forecast the concentration of particular matter (PM2.5) for a selected number of forward time steps. In a simulation of the trajectory of air pollutants, the high-dimension association rules (HDAR) approach considered the tempo-spatial relations, as well as the meteorological and geographical factors of the ambient regions, as parameters. In addition, the learning vector quantization (LVQ) network was adopted to select the appropriate inputs to improve the efficiency of the training process. Moreover, an adaptive fuzzy neural network (AFNN), a combination of neural and fuzzy logic, was utilized to analyse and predict the PM2.5 concentration. The experiment results of our study on two major urban agglomerations of China, the Jing-Jin-Ji area and Pearl River Delta, over a period of more than one year demonstrated that the developed hybrid HML-AFNN model outperforms a plain AFNN, an HM-AFNN model without LVQ and the least squares support vector machines (LS-SVM); this superior performance can be determined from the values of several error indexes, including MAE, MAPE and band errors. This hybrid model, which has robust and accurate results, shows the potential to be a political and administrative method to issue effective early warnings and to design suitable abatement strategies.


Cytogenetic and in situ DNA-hybridization studies in intracranial tumors of a patient with central neurofibromatosis.
We have studied a meningioma and an acoustic neurinoma of a patient with central neurofibromatosis. In the meningioma cells, one chromosome 22 was replaced by an almost metacentric, bisatellited marker chromosome that appeared monocentric after CBG-staining. In situ hybridization with a chromosome 22 centromere specific DNA probe (p22hom48.4) revealed specific signals in the pericentromeric region of the marker chromosome, indicating the presence of at least the short arm and the centromere of chromosome 22. The pericentromeric localization of the hybridization signals suggest the marker consists of an isoformation of the short arm of chromosome 22, resulting in a monosomy for the long arm of chromosome 22. In contrast to these findings in meningioma cells, no chromosomal abnormality could be detected in acoustic neurinoma cells. Our findings provide further evidence that loss of genetic material on the long arm of chromosome 22 is associated with the development of central neurofibromatosis.


Changing interactions between bipolar affective disorder and anoxic brain damage.
A manic-depressive young woman received mild brain damage from anoxia after attempting suicide by hanging. The case conference was held to elucidate whether her subsequent symptoms were functional or organic, and what courses of treatment should be tried in this very refractory case.


Paclitaxel and TRAIL synergize to kill paclitaxel-resistant small cell lung cancer cells through a caspase-independent mechanism mediated through AIF.
Small cell lung cancer (SCLC) is the most aggressive form of lung cancer with poor disease outcome. The chemotherapeutic agent paclitaxel (PA) is commonly used as a second-line treatment in SCLC, but response rates are low. 86M1 SCLC cells were treated in the presence or absence of paclitaxel and TRAIL or the combination for 24 hours. Western blot analysis was utilized to examine protein expression, cell surface protein expression and membrane integrity were elucidated by flow cytometry, and immunofluorescence microscopy was used to demonstrate translocation of proteins to the cell nucleus. Human 86M1 SCLC cells were found to be resistant to PA killing in vitro. This resistance is mediated by up-regulation of pro-survival protein BCL-xl. However, PA also increases surface expression of death receptors 4 and 5 (DR4 and DR5, respectively). The death receptors' ligand increased SCLC killing by PA through an apparent caspase-independent route involving activation/translocation of AIF. The addition of TRAIL to PA can potentiate apoptosis in a relatively PA-resistant SCLC line (specifically 86M1 cells). More importantly, we are the first to report an active method of resistance to paclitaxel in SCLC via BCL-xl up-regulation.


Comparison between the International Physical Activity Questionnaire and the American College of Sports Medicine/American Heart Association criteria to classify the physical activity profile in adults.
the study aims to evaluate the reproducibility between the International Physical Activity Questionnaire and the American College of Sports Medicine/American Heart Association criteria to classify the physical activity profile in an adult population living in Ribeirão Preto, SP, Brazil. population-based cross-sectional study, including 930 adults of both genders. The reliability was evaluated by Kappa statistics, estimated according to socio-demographic strata. the kappa estimates showed good agreement between the two criteria in all strata. However, higher prevalence of "actives" was found by using the American College of Sports Medicine/American Heart Association. although the estimates have indicated good agreement, the findings suggest caution in choosing the criteria to classify physical activity profile mainly when "walking" is the main modality of physical activity.


Crystallization of the MS2 translational repressor alone and complexed to bromouridine.
The coat protein from the MS2 bacteriophage plays a dual role by encapsidating viral RNA and also by binding RNA as a translational repressor. In order to study the isolated dimer in a conformation not influenced by capsid interactions, a mutant molecule was crystallized that is defective in capsid assembly but is an active repressor. The unassembled dimer crystallized in the space group P21212 with a = 76.2, b = 55.7, and c = 28.4 A. In these crystals, monomers were related by twofold symmetry. When this dimer was co-crystallized with 5-bromouridine, crystals formed in space group R3 with a = b = 155.9 A, c = 29.9 A, gamma = 120 degrees; the dimer was the asymmetric unit.


Co-contaminant effects on 1,4-dioxane biodegradation in packed soil column flow-through systems.
Biodegradation of 1,4-dioxane was examined in packed quartz and soil column flow-through systems. The inhibitory effects of co-contaminants, specifically trichloroethene (TCE), 1,1-dichloroethene (1,1-DCE), and copper (Cu2+) ions, were investigated in the columns either with or without bioaugmentation with a 1,4-dioxane degrading bacterium Pseudonocardia dioxanivorans CB1190. Results indicate that CB1190 cells readily grew and colonized in the columns, leading to significant degradation of 1,4-dioxane under oxic conditions. Degradation of 1,4-dioxane was also observed in the native soil (without bioaugmentation), which had been previously subjected to enhanced reductive dechlorination treatment for co-contaminants TCE and 1,1-DCE. Bioaugmentation of the soil with CB1190 resulted in nearly complete degradation at influent concentrations of 3-10 mg L-1 1,4-dioxane and a residence reaction time of 40-80 h, but the presence of co-contaminants, 1,1-DCE and Cu2+ ions (up to 10 mg L-1), partially inhibited 1,4-dioxane degradation in the untreated and bioaugmented soil columns. However, the inhibitory effects were much less severe in the column flow-through systems than those previously observed in planktonic cultures, which showed near complete inhibition at the same co-contaminant concentrations. These observations demonstrate a low susceptibility of soil microbes to the toxicity of 1,1-DCE and Cu2+ in packed soil flow-through systems, and thus have important implications for predicting biodegradation potential and developing sustainable, cost-effective technologies for in situ remediation of 1,4-dioxane contaminated soils and groundwater.


Is all plasma created equal? A pilot study of the effect of interdonor variability.
Clinical benefits of plasma as an adjunct for treatment of hemorrhagic shock (HS) have been well established. However, its use is not without risk. Little is understood regarding the clinical implications of plasma variability. We hypothesized there to be interdonor variability in plasma that would impact endothelial and organ function postinjury. Pulmonary endothelial cells (ECs) were incubated with plasma from 24 random donors, and transendothelial electrical resistance was measured. Plasma units with a more or less protective effect on reducing EC permeability were selected for testing in vivo. Syndecan-1 and cytokines were measured. Mice underwent laparotomy and then HS followed by resuscitation with the selected plasma units and were compared with mice receiving no resuscitation and shams. Lung tissue was sectioned and stained for myeloperoxidase and pulmonary syndecan-1 and scored for lung histopathologic injury. Plasma from 24 donors revealed variability in the reversal of EC monolayer hyperpermeability; transendothelial electrical resistance for the more protective plasma was significantly higher than that for the less protective plasma (0.801 ± 0.022 vs. 0.744 ± 0.035; p = 0.002). Syndecan-1 was also markedly increased in the less protective compared with the more protective plasma (38427 ± 1257 vs. 231 ± 172 pg/mL, p < 0.001), while cytokines varied. In vivo, the more protective plasma mitigated lung histopathologic injury compared with the less protective plasma (1.56 ± 0.27 vs. 2.33 ± 0.47, respectively; p = 0.005). Similarly, myeloperoxidase was significantly reduced in the more protective compared with the less protective plasma group (2.590 ± 0.559 vs. 6.045 ± 1.885; p = 0.02). Lastly, pulmonary syndecan-1 immunostaining was significantly increased in the more protective compared with the less protective plasma group (20.909 ± 8.202 vs. 9.325 ± 3.412; p = 0.018). These data demonstrate significant interdonor variability in plasma that can adversely influence the protective effects of plasma-based resuscitation on HS-induced lung injury. This may have important implications for patient safety and clinical outcomes.


Usefulness of surgical pleth index-guided analgesia during general anesthesia: a systematic review and meta-analysis of randomized controlled trials.
Previous studies comparing surgical pleth index (SPI)-guided and conventional analgesia have shown differing results. Therefore, we compared the intraoperative opioid requirement, extubation time, postoperative pain scores, and perioperative adverse events between these two modalities. A comprehensive literature search was conducted to identify randomized controlled trials comparing the intraoperative opioid requirement and other outcomes between the two modalities. The mean difference (MD) or the pooled risk ratio and corresponding 95% confidence interval (CI) were used for analysis. A heterogeneity (I2) assessment was performed. Six randomized controlled trials comparing 463 patients were included. Intraoperative opioid consumption was significantly lower in the SPI-guided than conventional analgesia group (standardized MD, -0.41; 95% CI, -0.70 to -0.11; I2 = 53%). No significant intergroup difference was observed in the pain score on the first postoperative day or the incidence of perioperative adverse events. The extubation time was considerably shorter in the SPI-guided than conventional analgesia group (MD, -1.91; 95% CI, -3.33 to -0.49; I2 = 67%). Compared with conventional analgesia, SPI-guided analgesia can reduce intraoperative opioid consumption and facilitate extubation. Moreover, no intergroup difference was observed in the degree of postoperative pain or incidence of perioperative adverse events.


Neuraminidase activity of NAG vibrios and of some representatives of the intestinal group of bacteria.
It was studied 203 strains of NAG vibrios and 71 strains of different enterobacteria for the ability to produce neuraminidase. The most frequent neuraminidase producers were found among the strains isolated from humans (99 strain of 131). There was no correlation between neuraminidase production and other properties of the vibrios. The examined strains of the family Enterobacteriaceae did not produce the enzyme.


Studies on the preservation of red blood cells. Attachment of the third component of human complement to erythrocytes during storage at 4 degrees C.
Utilizing an automated antiglobulin test, we have investigated the presence of the third and fourth components of human complement on normal red blood cells (RBCs). Only negligible amounts of the fourth component, C4, could be detected on either freshly collected or stored RBCs. The fragment C3d of the third component, C3, was detectable on both freshly collected and stored normal RBCs. A product derived from C3 and reacting with anti-C3c antibody was only barely detectable on freshly collected normal RBCs. During storage of blood at 4 degrees C, increasing quantities of this material were detected on the RBC membrane. Bromelin treatment rendered stored RBCs completely nonreactive with anit-C3c antibody, whereas only partial loss of reactivity was observed following incubation with heated plasma. In contrast, incubation of EC43 with heated plasma completely abolished their ability to react with anti-C3c antibody. We suggest that the presence of this C3 fragment on stored RBCs may contribute to the development of "preservation injury".


Factors associated with the successful removal of indwelling urinary catheters post-operatively in the fragility hip fracture patient.
Patients presenting to hospital with a fragility hip fracture are routinely catheterized in the emergency department. Studies have found that the duration of catheterization is the greatest and most important risk factor for developing a urinary tract infection. Whilst there is a considerable body of evidence around correct techniques for insertion of urinary catheters, there appears to be little evidence as to the timing of their removal. To describe the current practice of indwelling catheter (IDC) removal post operatively in the fragility hip fracture patient and to identify factors associated with the successful removal of IDCs post operatively in the same cohort of patients. This study was a retrospective cohort analysis of patients admitted to a large, tertiary hospital with an established ortho-geriatric model of care. Aperient regime was the only factor that appeared to have a significant impact on the successful IDC removal. The patient commenced on the aperient regime was three times more likely to have an unsuccessful IDC removal than the patient on a limited or no aperient regime. This study highlights the need for redesigning care that is patient focused, evidence-based, effective and efficient. The argument that a patient's bowel is required to be emptied prior to the successful removal of an IDC appears to be false, as in this study it was not identified as a predictor of successful IDC removal. A prospective clinical trial may be the next step forward in developing a clinical guideline for the successful removal of IDCs in the fragility hip fracture patient and/or surgical patient. Nurses have a crucial role to play in contributing to evidence-based practice and are continually challenged to do so.


Determination of residual 1,3-dichloro-2-propanol in protein hydrolysates by capillary gas chromatography.
This study describes a method for the quantitative determination of residual 1,3-dichloro-2-propanol in protein hydrolysates. The method is based on a continuous micro-steam distillation solvent extraction technique. The quantitative determination is performed by electron-capture gas chromatography using an "on column" injector and a fused silica capillary CP wax 52 CB column. The absolute detection limit for 1,3-dichloro-2-propanol in soy sauces is 10 pg and recoveries of 75.8% and 82.7% with a standard deviation of 4.0% and 2.5% are obtained for samples fortified in the range of 1 mg/kg and 0.1 mg/kg respectively.


Suppression of elevated plasma interleukin-8 levels due to total ischemia and reperfusion of the small intestine by luminal perfusion with fetal bovine serum.
A previous study demonstrated that continuous enteric luminal perfusion of fetal bovine serum (FBS) protects the small intestine from total ischemia/reperfusion injury (IRI) and increases the intestinal mass. In this study, we further investigated the changes in plasma interleukin-8 (IL-8) level caused by total ischemia/reperfusion of the small intestine and the effect of FBS on plasma IL-8 levels. A 3-h total ischemia was induced in a 15-cm segment of terminal ileum and then reperfusion was instituted. Luminal perfusion of FBS was conducted via an osmotic minipump connected to the stomach through a fine polyethylene tube, starting 3 days prior to total ischemia. The rats were killed after 10 and 30 min and 1 and 3 h of total ischemia, and 1, 6, and 12 h or 1, 2, and 3 days after initiation of reperfusion. Plasma IL-8 was measured by enzyme-linked immunosorbent assay. The results were compared among the FBS-treated and untreated groups. The plasma IL-8 level was elevated from 1 h of total ischemia to 6 h after initiation of reperfusion ( P< 0.05) with a peak of 641.5 +/- 36.9 pg/ml in the untreated group and 471.6 +/- 42.2 pg/ml in the treated group. Luminal perfusion of FBS significantly suppressed plasma IL-8 levels after 1 h of total ischemia and 1 h after initiation of reperfusion ( P< 0.05). The results suggest that FBS might play a role in the treatment of total IRI of the small intestine.


Qualitative versus automatic evaluation of CT perfusion parameters in acute posterior circulation ischaemic stroke.
To compare the diagnostic accuracy (ACC) in the detection of acute posterior circulation strokes between qualitative evaluation of software-generated colour maps and automatic assessment of CT perfusion (CTP) parameters. Were retrospectively collected 50 patients suspected of acute posterior circulation stroke who underwent to CTP (GE "Lightspeed", 64 slices) within 24 h after symptom onset between January 2016 and December 2018. The Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was used for quantifying the extent of ischaemic areas on non-contrast (NC)CT and colour-coded maps generated by CTP4 (GE) and RAPID (iSchemia View) software. Final pc-ASPECTS was calculated on follow-up NCCT and/or MRI (Philips Intera 3.0 T or Philips Achieva Ingenia 1.5 T). RAPID software also elaborated automatic quantitative mismatch maps. By qualitative evaluation of colour-coded maps, MTT-CTP4D and Tmax-RAPID showed the highest sensitivity (SE) (88.6% and 90.9%, respectively) and ACC (84% and 88%, respectively) compared with the other perfusion parameters (CBV, CBF). Baseline NCCT and CBF provided by RAPID quantitative perfusion mismatch maps had the lowest SE (29.6% and 6.8%, respectively) and ACC (38% and 18%, respectively). CBF and Tmax assessment provided by quantitative RAPID perfusion mismatch maps showed significant lower SE and ACC than qualitative evaluation. No significant differences were found between the pc-ASPECTSs assessed on colour-coded MTT and Tmax maps neither between the scores assessed on colour-coded CBV-CTP4D and CBF-RAPID maps. Qualitative analysis of colour-coded maps resulted more sensitive and accurate in the detection of ischaemic changes than automatic quantitative analysis.


The shrimp IKK-NF-κB signaling pathway regulates antimicrobial peptide expression and may be subverted by white spot syndrome virus to facilitate viral gene expression.
The IκB kinases IKKα and IKKβ and the IKK-related kinases TANK-binding kinase 1 (TBK1) and IKKε are the master regulators of the NF-κB signaling pathway. Although this pathway has been extensively studied in mammals, less attention has been paid in crustaceans, which have significant economic value. Here, we report the cloning and functional studies of two IKK homologs, LvIKKβ and LvIKKε, from Pacific white shrimp, Litopenaeus vannamei. LvIKKβ and LvIKKε mRNAs are widely expressed in different tissues and are responsive to white spot syndrome virus (WSSV) infection. When overexpressed in Drosophila S2 cells, LvIKKβ but not LvIKKε activates the promoters of NF-κB pathway-controlled antimicrobial peptide genes (AMPs), such as the Penaeidins (PENs). In HEK 293T cells, both LvIKKβ and LvIKKε activate an NF-κB reporter. The silencing of LvIKKβ or LvIKKε using double-stranded RNA (dsRNA)-mediated RNA interference (RNAi) decreases the expression of L. vannamei AMPs, including PENs, lysozyme and crustins. Intriguingly, LvIKKβ- or LvIKKε-silenced L. vannamei are resistant to WSSV infection. We hypothesized that successful infection with WSSV requires the activation of the IKK-NF-κB signaling pathway to modulate viral gene expression. We constructed luciferase reporters for 147 WSSV genes. By screening, we found that the WSV051, WSV059, WSV069, WSV083, WSV090, WSV107, WSV244, WSV303, WSV371 and WSV445 promoters can be activated by LvIKKβ or LvIKKε in Drosophila S2 cells. Taken together, our results reveal that LvIKKβ and LvIKKε may participate in the regulation of shrimp AMPs and that WSSV may subvert the L. vannamei IKK-NF-κB signaling pathway to facilitate viral gene expression.


Characterization of the p150,95 leukocyte integrin alpha subunit (CD11c) gene promoter. Identification of cis-acting elements.
The leukocyte integrin p150,95 (CD11c/CD18) is involved in a number of cell-cell and cell-extracellular matrix interactions and mediates signal transduction into the cytoplasm. p150,95 is expressed on cells of the myeloid lineage as well as on certain activated T and B lymphocytes, and its expression is regulated during cell activation and differentiation. Since CD18 is expressed on all leukocyte lineages, the restricted expression of p150,95 must be controlled at the level of CD11c gene transcription. To understand the mechanisms that direct the constitutive and regulated leukocyte expression of p150,95 we have structurally characterized the CD11c promoter region and initiated its functional dissection. The CD11c promoter lacks TATA- and CCAAT-boxes, directs the synthesis of transcripts with heterogeneous 5'-ends, and contains an initiator-like sequence at the major transcription initiation site. Several putative binding sequences for ubiquitous (Sp1, AP-1, AP-2, and NF-kB) and leukocyte-specific (PU.1) transcription factors have been identified in the proximal region of the CD11c promoter which may participate in the regulation of the expression of p150,95. Transient expression of CD11c-based reporter gene constructs indicates that the CD11c promoter dictates the tissue-specific expression of p150,95 and that sequences contained within 160 base pairs 5' from the major transcriptional start site are involved in the tissue-specific and regulated expression of p150,95. DNase I protection analysis on the promoter region spanning from -160 to +40 revealed four regions of DNA-protein interactions (FPI-FPIV), two of which (FPII and FPIV) correlate with the cell type-specific and regulated expression of the CD11c gene.


The Society of Thoracic Surgeons National Database status report.
This report describes the development of the first known national surgical database designed for the practicing community cardiothoracic surgeon. Acceptance by members of The Society of Thoracic Surgeons has been gratifying. The number of patients on the system has grown from 116,109 at the end of 1991 to an anticipated 350,000 to 450,000 by the end of 1993. At the time of this report, 842 surgeons were participating, and more than 1,200 will be on the system by the end of 1993. A risk stratification system has been incorporated into the software, which predicts each patient's risk based on the individual surgeon's past experience. Trend analyses demonstrate a substantial increase in the number of patients at increased risk for perioperative death for coronary artery bypass operations over the past 5 years, while observed mortality has remained relatively constant. Programs are available for adult and congenital heart disease, lung cancer, and esophageal cancer, and modules for mediastinal tumors, pleural disorders, and benign pulmonary disease will soon be added. We anticipate that growth will continue as the need for practice profile data increases because of reimbursement issues.


Apolipoprotein(a) phenotypes and serum lipoprotein(a) levels in maintenance hemodialysis patients with/without diabetes mellitus.
We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotypes in 152 patients (123 males, 29 females) undergoing maintenance hemodialysis (HD) with or without diabetes mellitus (DM), in 101 patients with diabetes mellitus without hemodialysis (58 males, 43 females), and in 421 normal controls (333 males, 88 females). Serum Lp(a) levels were significantly (P < 0.01) higher in patients than in controls (26.2 +/- 18.3 mg/dl in HD with DM, 26.4 +/- 22.0 mg/dl in HD without DM, 27.1 +/- 27.3 mg/dl in DM without HD, and 14.9 +/- 13.7 mg/dl in controls, respectively). Apo(a) phenotyping was performed by a sensitive, high resolution technique using SDS-agarose/gradient (3 to 6%) PAGE. In normal controls, the molecular weights of apo(a) isoforms were inversely correlated with plasma Lp(a) levels, and the same tendency was found in patients who were undergoing hemodialysis and/or who had diabetes mellitus. We assumed the differences in apo(a) phenotypes detectable with our method reflected consecutive differences in molecular weights of apo(a). The results of an analysis of covariance and a least square means comparison indicated that the regression lines between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in patient groups were significantly (P < 0.01) elevated for every apo(a) phenotype, as compared to the regression line of the control group. Even after the low molecular weight apo(a) phenotypes (A1-A8) were omitted, the same tendency was observed. However, no differences were observed between the patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Outpatient arteriography--a safe and practical proposition?
Ninety-five patients, who underwent fine catheter peripheral angiography as outpatients, were followed up and assessed to determine the safety of this procedure. No patients reported any major side effects and in particular no patients experienced a rebleed from the arterial puncture site. This procedure could be safely adopted in any radiology department.


Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewing's sarcoma.
Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its antitumor activity. We tested 69 anticancer drugs in combination with YK-4-279 and found that vinca alkaloids exhibited synergy with YK-4-279 in five ES cell lines. The combination of YK-4-279 and vincristine reduced tumor burden and increased survival in mice bearing ES xenografts. We determined that independent drug-induced events converged to cause this synergistic therapeutic effect. YK-4-279 rapidly induced G2-M arrest, increased the abundance of cyclin B1, and decreased EWS-FLI1-mediated generation of microtubule-associated proteins, which rendered cells more susceptible to microtubule depolymerization by vincristine. YK-4-279 reduced the expression of the EWS-FLI1 target gene encoding the ubiquitin ligase UBE2C, which, in part, contributed to the increase in cyclin B1. YK-4-279 also increased the abundance of proapoptotic isoforms of MCL1 and BCL2, presumably through inhibition of alternative splicing by EWS-FLI1, thus promoting cell death in response to vincristine. Thus, a combination of vincristine and YK-4-279 might be therapeutically effective in ES patients.


Applying MCM-48 mesoporous material, equilibrium, isotherm, and mechanism for the effective adsorption of 4-nitroaniline from wastewater.
In this work, the MCM-48 mesoporous material was prepared and characterized to apply it as an active adsorbent for the adsorption of 4-nitroaniline (4-Nitrobenzenamine) from wastewater. The MCM-48 characterizations were specified by implementing various techniques such as; scanning electron microscopy (SEM), Energy dispersive X-ray analysis (EDAX), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area, pore size distribution (PSD), and Fourier transform infrared (FTIR). The batch adsorption results showed that the MCM-48 was very active for the 4-nitroaniline adsorption from wastewater. The adsorption equilibrium results were analyzed by applying isotherms like Langmuir, Freundlich, and Temkin. The maximum experimental uptake according to type I Langmuir adsorption was found to be 90 mg g-1 approximately. The Langmuir model with determination coefficient R2 = 0.9965 is superior than the Freundlich model R2 = 0.99628 and Temkin model R2 = 0.9834. The kinetic adsorption was investigated according to pseudo 1st order, pseudo 2nd order, and Intraparticle diffusion model. The kinetic results demonstrated that the regression coefficients are so high R2 = 0.9949, that mean the pseudo 2nd order hypothesis for the adsorption mechanism process appears to be well-supported. The findings of adsorption isotherms and kinetics studies indicate the adsorption mechanism is a chemisorption and physical adsorption process.


Selective bundle tensioning in double-bundle MPFL reconstruction to improve restoration of dynamic patellofemoral contact pressure.
To evaluate the optimal graft tension angles in a medial patellofemoral ligament (MPFL) reconstruction with selective bundle tensioning in order to restore patellofemoral contact pressure distributions closest to the native state. Twelve human cadaveric knee specimens were mounted with the femur on a custom-made fixation device allowing free range of motion in the knee joint for testing. Using a sensitive pressure film (Tekscan) patellofemoral contact pressure was measured in 15° intervals during a dynamic flexion movement from 0°-90° in the native state, in cut MPFL and after MPFL-reconstruction with a gracilis tendon. The graft was separated in two bundles and was fixed independently on the patella using two knotless anchors. Two groups were made with either the proximal or distal bundle fixed at the femur at a knee flexion angle of 30° and the corresponding other bundle subsequently fixed at the femur at 15°, 45°, 60°, 75° and 90° of knee flexion using extra-cortical fixation and controlled tension of 2N in both groups. The sequence of the flexion angles at the graft fixation was alternated. Pressure measurements were repeated after every fixation of the graft. Cutting the MPFL resulted in significantly reduced patellofemoral contact pressure at all flexion angles. After MPFL reconstruction the patellofemoral contact pressure remained significantly reduced during dynamic knee flexion in all tested double-bundle combinations (p < 0.05) except for fixation of the proximal bundle in 30° and the distal bundle in 75°. Selective evaluation of lateral patellofemoral contact pressure, however, showed significant reduction in all tested double-bundle combinations (p < 0.05) from 15° to 90°. Evaluation of isolated medial patellofemoral pressure changes showed no significant difference in all tested combinations compared to the intact knee. Furthermore, evaluation of the isolated proximal and distal patellofemoral contact pressure also revealed a significantly reduced contact pressure in all tested double-bundle combinations (p < 0.05) except for fixation of the proximal bundle in 30° and the distal bundle in 75°. According to this study, selective bundle tensioning in anatomic MPFL-reconstruction should be considered as an easy and more anatomic alternative to current popular techniques to restore patella kinematics and give clear recommendation about knee flexion angle and tension during fixation. Although tensioning two bundles separately may further improve clinical results. If performed, fixation of the graft is recommended under low tension (2N) with the proximal bundle at 30° and the distal bundle at 75° of knee flexion.


The association between corticosteroid use and development of fractures among IBD patients in a population-based database.
Because the rate of fracture among patients with inflammatory bowel disease (IBD) is only slightly higher than that in the general population, it is important to define high-risk groups worthy of diagnostic evaluation or prophylactic interventions. Corticosteroid use has been considered in other diseases to be a risk for fracture, although not all studies in IBD are concordant on this point. We aimed to determine whether patients with IBD drawn from a population-based database who sustain fractures are more likely to have been using corticosteroids than a matched group of IBD patients who did not fracture. We extracted from our population-based University of Manitoba Inflammatory Bowel Disease Epidemiology Database the number of patients with a new diagnosis of fracture between the years 1997-2000. From within our Inflammatory Bowel Disease Epidemiology Database, we extracted a control group of IBD patients who did not develop fractures matched to the case group who did by age, gender, diagnosis, year of diagnosis, and geographic area of residence. We linked our cohorts with Manitoba Health's Drug Program Information Network to study corticosteroid use within 2 yr before fracture diagnosis. The Drug Program Information Network is a population-based database, established in 1995, which records all prescription drugs. Fractures were identified in 13 patients with Crohn's disease and in 28 patients with ulcerative colitis. The control group included 103 Crohn's disease and 173 ulcerative colitis patients who did not fracture. In Crohn's disease, for the group who fractured compared with the controls who did not fracture, corticosteroid use before fracture was evident in seven (54%) compared with 21 (22%) who did not fracture (chi(2) = 4.45, df = 1, p = 0.035). In ulcerative colitis, for the group who fractured compared with the controls who did not fracture, corticosteroid use before fracture was evident in five (18%) compared with 37 (21%) who did not fracture (chi(2) = 0.031, df = 1, p = 0.861). Fracture cases were more likely to be exposed to oral corticosteroids (OR = 1.75; 95% CI = 0.82-3.75), but this result is not significant. Regarding corticosteroid dosing among the 12 patients with IBD who fractured and used corticosteroids, the mean total days supply was 314 days +/- 236 days compared with 258 days +/- 278 days in those who did not fracture (p = 0.16). The prescribed daily dose among corticosteroid users was comparable for those who fractured versus those who did not fracture (18 mg/day vs 21 mg/day, p = 0.90). Patients who require corticosteroids in Crohn's disease should be considered at risk for fracture. Further research is required to delineate after how much corticosteroid use are subjects at risk and/or after what duration of active disease.


Bridging the gap between scientists and facilities - from proposal to performance of experiments in space.
Although the assembly of the Space Station is not yet complete, now is the time to start on ground the scientific and technical realisations for the maximum return in life sciences. An important prerequisite is that all suitable ground-based techniques and scientifcal and technical infrastructures are available to plan, prepare and perform space experiments.


Effects of immersive virtual reality for managing anxiety, nausea and vomiting among paediatric cancer patients receiving their first chemotherapy: An exploratory randomised controlled trial.
To assess the feasibility and acceptability of immersive virtual reality for managing anxiety, nausea and vomiting amongst paediatric patients with cancer receiving their first chemotherapy. An exploratory randomised control trial supplemented with qualitative interviews was conducted to enrol Chinese paediatric patients receiving their first intravenous chemotherapy. Participants were randomly assigned to intervention (three immersive virtual reality sessions) or control (standard care) groups. The main outcome measures included (1) feasibility parameters; (2) anxiety, nausea and vomiting; and (3) satisfaction with the chemotherapy procedures. Qualitative data were collected by semi-structured individual interviews with patients, parents and nurses. A total of 19 patients, 19 accompanying parents and 9 nurses were recruited. Results suggested that the intervention was feasible as evidenced by the high consent rate, low withdrawal rate and attrition rate. The intervention group showed significantly better improvement in anxiety at T2 [Hedges' effect size, ES = 1.25, 95% confidence interval (CI): 0.22-2.17)] and T4 [ES = 1.87, 95% CI: 0.72-2.85], as well as greater reduction in acute nausea at T4 [ES = 0.97, 95% CI: 0.02-1.87] than the control group. Qualitative data yielded three categories including positive experiences and perceived benefits of the intervention, and suggested improvements. This study demonstrated the potential effectiveness, feasibility and acceptability of immersive virtual reality for managing anxiety and acute nausea amongst paediatric patients with cancer receiving their first chemotherapy.


The tribology of cartilage: Mechanisms, experimental techniques, and relevance to translational tissue engineering.
Diarthrodial joints, found at the ends of long bones, function to dissipate load and allow for effortless articulation. Essential to these functions are cartilages, soft hydrated tissues such as hyaline articular cartilage and the knee meniscus, as well as lubricating synovial fluid. Maintaining adequate lubrication protects cartilages from wear, but a decrease in this function leads to tissue degeneration and pathologies such as osteoarthritis. To study cartilage physiology, articular cartilage researchers have employed tribology, the study of lubrication and wear between two opposing surfaces, to characterize both native and engineered tissues. The biochemical components of synovial fluid allow it to function as an effective lubricant that exhibits shear-thinning behavior. Although tribological properties are recognized to be essential to native tissue function and a critical characteristic for translational tissue engineering, tribology is vastly understudied when compared to other mechanical properties such as compressive moduli. Further, tribometer configurations and testing modalities vary greatly across laboratories. This review aims to define commonly examined tribological characteristics and discuss the structure-function relationships of biochemical constituents known to contribute to tribological properties in native tissue, address the variations in experimental set-ups by suggesting a move toward standard testing practices, and describe how tissue-engineered cartilages may be augmented to improve their tribological properties.


Total 102 natural orifice specimen extraction following laparoscopic colorectal resections.
Natural orifice surgery has been used with increasing frequency in colon surgeries since the early 2000's. Our aim was to examine the patients retrospectively who underwent Natural Orifice Specimen Excision (NOSE) following laparoscopic colorectal resection. A total of 102 patients 2013 and 2018 were evaluated. The demographic characteristics, intra-operative and post-operative findings, pathology results, pain, incontinence, sexual dysfunction and cosmetic scores were examined. Mean age was 57.0 ± 14 and 52 of them (51%) were female. Specimen extraction was transanal in 72 (70%) (eventration technique in 10 patients) and transvaginal in the remaining 30 patients. The mean operating time was 272 ± 108 (median 240, range 120-540) minutes, and the mean blood loss was 92 ± 87 ml (median 54, range 5-400). The mean hospital stay was 7.0 ± 4.7 days (median 6, range 3-30). The main pain scores (visual analog score) on days 1-2-3 were 3.9 ± 2.0 (median 4, range 1-9), 3.1 ± 1.7 (median 3, range 0-8), 1.9 ± 1.5 (median 1.5, range 0-7), respectively. The mean cosmetic scores were 9.1 ± 1.5 (median 10, range 3-10). The median Wexner Incontinence score was 0 (0-9). Hospital mortality was 1% and unrelated with the NOSE. The 5-year overall survival and disease-free survival rates for cancer patients were 77.2-63.3%, respectively. NOSE has advantages in laparoscopic colorectal resections. It increases patient comfort and decreases incision related complications. CLINICAL TRIALS: www.clinicaltrials.gov (NCT04394988).


The effects of acute normovolemic hemodilution on left ventricular systolic and diastolic function in the absence or presence of beta-adrenergic blockade in dogs.
Acute normovolemic hemodilution (ANH) increases cardiac output because of a reduction in blood viscosity and enhancement of left ventricular (LV) contractility. The status of LV function, especially LV diastolic function during ANH, remains controversial. We therefore examined LV systolic and diastolic function during ANH. Sixteen dogs were anesthetized with isoflurane in the absence (Group 1) and presence (Group 2) of beta-adrenergic blockade (propranolol 1 mg/kg). LV contractility was quantified by the slope (M(w)) of the stroke work and end-diastolic volume relation. Diastolic function was evaluated with the time constant of LV relaxation (T), chamber stiffness constant (K(c)), peak LV diastolic filling rate during early filling (peak E) and atrial contraction (peak A), and ratio of peak E to peak A (E/A). Normovolemic exchange of blood (50 mL/kg) for 6% hydroxyethyl starch (ANH50) significantly increased M(w) in Group 1 but not in Group 2. In both groups, ANH50 significantly decreased T. ANH50 significantly increased peak E in both groups and peak A in Group 1, and it did not change the E/A ratio or K(c) in either group. ANH causes positive inotropic effects and enhances diastolic function without beta-blockade. Even after beta-adrenergic blockade, ANH improves diastolic function through the reduction of LV ejection impedance. Acute normovolemic hemodilution enhances LV (left ventricular) diastolic function by alterations in the LV loading condition produced by hemodilution, which mainly contributes to a compensatory increase in cardiac output.


Second generation liposomal cancer therapeutics: transition from laboratory to clinic.
Recent innovations and developments in nanotechnology have revolutionized cancer therapeutics. Engineered nanomaterials are the current workhorses in the emerging field of cancer nano-therapeutics. Lipid vesicles bearing anti-tumor drugs have turned out to be a clinically feasible and promising nano-therapeutic approach to treat cancer. Efficient entrapment of therapeutics, biocompatibility, biodegradability, low systemic toxicity, low immunogenicity and ability to bypass multidrug resistance mechanisms has made liposomes a versatile drug/gene delivery system in cancer chemotherapy. The present review attempts to explore the recent key advances in liposomal research and the vast arsenal of liposomal formulations currently being utilized in treatment and diagnosis of cancer.


Relationship of fetuin-A levels to weight-dependent insulin resistance and type 2 diabetes mellitus.
Weight gain and obesity are of substantial importance for the development of insulin-resistance and type-2 diabetes mellitus. Fetuin-A, a liver-derived glycoprotein, may also play a role in these alterations. Several studies have demonstrated an association between fetuin-A and body weight which, however, was within a fairly small range at the border of overweight to obesity. The present study examines the relationship between fetuin-A and a wide range of BMI, together with basal insulin, and HOMA-IR. In addition, matched groups of non-diabetic patients and those with type-2 diabetes mellitus were compared. We examined the relationship between fetuin-A and BMI, insulin, HOMA-IR, glucose and HbA1c in a cohort of 445 non-diabetic obese subjects and 150 obese patients with type-2-diabetes mellitus (DM2). In relation to quintiles of fetuin-A a significant increase of BMI, basal insulin and HOMA-IR was observed between the 1st and 2nd quintile with no further change thereafter. Correspondingly, fetuin-A levels increased significantly only between the 1st and 2nd quintile of BMI, insulin or HOMA-IR, respectively. When patients with type 2 diabetes were compared with non-diabetic subjects matched for BMI, insulin, and age median fetuin-A levels were not significantly different. At the early stage of weight gain fetuin-A could be of relevance for the development of insulin resistance. For the further progressive resistance with increasing weight in the obesity range the present data do not support a role of fetuin-A. Similarly its contribution to the resistance of type-2 diabetes seems to be of minor importance.


Genetic polymorphisms at FCER1B and PAI-1 and asthma susceptibility.
We previously detected a promoter polymorphism (- 109C/T) in the gene for the beta-chain of the high-affinity receptor for IgE (FCER1B), which was associated with total serum IgE levels but not with asthma in a Japanese population. A genetic interaction is biologically plausible between FcepsilonRI-beta and the plasminogen activator inhibitor 1 (PAI-1), which is highly expressed in mast cells in asthmatics and plays an essential role in airway remodelling. We hypothesized that FCER1B promoter polymorphisms, by modifying the intensity of mast cell activation signals, modulate the genetic effects of a functional 4G/5G polymorphism in the PAI-1 gene on asthma. OBJECTICIVE: To examine whether FCER1B promoter polymorphisms (- 109C/T and - 654C/T) influence the genetic effects of the functional polymorphism (4G/5G) at the PAI-1 promoter region on asthma susceptibility using a case-control analysis. Subjects (374 asthmatic patients and 374 non-asthmatic controls) were divided into combined genotype groups based on the presence of FCER1B - 109TT and - 654CC genotypes and the PAI-1 4G allele. Logistic regression analysis was used to estimate adjusted odds ratios for asthma associated with the different genotype groups. Individuals homozygous for the FCER1B - 109T/ - 654C haplotype and the PAI - 1 5G allele had a reduced susceptibility to asthma; the odds ratio for the development of asthma was 0.20 (95% confidence interval, 0.084 - 0.46; P = 0.00015) for them, compared with individuals also homozygous for the - 109T/- 654C haplotype at FCER1B but carrying the 4G allele at PAI-1. The regression model also showed an interaction of the PAI-1 4G/5G genotype with the FCER1B-109C/T (P for interaction = 0.0017) or FCER1B-654C/T (P for interaction = 0.031) on asthma. The present findings suggest a synergistic interaction between FCER1B and PAI-1 genes in asthma susceptibility.


Study of the operative conditions and the optimum amount of municipal incinerator bottom ash for the obtainment of ceramic floor tiles.
The idea of reusing municipal incinerator bottom ash (MIBA), the residue from incinerating municipal solid wastes, fits nicely in a circular economy scheme, which leads to an avoided impact of landfill disposal, and at the same time reduces the demand of natural resources. Past studies have attempted to add 20 to 60% MIBA for ceramic production, and resulted in some inspiring success. Focused on delivering quality interior and exterior floor tiles meeting industrial standards, this study investigated the operative conditions and the optimum amount of MIBA in the mix. In this study, only the kaolinite clay and MIBA were used. Before making specimens, raw materials of clay and MIBA underwent SEM, EDS, and TCLP tests to determine their chemical contents. Six sets of specimens with different replacement levels of MIBA (0%, 5%, 10%, 15%, 20%, and 30%) were then prepared. These specimens were fired at 1000°C, 1050°C,1100°C, and 1150°C and the products underwent a series of mechanical tests to verify their performance. NMR (nuclear magnetic resonance spectroscopy) were also used to determining the organic compound structure after each specimens' crystallization. Research results showed that proper mix of MIBA up to 20% could result in quality tiles complying with specifications for interior and exterior flooring applications at certain kiln temperatures, while the specimens with 30% MIBA failed to meet either bending strength or size shrinkage requirement at all four kiln temperatures, and could not deliver a satisfactory result.


Cytochrome C oxidase-deficient mitochondria in mitochondrial myopathy.
Electron microscopic cytochemistry was used to evaluate the behavior of cytochrome c oxidase (COX) in cultured skin fibroblasts from 4 patients with decreased COX activity (Leigh encephalopathy, fatal infantile COX deficiency). In patients with Leigh encephalopathy, all mitochondria reacted to COX staining either equivocally or negatively, indicating that all mitochondria were abnormal in these patients. In 1 patient with fatal infantile COX deficiency, intercellular heterogeneity of mitochondria was observed by COX staining. In another patient with fatal infantile COX deficiency, intracellular heterogeneity of mitochondria was observed. Patients with Leigh encephalopathy appeared to have a different type of mitochondrial COX deficiency than those with fatal infantile COX deficiency. Our result suggest that these 2 diseases may result from different genetic mechanisms.