HIV self-testing implementation, distribution and use among female sex workers in Cotonou, Benin: a qualitative evaluation of acceptability and feasibility.
In Benin, the burden of HIV is disproportionately high among female sex workers (FSWs). HIV testing and knowledge of status are starting points for HIV treatment and prevention interventions. Despite the importance given to testing services in HIV control, its uptake among FSWs remains suboptimal in Benin. HIV self-testing (HIVST) may be useful for increasing testing rates in FSWs. We conducted a pilot study of the distribution of saliva-based HIVST among FSWs in Cotonou and its surroundings, Benin. The HIVST promotion and distribution model included three complementary strategies: community-based, facility-based and secondary distribution. In this qualitative study, we explored the elements influencing HIVST implementation, distribution and use among FSWs. We assessed HIVST acceptability and feasibility in this population. We conducted 29 semi-structured individual interviews with FSWs. Data were interpreted with a thematic analysis method, using the Theoretical Domains Framework. Only two FSWs (6.9%) were aware of HIVST before participating in the study. All participants were interested in using HIVST if available in Benin. Many advantages of HIVST were mentioned, including: autonomy, privacy, accessibility, time saving, and the fact that it is a painless test. Barriers to the use of HIVST included: the fear of unreliability, the lack of psychological support and medical follow-up and the possibility of result dissimulation. Participants thought HIVST was easy to use without assistance. HIVST enabled linkage to care for a few FSWs in denial of their HIV-positive status. No case of suicide or violence associated with HIVST was reported. HIVST secondary distribution within FSWs social network was well received. FSWs' boyfriends and clients showed interest in using the device. Some FSWs reported using HIVST to practice serosorting or to guide their decisions regarding condom use. Our study shows a very high level of acceptability for HIVST among FSWs in Cotonou and its surroundings. Results also demonstrate the feasibility of implementing HIVST distribution in Benin. HIVST should be implemented in Benin quickly and free of charge for all individuals at risk of HIV. HIVST offer should be integrated with comprehensive sexual health and prevention services.


Probabilistic model-based approach for heart beat detection.
Nowadays, hospitals are ubiquitous and integral to modern society. Patients flow in and out of a veritable whirlwind of paperwork, consultations, and potential inpatient admissions, through an abstracted system that is not without flaws. One of the biggest flaws in the medical system is perhaps an unexpected one: the patient alarm system. One longitudinal study reported an 88.8% rate of false alarms, with other studies reporting numbers of similar magnitudes. These false alarm rates lead to deleterious effects that manifest in a lower standard of care across clinics. This paper discusses a model-based probabilistic inference approach to estimate physiological variables at a detection level. We design a generative model that complies with a layman's understanding of human physiology and perform approximate Bayesian inference. One primary goal of this paper is to justify a Bayesian modeling approach to increasing robustness in a physiological domain. In order to evaluate our algorithm we look at the application of heart beat detection using four datasets provided by PhysioNet, a research resource for complex physiological signals, in the form of the PhysioNet 2014 Challenge set-p1 and set-p2, the MIT-BIH Polysomnographic Database, and the MGH/MF Waveform Database. On these data sets our algorithm performs on par with the other top six submissions to the PhysioNet 2014 challenge. The overall evaluation scores in terms of sensitivity and positive predictivity values obtained were as follows: set-p1 (99.72%), set-p2 (93.51%), MIT-BIH (99.66%), and MGH/MF (95.53%). These scores are based on the averaging of gross sensitivity, gross positive predictivity, average sensitivity, and average positive predictivity.


Downregulated KIF3B Induced by miR-605-3p Inhibits the Progression of Colon Cancer via Inactivating Wnt/β-Catenin.
Colon cancer is a common malignant disease with high morbidity and mortality, and miRNA dysfunction has been confirmed as an important reason for cancer development. Several studies have verified miR-605-3p as a tumor inhibitor while its roles in colon cancer remain uncertain. In this study, the specimen of the patients and the cell lines of colon cancer were used to observe the expression of miR-605-3p, and the CCK-8, Transwell assay, and flow cytometry assay were used to observe the functions of miR-605-3p in colon cancer cells. The downstream factors of miR-605-3p were predicted by TargetScan and then were verified by dual-luciferase reporter assay. Moreover, western blot was used to investigate the effect of miR-605-3p on Wnt/β-catenin signal pathway. The result showed that miR-605-3p was extremely downregulated in the pathological tissues and tumor cells, and miR-605-3p could effectively induce the apoptosis and impede the proliferation and invasion of the tumor cells. It was found that KIF3B was a target of KIF3B; decreased KIF3B could reverse the effects of miR-605-3p on colon cancer. Besides, the inactivated Wnt/β-catenin pathway was also observed in colon cells when miR-605-3p was upregulated, and the phenomenon could be rescued by KIF3B upregulation. In conclusion, miR-605-3p could inactivate the Wnt/β-catenin pathway induced via promoting KIF3B expression.


[Isolation and properties of the acid carboxypeptidase of Aspergillus oryzae].
Caboxypeptidase with pH optimum 4--5 for peptide substrates is isolated from "oryzine", the enzyme mixture produced by Aspergillus oryzae, by means of successive salt fractionation, Sephadex G-75 gel filtration, chromatography on amberlite IRC-50, hydroxylapatite, DEAE-cellulose and polyacrylamide gel electrophoresis. Its molecular weight, as determined by means of polyacrylamide gel electrophoresis in the presence of sodium dolecylsulphate, was found to be 37 000. The enzyme has a broad substrate specificity and does not possess dipeptidase and esterase activities. Acid carboxypeptidase from Asp. oryzae is not a metalloenzyme, it is inactivated by specific inhibitors of serine proteases and by compounds blocking SH-groups. The enzyme is suggested to contain functionally important serine and cysteine residues and to be acid carboxipeptidase.


Integrated Optical Modulator Based on Transition between Photonic Bands.
An area efficient novel optical modulator with low operation voltage is designed based on integrated Mach-Zehnder Interferometer with a photonic crystal slab structure as the phase shifter. Plasma dispersion effect is utilized so that photonic band-to-band transition occurs at the operating frequency leading to a high index change (Δn = ~4) for π-phase shift on the modulator. This approach reduces the phase shifter length to a few micrometers (~5 µm) in a silicon on insulator platform and operating voltage required is around 1 V. Low voltage together with short optical interaction length decrease optical losses and power consumption during modulation process providing a great opportunity for size and system cost optimization.


Clarification of the Relationship between Awareness of Doping of Competitive Sports Coaches and Their Instructions to Prevent Doping.
It has been 6 years since the establishment of the position of "sports pharmacist" as one type of pharmacist. In the sporting world of Japan, sports pharmacists are expected to promote athletes' awareness of antidoping regulations and provide them with relevant education. However, currently, these pharmacists' main duty is to provide athletes and their coaches with guidance on medication. Using a model for the prediction of athletes' actions, we have worked to promote athletes' awareness of antidoping regulations and encourage sports pharmacists to perform relevant activities, such as antidoping education. As a result, we clarified that athletes' awareness regarding antidoping rules influences their actions when experiencing minor illnesses. In addition, we have proposed approaches to encourage athletes to undertake antidoping activities. The present study aimed to clarify competitive sports coaches' awareness of antidoping regulations, the instructions that those coaches give athletes when they experience minor illnesses, and coaches' awareness of athletes' usage of drugs and supplements. Analysis using a model for the prediction of actions revealed that to promote coaches' awareness of antidoping regulations, education aimed at raising their level of knowledge of doping is warranted. Furthermore, coaches were aware of the necessity of continuously providing athletes with antidoping instructions, but they did not keep sufficient track of athletes' usage of drugs and supplements. To encourage sports coaches to perform antidoping activities, it is effective to provide them with opportunities to develop their knowledge of doping prevention in their areas.


Referring physicians' attitudes toward international interpretation of teleradiology images.
We evaluated referring physician attitudes toward the international interpretation of radiologic images. A five-question, scenario-based survey describing features of a hypothetic local radiology firm compared with those of its hypothetic overseas counterpart, international radiology, was sent by mail to 350 physicians from a broad range of medical and surgical specialties. One hundred nineteen physicians responded, for a response rate of 34%. Referring physicians were asked to indicate their preference for local versus international interpretation in each scenario using a 5-point Likert scale, with a score of -2 indicating a strong preference for international services, 0 indicating no preference, and 2 indicating a strong preference for local services. When all variables are held to be equal, referring physicians strongly prefer local services (mean score, 1.77; SD, 0.77). When international teleradiology provides either a 2-day faster turnaround time for reports or a 30 dollars lower out-of-pocket cost to the patient, referring physicians still prefer local services, although less than they did with all variables held equal (mean score, 0.42-0.44; SD, 1.30-1.40). When international teleradiology provides both a 2-day faster turnaround time and a 30 dollars lower out-of-pocket cost to the patient, referring physicians preferred international teleradiology, albeit only slightly (mean, -0.25; SD, 1.50). Finally, when the credentials of the international radiologists are perceived to be less than those of the local radiologists, even in the face of faster turnaround time and 30 dollars lower cost to the patient, referring physicians overall strongly prefer local services (mean, 1.51; SD, 0.86). Referring physicians prefer local interpretation of radiologic images to international interpretation when all things are equal. However, the timeliness of image interpretation and the cost to the patient are important factors in this decision.


Successful grant applications: Follow the 4 F's.
All nurses have the potential to influence the healthcare industry and the nursing profession through research, but preparing a grant application can be intimidating. This article addresses the process of writing and developing successful grant proposals.


'Isopathic phenomenon' in leprosy.
Isopathic phenomenon of SAGHER was elicited in 21 proved leprosy patients (consisting of 7 lepromatous, 7 tuberculoid, 3 neuritic, 2 borderline, and 2 indeterminate types). The substances used to elicit the isopathic phenomenon were BCG lepromin, Indian ink and staphylococcal vaccine. Isopathic phenomenon was elicited in most of the cases and BCG was the substance which produced the most responses. The phenomenon could be used to classify difficult cases of leprosy.


The effects of chronic renal failure and hemodialysis on human red and white cell calmodulin levels.
Red blood cell (RBC) and polymorphonuclear white blood cell (WBC) calmodulin levels were measured in 25 uremic patients on regular hemodialysis. Uremic patients had significantly higher RBC [11.45 +/- 0.66 (+/-SE) fg/cell] and WBC (590.5 +/- 110 fg/cell) calmodulin levels than normal subjects (8.62 +/- 0.37 and 130 +/- 30 fg/cell; P less than 0.05). An extremely high RBC calmodulin level (20.58 fg/cell) was found in a patient with sickle cell anemia. Uremic patients on dialysis for 2 yr or more had lower RBC (10.99 +/- 0.58 fg/cell) and WBC (390 +/- 50 fg/cell) calmodulin levels than those who were on dialysis for less than 2 yr (RBC, 12.30 +/- 1.56 fg/cell; WBC, 943 +/- 256 fg/cell; P less than 0.05). There were no statistically significant differences in calmodulin levels when different subgroups of uremic patients were compared, e.g. patients with diabetes mellitus or those receiving supplemental vitamin D, anabolic steroids, or antihypertensive medications. We conclude that calmodulin levels are elevated in uremic patients on regular hemodialysis.


Bactericidal and fungicidal activities of novel ProtecTeaV formulations - alcohol-based hand hygiene and surface disinfectant prototypes containing epigallocatechin-3-gallate-palmitate (EC16).
Currently used alcohol-based hand sanitizers and surgical hand rubs are not effective against alcohol-resistant microorganisms. We reported previously that nontoxic antioxidant food additive compounds derived from green tea polyphenols, particularly epigallocatechin-3-gallate-palmitate (EC16), are suitable in alcohol formulations to effectively inactivate nonenveloped viruses and bacterial spores. However, whether EC16 influences the bactericidal and fungicidal activity of alcohol is not clear. The objective of the current study was to determine the bactericidal and fungicidal activities of ProtecTeaV hand sanitizer and surface spray prototypes containing EC16. The prototypes were tested according to the guidelines from the Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA). As expected, EC16 did not reduce the bactericidal and fungicidal activities of ethanol. The hand sanitizer gel formulation was equally effective as 70% ethanol and met the tested standard, and the surface spray prototype met the EPA performance standard. EC16 can be combined with ethanol without reducing antibacterial or antifungal activity, and the ProtecTeaV prototypes could be further developed into novel hand hygiene and surface disinfectant products with virucidal, bactericidal, fungicidal and sporicidal activities.


Novel engineered systems for oral, mucosal and transdermal drug delivery.
Technological advances in drug discovery have resulted in increasing number of molecules including proteins and peptides as drug candidates. However, how to deliver drugs with satisfactory therapeutic effect, minimal side effects and increased patient compliance is a question posted before researchers, especially for those drugs with poor solubility, large molecular weight or instability. Microfabrication technology, polymer science and bioconjugate chemistry combine to address these problems and generate a number of novel engineered drug delivery systems. Injection routes usually have poor patient compliance due to their invasive nature and potential safety concerns over needle reuse. The alternative non-invasive routes, such as oral, mucosal (pulmonary, nasal, ocular, buccal, rectal, vaginal), and transdermal drug delivery have thus attracted many attentions. Here, we review the applications of the novel engineered systems for oral, mucosal and transdermal drug delivery.


Rous sarcoma virus mutant dlPA105 induces different transformed phenotypes in quail embryonic fibroblasts and neuroretina cells.
dlPA105 is a spontaneous variant of Rous sarcoma virus, subgroup E, which carries a deletion in the N-terminal portion of the v-src gene coding sequence. This virus was isolated on the basis of its ability to induce proliferation of quiescent quail neuroretina cells. The altered v-src gene encodes a phosphoprotein of 45,000 daltons which possesses tyrosine kinase activity. DNA sequencing of the mutant v-src gene has shown that deletion extends from amino acid 33 to 126 of wild-type p60v-src. We investigated the tumorigenic and transforming properties of this mutant virus. dlPA105 induced fibrosarcomas in quails with an incidence identical to that induced by wild-type virus. Quail neuroretina cells infected with the mutant virus were morphologically transformed and formed colonies in soft agar. In contrast, dlPA105 induced only limited morphological alterations in quail fibroblasts and was defective in promoting anchorage-independent growth of these cells. Synthesis and tyrosine kinase activity of the mutant p45v-src were similar in both cell types. These data indicate that the portion of the v-src protein deleted in p45v-src is dispensable for the mitogenic and tumorigenic properties of wild-type p60v-src, whereas it is required for in vitro transformation of fibroblasts. The ability of dlPA105 to induce different transformation phenotypes in quail fibroblasts and quail neuroretina cells is a property unique to this Rous sarcoma virus mutant and provides evidence for the existence of cell-type-specific response to v-src proteins.


[The expression and meaning of Hippo signaling pathway in carotid artery ligation induced arterial remodeling model of rats].
To establish an arterial remodeling model of rats and to investigate the expression and role of Hippo signaling pathway in this model. In the model group (n=40), the left common carotid artery was removed through the median incision of the neck. The 6-0 non-absorbable line was used to ligate the carotid artery near the proximal end as far as possible, completely blocking the blood flow. The common carotid artery of rats in control group (n=20) was not ligated using the operative line. After 14 days, the animals were sacrificed and the common carotid arteries were separated through the original surgical pathway and the arteries from the ligature to the distal end were collected. Arterial morphology and fibrosis were observed by HE and MASSON staining. Immunohistochemical staining was used to detect the expressions of anti-α smooth muscle actin (α-MSA) and proliferating cell nuclear antigen (PCNA) in the carotid artery. Western blot was used to detect the expressions of yes associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), TEAD1, Bcl-2-like protein 4 (Bax), and B-cell lymphoma-2 (Bcl-2). Compared with the control group, the HE staining showed that the vascular remodeling was obvious, the ratio of the neointima/middle membrane was increased significantly, and the MASSON staining indicated that the fibrosis was significantly increased in model group. The immunohistochemical staining suggested that the expressions of α-SMA and PCNA were increased significantly; Western blot suggested that the expressions of YAP, TAZ, TEAD1, and Bcl-2 were increased in carotid artery of the model group. While the expression of Bax and the ratio of Bax/Bcl-2 were decreased. A rat model of arterial remodeling mediated by carotid artery ligation was established successfully in this study. Hippo signaling pathway was proved to be activated in the arterial remodeling model induced by carotid artery ligation in rats, and might regulate the change of Bax/Bcl-2 ratio related to proliferation and apoptosis, and subsequently involved in the proliferation of smooth muscle cells to promote vascular remodeling.


Stage model of recovery for chemically dependent adolescents: part 1--methods and model.
This qualitative study, presented in two parts, refines the model of how chemically dependent adolescents initiate and engage in the recovery process. Part 1 describes the research process and results used to derive the model. The model was derived from theory grounded in verbatim reports of 30 chemically dependent participants who first attempted recovery from chemical dependence during adolescence. The constant comparative method of grounded theory was used to analyze the data. This stage model of adolescent recovery includes the using/precontemplation, transition, early recovery, and ongoing recovery stages; the transition stage is divided into contemplation and action phases. The stages, phases, and significant events are similar, but not identical to, those presented in adult-based models of recovery from chemical dependence. In Part 2, the resulting theory is compared with extant theories on stages of recovery in chemically dependent adults, treatment implications for the adolescent population are reviewed, and topics for further research are suggested.


Targeted Disruption of Aromatase Reveals Dual Functions of cyp19a1a During Sex Differentiation in Zebrafish.
Aromatase (encoded by the cyp19a1a and cyp19a1b genes) plays a central role in sex differentiation in fish, but its precise roles during sex differentiation are still largely unknown. Here, we systematically generated cyp19a1a and cyp19a1b mutant lines as well as a cyp19a1a;cyp19a1b double mutant line in zebrafish using transcription activatorlike effector nucleases. Our results showed that cyp19a1a mutants and cyp19a1a;cyp19a1b double mutants, but not cyp19a1b mutants, had impaired sex differentiation, and all cyp19a1a mutants and cyp19a1a;cyp19a1b double mutants were males. During sex differentiation, the ovary-like gonads were not observed and the male sex differentiation program was delayed in the cyp19a1a-null fish, and these phenotypes could be partially rescued by 17β-estradiol treatment. Gene expression analysis indicated that male and female sex differentiation-related genes were significantly decreased in the cyp19a1a mutant. Collectively, our results revealed dual functions of the cyp19a1a gene during sex differentiation: cyp19a1a is not only indispensable for female sex differentiation but also required for male sex differentiation.


Low risk for tuberculosis in a regional pediatric hospital: nine-year study of community rates and the mandatory employee tuberculin skin-test program.
To assess the risk of Mycobacterium tuberculosis infection and disease among patients and workers in a regional pediatric hospital. Descriptive epidemiological study of the mandatory tuberculin skin testing program of hospital employees at hire and during annual reevaluation, pediatric patients with tuberculosis (TB), efficacy of hospital infection control measures, and community rates of TB. 361-bed, university, pediatric hospital serving Cincinnati (1.7 million population). During 1986 through 1994, 2,275 to 4,356 employees were compliant with Mantoux skin testing and screening each year. This represented >97% of the population who were eligible for screening. The cumulative rate of M tuberculosis infection from a previous positive tuberculin skin test was 10% to 12% per year during 1986 through 1994. Among new Mantoux skin-test converters in employees at annual reevaluation, the risk of TB infection was 0.3% in 1993 and 1994. There were no active cases of TB identified during new employee screening or annual reevaluation. Of 62 new Mantoux skin-test converters in 9 years, 23% were foreign-born, 13% were Asian, 23% were African American, 11% received the bacillus of Calmette-Guérin vaccine, and 60% had direct patient care or indirect patient contact. A cluster of five converters occurred in a department with no patient care or contact. Mantoux conversion rates were 1.9 per 1,000 employee patient-care or contact-years and 2.2 per 1,000 employee non-patient-contact years. Twenty pediatric patients with active TB were identified during 1991 to 1994, with < or =6 cases per year, placing this hospital in the low-risk category for M tuberculosis disease. Three children with pulmonary TB were admitted without immediate respiratory isolation, possibly exposing 9 patients and 42 employees; none converted their Mantoux skin tests on retesting. Rates of active TB in Cincinnati were stable during the period (eg, 8/100,000 population in 1994). Despite intense active surveillance among thousands of hospital employees with >97% annual compliance, tuberculin conversion rates were low, and no cases of active TB were identified during 9 years of follow-up. There was no evidence of transmission of M tuberculosis from infected patients to employees during uncontrolled exposures. Rates of TB in the community were low. These data suggest that rigorous application of the Centers for Disease Control and Prevention guidelines and Occupation Safety and Health Administration regulations for preventing nosocomial TB in pediatric hospitals may be excessive and costly. Special provisions should be made for pediatric hospitals with a proven low risk of transmission of M tuberculosis.


Elevated perioptic lipocalin-type prostaglandin D synthase concentration in patients with idiopathic intracranial hypertension.
The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l; P < 0.0001, Mann-Whitney U-test). These measurements demonstrate a change and imbalance in the biochemical environment of the optic nerve. Its possible effect is discussed.


Self-Perceived Mental Health and Perceived Discrimination in Family Physicians and Residents: A Comparative Study Between Men and Women.
The present study aims to examine sex differences in demographic variables, professional activities and adversities, self-reported mental health problems, and perceived discrimination in a sample of family doctors and family medicine residents in Mexico. METHODS: From a larger sample of medical specialists, an analytic, cross-sectional study was conducted with 566 participants, including 317 (56%) family medicine residents and 249 (44%) family doctors in Mexico through an online survey. Demographic features, professional activities and adversities, mental health, and perceived discrimination were examined. Descriptive and comparative analyses were performed. Cramer's V for chi-square tests and Hedge's g for t test were conducted to determine effect sizes. RESULTS: Both sexes displayed similar percentages of professional adversities (such as attending patients with suicidal behavior or who died not by suicide under their care), and a higher number of women reported seeking specialized support to cope with these deaths (Fisher = 0.04). Men perceived greater discrimination (P = .01), worked more hours per day (P < .001) and were more verbally assaulted (P = .04), whereas women reported mental health problems more frequently (P < .001) particularly depression, anxiety, burnout and sleeping problems. Women also reported worse health status (P < .001) when compared with men. CONCLUSION: Family medicine specialists constitute a vulnerable group for mental health problems and perceived discrimination. Particular attention should be paid to how men and women cope with professional adversities to determine whether additional support is required. Interventions should encourage self-care and promote the well-being of health personnel.


Fatty acid binding protein: stimulation of microsomal phosphatidic acid formation.
The effect of fatty acid binding proteins (FABPs) on two key steps of microsomal phosphatidic acid formation was examined. Rat liver microsomes were purified by size-exclusion chromatography to remove endogenous cytosolic fatty acid and fatty acyl-CoA binding proteins while recombinant FABPs were used to avoid cross-contamination with such proteins from native tissue. Neither rat liver (L-FABP) nor rat intestinal fatty acid binding protein (I-FABP) stimulated liver microsomal fatty acyl-CoA synthase. In contrast, L-FABP and I-FABP enhanced microsomal conversion of [14C]oleoyl-CoA and glycerol 3-phosphate to [14C]phosphatidic acid by 18- and 7-fold, respectively. The mechanism for this stimulation, especially by I-FABP, is not known. However, several observations presented here suggest that, like L-FABP, I-FABP may interact with fatty acyl-CoA and thereby stimulate enzyme activity. First, I-FABP decreased microsomal membrane-bound oleoyl-CoA. Second, oleoyl-CoA displaced I-FABP bound fluorescent fatty acid, cis-parinaric acid, with Ki of 5.3 microM and 1.1 sites. Third, oleoyl-CoA decreased I-FABP tryptophan fluorescence with a Kd of 4.2 microM. Fourth, oleoyl-CoA red shifted emission spectra of acrylodated I-FABP, a sensitive marker of I-FABP interactions with ligands. In summary, the results demonstrate for the first time that both L-FABP and I-FABP stimulate liver microsomal phosphatidic acid formation by enhancing synthesis of phosphatidate from fatty acyl-CoA and glycerol 3-phosphate.


Prognostic value of plasma DPP4 activity in ST-elevation myocardial infarction.
Dipeptidyl peptidase-4 (DPP4) regulates blood glucose levels and inflammation, and it is also implicated in the pathophysiological process of myocardial infarction (MI). Plasma DPP4 activity (DPP4a) may provide prognostic information regarding outcomes for ST-segment elevation MI (STEMI) patients. Blood samples were obtained from 625 consecutively admitted, percutaneous coronary intervention-treated STEMI patients with a mean age of 57 years old. DPP4a was quantified using enzymatic assays. The median follow-up period was 30 months. Multivariate Cox-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase of DPP4a did not associate with risks of major adverse cardiac or cerebrovascular events (MACCE), cardiovascular mortality, MI, heart failure readmission, stroke, non-cardiovascular mortality and repeated revascularization. However, in a subset of 149 diabetic STEMI patients, DPP4a associated with an increased risk of MACCE (HR 1.16; 95% CI 1.04-1.30; p = 0.01). DPP4a did not associate with cardiovascular events and non-cardiovascular mortality in non-diabetic STEMI patients. However, DPP4a may be associated with future MACCE in diabetic STEMI patients. Trial registration NCT03046576, registered on 5 February, 2017, retrospectively registered.


β-Alanine dose for maintaining moderately elevated muscle carnosine levels.
Chronic β-alanine (BA) supplementation is an increasingly popular nutritional strategy, because it can elevate muscle carnosine content and thereby enhance high-intensity exercise performance. The current study investigated 1) whether sex and body mass are determinants of BA-induced muscle carnosine loading and 2) the optimal maintenance dose for ensuring constantly elevated muscle carnosine stores. During the loading phase, 34 participants (men and women) were supplemented with 3.2 g (4 × 800 mg) BA per day for 46 d (slightly different loading strategies were applied concerning the effect of meal timing and supplementation form). Thereafter, 19 participants (men and women) continued taking free-powder BA for six more weeks (maintenance phase). The participants were matched and redivided into three groups receiving 0.4, 0.8, and 1.2 g·d(-1) BA, respectively. Muscle carnosine content was measured in the soleus and gastrocnemius muscles using proton magnetic resonance spectroscopy. Body mass and sex had only minimal effect on the absolute increase in muscle carnosine. Given the lower baseline values in women, the relative increase for women was higher, indicating that women required less BA for the same relative increase. In addition, a significant negative correlation was observed between body mass and the relative increase in muscle carnosine (r = -0.45, P = 0.007). A maintenance dose of ∼1.2 g·d(-1) BA was the most effective in keeping muscle carnosine content elevated at the postsupplementation level. Sex and body mass did not markedly affect the absolute increase during muscle carnosine loading, although they are determinants for the relative increase. In addition, we established for the first time an effective maintenance dose of ∼1.2 g·d(-1) BA to keep muscle carnosine content elevated at 30%-50% above baseline for a prolonged period.


In vivo responsiveness to ezetimibe correlates with niemann-pick C1 like-1 (NPC1L1) binding affinity: Comparison of multiple species NPC1L1 orthologs.
Ezetimibe is the first in class 2-azetidinone that decreases plasma cholesterol by blocking intestinal cholesterol absorption. Ezetimibe effectively reduces plasma cholesterol in several species including human, monkey, dog, hamster, rat, and mouse, but the potency ranges widely. One potential factor responsible for this variation in responsiveness is diversity in ezetimibe metabolism. After oral administration, ezetimibe is glucuronidated. Both ezetimibe and the glucuronide lower plasma cholesterol; however, the glucuronide exhibits greater potency. Recent identification of Niemann-Pick C1 Like-1 (NPC1L1) as the molecular target of ezetimibe enables direct binding studies to be performed. Here, we report the cloning of NPC1L1 derived from multiple species and assess amino acid sequence homology among human, monkey, dog, hamster, rat, and mouse. The rank order of affinity of glucuronidated ezetimibe for NPC1L1 in each species correlates with the rank order of in vivo activity with monkey > dog > hamster and rat >> mouse. Ezetimibe analogs that bind to NPC1L1 exhibit in vivo cholesterol-lowering activity, whereas compounds that do not bind NPC1L1 are inactive. Specific structural components of ezetimibe are identified as critical for binding to NPC1L1. The results demonstrate that small variations in ezetimibe structure or in NPC1L1 amino acid sequence can profoundly influence ezetimibe/NPC1L1 interaction and consequently in vivo activity. The results demonstrate that the ability of compounds to bind to NPC1L1 is the major determinant of in vivo responsiveness.


Photocatalytic Degradation of Methylene Blue and Anticancer Response of In2O3/RGO Nanocomposites Prepared by a Microwave-Assisted Hydrothermal Synthesis Process.
The incorporation of graphene with metal oxide has been widely explored in various fields, including energy storage devices, optical applications, biomedical applications, and water remediation. This research aimed to assess the impact of reduced graphene oxide (RGO) doping on the photocatalytic and anticancer properties of In2O3 nanoparticles. Pure and In2O3/RGO nanocomposites were effectively synthesized using the single-step microwave hydrothermal process. XRD, TEM, SEM, EDX, XPS, Raman, UV-Vis, and PL spectroscopy were carefully utilized to characterize the prepared samples. XRD data showed that synthesized In2O3 nanoparticles had high crystallinity with a decreased crystal size after RGO doping. TEM and SEM images revealed that the In2O3 NPs were spherical and uniformly embedded onto the surface of RGO sheets. Elemental analysis of In2O3/RGO NC confirmed the presence of In, O, and C without impurities. Raman analysis indicated the successful fabrication of In2O3 onto the RGO surface. Uv-Vis analysis showed that the band gap energy was changed with RGO addition. Raman spectra confirmed that In2O3 nanoparticles were successfully anchored onto the RGO sheet. PL results indicated that the prepared In2O3/RGO NCs can be applied to enhance photocatalytic activity and biomedical applications. In the degradation experiment, In2O3/RGO NCs exhibited superior photocatalytic activity compared to that of pure In2O3. The degradation efficiency of In2O3/RGO NCs for MB dye was up to 90%. Biological data revealed that the cytotoxicity effect of In2O3/RGO NCs was higher than In2O3 NPs in human colorectal (HCT116) and liver (HepG2) cancer cells. Importantly, the In2O3/RGO NCs exhibited better biocompatibility against human normal peripheral blood mononuclear cells (PBMCs). All the results suggest that RGO addition improves the photocatalytic and anticancer activity of In2O3 NPs. This study highlights the potential of In2O3/RGO NCs as an efficient photocatalyst and therapeutic material for water remediation and biomedicine.


Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment.
The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.


Ceftriaxone is twice as cost-effective as standard therapy in biliary tract infection.
Various antibiotics, mainly cephalosporins and broad-spectrum penicillins, are indicated in biliary tract infection. The primary endpoint was to compare the cost-effectiveness of ceftriaxone (Rocephin) 1 g once daily vs. standard therapy two or three times daily. A prospective multicenter observational study, matched-pair analysis of 902 patients receiving ceftriaxone or standard therapy (second-generation cephalosporin, broad-spectrum penicillin or a combination of aminopenicillin and beta-lactamase inhibitor) in 75 hospitals yielded 173 pairs matched for definite risk criteria. Both groups received comparable accompanying endoscopic antiobstructive treatment. Cost parameters included primary antibiotic purchase, total antibiotic purchase (including combination and second-line drugs), and infusion preparation and administration. 87.9% of patients in the ceftriaxone group vs. 73.4% in the standard group received antibacterial monotherapy, for 7.5 vs. 9.1 days respectively (p=0.001). Therapy was equally effective in both groups. Overall treatment costs, including antibiotic purchase and infusion preparation/administration, were 170.84 vs. 320.46, respectively (p=0.0001). Ceftriaxone 1 g once daily is approximately twice as cost-effective as standard therapy in biliary tract infection: lower concomitant medication costs, a shorter treatment course, and lower antibiotic administration costs achieved an approximate 50% saving.


[Comparison of the effectiveness of two kinds of surgeries for treatment of flexible flatfoot combined with painful accessory navicular bone in children].
To compare the effectiveness of subtalar arthroereisis (STA) combined with modified Kidner procedure versus STA alone in the treatment of flexible flatfoot combined with painful accessory navicular bone in children. The clinical data of 33 children with flexible flatfoot combined with painful accessory navicular bone who were admitted between August 2018 and August 2021 and met the selection criteria were retrospectively analyzed. They were divided into a combination group (17 cases, treated by STA combined with modified Kidner procedure) and a control group (16 cases, treated by STA alone) according to the surgical methods. There was no significant difference in baseline data between the two groups ( P>0.05), such as gender, age, affected side of the foot, disease duration, and preoperative visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, talus-first metatarsal angle (T1MT), talus-second metatarsal angle (T2MT), talonavicular coverage angle (TCA), talus first plantar angle (Meary angle), calcaneal inclination angle (Pitch angle), and heel valgus angle (HV). The operation time, incision length, intraoperative blood loss, number of intraoperative fluoroscopies, and perioperative complications were recorded in both groups. The anteroposterior, lateral, and calcaneal axial X-ray films for the affected feet were taken regularly, and T1MT, T2MT, TCA, Meary angle, Pitch angle, and HV were measured. The VAS score, AOFAS ankle-hindfoot score were used to evaluate pain and functional recovery before and after operation. Surgeries in both groups were successfully performed without surgical complication such as vascular, nerve, or tendon injuries. Less operation time, shorter incision length, less intraoperative blood loss, and fewer intraoperative fluoroscopies were found in the control group than in the combination group ( P<0.05). One case in the combination group had partial necrosis of the skin at the edge of the incision, which healed after the dressing change and infrared light therapy, and the rest of the incisions healed by first intention. All children were followed up 12-36 months, with a mean of 19.6 months. At last follow-up, VAS score and AOFAS ankle-hindfoot score significantly improved in both groups when compared with preoperative ones ( P<0.05), and the differences of these scores between before and after operation improved more significantly in the combination group than in the control group ( P<0.05). Imaging results showed that the T1MT, T2MT, TCA, Meary angle, and HV significantly improved in both groups at last follow-up when compared with preoperative ones ( P<0.05), and the Pitch angle had no significant difference when compared with preoperative one ( P>0.05). But there was no significant difference in the difference of these indicators between before and after operation between the two groups ( P>0.05). Both procedures are effective in the treatment of flexible flatfoot children with painful accessory navicular bone. STA has the advantage of minimally invasive, while STA combined with modified Kidner procedure has better effectiveness.


Antibiotic Resistance and Therapy for H. pylori Infection in Immigrant Patients Treated in Italy.
Background: Helicobacter pylori (H. pylori) infection is the leading cause of both peptic ulcers and gastric tumors, including low-grade MALT-lymphoma and adenocarcinoma. Although it is decreasing in developed countries, H. pylori prevalence remains high in developing areas, mainly due to low socio-economic levels, and the potential consumption of contaminated water. Moreover, a different pattern of primary antibiotic resistance is expected in their H. pylori isolates, potentially affecting the efficacy of standard eradication therapies. Indeed, a previous study showed the eradication rate following triple therapy was distinctly lower in dyspeptic H. pylori infected immigrants living in Italy as compared to Italian patients. Aims: to evaluate the resistance pattern in H. pylori isolates from immigrant patients in Italy, and the success rate of first-line therapy in these patients. Materials and Methods: This retrospective study evaluated data of consecutive immigrant patients, diagnosed with H. pylori infection in a single center (Bologna, Italy) between January 2009 and January 2019. Patients underwent first-line therapy with either sequential or Pylera® (Allergan USA, Inc. Madison, NJ, USA) therapy. Results: A total of 609 immigrants were diagnosed with H. pylori infection during the study period, but 264 previously received an eradication therapy. Therefore, the study was focused on 294 out of 345 naïve patients with a successful bacterial culture with antibiogram. Latin America immigrants had the highest overall resistance rate. Levofloxacin resistance rate was significantly higher in Latin Americans and Asians as compared with Europeans. Based on resistance patterns, sequential therapy showed a clear decreasing trend in eradication rates. Conclusions: while antibiotic resistance rates are generally increasing worldwide, Pylera® seems to achieve a good performance as first-line treatment in all naïve foreigner patients, except for Africans.


Expression of alpha-smooth muscle actin in the stromal cells of bone marrow in fetuses in different stages of development, in multiple myeloma and monoclonal gammopathy of unknown significance.
Several disorders are associated with a monoclonal immunoglobulin detected by serum or urine electrophoresis, the most common being a monoclonal gammopathy of unknown significance, multiple myeloma, Waldenstrom's macroglobulinemia, and amyloidosis. Plasma cells, the immunoglobulin secretory cells of the immune system, are normal constituents of bone marrow (BM). Plasma cells are seen in small numbers in the stroma, surrounding blood vessels in the marrow. Their perivascular disposition is consistent with their secreting capacity. The hematopoietic microenvironment has a crucial role homing and regulating precursor cell growth both in physiologic and pathologic conditions. Cellular components such as branched adventitial reticular cells, macrophages, endothelial cells and fat cells constitute the supporting framework (stroma) for hematopoiesis, which takes place in the extravascular compartment. The presence of myiod cells (MCs) in human bone marrow has been observed during hematopoiesis in embryonic life, whereas during adult life, it is strictly related to various pathologic conditions. The aim of this study was to examine in the stroma of BM the presence, distribution and quantitation of cells expressing a-smooth muscle actin (MCs) from patients with monoclonal gammopathy of unknown significance, those with plasma cell myeloma and embryos (gestational age 15 to 25 weeks). For this reason, a series of 20 trephine bone marrow biopsies from adult patients and ten fetal specimens of the spine and femur were examined for the presence of stromal myoid cells using a monoclonal recognising alpha-smooth muscle actin, a contractile microfilament expressed solely by smooth muscle cells, myofibroblasts and related cells. Our results suggest that the appearance of MCs and subsequent fibrosis is not a feature of malignant BM disorders such as MM but it is also seen to a lesser degree in the BM stroma of individuals with monoclonal gammopathy of unknown significance (MGUS). Stromal cells with phenotypic smooth muscle features appear in bone marrow during pathological situations in a manner reminiscent of what occurs during normal development.


A Review of Efficacy and Safety of Checkpoint Inhibitor for the Treatment of Acute Myeloid Leukemia.
Immune checkpoint inhibitors (ICIs) as positive modulators of immune response have revolutionized the treatment of cancer and have achieved impressive efficacy in melanoma and numerous solid tumor malignancies. These agents are being investigated in acute myeloid leukemia (AML) to further enhance response rate as induction therapy and to improve relapse-free survival (RFS) post chemotherapy and bone marrow transplantation. PD-1 and CTLA-4 are the two most actively investigated checkpoint receptors, which play a role in different stages of anti-tumor immune response. This study reviews data from ongoing phase I, II clinical trials evaluating PD-1 and CTLA-4 inhibitors on AML patients and discusses especially efficacy and adverse events as well as prospects of these drugs in treating AML. Single anti-PD-1 monoclonal antibody infusion shows rather modest clinical efficacy. While combinations of PD-1 inhibitor with hypomethylating agents (HMAs) represent encouraging outcome for relapsed/refractory (R/R) AML patients as well as for elderly patients as first-line therapy option. Adding PD-1 inhibitor to traditional induction therapy regimen is also safe and feasible. CTLA-4 inhibitor ipilimumab exhibits specific potency in treating relapsed AML patients with extramedullary disease in later post-transplantation stage. In terms of side effects, irAEs found in these trials can mostly be appropriately managed with steroids but are occasionally fatal. More rationally designed combinational therapies are under investigation in ongoing clinical trials and will further advance our understanding of checkpoint inhibitors as well as lead us to the most appropriate application of these agents.


Inhibition of tumor high-energy phosphate metabolism by insulin combined with rhodamine 123.
The purpose of this study was to determine whether the energy metabolism of an experimental rodent sarcoma was selectively depressed by the combination of inhibition of glycolysis and respiration. In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to monitor the response of tumor or brain high-energy phosphate compounds to insulin hypoglycemia, rhodamine 123, or both agents in fasting rats with subcutaneous methylcholanthrene-induced sarcomas. Insulin or rhodamine 123 alone produced a similar 50% to 60% reduction in tumor adenosine triphosphate (ATP) concentration compared with controls injected with saline solution (p less than 0.05, one-way analysis of variance [ANOVA]). The combination of insulin plus rhodamine 123 resulted in a 90% reduction of tumor ATP concentration, which was significantly different from the effect of either agent alone (p less than 0.05, one-way ANOVA). Brain phosphocreatine and ATP concentrations were unchanged by these agents. Administration of dimethyl sulfoxide (DMSO)/glycerol, the vehicle for rhodamine, produced a 35% reduction of tumor ATP, which was similar to the effect of insulin alone but significantly different from rhodamine. The combination of DMSO/glycerol plus insulin hypoglycemia resulted in a 70% reduction in tumor ATP, which was significantly elevated compared with the combination of rhodamine plus insulin. Glucose deprivation induced by insulin, and combined with the inhibition of oxidative phosphorylation, produces an additive depression of tumor energetics. The drug vehicle DMSO/glycerol significantly depresses tumor energy metabolism, presumably because of its DMSO component, which may explain the previously reported antineoplastic efficacy of this solvent. Combinations of inhibitors directed at different points of tumor metabolism produced an enhanced depression of tumor energetics, whereas host tissue was protected.


[Practical application of nutritional assessment protein and inflammatory marker in the nutrition support team (NST)].
Recently nutrition support team (NST) has been established for the purpose of prevention of complications which are caused by nutrition disorders and reduction of the medical expenses. Although physical examinations and blood biochemical data had been used as the indexes evaluating nutritional of patients, they were not suitable for the evaluation for the short-term in-patient. On the contrary, serum albumin (ALB) has been wildly used as a nutritional marker. However, it is impossible to evaluate nutrition state for the short-term in-patient and acute phase disease patient accurately, because the plasma half-life is 21 days and it takes long time to detect the change in nutritional state by its value. Rapid turnover proteins (RTP), whose plasma half-life is shorter, has paid attention to evaluate nutritional state for the short-term in-patients and acute phase disease patients. Although, prognostic inflammatory and nutritional index (PINI) was considered as a useful maker for evaluating inflammatory and nutritional states using the concentrations of transthyretin (TTR), a RTP, alpha1-acid glycoprotein (alpha1-AG), a chronic inflammation marker, C reactive protein (CRP), a acute inflammation marker, and ALB, However, it has several pitfalls. We newly made serum amyloid A (SAA) index using SAA instead of CRP. When we compared SAA index with PINI in many diseases, it turned out that SAA index became a more effective index which reflected the patient condition than did PINI. As for this index, it is expected to be used by NST while further alternation may be needed.


Hindbrain signals in otic regionalization: walk on the wild side.
The inner ear, the sensory organ responsible for hearing and balance, contains specialized sensory and non-sensory epithelia arranged in a highly complex three-dimensional structure. To achieve this level of complexity, a tight coordination between morphogenesis and cell fate specification is essential during otic development. Tissues surrounding the otic primordium and more particularly the adjacent segmented hindbrain, have been implicated in conferring signals required for inner ear development. In this review, we present the current view on the role of hindbrain signals in axial specification of the inner ear. The functional analysis of mutants of hindbrain segmentation genes, as well as the investigation of signaling pathways potentially involved, all point to an essential role of FGF, Wnt and Hh signaling in otic regionalization. However, these data provide conflicting evidence regarding the involvement of hindbrain signals in otic regionalization in fish and in amniotes. We discuss the possible origin of these differences.


On the variability of the human flocculus and paraflocculus accessorius.
42 human cerebelli were examined macroscopically in order to ascertain the general morphological, conformation of the flocculus and accessory paraflocculus, as well as their variability. The flocculus had a mean number of 14.2 +/- 0.3 (s.e.) folia and 7.0 +/- 0.4 (s.e.) subfolia arranged in a rosette-like cluster of relatively constant shape. The coefficient of variability of the number of folia and subfolia was respectively 22.1% and 47.4%. The accessory paraflocculus had a mean number of 4.2 +/- 0.2 (s.e.) folia and 2.0 +/- 0.2 (s.e.) subfolia, with a variability coefficient of respectively 50.2% and 102.8% which was more than double that of the flocculus. In fact the conformation of the accessory paraflocculus varied from a single small flattened lamella to a rosette-like cluster of folia similar in shape and size to those of the flocculus. There was no correlation between the variability of the flocculus and accessory paraflocculus. The possible reason for this marked variability is discussed in the light of the phylogenetic evolution of the structures examined.


Curcumin converts Foxp3+ regulatory T cells to T helper 1 cells in patients with lung cancer.
The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The mechanism by which curcumin regulated the Tregs was observed by cell culture approaches. The results showed that the frequency of peripheral Treg was markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for 2 weeks. The peripheral Th1 cells were increased in LC patients after the curcumin therapy. The data of the in vitro experiments showed that curcumin converted the LC patient-isolated Tregs to Th1 cells via repressing the gene transcription of forkhead protein-3 and increasing the expression of interferon-γ. In conclusion, curcumin can convert LC patient-isolated Tregs to Th1 cells. The results suggest that curcumin may improve the antitumor immunity by regulating the tumor specific immune tolerance.


Determinants of stunting and severe stunting among Burundian children aged 6-23 months: evidence from a national cross-sectional household survey, 2014.
Burundi is one of the poorest countries and is among the four countries with the highest prevalence of stunting (58%) among children aged less than 5 years. This situation undermines the economic growth of the country as undernutrition is strongly associated with less schooling and reduced economic productivity. Identifying the determinants of stunting and severe stunting may help policy-makers to direct the limited Burundian resources to the most vulnerable segments of the population, and thus make it more cost effective. This study aimed to identify predictors of stunting and severe stunting among children aged less than two years in Burundi. The sample is made up of 6199 children aged 6 to 23 months with complete anthropometric measurements from the baseline survey of an impact evaluation study of the Performance-Based financing (PBF) scheme applied to nutrition services in Burundi from 2015 to 2017. Binary and multivariable logistic regression analyses were used to examine stunting and severe stunting against a set of child, parental and household variables such as child's age or breastfeeding pattern, mother's age or knowledge of malnutrition, household size or socio-economic status. The prevalence of stunting and severe stunting were 53% [95%CI: 51.8-54.3] and 20.9% [95%CI: 19.9-22.0] respectively. Compared to children from 6-11 months, children of 12-17 months and 18-23 months had a higher risk of stunting (AdjOR:2.1; 95% CI: 1.8-2.4 and 3.2; 95% CI: 2.8-3.7). Other predictors for stunting were small babies (AdjOR=1.5; 95% CI: 1.3-1.7 for medium-size babies at birth and AdjOR=2.9; 95% CI: 2.4-3.6 for small-size babies at birth) and male children (AdjOR=1.5, 95% CI: 1.4-1.8). In addition, having no education for mothers (AdjOR=1.6; 95% CI: 1.2-2.1), incorrect mothers' child nutrition status assessment (AdjOR=3.3; 95% CI: 2.8-4), delivering at home (AdjOR=1.4; 95% CI: 1.2-1.6) were found to be predictors for stunting. More than to 2 under five children in the household (AdjOR=1.45; 95% CI: 1.1-1.9 for stunting and AdjOR= 1.5; 95% CI: 1.2-1.9 for severe stunting) and wealth were found to be predictors for both stunting and severe stunting. The factors associated with stunting were found to be applicable for severe stunting as well. Mother's education level, mother's knowledge about child nutrition status assessment and health facility delivery were predictors of child stunting. Our study confirms that stunting and severe stunting is in Burundi, as elsewhere, a multi-sectorial problem. Some determinants relate to the general development of Burundi: education of girls, poverty, and food security; will be addressed by a large array of actions. Some others relate to the health sector and its performance - we think in particular of the number of children under five in the household (birth spacing), the relationship with the health center and the knowledge of the mother on malnutrition. Our findings confirm that the Ministry of Health and its partners should strive for better performing and holistic nutrition services: they can contribute to better nutrition outcomes.


Effects of Atmospheric Water on ·OH-initiated Oxidation of Organophosphate Flame Retardants: A DFT Investigation on TCPP.
Tris(2-chloroisopropyl) phosphate (TCPP), a widely used organophosphate flame retardant, has been recognized as an important atmospheric pollutant. It is notable that TCPP has potential for long-range atmospheric transport. However, its atmospheric fate is unknown, restricting its environmental risk assessment. Herein we performed quantum chemical calculations to investigate the atmospheric transformation mechanisms and kinetics of TCPP initiated by ·OH in the presence of O2/NO/NO2, and the effects of ubiquitous water on these reactions. Results show the H-abstraction pathways are the most favorable for the titled reaction. The calculated gaseous rate constant and lifetime at 298 K are 1.7 × 10-10 cm3molecule-1 s-1 and 1.7 h, respectively. However, when considering atmospheric water, the corresponding lifetime is about 0.5-20.2 days. This study reveals for the first time that water has a negative role in the ·OH-initiated degradation of TCPP by modifying the stabilities of prereactive complexes and transition states via forming hydrogen bonds, which unveils one underlying mechanism for the observed persistence of TCPP in the atmosphere. Water also influences secondary reaction pathways of selected TCPP radicals formed from the primary H-abstraction. These results demonstrate the importance of water in the evaluation of the atmospheric fate of newly synthesized chemicals and emerging pollutants.


Defect energy of infinite-component vector spin glasses.
We compute numerically the zero-temperature defect energy DeltaE of the vector spin glass in the limit of an infinite number of spin components m , for a range of dimensions 2< or d < or =5 . Fitting to DeltaE approximately L(theta) , where L is the system size, we obtain: theta similar to-1.54 (d=2) , theta similar to-1.04 (d=3) , theta similar to -0.67 (d=4) , and theta similar to -0.37 (d=5) . These results show that the lower critical dimension dl (the dimension where theta changes sign) is significantly higher for m=infinity than for finite m (where 2< dl <3 ).


Estimating the rate of gene conversion on human chromosome 21.
There is a growing recognition that gene conversion can be an important factor in shaping fine-scale patterns of linkage disequilibrium in the human genome. We devised simple multilocus summary statistics for estimating gene-conversion rates from genomewide polymorphism data sets. In addition to being computationally feasible for very large data sets, these summaries were designed to yield robust estimates of gene-conversion rates in the presence of variation in crossing-over rates. Using our summaries, we analyzed 21,840 biallelic single-nucleotide polymorphisms (SNPs) on human chromosome 21. Our results indicate that models including both crossing over and gene conversion fit the overall short-range data (0-5 kb) of chromosome 21 much better than do models including crossing over alone. The estimated ratio of gene-conversion rate to crossing-over rate has a range of 1.6-9.4, depending on the assumed conversion tract length (in the range of 500-50 bp). Removal of the 5,696 SNPs that occur in known mutational hotspots (CpG sites) did not significantly change our conclusions, suggesting that recurrent mutations alone cannot explain our data.


On the propagation of a wave front in viscoelastic arteries.
In formulating a mathematical model of the arterial system, the one-dimensional flow approximation yields realistic pressure and flow pulses in the proximal as well as in the distal regions of a simulated arterial conduit, provided that the viscoelastic damping induced by the vessel wall is properly taken into account. Models which are based on a purely elastic formulation of the arterial wall properties are known to produce shocklike transitions in the propagating pulses which are not observed in man under physiological conditions. The viscoelastic damping characteristics are such that they are expected to reduce the tendency of shock formation in the model. In order to analyze this phenomenon, the propagation of first and second-order pressure waves is calculated with the aid of a wave front expansion, and criteria for the formation of shocks are derived. The application of the results to the human arterial system show that shock waves are not to be expected under normal conditions, while in case of a pathologically increased pressure rise at the root of the aorta, shocklike transitions may develop in the periphery. In particular, it is shown that second-order waves never lead to shock formation in finite time for the class of initial conditions and mechanical wave guides which are of interest in the mammalian circulation.


Sex differences in neurobehavioral consequences of methamphetamine exposure in adult mice.
Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied. Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments. Groups of 4-month-old male and female C57BL/6 J mice were administered non-contingent intraperitoneal injections of either saline or METH (1.4 mg/kg) twice a day for 4 weeks. Mice were randomly assigned to one experimental group: (i) short-term cognitive assessments (at 5 months), (ii) long-term cognitive assessments (at 9.5 months), and (ii) longitudinal motor assessments (at 5, 7, and 9 months). Brain regions were assessed for oxidative stress and markers of neurotoxicity after behavior testing. Chronic METH exposure induced short-term effects on associative memory, gait speed, dopamine (DA) signaling, astrogliosis in females, and spatial learning and memory, balance, DA signaling, and excitotoxicity in males. There were no long-term effects of chronic METH on cognition; however, it decreased markers of excitotoxicity in the striatum and exacerbated age-associated motor impairments in males. In conclusion, cognitive and motor functions were differentially and sex-dependently affected by METH exposure, and oxidative stress did not seem to play a role in the observed behavioral outcomes. Future studies are necessary to continue exploring the long-term neurobehavioral consequences of drug use in both sexes and the relationship between aging and drugs.


Early Peribiliary Hyperenhancement on MRI in Patients with Primary Sclerosing Cholangitis: Significance and Association with the Mayo Risk Score.
The aims of this study are to assess any relationship between peribiliary hyperenhancement on MRI in patients with primary sclerosing cholangitis (PSC) and their Mayo risk score and to assess which timing of peribiliary hyperenhancement correlates best with the Mayo risk score. In this HIPAA-compliant, IRB-approved retrospective study, 101 patients who underwent MRI for known or suspected PSC were identified. Of those, 62 patients (mean age 48 years; 40 males) were diagnosed with PSC by a hepatologist based on findings on MRI, ERCP, and/or liver biopsy, and comprise the final cohort. Data were recorded on whether peribiliary hyperenhancement was present, the post-contrast phase and the extent of involvement. The components to calculate the Mayo risk score were recorded. Statistical analysis was performed using the student T test, Fisher's exact test, and the Kaplan-Meier estimate. Of 62 patients, 41 (66.1%) patients had a low-Mayo risk score (<0), 14 (22.6%) had an intermediate-risk score (≤2 and >0), and 7 (11.3%) had a high-risk score (>2). On MRI, 29 (46.8%) patients demonstrated arterial peribiliary hyperenhancement. Both the presence and extent of peribiliary hyperenhancement showed significant associations with Mayo risk score (p < 0.01). Using the combined end point of liver transplantation or death, there was a statistically significant difference in survival times between those with and those without arterial peribiliary hyperenhancement (p < 0.05). The presence of arterial peribiliary hyperenhancement in patients with PSC on MRI is associated with higher Mayo risk scores and may suggest a poorer prognosis.


A picture of progress.
A group of trusts in the North have banded together to develop a model based on 13 clusters of care which allow a variety of interventions. The Information Centre for health and social care is collecting patient data in preparation for developing its own classification system. Getting staff on board is seen as vital for both projects.


Predicting successful treatment outcome of web-based self-help for problem drinkers: secondary analysis from a randomized controlled trial.
Web-based self-help interventions for problem drinking are coming of age. They have shown promising results in terms of cost-effectiveness, and they offer opportunities to reach out on a broad scale to problem drinkers. The question now is whether certain groups of problem drinkers benefit more from such Web-based interventions than others. We sought to identify baseline, client-related predictors of the effectiveness of Drinking Less, a 24/7, free-access, interactive, Web-based self-help intervention without therapist guidance for problem drinkers who want to reduce their alcohol consumption. The intervention is based on cognitive-behavioral and self-control principles. We conducted secondary analysis of data from a pragmatic randomized trial with follow-up at 6 and 12 months. Participants (N = 261) were adult problem drinkers in the Dutch general population with a weekly alcohol consumption above 210 g of ethanol for men or 140 g for women, or consumption of at least 60 g (men) or 40 g (women) one or more days a week over the past 3 months. Six baseline participant characteristics were designated as putative predictors of treatment response: (1) gender, (2) education, (3) Internet use competence (sociodemographics), (4) mean weekly alcohol consumption, (5) prior professional help for alcohol problems (level of problem drinking), and (6) participants' expectancies of Web-based interventions for problem drinking. Intention-to-treat (ITT) analyses, using last-observation-carried-forward (LOCF) data, and regression imputation (RI) were performed to deal with loss to follow-up. Statistical tests for interaction terms were conducted and linear regression analysis was performed to investigate whether the participants' characteristics as measured at baseline predicted positive treatment responses at 6- and 12-month follow-ups. At 6 months, prior help for alcohol problems predicted a small, marginally significant positive treatment outcome in the RI model only (beta = .18, P = .05, R(2) = .11). At 12 months, females displayed modest predictive power in both imputation models (LOCF: beta = .22, P = .045, R(2) = .02; regression: beta = .27, P = .01, R(2) = .03). Those with higher levels of education exhibited modest predictive power in the LOCF model only (beta = .33, P = .01, R(2) = .03). Although female and more highly educated users appeared slightly more likely to derive benefit from the Drinking Less intervention, none of the baseline characteristics we studied persuasively predicted a favorable treatment outcome. The Web-based intervention therefore seems well suited for a heterogeneous group of problem drinkers and could hence be offered as a first-step treatment in a stepped-care approach directed at problem drinkers in the general population. International Standard Randomized Controlled Trial Number (ISRCTN): 47285230; http://www.controlled-trials.com/isrctn47285230 (Archived by WebCite at http://www.webcitation.org/5cSR2sMkp).


The novel HLA-DRB1*0807 allele is present in a Carib Amerindian population: the Yucpa.
Nucleotide sequences of five novel HLA-DRB1*08 alleles have been recently reported but their frequency in different populations is still unknown. The presence of DRB1*08 variants among Carib-speaking Yucpa Amerindians of the Perijá Range in the border between Colombia and Venezuela was tested by PCR-DNA typing. DRB1*0807 was the only DRB1*08 variant found in this population with a frequency of 0.1250. Until very recently, DRB1*0802 was the predominant DRB1*08 allele present among full-blooded Amerindians, but in the last 3 years DRB1*0804 has been found in 2 South American tribes and *0811 in 2 North American tribes. The description of a new functional DRB1*08 variant in Amerindians suggests that extensive gene polymorphism among Amerindians might not be limited to the HLA-B Class I locus.


Mammalian alpha beta hydrolase domain (ABHD) proteins: Lipid metabolizing enzymes at the interface of cell signaling and energy metabolism.
Dysregulation of lipid metabolism underlies many chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Therefore, understanding enzymatic mechanisms controlling lipid synthesis and degradation is imperative for successful drug discovery for these human diseases. Genes encoding α/β hydrolase fold domain (ABHD) proteins are present in virtually all reported genomes, and conserved structural motifs shared by these proteins predict common roles in lipid synthesis and degradation. However, the physiological substrates and products for these lipid metabolizing enzymes and their broader role in metabolic pathways remain largely uncharacterized. Recently, mutations in several members of the ABHD protein family have been implicated in inherited inborn errors of lipid metabolism. Furthermore, studies in cell and animal models have revealed important roles for ABHD proteins in lipid metabolism, lipid signal transduction, and metabolic disease. The purpose of this review is to provide a comprehensive summary surrounding the current state of knowledge regarding mammalian ABHD protein family members. In particular, we will discuss how ABHD proteins are ideally suited to act at the interface of lipid metabolism and signal transduction. Although, the current state of knowledge regarding mammalian ABHD proteins is still in its infancy, this review highlights the potential for the ABHD enzymes as being attractive targets for novel therapies targeting metabolic disease.


[Regional differences of nucleosides and amino acids in Elaphuri Davidiani Cornu].
In order to reveal the regional characteristics of nucleosides and amino acids in Elaphuri Davidiani Cornu,39 samples of Elaphuri Davidiani Cornu collected from 4 different regions were analyzed by UPLC-QTRAP ~®/MS2 method followed by orthogonal partial least-squares discrimination analysis( OPLS-DA) and cluster analysis( CA). The results showed all the samples contained abundant nucleosides and amino acids,with the total content of 45. 09 μg·g~(-1) and 634. 80 μg·g-1,respectively. The samples presented significant regional differences in the contents of individual components,and the main differential components included Ura,Hpro,Thr,Glu,G5 P,2'-dG,Adeno,Met,Ade,Gln,Orni,Phe,2'-dA,Hit,Lys,and Ile. Among them,Ura,Met,Glu,and Ile had the highest content in the samples from Dafeng in Jiangsu,Qinhu in Jiangsu,Beijing,and Shishou in Hubei,respectively. OPLS-DA and CA demonstrated that all the samples of Elaphuri Davidiani Cornu could be divided into three categories,reflecting the regional characteristics. The results indicated that the accumulation of nucleosides and amino acids in Elaphuri Davidiani Cornu was closely related to its habitat,providing a useful reference for the research on the quality formation,quality evaluation and control,as well as the comprehensive utilization of Elaphuri Davidiani Cornu. The findings suggested that the content factors of Ura,Met,Glu,and Ile could be included into the quality standard system of Elaphuri Davidiani Cornu as the characteristics of medicinal materials from different regions.


Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.
Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.


Stability of suspensions of influenza virus dried to different contents of residual moisture by sublimation in vacuo.
After freezing, suspensions of influenza virus were dried by sublimation of water in vacuo to contents of residual moisture of 3.2, 2.1, 1.7, 1, or 0.4%. The stability of the several suspensions was determined by an accelerated storage test. Based on the times predicted for the dried preparations stored at different temperatures to lose 1 log of infectivity titer, the order of stability in relation to residual moistures was as follows: 1.7% > 2.1% > 1% > 3.2% > 0.4%.


Concealing the taste of the Guinness World's most bitter substance by using a synthetic nanocontainer.
Upon supramolecular encapsulation by using a synthetic nanocontainer (cucurbit[7]uril), the taste of the Guinness World's most bitter substance, denatonium benzoate, was dramatically concealed during a two-bottle preference drinking test in a mammalian model, demonstrating the significant potential of cucurbit[7]uril as a taste-masking nanocontainer for the first time.


PPAR-gamma: Therapeutic Potential for Multiple Sclerosis.
The role of peroxisome proliferator-activated receptors (PPARs) in altering lipid and glucose metabolism is well established. More recent studies indicate that PPARs also play critical roles in controlling immune responses. We and others have previously demonstrated that PPAR-gamma agonists modulate the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). This review will discuss the cellular and molecular mechanisms by which these agonists are believed to modulate disease. The therapeutic potential of PPAR-gamma agonists in the treatment of multiple sclerosis will also be considered.


Age is associated with time in therapeutic range for warfarin therapy in patients with atrial fibrillation.
Warfarin is the most prescribed oral anticoagulant used for preventing stroke in patients with atrial fibrillation. Time in the therapeutic range (TTR) has been accepted as the best method to evaluate the quality of warfarin therapy. The main aim of the present study was to evaluate the impact of variables on the time in the therapeutic range for warfarin therapy in patients with atrial fibrillation from a referral cardiovascular hospital. This retrospective study included 443 patients were included (190 patients with age < 65 years and 253 patients with age ≥65 years) from 2011 to 2014 and TTR was computed according to Rosendaal's method. Patients with age ≥65 years had higher TTR value (67±22%) compared with patients with < 65 years (60±24%) (p = 0.004). In a linear regression model, only age ≥65 years emerged as a significant predictor of greater TTR values. In multivariate logistic regression model, the variable age ≥65 years was associated with higher OR for having a TTR higher than the median value (OR = 2.17, p < 0.001). We suggest that the age influenced TTR through greater drug adherence. Strategies for increasing drug adherence might improve quality of warfarin anticoagulation.


Prevention of Incisional Surgical Site Infection Using a Subcuticular Absorbable Suture in Elective Surgery for Gastrointestinal Cancer.
This study examined whether subcuticular absorbable sutures actually reduce incisional SSI in patients undergoing surgery for gastrointestinal (GI) cancer. Surgical site infection (SSI) is still a source of major complications in digestive tract surgery. Reportedly, incisional SSI can be reduced using subcuticular suturing. We performed subcuticular suturing using a 4-0 absorbable monofilament in patients undergoing elective surgery for GI cancer beginning in 2008. Using an interrupted technique, sutures were placed 1.5-2.0cm from the edge of the wound, with everted subcuticular sutures created at intervals of 1.5-2.0cm. The control group consisted of cases in which the common subcutaneous suture method using clip. One hundred cases were examined in the subcuticular group. The incidence of SSI was 0% in the subcuticular suture group, compared with 13.9% in the control group; this difference was significant. Incisional SSI can be prevented using the devised subcuticular absorbable sutures in patients undergoing elective surgery for GI cancer.


High precision determination of the Planck constant by modern photoemission spectroscopy.
The Planck constant, with its mathematical symbol h, is a fundamental constant in quantum mechanics that is associated with the quantization of light and matter. It is also of fundamental importance to metrology, such as the definition of ohm and volt and the latest definition of kilogram. One of the first measurements to determine the Planck constant is based on the photoelectric effect; however, the values thus obtained so far have exhibited a large uncertainty. The accepted value of the Planck constant, 6.626 070 15 × 10-34 J s, is obtained from one of the most precise methods, the Kibble balance, which involves the quantum Hall effect, the Josephson effect, and the use of the international prototype of the kilogram or its copies. Here, we present a precise determination of the Planck constant by modern photoemission spectroscopy technique. Through the direct use of Einstein's photoelectric equation, the Planck constant is determined by accurately measuring the energy position of the gold Fermi level using light sources with various photon wavelengths. The precision of the Planck constant as measured in this work, 6.626 10(13) × 10-34 J s, is improved by four to five orders of magnitude from the previous photoelectric effect measurements. We propose that this direct method of photoemission spectroscopy has potential to further increase its measurement precision of the Planck constant to be comparable to the most accurate methods available at present.


Overview of cyclins D1 function in cancer and the CDK inhibitor landscape: past and present.
Intensive efforts, over the last decade, have been made to inhibit the kinase activity of cyclins that act as mediators during cell-cycle progression. Activation of the cyclin D1 oncogene, often by amplification or rearrangement, is a major driver of multiple types of human tumors including breast and squamous cell cancers, B-cell lymphoma, myeloma and parathyroid adenoma. In this review, the authors summarize the activity of cyclins and cyclin-dependent kinases in cell-cycle progression and transcription. They focus on cyclin D1/CDK4/CDK6, a central mediator in the transition from G1 to S phase. Furthermore, the authors discuss the first generation of pan-cyclin-dependent kinase inhibitors that failed to meet expectation and discuss, in detail, the second generation of highly specific cyclin D1/CDK4/CDK6 inhibitors that are proving to be more efficacious. The mechanism by which cyclin D1 drives tumorigenesis may be dependent on kinase and kinase-independent functions. Further evidence is necessary to delineate the roles of cyclin D1 in early pre-neoplastic lesions where its overexpression may promote genomic instability in a kinase-independent manner.


Donor age-dependent decline in response of human red cell Ca2+-ATPase activity to thyroid hormone in vitro.
The effect of increasing donor age on the susceptibility of human red blood cell Ca2+-ATPase activity to stimulation in vitro by thyroid hormone was studied in 26 normal subjects, aged 15-81 yr. Basal enzyme activity (no added thyroid hormone) was unaffected by donor age. Group analysis, young (less than or equal to 50 yr) vs. elderly (greater than 60 yr old), revealed a 23% decrease in responsiveness of the enzyme to L-T4 (P less than 0.001). Regression analysis confirmed an age-dependent decline in thyroid hormone stimulability of Ca2+-ATPase [r = -0.42 (T4 effect) and -0.38 (T3 effect); P less than 0.01]. Red cell membrane Na,K-ATPase activity was not affected by donor age. Plasma T4 and T3 concentrations in these normal subjects also did not change with age. Possible contributions of the following mechanisms to this age-correlated change in enzyme activity were examined: altered responsiveness to calmodulin of membrane Ca2+-ATPase; membrane content of endogenous calmodulin, endogenous plasma T4 and T3 concentrations, and plasma glucose concentrations. Calmodulin responsiveness is required for iodothyronine action on the enzyme, but the calmodulin responsiveness of cells from elderly donors was not significantly different from that of cells from younger donors (P greater than 0.10). There was no relationship between membrane immunoassayable calmodulin and donor age or membrane calmodulin and Ca2+-ATPase activity. There were positive correlations between donor plasma T4 level and basal enzyme activity (P less than 0.05) and between donor plasma T3 concentration and hormone-responsive Ca2+-ATPase (P less than 0.01), but these did not contribute to the age effect. Plasma glucose previously was found to modulate red cell Ca2+-ATPase activity, but did not correlate with decreased hormone responsiveness of the enzyme in elderly donors. In conclusion, we found that the susceptibility of human red cell Ca2+-ATPase to in vitro thyroid hormone stimulation declined significantly with advancing donor age. Several possible calmodulin-dependent mechanisms for this age-dependent change were excluded, and thus, we postulate that the altered hormone sensitivity of the enzyme is membrane phospholipid mediated.


Efficiency of pharmacologically-active antioxidant phytomedicine Radical Fruits in treatment hypercholesteremia at men.
The purpose of this randomized, double-blind, placebo controlled intervention clinical trial was to investigate the effect of orally administered dietary supplement Radical Fruits (www.gardenoflife.com) consisting of highly concentrated edible fruits and berries on the concentration of plasma cholesterol, urinary 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) and 11-dehydrothromboxane B2 (11-dehydro-TXB2) in none-obese, non-smoking, non-diabetic hypercholesteremic male volunteers. Forty four (n=44) none-obese, non-smoking, non-diabetic male volunteers with an average age of 40+/-12 years, average body weight of 77,4+/-5,0 kg, average body mass index (BMI) of 22,2+/-2,7 kg/m2 and average total plasma cholesterol level 280+/-22 mg/dL were recruited to take part in a 4 week double-blind, randomized, placebo-controlled clinical trial. After evaluating 12 different antioxidant supplements for their phytochemical compositions and bioavailability, a dietary supplement Radical Fruits was chosen for this clinical trial. Radical Fruits contains standardized extracts and concentrates of prune, pomegranate, apple, grape, raspberry, blueberry, white cherry and strawberry. Subjects were randomly assigned to the treatment group and the placebo group using Simple Randomization Procedure. Subjects in the treatment group (n=22) were directed to take 900 mg of Radical Fruits supplement three times a day before meals. Subjects in the control group (n=22) were directed to take placebo according to the same schedule. Food record analysis, body composition, blood and urine samples were assessed on admission and then once a week. The duration of the clinical trial was 4 weeks. Administration of Radical Fruits(TM) for 4 weeks resulted in statistically significant reduction of total plasma cholesterol from 280+/-23 to 250+/-11 mg/dL, (p<0,001). Total plasma cholesterol changes in the placebo group were not statistically significant. The average plasma LDL was reduced from 195+/-23 to 169+/-21 mg/dL (p<0,001) in the Radical Fruits(TM) group, while in the placebo group there were no statistically significant changes. Plasma HDL increased by 3,2=/-0,6% in the Radical Fruits treated group (p<0,001). No significant changes in the HDL levels were observed in the placebo group. Urinary 8-epi-PGF2alpha level decreased from 450+/-170 to 330+/-159 pg/mg creatinine (p<0,001); urinary 11-dehydro-TXB2 level decreased from 1,200+/-420 to 790+/-320 pg/mg creatinine (p<0,001) with no changes in the placebo group. Administration of pharmacologically active antioxidant supplement Radical Fruit(TM) in hypercholesteremic men significantly increased plasma HDL and reduced total cholesterol and LDL, and urinary oxidative and inflammatory isoprostanes and thromboxane.


Heritability of acquiescence bias and item keying response style associated with the HEXACO personality scale.
The current research investigates the heritability of two of the most common response styles: acquiescence bias (tendency to agree or disagree with survey items regardless of the items' actual content) and item keying (differential responding related to the use of regular- and reverse-keyed items). We estimated response styles from a common personality measure (HEXACO) and examined the heritability of each with univariate genetics analyses. The results show item keying effect was heritable but acquiescence bias was not. Neither response style was strongly influenced by the shared environment of the twins. Unique environmental effects were found to be substantial for response styles. The current findings have important implications for future research of response behaviors that are often overlooked by behavioral geneticists.


Salmonella and Enteropathogenic Escherichia coli Interactions with Host Cells: Signaling Pathways.
The host-pathogen interaction involves a myriad of initiations and responses from both sides. Bacterial pathogens such as enteropathogenic Escherichia coli (EPEC) and Salmonella enterica have numerous virulence factors that interact with and alter signaling components of the host cell to initiate responses that are beneficial to pathogen survival and persistence. The study of Salmonella and EPEC infection reveals intricate connections between host signal transduction, cytoskeletal architecture, membrane trafficking, and cytokine gene expression. The emerging picture includes elements of molecular mimicry by bacterial effectors and bacterial subversion of typical host events, with the result that EPEC is able to survive and persist in an extracellular milieu, while Salmonella establishes an intracellular niche and is able to spread systemically throughout the host. This review focuses on recent advances in our understanding of the signaling events stemming from the host-pathogen interactions specific to Salmonella and EPEC.


Observation of electrostatically released DNA from gold electrodes with controlled threshold voltages.
DNA oligo-nucleotides, localized at Au metal electrodes in aqueous solution, are found to be released when applying a negative bias voltage to the electrode. The release was confirmed by monitoring the intensity of the fluorescence of cyanine dyes (Cy3) linked to the 5' end of the DNA. The threshold voltage of the release changes depending on the kind of linker added to the DNA 3'-terminal. The amount of released DNA depends on the duration of the voltage pulse. Using this technique, we can retain DNA at Au electrodes or Au needles, and release the desired amount of DNA at a precise location in a target. The results suggest that DNA injection into living cells is possible with this method.


Road traffic accident: an emerging public health problem in assam.
In the northern states, there is hardly any scientific study except road traffic accidents (RTAs) statistics obtained by the Ministry of Home whereas the main way of transportation is by road. There is the increasing load of motor vehicles on the already dilapidated roadways which has resulted in the increasing trend of RTAs in Assam. To find out the prevalence, probable epidemiological factors and morbidity and mortality pattern due to RTAs in Dibrugarh district. Descriptive study was carried out in Dibrugarh district from September 1998 to August 1999 under the department of Community Medicine. The information was collected from Assam Medical College and Hospital and cross checked with the police report. A medical investigation including interview, clinical and radiological investigation was carried out; in case of fatality, post-mortem examination was examined in details. An on the spot investigation was carried out in accessible RTAs to collect the probable epidemiological factors. RTAs affected mainly the people of productive age group which were predominantly male. Majority of the RTAs were single vehicle accidents and half of the victims were passengers. Accident rate was maximum in twilight and winter season demanding high morbidity and mortality. Head and neck, U.limb and L.limb were commonly involved. RTAs is a major public health problem in Assam which needs more scientific study.


Identification of cell-wall stress as a hexose-dependent and osmosensitive regulator of plant responses.
Development, abiotic and biotic stress each affect the physical architecture and chemical composition of the plant cell wall, making maintenance of cell-wall integrity an important component of many plant processes. Cellulose biosynthesis inhibition (CBI) was employed to impair the functional integrity of the cell wall, and the plant's response to this specific stress was characterized in an Arabidopsis seedling model system. CBI caused changes in the expression of genes involved in mechanoperception, the response to microbial challenge, and lignin and cell-wall polysaccharide biosynthesis. Following CBI, activation of a UDP-D-xylose 4-epimerase gene correlated with increases in arabinose and uronic acid content in seedling cell walls. Activation of pathogen response genes, lignin deposition and lesion formation were dependent on externally supplied sugars and were suppressed by osmotic support. Lignin deposition in the root elongation zone caused by CBI was reduced in atrbohd (NADPH oxidase) mutant seedlings but increased in jasmonic acid resistant1 (jar1-1) mutant seedlings. Phytohormone measurements showed that CBI-induced increases in jasmonic (JA) and salicylic acids were dependent on sugar availability and prevented by osmotic support. We show that CBI activates responses commonly attributed to both abiotic and microbial challenges. Glucose/sucrose and turgor pressure are critical components in maintenance of cell-wall integrity and the regulation of induced responses, including JA biosynthesis. Lignin deposition induced by CBI is regulated by JAR1-1 and NADPH oxidase-dependent signalling processes. Our results identify components of the mechanism that mediates the response to impairment of cell-wall integrity in Arabidopsis thaliana.


In silico modeling of the Moniliophthora perniciosa Atg8 protein.
Autophagy is defined as an intracellular system of lysosomal degradation in eukaryotic cells, and the genes involved in this process are conserved from yeast to humans. Among these genes, ATG8 encodes a ubiquitin-like protein that is conjugated to a phosphatidylethanolamine (PE) membrane by the ubiquitination system. The Atg8p-PE complex is important in initiating the formation of the autophagosome and thus plays a critical role in autophagy. In silico modeling of Atg8p of Moniliophthora perniciosa revealed its three-dimensional structure and enabled comparison with its Saccharomyces cerevisiae homologue ScAtg8p. Some common and distinct features were observed between these two proteins, including the conservation of residues required to allow the interaction of α-helix1 with the ubiquitin core. However, the electrostatic potential surfaces of these helices differ, implying particular roles in selecting specific binding partners. The proposed structure was validated by the programs PROCHECK 3.4, ANOLEA, and QMEAN, which demonstrated 100% of amino acids located in favorable regions with low total energy. Our results showed that MpAtg8p contains the same functional domains (3 α-helices and 4 β-sheets) and is similar in structure as the ScAtg8p yeast. Both proteins have many conserved sequences in common, and therefore, their proposed three-dimensional models show similar configuration.