Trends in cardiovascular diseases mortality in the Philippines.
Cardiovascular disease mortality in the Philippines was studied from the existing vital statistics for 1963-76. Death rates from rheumatic fever and rheumatic heart disease remained unchanged, those for cerebrovascular diseases decreased, whereas mortality rates of ischaemic heart disease (IHD) and hypertensive disease (HPN) increased enormously both in men and women. This increase in IHD and HPN mortality was seen in all age groups. The age-standardized IHD mortality rate in men rose from 33.3 in 1964 to 78.0 in 1976, and that of women from 15.4 to 34.5. The age-standardized HPN mortality rate in men rose from 21.0 in 1964 to 45.6 in 1976, and that of women from 15.6 to 25.5. The male to female ratios in the age-standardized death rates for IHD, HPN and also for all causes increased during this 12-year period. Age-standardized all causes mortality increased clearly in the male population but decreased in the female population of the Philippines. This excess mortality in males is mostly due to the increased cardiovascular disease death rate. This is a clear example of how chronic non-communicable diseases are becoming major health problems in countries where they previously have not been prevalent. Immediate preventive measures are needed in order to control cardiovascular diseases in these countries where disease rates are rapidly increasing.


Correlation of genetic variation among wild Trigonella foenum-graecum L. accessions with their antioxidant potential status.
In this study, we analyzed the correlation between genetic variation based on random amplified polymorphic DNA (RAPD), acid phosphatase, and glutamate-oxaloacetate transaminase isozymes, and amino acid composition with the antioxidant potential status of 7 wild Trigonella foenum-graecum L. accessions collected from diverse ecogeographical regions. RAPD revealed that 90 DNA products had highly polymorphism value (94.12%) based on band numbers, with sizes ranging from 50-2100 base pairs, and band intensity. Of 49 DNA polymorphic bands, 31 unique and 3 monomorphic bands were scored. Acid phosphatase and glutamate-oxaloacetate transaminase showed total polymorphism values of 90.00 and 93.75%, respectively, based on zymogram number, relative front (Rf), and optical intensity. Because isozymes are composed of amino acids, they were analyzed using high-performance liquid chromatography, which revealed the presences of 16 amino acids of variable content ranging from 13.21-15.35%, 9 of which are essential amino acids in humans. RAPD and isozymes showed similarly high estimates of genetic variability. Genetic relationships revealed by unweighted pair group method with arithmetic mean clustering analysis based on data obtained from all primers of RAPD and each isozyme were very similar. The antioxidant potential based on free radical scavenging, 2, 2-diphenyl-1-picrylhydrazyl, b-carotene-linoleate, total phenolic, and flavonoid contents values were variable among accessions. We found that fenugreek is a valuable genetic resource with high antioxidant activity. Their genotypes, based on data and clustering of RAPD, isozymes, and variable amino acid contents, combined with their antioxidant potential statues are important in fenugreek breeding and improvement programs.


Position of positron emission tomography and other imaging diagnostic modalities in esophageal cancer.
Positron emission tomography (PET) using the positron emitting glucose analogue 18F-fluorodeoxyglucose (FDG) has emerged as a useful metabolism-based wholebody imaging tool for gastro-esophageal cancer diagnosis and follow up. Most large cancer centers worldwide are now equipped for PET (or even PET-CT). Therefore, there is a growing need for a clear definition of the relative position of PET within the currently available diagnostic modalities. Significant scientific data indicate that FDG-PET adds clinically useful information to the information obtained by standard means (mainly CT and endoscopic ultrasound) throughout the different phases of clinical patient management: 1) at initial diagnosis: PET detects more frequently distant lymph node involvement and organ metastases compared to conventional diagnostics, allowing a more accurate selection of the most appropriate treatment; 2) during chemotherapy: semi-quantitative FDG-PET allows early identification of non-responding patients. Indeed, the metabolic response as measured by serial FDG-PET can be used to predict the clinical and histopathological response. Moreover, the PET-response seems to be related to overall and disease free survival; 3) after a treatment: FDG-PET allows accurate assessment of the residual tumor load; 4) in the follow up: FDG-PET allows accurate detection and restaging of recurrent disease.


Ulnar-sided cleft hand.
Three cases of ulnar-sided cleft hand are presented in which clefting was accompanied by ring finger absence in 2 and by small finger abduction, supination, shortening, and camptodactyly in all 3. An approach to surgical reconstruction is described with marked improvement in appearance.


Frequency-Specific Microcurrent as Adjunctive Therapy for Three Wounded Warriors.
Background: Acupuncture is frequently offered for wounded warriors as a component of an integrated approach to pain and associated symptoms, with increasing availability at military treatment facilities and Veterans Administration hospitals. While medications can be effective for many patients, acupuncture and microcurrent therapies address the growing need to offer nonopiate, nonpharmaceutical therapeutics in integrative pain management. Frequency-specific microcurrent (FSM) is a newer, adjustable, microcurrent, electrical stimulation modality with applications for pain and other associated symptoms. Using low amperage, electrical current delivered transcutaneously affects and repairs tissues at the cellular level. Additionally, concomitant treatment with acupuncture is possible, which is particularly helpful when space and time limit the frequency with which acupuncture treatments can be provided. Cases: For 3 wounded warriors, FSM was combined with acupuncture treatments, resulting in more-rapid reduction of their pain and associated symptoms; including memory problems, mental sluggishness, and post-traumatic stress disorder. Results: FSM was found to be a safe, nonpainful, noninvasive treatment that could be administered concurrently and beneficially with acupuncture. Conclusions: While additional, more-rigorous studies are needed, this case series demonstrates the potential that FSM has within an integrated pain treatment program for wounded warriors.


Molecular Identification of Mucor and Lichtheimia Species in Pure Cultures of Zygomycetes.
The Mucorales are an important opportunistic fungi that can cause mucormycosis in immunocompromised patients. The fast and precise diagnosis of mucormycosis is very important because, if the diagnosis is not made early enough, dissemination often occurs. It is now well established that molecular methods such as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) are feasible and reliable tools for the early and accurate diagnosis of mucormycosis agents. The present study was conducted to evaluate the validity of PCR-RFLP for the identification of Mucorales and some important Mucor and Lichtheimia species in pure cultures of Zygomycetes. Specific sense and anti-sense primers were used to amplify the Mucorales, Mucor, and Lichtheimia DNA. The PCR products were digested by AfIII, XmnI, and AcII restriction enzymes, and the resultant restriction pattern was analyzed. On the basis of the molecular and morphological data, we identified Mucor plumbeus (10.83%), M. circinelloides (9.17%), Lichtheimia corymbifera (9.17%), M. racemosus (5.83%), M. ramosissimus (3.33%), and L. blakesleeana (0.83%). It seems that PCR-RFLP is a suitable technique for the identification of Mucorales at the species level.


Hormonal contraceptive use in Australian women: Who is using what?
In Australia many hormonal contraceptives are not Pharmaceutical Benefits Scheme (PBS) supported, hence the use of different formulations have not been quantified. To document the use of hormonal contraceptives and factors associated with their use. Cross-sectional, online questionnaire-based study of 6986 Australian women, aged 18-39 years, recruited by email invitation from two large, representative databases. Main outcome measures were the prevalence of use of hormonal contraceptives and associated socio-demographic characteristics. Of the 6600 potential hormone contraceptive users, 43.2% were current users. Most (63.6%) reported using a combined oral contraceptive (COC) of which 30.9% were non-PBS-supported anti-androgenic progestin-containing COCs. Use of long-acting reversible contraceptives (LARC) or an injectable contraceptive was reported by 26.8%. Education beyond secondary school, being Australian born, rural residency, normal body mass index, age <25 years and nulliparity were significantly associated with hormonal contraceptive use. Women who reported polycystic ovary syndrome or acne were more likely to be taking a third or fourth generation COC (P < 0.0001) and endometriosis was significantly associated with intrauterine system (IUS) use. Third or fourth generation COC use was reported by 12.1% of obese, current smokers. An estimated one-third of Australian women aged 18-39 are taking a non-PBS-supported anti-androgenic progestin COC, highlighting inequity in access to COC options. That hormonal contraceptive use is higher in rural areas is a novel finding and the proportion of LARC or injectable use suggests that uptake in Australia is higher than previously reported.


Stimulation of DNA synthesis, activation of mitogen-activated protein kinase ERK2 and nuclear accumulation of c-fos in human aortic smooth muscle cells by ketamine.
Proliferation of vascular smooth muscle cells is known to be regulated by autocrine and paracrine stimuli, including extracellular matrix, reactive oxygen species, lipids, and biomechanical forces. The effect of many pharmacological agents to which smooth muscle cells may be exposed, however, is widely unexplored. Ketamine, an intravenous anaesthetic and a phencyclidine derivative, regulates diverse intracellular signalling pathways in smooth muscle cells, several of which are known to affect cell proliferation. The effect of ketamine on proliferative response of smooth muscle cells, however, is not determined. We tested the hypothesis that ketamine may regulate proliferation of smooth muscle cells, and investigated the effects of pharmacological doses of ketamine on their proliferative capacity by measuring DNA synthesis and activation of mitogen-activated protein (MAP) kinase signalling pathway in human aortic smooth muscle cells. DNA synthesis, as determined by incorporation of 3H-thymidine into DNA, was enhanced by 73% (P < 0.0001) and 130% (P < 0.0001) with 10 and 100 microm ketamine, respectively. Ketamine-induced DNA synthesis was dependent on de novo protein synthesis, as it was abolished by an inhibitor of protein synthesis, cycloheximide. A synthetic inhibitor of MAP kinase pathway, PD98059, decreased 50% (P < 0.0001) of ketamine-induced DNA synthesis, suggesting that the activation of MAP kinase pathway was partially responsible for ketamine-induced effects. Consistently, in-gel kinase assay and in vitro kinase assay of cell lysates showed ketamine-induced MAP kinase activation and expression of ERK2 (extracellular signal-regulated kinase) in smooth muscle cells. This effect of ketamine was not dependent on de novo protein synthesis. Immunofluorescent light microscopy showed ketamine-induced nuclear accumulation of c-fos, a downstream effect of MAP kinase activation, in smooth muscle cells. In conclusion, these data support the hypothesis of the study and demonstrate that ketamine, by stimulating DNA synthesis in human aortic smooth muscle cells, may have an impact on proliferative capacity of these cells. The present results also demonstrate that ketamine induces the activation of MAP kinase pathway and nuclear accumulation of transcription factor c-fos in smooth muscle cells. They further demonstrate that the activation of MAP kinases is partially responsible for ketamine-induced DNA synthesis in human aortic smooth muscle cells. Together, these findings suggest that ketamine may play a role as a pharmacological regulator of mechanisms involved in proliferation of smooth muscle cells.


In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells.
Inhalation of particles has been shown to induce mutations in the male germline in mice following both prenatal and adult exposures in several experiments. In contrast, the effects of particles on female germ cell mutagenesis are not well established. Germline mutations are induced during active cell division, which occurs during fetal development in females. We investigated the effects of prenatal exposure to carbon black nanoparticles (CB) on induction of mutations in the female mouse germline during fetal development, spanning the critical developmental stages of oogenesis. Pregnant C57BL/6J mice were exposed four times during gestation by intratracheal instillation of 67μg/animal of nanosized carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female offspring were raised to maturity and mated with unexposed CBA males. Expanded simple tandem repeat (ESTR) germline mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring.


T-2 toxin induces apoptosis via the Bax-dependent caspase-3 activation in mouse primary Leydig cells.
To explore the toxic effect of T-2 toxin on mouse Leydig cells and its underlying molecular mechanisms, we isolated Leydig cells from mature mice, set-up Leydig cells culture, treated cells with T-2 toxin, evaluated cell proliferation, detected the caspase-3 activity, mitochondrial activity and apoptosis rate, and measured the mRNA levels of Bcl-2, Bax, PARP and caspase-3. T-2 toxin inhibited cell proliferation at concentrations higher than 10-9 M or time more than 12 h, T-2 toxin also decreased Bcl-2 expression at the mRNA levels and mitochondrial activity at concentrations higher than 10-9 M. While, T-2 toxin increased the mRNA expressions of Bax and PARP at concentrations higher than 10-8 M and 10-9 M, respectively, triggered mitochondria-mediated apoptosis, activated downstream caspase-3, and then increased caspase-3 at the activity and mRNA levels at concentrations higher than 10-9 M. These data showed that T-2 toxin appears to activate specific intracellular death-related pathways leading to Bax-dependent caspase-3 activation and the induction of apoptosis in Leydig cells.


Identification of seizure onset zone and preictal state based on characteristics of high frequency oscillations.
We investigate the relevance of high frequency oscillations (HFO) for biomarkers of epileptogenic tissue and indicators of preictal state before complex partial seizures in humans. We introduce a novel automated HFO detection method based on the amplitude and features of the HFO events. We examined intracranial recordings from 33 patients and compared HFO rates and characteristics between channels within and outside the seizure onset zone (SOZ). We analyzed changes of HFO activity from interictal to preictal and to ictal periods. The average HFO rate is higher for SOZ channels compared to non-SOZ channels during all periods. Amplitudes and durations of HFO are higher for events within the SOZ in all periods compared to non-SOZ events, while their frequency is lower. All analyzed HFO features increase for the ictal period. HFO may occur in all channels but their rate is significantly higher within SOZ and HFO characteristics differ from HFO outside the SOZ, but the effect size of difference is small. The present results show that based on accumulated dataset it is possible to distinguish HFO features different for SOZ and non-SOZ channels, and to show changes in HFO characteristics during the transition from interictal to preictal and to ictal periods.


In vitro activity of guinea pig transfer factor released into plasma.
Plasma fractions and plasma dialysate from 2,4-dinitrochlorobenzene- and tuberculin-sensitive guinea pigs that had been treated with either antilymphocytic serum or normal control serum were analyzed for their ability to transfer lymphocyte transformation, passive cutaneous anaphylaxis, and macrophage migration inhibition, as well as delayed hypersensitivity in vivo. Antilymphocytic serum caused rapid release of material, which has characteristics of transfer factor, into the plasma. It was dialyzable, migrated electrophoretically with the alpha globulins and albumin, possessed a 280/260 (nm) optical density ratio of 0.7, and caused in vitro lymphocyte transformation in the presence of the specific antigen. Passive cutaneous anaphylaxis antibodies were also present in the plasma of sensitive animals, but they were isolated in electrophoretic or dialysis fractions separate from those containing transfer activity.


[The first national experience of laparoscopic removal of the transplanted kidney].
As a rule, the excision of a non-functioning renal graft in late (over 12 months) post-transplant period is performed using Fedorov subcapsular technique. This is because the kidney is embedded in scar tissue due to immune response to the allograft. This surgical approach is associated with the two major complications: bleeding during surgery or early postoperative hematoma and infection of hematoma confined in the remaining kidney capsule. To reduce blood loss and the risk of inflammatory complications, we, for the first time, carried out laparoscopic transplantectomy in a 42 year old female patient using the extracapsular technique. The operative time was 245 min, intraoperative blood loss - 350 ml. The patient was discharged to outpatient treatment on the 10th day. For the first time, such a surgery was successfully performed in 2010 in Turkey; in 2014 robotic transplantectomy was reported in the United States. No data on laparoscopic transplantectomy was found in the available national sources.


Effect of maitland mobilization in cervical and thoracic spine and therapeutic exercise on functional impairment in individuals with chronic neck pain.
[Purpose] This study evaluated joint mobilization and therapeutic exercise applied to the cervical spine and upper thoracic spine for functional impairment caused by chronic neck pain. [Subjects and Methods] Eighteen study subjects were randomly assigned to two groups of nine people each. Therapeutic exercise only was applied to the cervical and upper thoracic spine for Group I, while both therapeutic exercise and joint mobilization were applied to Group II. The visual analog scale, neck disability index, active cervical range of motion, static balance capacity, and muscle tone were assessed with a pre-test. The intervention was carried out for 60 minutes a day, three times a week, for two weeks for each group, followed by a post-test using the same protocol as the pre-test. [Results] The visual analog scale, neck disability index, and active cervical range of motion improved significantly in both groups. Group II improved significantly more on right lateral flexion and rightward rotation. Muscle tone improved significantly in the upper trapezius in both groups. [Conclusion] The joint mobilization and therapeutic exercise for functional impairments caused by chronic neck pain had a significant effect on several types of functional impairment.


Common iliac and hypogastric aneurysms: open and endovascular repair.
Currently, there are a variety of open surgical, endovascular, and hybrid options to treat iliac artery aneurysms (IAA). Anatomy of the common iliac artery (CIA) with regard to proximal and distal neck, involvement of the iliac bifurcation, and choice to preserve the ipsilateral internal iliac artery (IIA) all play a role in the decision process towards the preferred treatment method. This manuscript describes the available open surgical and endovascular techniques for the treatment of IAA. Indications, advantages and limitations, and outcomes of each technique are discussed.


[Exchange rates of dissolved nutrients at the sediment-water interface before and after diatom bloom in the East China Sea in spring].
Exchange rates of dissolved nutrients at the sediment-water interface were studied before and after diatom bloom from March to May in the East China Sea in 2005. Intact sediment cores which were sampled at 10 sites were incubated on board, and exchange rates were calculated in the function method. It was shown that sediment absorbed NO3(-) -N before bloom with the exchange rate ranging from - 1.33 mmol/(m2 d) to - 0.68 mmol/(m2 d). The sediment released NO3(-) -N after bloom with the exchange rate ranging from - 0.69 mmol/( m2 d) to 0.82 mmol/( m2 d). NH4(+) -N was almost released from sediment with the exchange rate ranging from -0.65 mmol/(m d) to 1.46 mmol/( m2 d), and the rate was higher before bloom than that after bloom. NO2(-) -N moved into sediment all along except at Zc17 with the exchange rate ranging from - 0.09 mmol/(m2 d) to 0.05 mmol/(m2 d), and the rate was a little higher after bloom than that before bloom. SiO3(2-) -Si was released from sediment all the time with the exchange rate ranging from 0.85 mmol/(m d) to 9.23 mmol/( m2 d), and the rate was higher after bloom than that before bloom. The sediment absorbed PO4(3-) -P before bloom with the exchange rate ranging from -0.06 mmol/(m2 d) to -0.01 mmol/(m2 d), but released PO4(3-) -P after bloom with the exchange rate ranging from 0 mmol/(m2 d) to 1.26 mmol/(m2 d). PO4(3-) -P and NO3(-) -N which were absorbed by sediment in spring restricted the diatom bloom, but their release from sediment after diatom bloom may make a great contribution to subsequent dinoflagellate bloom.


The predominance of beta (CC) chemokine transcripts in idiopathic inflammatory muscle diseases.
Cytokines and chemokines that upregulate major histocompatibility complex class I antigens, recruit lymphocytes, and enhance T-cell-mediated myotoxicity may be important in the pathogenesis of dermatomyositis and polymyositis. We searched for cytokine and chemokine transcripts in inflammatory muscle specimens from 14 newly diagnosed or treated patients. Control specimens from six patients without inflammatory muscle disease were analyzed for transcripts of interleukins-1 beta, -2, -4, -6, -10, and -15, and interferon-gamma, tumor necrosis factor-alpha, transforming growth factor-beta 1, macrophage inflammatory proteins-1 alpha and -1 beta (MIP-1 alpha, MIP-1 beta), and the chemokine "regulated on activation, normally T expressed and secreted" (RANTES). Surprisingly, the proinflammatory and lymphocyte cytokines were detected only sporadically in myositis muscle specimens, and their presence did not correlate with disease activity or treatment status of the patient. In contrast, MIP-1 alpha and MIP-1 beta were detected in 13 and 6 myositis biopsies, respectively, and RANTES, another beta (CC) chemokine, was detected in eight myositis biopsies. This study and other reports of low levels of acute-phase cytokines in myositis patients suggest that the proinflammatory cytokines do not play a major role in ongoing muscle damage. The CC chemokines studied here, in particular MIP-1 alpha, might contribute to ongoing muscle inflammation, and the pathogenesis of inflammation in myositis may follow a previously unrecognized pathway.


Cyclic AMP underpins suppression by regulatory T cells.
Elevated levels of intracellular cyclic adenosine monophosphate (cAMP) in naturally occurring T regulatory (nTreg) cells play a key role in nTreg-cell-mediated suppression. Upon contact with nTreg cells, cAMP is transferred from nTreg cells into activated target CD4(+) T cells and/or antigen-presenting cells (APCs) via gap junctions to suppress CD4(+) T-cell function. cAMP facilitates the expression and nuclear function of a potent transcriptional inhibitor, inducible cAMP early repressor (ICER), resulting in ICER-mediated suppression of interleukin-2 (IL-2). Furthermore, ICER inhibits transcription of nuclear factor of activated T cell c1/α (NFATc1/α) and forms inhibitory complexes with preexisting NFATc1/c2, thereby inhibiting NFAT-driven transcription, including that of IL-2. In addition to its suppressive effects mediated via ICER, cAMP can also modulate the levels of surface-expressed cytotoxic T lymphocyte antigen-4 (CTLA-4) and its cognate B7 ligands on conventional CD4(+) T cells and/or APCs, fine-tuning suppression. These cAMP-driven nTreg-cell suppression mechanisms are the focus of this review.


Small Regulatory RNAs in the Control of Motility and Biofilm Formation in E. coli and Salmonella.
Biofilm formation in Escherichia coli and other enteric bacteria involves the inverse regulation of the synthesis of flagella and biofilm matrix components such as amyloid curli fibres, cellulose, colanic acid and poly-N-acetylglucosamine (PGA). Physiologically, these processes reflect the transition from growth to stationary phase. At the molecular level, they are tightly controlled by various sigma factors competing for RNA polymerase, a series of transcription factors acting in hierarchical regulatory cascades and several nucleotide messengers, including cyclic-di-GMP. In addition, a surprisingly large number of small regulatory RNAs (sRNAs) have been shown to directly or indirectly modulate motility and/or biofilm formation. This review aims at giving an overview of these sRNA regulators and their impact in biofilm formation in E. coli and Salmonella. Special emphasis will be put on sRNAs, that have known targets such as the mRNAs of the flagellar master regulator FlhDC, the stationary phase sigma factor σS (RpoS) and the key biofilm regulator CsgD that have recently been shown to act as major hubs for regulation by multiple sRNAs.


Two-Dimensional Spectroscopy at Terahertz Frequencies.
Multidimensional spectroscopy in the visible and infrared spectral ranges has become a powerful technique to retrieve dynamic correlations and couplings in wide-ranging systems by utilizing multiple correlated light-matter interactions. Its extension to the terahertz (THz) regime of the electromagnetic spectrum, where rich material degrees of freedom reside, however, has been progressing slowly. This chapter reviews some of the THz-frequency two-dimensional (2D) spectroscopy techniques and experimental results realized in recent years. Examples include gas molecule rotations, spin precessions in magnetic systems, and liquid molecular dynamics studied by 2D THz or hybrid 2D THz-Raman spectroscopy techniques. The methodology shows promising applications to different THz-frequency degrees of freedom in various chemical systems and processes.


Telehealth provides effective pediatric surgery care to remote locations.
The aim of this study was to document the experience and patient satisfaction with providing pediatric surgery consultations and follow-up appointments to remote locations via audiovisual telecommunications technology. From January 2000 to April 2001, 16 consecutive pediatric general surgery clinics were reviewed for the type of patient (new or review), the diagnosis, the adequacy and accuracy of the evaluation, and the ability to formulate a plan. In the first year, first-time users were requested to complete a satisfaction survey of 15 questions. Responses to 13 questions were recorded on a 4-point Likert scale, and 2 questions required a "yes" or "no" response. One hundred eighteen appointments were scheduled. Twenty patients did not show up or cancelled. There were 45 new patient consultations. Thirty-three patients were scheduled for surgery, of which, 21 are completed, and 12 are pending. There were no errors in diagnosis or changes in planned procedures. There were 42 patients seen in 53 follow-up sessions. Thirty-six surveys of a possible 53 were available for analysis. The mean rating of overall treatment experience at Telehealth was 3.47 (95% confidence interval 0.17). One hundred percent responded they would use Telehealth again and would recommend it to another person. Telehealth is an effective and acceptable way to provide pediatric general surgery clinics to remote locations.


Physiology and emerging biochemistry of the glucagon-like peptide-1 receptor.
The glucagon-like peptide-1 (GLP-1) receptor is one of the best validated therapeutic targets for the treatment of type 2 diabetes mellitus (T2DM). Over several years, the accumulation of basic, translational, and clinical research helped define the physiologic roles of GLP-1 and its receptor in regulating glucose homeostasis and energy metabolism. These efforts provided much of the foundation for pharmaceutical development of the GLP-1 receptor peptide agonists, exenatide and liraglutide, as novel medicines for patients suffering from T2DM. Now, much attention is focused on better understanding the molecular mechanisms involved in ligand induced signaling of the GLP-1 receptor. For example, advancements in biophysical and structural biology techniques are being applied in attempts to more precisely determine ligand binding and receptor occupancy characteristics at the atomic level. These efforts should better inform three-dimensional modeling of the GLP-1 receptor that will help inspire more rational approaches to identify and optimize small molecule agonists or allosteric modulators targeting the GLP-1 receptor. This article reviews GLP-1 receptor physiology with an emphasis on GLP-1 induced signaling mechanisms in order to highlight new molecular strategies that help determine desired pharmacologic characteristics for guiding development of future nonpeptide GLP-1 receptor activators.


Incidental mucocutaneous cytomegalovirus detection and its predictive value for systemic disease.
Multiplex polymerase chain reaction (PCR) testing has revolutionised microbiological practice but also increased the number of positive results of uncertain significance. This phenomenon has been seen in the increasing detection of cytomegalovirus (CMV) in mucocutaneous swabs for herpesviruses, the microbiological significance of which is a priori unclear. The aim of our study was to determine if an incidental finding of a positive CMV result represented CMV disease, if it facilitated a timely diagnosis of CMV disease or whether there were any deleterious outcomes. We performed a retrospective review of patients with an incidentally positive PCR result for CMV on external and mucosal swabs, including medical comorbidities and presence of immunosuppression, subsequent investigations, whether a diagnosis of CMV disease was made, and treatment. CMV detection was infrequent, detected in 158 (3.4%) of 4626 herpes multiplex PCR tests performed. The majority (60.4%) of patients were immunocompromised, and amongst these patients a positive swab represented a new diagnosis or already known CMV disease in 14%. In seven patients (5%), all of whom were immunocompromised, the positive CMV PCR on a swab led to further investigation and subsequent diagnosis and treatment of CMV disease. Whilst not recommended for diagnosis of CMV disease, if CMV is detected on a mucocutaneous swab in an immunocompromised patient, further assessment and investigation for CMV disease should be undertaken.


Diagnostic imaging and endoscopic finding in dogs and cats with gastric tumors: a review.
Medical imaging is an essential part of the diagnostic workup of many gastrointestinal disorders. This paper reviews imaging and endoscopy of gastric tumors in dogs and cats and the techniques used. The appearance of the normal as well as the various aspects of gastric tumors are described for these different modalities. Plain radiography is widely available but has limited diagnostic value. Contrast radiography has higher sensitivity but is laborious and time-consuming. Ultrasonography (if an adequate acoustic window is available), endosonography and endoscopy are the most appropriate modalities for diagnosing gastric tumors. They are especially useful when obtaining samples for cytologic or histopathologic examination, because the imaging modalities do not always differentiate between inflammatory or infectious conditions and neoplastic disorders. Hydro-helical CT was found helpful for evaluating the location and local invasiveness of the lesion. Ultrasonography and endoscopy are useful modalities for taking adequate biopsies.


Effects of opiate manipulations on latent inhibition in rabbits: sensitivity of the medial septal region to intracranial treatments.
The effects of opiate manipulations were examined on latent inhibition of classically conditioned heart rate in rabbits. Animals were exposed to an auditory stimulus that was later used as a conditioned stimulus (CS). Administration of the agonist levorphanol into the medial septal region either preceding or immediately following CS preexposure sessions attenuated latent inhibition of the conditioned response. This effect was observed in animals that showed no change in long-term retention of habituation. Administration of levorphanol into the central nucleus of the amygdala, a sensitive site for opiate manipulations on aversive conditioning tasks, was ineffective. Further analysis of the effect obtained within the septal region revealed pharmacological specificity. The effect of posttraining levorphanol was also time dependent and exhibited neuroanatomical specificity. Posttraining opiate antagonist administration into the medial septum produced a modest augmentation of latent inhibition. The medial septal region appears to provide a site where opiate manipulations alter some aspect of retention for events that occur in the absence of reinforcement.


Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease.
The purpose of this study is to provide an overview of the role of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in inflammatory bowel disease (IBD). Human genetic studies have identified several UPR-related genes and autophagy-related genes as IBD risk loci. Impairment of each branch of the UPR causes spontaneous enteritis or creates higher susceptibility for intestinal inflammation in model systems. Deficiency of either UPR or autophagy in small intestinal epithelial cells promotes each other's compensatory engagement, which is especially prominent in Paneth cells such that, in the absence of both, severe spontaneous enteritis emerges. Interactions between the UPR and autophagy exhibit critical synergistic interactions within the intestinal epithelium and especially Paneth cells that are of considerable importance to the maintenance of homeostasis. When dysfunctional in the Paneth cell, spontaneous inflammation can emerge that may extend beyond the epithelium providing direct experimental evidence that subsets of Crohn's disease may emanate from primary Paneth cell disturbances.


Total Synthesis of Parvineostemonine by Structure Pattern Recognition: A Unified Approach to Stemona and Sarpagine Alkaloids.
Through structure pattern recognition based total synthesis we designed a synthesis in which two biogenetically unrelated natural product families (Stemona- and Sarpagine alkaloids) share 50 % of their synthetic sequence. In this report, the efficiency of such a strategic approach is demonstrated in the total synthesis of the Stemona alkaloid parvineostemonine, proceeding through a privileged intermediate that we have previously transformed into biogenetically completely unrelated Sarpagine alkaloids. In addition, we capitalized on the symmetry properties of the privileged intermediate, which was obtained as two regioisomers. After their separation by column chromatography the two regioisomers were converted to the corresponding pair of enantiomers by one transformation. To the best of our knowledge, this feature (conversion of regioisomers to enantiomers) has never been applied to natural product synthesis, and proved to be very valuable, since it allowed to obtain both optical antipodes of parvineostemonine in a single synthetic campaign. This not only enabled the determination of the previously undisclosed absolute configuration of the natural product, but gave 60-200 mg amounts of both enantiomers of the natural product.


Selective incorporation of rare earth elements by seaweeds from Cape Mondego, western Portuguese coast.
This study examined the mechanism of incorporation of the rare earth elements (REEs), La, Ce, Nd, Eu, Gd, Tb, Yb, into green (Codium tomentosum, Ulva rigida), red (Gracilaria gracilis, Osmundea pinnatifida, Porphyra sp), and brown seaweeds (Saccorhiza polyschides, Undaria pinnatifida) collected from a single site near the coastline of the Cape Mondego, western Portugal. The concentrations of REEs, Mg, Ca, Al, Fe, Zn, and Cu in the biomasses were determined by inductively-coupled plasma mass spectrometry (ICP-MS). The species showed differences in their incorporation and fractionation of REEs from the same environment: the sum of REEs was higher in U. rigida, C. tomentosum, G. gracilis, and O. pinnatifida (0.7-1.7 μg g-1) than in Porphyra sp., S. polyschides, and U. pinnatifida (0.1-0.2 μg g-1). Ratios of Ce/Yb ranged from 13 (in S. polyschides) to 103 (in U. rigida), indicating different proportions of light and heavy REEs among species. Good correlations were found between Al and Fe (R2 = 0.98), and between these elements and La, Ce, Nd, Gd (R2 = 0.88-0.97) and Yb (R2 = 0.66-0.71) for all species except C. tomentosum and G. gracilis. Profiles of REE values normalised to average upper-continental crust composition indicated positive anomalies of Eu and Tb that reinforced the singularity of these elements in the REE group. Correlations between the REEs and Al or Fe suggest that detrital terrigenous particles, adhered to seaweed walls, may be an important mechanism for the incorporation of REEs by seaweeds. Different patterns for C. tomentosum and G. gracilis may also be indicative of the higher influence of cell wall composition on REE incorporation.


An update on Curcuma as a functional food in the control of cancer and inflammation.
Curcumin, commonly known as turmeric, is a spice that comes from the root Curcuma longa. The present article presents an update of new studies of curcumin activities as tested in anticancer models from 2011 to 2015. Evidence from in-vitro and in-vivo research, together with clinical trials conducted over the past few decades, substantiates the potential of curcumin as an anticancer and anti-inflammatory agent. The development of formulations of curcumin in the form of nanoparticles, liposomes, micelles, or phospholipid complexes to enhance its bioavailability and efficacy are still in the early stages. Clinical trials with curcumin indicate safety, tolerability, and nontoxicity. However, the efficacy is questionable, based on the small numbers of patients in each study. The laboratory and the clinical studies until 2011 were summarized in a review published in this journal. An update of the new studies and knowledge from 2011 to March 2015 focuses on new ways to overcome its low bioavailability and data from clinical trials.


A Human-Machine Interface Based on an EOG and a Gyroscope for Humanoid Robot Control and Its Application to Home Services.
The human-machine interface (HMI) has been studied for robot teleoperation with the aim of empowering people who experience motor disabilities to increase their interaction with the physical environment. The challenge of an HMI for robot control is to rapidly, accurately, and sufficiently produce control commands. In this paper, an asynchronous HMI based on an electrooculogram (EOG) and a gyroscope is proposed using two self-paced and endogenous features, double blink and head rotation. By designing the multilevel graphical user interface (GUI), the user can rotate his head to move the cursor of the GUI and create a double blink to trigger the button in the interface. The proposed HMI is able to supply sufficient commands at the same time with high accuracy (ACC) and low response time (RT). In the trigger task of sixteen healthy subjects, the target was clicked from 20 options with ACC of 99.2% and RT 2.34 s. Furthermore, a continuous strategy that uses motion start and motion stop commands to create a certain robot motion is proposed to control a humanoid robot based on the HMI. It avoids the situation that combines some commands to achieve one motion or converts the certain motion to a command directly. In the home service experiment, all subjects operated a humanoid robot changing the state of a switch, grasping a key, and putting it into a box. The time ratio between HMI control and manual control was 1.22, and the number of commands ratio was 1.18. The results demonstrated that the continuous strategy and proposed HMI can improve performance in humanoid robot control.


How far from the SNP may the causative genes be?
While GWAS identify many disease-associated SNPs, using them to decipher disease mechanisms is hindered by the difficulty in mapping SNPs to genes. Most SNPs are in non-coding regions and it is often hard to identify the genes they implicate. To explore how far the SNP may be from the affected genes we used a pathway-based approach. We found that affected genes are often up to 2 Mbps away from the associated SNP, and are not necessarily the closest genes to the SNP. Existing approaches for mapping SNPs to genes leave many SNPs unmapped to genes and reveal only 86 significant phenotype-pathway associations for all known GWAS hits combined. Using the pathway-based approach we propose here allows mapping of virtually all SNPs to genes and reveals 435 statistically significant phenotype-pathway associations. In search for mechanisms that may explain the relationships between SNPs and distant genes, we found that SNPs that are mapped to distant genes have significantly more large insertions/deletions around them than other SNPs, suggesting that these SNPs may sometimes be markers for large insertions/deletions that may affect large genomic regions.


Evidence based route of administration of vaccines.
Vaccination is a proven public health initiative, however it is imperative in the context of increasing concerns about vaccine induced adverse reactions and a decreasing incidence of diseases they prevent that the optimal route for their administration is defined. Traditionally all vaccines were given by subcutaneous injection until it was recognized that adjuvanted vaccines given via this route induced an unacceptable rate of injection site reaction. Evidence-based medicine has been championed as a way of improving the quality of patient care. Application of this methodology to the route of administration of vaccines demonstrates that vaccines should be given by intramuscular injection in preference to subcutaneous injection as the intramuscular route is associated with better immune response and a lower rate of injection site reaction. The basis of this superiority is discussed.


Left atrial enlargement and high uric acid level are risk factors for left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate embolic risk assessed by CHA2DS2-VASC score.
To investigate the correlation and predictive value of left atrial diameter and blood uric acid levels with the occurrence of left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate CHA2DS2-VASc scores. A total of 849 inpatients diagnosed with atrial fibrillation who had low to moderate CHA2DS2-VASc scores and complete transesophageal echocardiography were included in this study. Among them, 66 patients had left atrial thrombus or dense spontaneous echo contrast. When different models were used to correct other known risk factors, acid levels and abnormal left atrial diameter were identified as additional risk factors for left atrial thrombus or dense spontaneous echo contrast. The incidence of left atrial thrombus or dense spontaneous echo contrast was higher in patients with abnormal serum uric acid levels than in the control group (12.4% vs. 5.6%, p < 0.05), and this difference persisted after correcting the baseline data with propensity score matching (10.6% vs. 4.1%, p < 0.05). Abnormal left atrial diameter was another risk factor suggested by regression analysis, with an increased incidence of left atrial thrombus or dense spontaneous echo contrast in the abnormal left atrial diameter group compared to the control group, both before (18.0% vs. 3.5%, p < 0.05) and after (15.5% vs. 5.2%, p < 0.05) propensity score matching. The best predictive value was obtained by adding both abnormal serum uric acid levels and abnormal left atrial diameter. Left atrial enlargement and high uric acid levels increase the risk of left atrial thrombus or dense spontaneous echo contrast in atrial fibrillation patients with low to moderate CHA2DS2-VASc scores.


Is the Grass Always Greener in Suburban Neighborhoods? Outdoors Play in Suburban and Inner-City Neighborhoods.
Children's outdoors play (OP) is an important source of physical activity that has been decreasing in recent years due to changes in neighborhood design, parent safety concerns and child sedentary leisure. However, few studies examined such determinants from children's perspectives. This study explores environmental and socio-cultural aspects of children's OP using a qualitative and quantitative approach. Data was collected in two phases: (1) a survey on OP and related variables among 5th and 6th graders (10-12 years old) (n = 573); and (2) a mapping activity and semi-structured interview among a subsample of the survey (n = 80). The most common locations for routine OP were parks (40%) followed by public facilities (26%) and streets (17%). OP was significantly associated with perceived environment, independent mobility and gender, but not with neighborhood type. Inner-city participants reported a higher number and greater variety of OP areas (23 vs. 14). Three main barriers of OP were identified-low quality and poorly maintained play areas, other people in public spaces, and social norms that undermine OP. Thus, in order to encourage routine OP, environmental change to create safe and attractive OP settings should be accompanied by community interventions to enhance social norms that are supportive of OP.


[Study on treatment of climacteric depression with bushen tiaogan qingxin recipe].
To observe the effects of bushen tiaogan qingxin recipe (BTQR) on Hamilton rating scale for depression (HAMD), monoamine meurotransmitter and endocrinal function in patients with climacteric depression, and to explore its mechanism. Patients were randomly divided into two groups, the 25 patients in the treated group treated with BTQR and 15 patients in the control group treated with hormone replacement therapy (HRT). The HAMD scoring, levels of 5-HT, NE in plasma, serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH) were determined before and after treatment, and the thickness of endometrium was measured by B-Doppler ultrasonographic technique. The total effective rate, evaluated by the HAMD score reducing rate, in the treated group was 87.2%, and in the control group was 67.3%, showing significant difference (P<0.05). After treatment, 5-HT decreased (P<0.01), NE increased (P<0.05) and 5-HT/NE ratio lowered (P<0.01) in the treated group; E2 increased in both groups; FSH, LH and FSH/LH ratio decreased in the treated group (P<0.05 or P<0.01), FSH/LH ratio decreased in the control group (P<0.05). The thickness of endometrium increased in the control group after treatment (P<0.05). The mechanism of BTQR in treating climacteric depression might be related with its actions in: (1) To regulate the synthesis and release of monoamine neurotransmitter; (2) To adjust reproductive endocrine function; (3) To coordinate the neuroendocrinal function.


Mental health and interpersonal factors associated with HIV-related risk behaviors among non-institutionalized female injection drug users who are also sex workers in China.
Female injecting drug users who are sex workers (IDUFSWs) are an important bridge population in HIV transmission. Few studies have investigated the associations between mental health, interpersonal problems, and HIV-related risk behaviors among injecting drug users who are sex workers. A total of 234 non-institutionalized injecting drug users who are sex workers were recruited using the snowball method. Multiple logistic regression was used for data analysis. A high prevalence of mental health (depression, hopelessness, pessimism) and interpersonal (lack of social support and submissive gender power) problems was reported. Optimism and social support were negatively associated with inconsistent condom use during sex work in the last six months (adjusted odds ratios [AOR] = 0.62-0.86); positive associations were observed for depression, hopelessness, pessimism, and gender power (AOR = 1.17 to 1.68). Injecting with others' used syringes in the last six months was negatively associated with social support (AOR = 0.75) and positively associated with hopelessness and gender power (AOR = 1.13-1.27). In two summary models using all significant independent variables as candidates, optimism was negatively (OR = 0.62) and submissive gender powers were positively (OR = 1.67) associated with inconsistent condom use during sex work; submissive gender power was positively associated with injecting with others' used syringes (OR = 1.38). HIV interventions targeting mental health and interpersonal problems are needed among injecting drug users who are sex workers.


van der Waals density functional for general geometries.
A scheme within density functional theory is proposed that provides a practical way to generalize to unrestricted geometries the method applied with some success to layered geometries [Phys. Rev. Lett. 91, 126402 (2003)]]. It includes van der Waals forces in a seamless fashion. By expansion to second order in a carefully chosen quantity contained in the long-range part of the correlation functional, the nonlocal correlations are expressed in terms of a density-density interaction formula. It contains a relatively simple parametrized kernel, with parameters determined by the local density and its gradient. The proposed functional is applied to rare gas and benzene dimers, where it is shown to give a realistic description.


Phylogenetic analysis of a partial L1 gene from bovine papillomavirus type 1 isolated from naturally occurring papilloma cases in the northwestern region of Turkey.
This study was aimed at the molecular characterisation of bovine papillomavirus type 1 (BPV-1) isolated from papilloma cases in the northwestern region of Turkey. BPV-1 is a widely occurring oncogenic virus in cattle and is associated with benign epithelial neoplasia which causes significant economic losses in dairy and beef cattle because of treatment costs. In this study, 29 suspected papilloma specimens were collected from cattle in northwestern Turkey. These samples underwent molecular characterisation via the polymerase chain reaction (PCR) and sequencing analysis as well as macroscopic and histopathological examination. The histopathological examinations confirmed papilloma as the main lesion type in the specimens. Of the 29 papilloma-like tissue samples that were collected, 11 (i.e. 37.93%) were detected as positive and determined as containing BPV-1 (11 of 11, 100%). Using a partial sequence for the L1 gene acquired from GenBank, phylogenetic analysis confirmed the presence of BPV-1 and revealed that the infection might have originated in cross bred domestic and imported cattle. This study provides potentially useful information on the origin and spread of this disease. Its results can potentially aid in the development of appropriate control measures and therapeutic or vaccination strategies against the BPV-1 strain of bovine papillomatosis.


Effects of furosemide and chlorothiazide on blood pressure and plasma renin activity.
Short (2 weeks) and long (12 weeks) term effects of furosemide and chlorothiazide on blood pressure, plasma renin activity, and uric acid concentration were studied in 69 hypertensive patients. Both treatments caused significant reductions in blood pressure and increases in plasma renin activity and uric acid at 2 and 12 weeks in 6) normal renin patients; there was no difference between the effects of furosemide and that of chlorothiazide. Reduction in blood pressure in eight low renin patients who showed smaller changes in plasma renin activity and uric acid was not significant at 2 weeks but significant after 12 weeks of treatment.


Technetium-fibrinogen lung scanning in canine lung contusion.
To detect experimentally induced acute lung contusion in anesthetized dogs, serial radionuclide images of the lung were recorded following intravenous infusion of 99mTc-labelled human fibrinogen (Tc-HF). The accumulation of Tc-HF in canine lungs was serially quantitated for up to 20 hours after lung contusion. A contusion (#1) was produced in one lung, Tc-HF was injected IV after 15 minutes, and 75 minutes later a contralateral lung contusion (#2) was produced in a series of 14 dogs. At autopsy the excised lungs were scanned, sectioned, and counted for radioactivity. Radiolabelled fibrinogen accumulated within 2-4 minutes of contusion #2 and remained stable over the next 20 hours in 14 dogs; contusion #1 was barely visible in four dogs. Lung Tc-HF activity in the central region of contusion #2 remained sixfold higher than in normal lung tissue. These data suggest that following lung contusion, fibrinogen deposition occurs rapidly and remains stable over a 20-hour interval of observation.


Mechanisms involved in the potentiation of paclitaxel or 5-fU by the hypoxic cytotoxin NLCQ-1 (NSC 709257) in vitro.
4-[3- (2-Nitro-1-imidazolyl)-propylamino]-7-chloroquinoline hydrochloride (NLCQ-1) is a novel, weakly DNA-intercalating hypoxia selective cytotoxin, which significantly potentiates the antitumor effect, but not the systemic toxicity, of commonly used chemotherapeutic agents. In the present study, we investigated if the same schedule-dependent synergism seen in vivo exists in vitro as well, between NLCQ-1 and paclitaxel or 5-fluorouracil (5FU), and some of the mechanisms involved in such interactions. V79 cells, while in monolayers, were exposed to paclitaxel or 5FU under aerobic conditions at various time-intervals before or after their hypoxic exposure to NLCQ-1, while in suspension. Survival was assessed by the clonogenic assay and synergistic interactions were evaluated by using the fractional product analysis. Cells treated as above were examined for apoptosis, DNA damage and repair, as well as DNA, RNA and protein syntheses inhibition. A schedule-dependent synergistic interaction existed between NLCQ-1 and paclitaxel/5FU, similar to that seen in transplanted EMT6 murine tumors. Optimal potentiation was observed when NLCQ-1 was administered 2 or 4 h after the antimitotic paclitaxel or the thymidylate synthase inhibitor 5FU. Apoptosis induced by paclitaxel or 5FU alone was enhanced by NLCQ-1 up to 2.5- and 1.7-fold, respectively. DNA damage was detected as single-strand breaks (ssbs) in the combination treatments and was unrepairable at least up to 24 h post treatment. DNA, RNA and protein syntheses were inhibited by paclitaxel/5FU alone ca. 50% immediately post treatment and this inhibition was persistent up to 24 h post treatment. In combination with NLCQ-1, a slight synergistic and persistent inhibition was observed in all three syntheses. Enhancement in apoptosis, unrepairable DNA damage and inhibition of DNA, RNA and protein syntheses are some of the mechanisms involved in the potentiation of paclitaxel or 5FU by NLCQ-1.


Reversal of impurity pinch velocity in tokamaks plasma with a reversed magnetic shear configuration.
Impurity transport in tokamak core plasmas is investigated with a three-dimensional fluid global code. It is shown that, in the presence of an internal transport barrier (ITB) created by a reversed magnetic shear configuration, one can obtain a reversal of the impurity pinch velocity which can change from the inward direction to the outward direction. This scenario is favorable for expelling impurities from the central region and decontaminating the core plasma. The mechanism of pinch reversal is attributed to a change of direction of the curvature pinch and to a modification of the dominant underlying instability caused by a change of the gradient of the ion temperature and consequently of the ITB formation.


Impact of Childhood Adversity, as Early Life Distress, on Cytokine Alterations in Schizophrenia.
Even though inflammation theory has been introduced in the pathophysiology of psychosis almost a century ago, many of its aspects have remained unelucidated. Numerous studies have shown cytokine dysregulation in schizophrenia and a predominance of pro-inflammatory cytokines, but on another side, various cytokines in a pro-inflammatory group have different trends in all subtypes of schizophrenia. Alterations are also present in anti-inflammatory and regulatory cytokines, but findings are still not consistent. On the other hand, it is well known that abuse and neglect in childhood may be predictors of psychotic disorders, and childhood adversity is also associated with alterations of the immune and inflammatory response (through various mechanisms including HPA dysregulation as well). This review aims to analyze conducted studies and elucidate the link between childhood abuse, schizophrenia, and cytokine alterations. Putting together this complex psycho-immunological puzzle for the subgroup of schizophrenia-diagnosed patients with distinct immunological abnormalities and a history of childhood abuse can help us to answer the question about the future treatment of these patients.


Ophthalmic complications of bariatric surgery.
Obesity is increasing vastly in the world, and the number of bariatric surgeries being performed is also increasing. Patients being submitted to bariatric surgeries, especially malabsorptive procedures, have an increased risk of developing nutrient deficiencies, which can culminate in symptomatic hypovitaminosis, if supplementation is not done correctly. The eye and the optic system need an adequate level of several vitamins and minerals to perform properly, especially vitamin A, and this article wants to cover the main nutrients involved, the possible ophthalmic complications that can arise by their deficiency, and the management of those complications.


Prevalence and pattern of birth defects in a tertiary health facility in the Niger Delta area of Nigeria.
To ascertain the prevalence and pattern of congenital abnormalities that are peculiar to the Niger Delta area of Nigeria. This is a descriptive retrospective cross-sectional study. It involved data from the labor ward and neonatal birth registers of the University of Port Harcourt Teaching Hospital on the total number of births and the babies that were delivered with major birth defects between August 2011 and December 2014. We also conducted a statistical comparison of the prevalence of congenital abnormalities in the Niger Delta with that in other regions of Nigeria and the developed world of Europe. Out of the 7,670 deliveries that occurred, 159 maternities had babies with major birth defects giving a prevalence of 20.73 cases per 1,000 live births. This figure is far more than that which was obtained in other regions of Nigeria -4.15:cases per 1,000 live births in the South East (P<0.001), 15.84:1,000 in the South West (P<0.01), and 5.51:1,000 in the North East (P<0.001). Eighty-five (53.46%) of the defects occurred in 1,681 unbooked patients, while 74 (46.54%) happened in 5,989 booked maternities (P<0.001). The predominant abnormalities were those of the central nervous system at 27.0%, gastrointestinal system 11.95%, cardiovascular system 10.69%, anterior abdominal wall 8.18%, skeleton 6.29%, and chromosomal abnormalities at 5.66%. The prevalence of major birth defects at the University of Port Harcourt Teaching Hospital was 20.73 cases per 1,000 live births and it was more in the unbooked than the booked maternities. All body systems were affected with those of the central nervous system predominating at 27.0% of the total diagnosed defects.


The neurogenic bladder in multiple sclerosis: review of the literature and proposal of management guidelines.
Vesicourethral dysfunction is very frequent in multiple sclerosis (MS) and has functional consequences for patients' quality of life and also an organic impact following complications of the neurogenic bladder on the upper urinary tract. While the functional impact and its management are well documented in the literature, the organic impact remains underestimated and there are no consensual practical guidelines for the screening and prevention of MS neurogenic bladder complications. The aim of this review of the literature, focused on identifying the risk factors of urinary tract complications in MS, is to put forward well informed considerations to help in the definition of practical guidelines for the follow-up of the neurogenic bladder in MS in order to improve its prevention and patient management. Four main risk factors have been identified for upper urinary tract damage: the duration of MS, the presence of an indwelling catheter, high-amplitude neurogenic detrusor contractions and permanent high detrusor pressure. Detrusor-sphincter dyssynergia, age over 50 and male sex may form three additional risk factors. Recommendations for long-term urological follow-up, taking into account these specific risks are constructed according to the procedures recommended by the French Health Authorities.


The use of bioerodible polymers and 5-fluorouracil in glaucoma filtration surgery.
A study was performed to examine the effect of a localized and sustained delivery of 5-fluorouracil (5-FU) on the success of glaucoma filtration surgery in 18 rabbits in a prospective, randomized, double-masked and placebo-controlled fashion. A bioerodible polyanhydride composed of bis (p-carboxyphenoxy) propane and sebacic acid was used as the drug carrier. The polymer and 5-FU (20% by weight) were compressed into 3 mm diameter discs, 1 mm thick. The polymer with the 5-FU was randomized to one eye and the fellow eye received the blank polymer. The results showed that intraocular pressures (IOP) were lower in the experimental eyes during the 5th through 17th postoperative days, but eventually both experimental and control eyes returned to preoperative levels. Filtration blebs lasted longer in experimental eyes when compared to control eyes. Implant disappearance occurred after IOP elevations and bleb failure. Eventually, the filtration surgery failed in both the experimental and control rabbit eyes.


Impact of Social Media News Overload on Social Media News Avoidance and Filtering: Moderating Effect of Media Literacy.
In the present era of information technology, people tend to seek out news to enhance their current knowledge and awareness and to gain literacy. The reliance on seeking out news and relevant information has become very necessary to accomplish personal and organizational objectives. The present study has undertaken an inquiry to investigate the impact of social media news overload on news avoidance and news filtering with the mediating and moderating mechanisms of the need for news and media literacy, respectively. For this purpose, data were obtained from 358 Chinese social media users through the aid of survey forms. The data obtained were then analyzed through Smart-PLS software. The statistical technique used for analysis is structural equation modeling (SEM) to determine the validity of the proposed hypotheses. The results of the study indicated that social media news overload has a significant effect on news avoidance, the need for news, and news filtering behavior. It was also observed that the need for news had a significant impact on news avoidance. In addition to this, it was also revealed that the need for news significantly mediated the relationship between social media news overload and news avoidance; however, it did not mediate the relationship between social media news overload and news filtering. Lastly, it was identified that media literacy significantly moderated the relationship between the need for news and news avoidance and it did not moderate the relationship between the need for news and news filtering behavior. This study has made important theoretical contributions by advancing the current literature in terms of the empirical evidence that indicates a significant relationship between social media news overload, news avoidance, and news filtering. Practically, this study contributed by emphasizing the need to encourage and train people to use strategies to seek relevant news in a vast repository of information available through information technology.


Automatic image modality based classification and annotation to improve medical image retrieval.
Medical image retrieval can play an important role for diagnostic and teaching purposes in medicine. Image modality is an important visual characteristic that can be used to improve retrieval performance. Many test and online collections do not contain information about the image modality. We have created an automatic image classifier for both grey-scale and colour medical images. We evaluated the performance of the two modality classifiers, one for grey-scale images and the other for colour images on the CISMeF and the ImageCLEFmed 2006 databases. Both classifiers were created using a neural network architecture for learning. Low level colour and texture based feature vectors were extracted to train the network. Both classifiers achieved an accuracy of >95% on the test collections that they were tested on. We also evaluated the performance of these classifiers on a selection of queries from the ImageCLEFmed 2006. The precision of the results was improved by using the modality classifier to resort the results of a textual query.


Intention Attribution and the Development of Moral Evaluation.
Research with infants and toddlers suggests that even early in development, humans evaluate others by considering the outcome of an action in relation to the intention underlying it. When someone tries but fails to do a good deed, for example, it seems that it is "the thought that counts." However, research with slightly older children in the preschool years has produced mixed results: in some cases, children are solely considering the positive or negative outcome of an action when evaluating others, while in others, intention attributions are integrated. Such contradictory findings have prompted debate about the development of moral reasoning. Here, we examine extant research on early moral evaluation and propose that differences in the way that task procedures present intention and outcome information can (1) support or preclude young children's intention attribution and (2) alter the relative saliency or predominance of each kind of information. In turn, these differences would influence the frequency and degree to which young children generate intention-oriented moral evaluations.


[Endovascular Technology for Thoracic Aortic Pathology].
A quarter of a century has passed since development and application of stent-graft technology. The application field has widened to aortic arch and thoracoabdominal area, with the development of stent grafts such as frozen elephant trunk, debranching plus thoracic endovascular aneurysm repair(TEVAR) and fenestrated/branched stent graft. Further development of stent-graft technology will continue to bring about less invasive intervention and better results for patients with thoracic aortic pathology.


Metal removal and associated binding fraction transformation in contaminated river sediment washed by different types of agents.
In ex-situ washing, HCl, EDTA and H2O2 solutions can effectively extract heavy metals in river sediment. Nevertheless they often target different sediment components, possibly transforming metal species into more bioavailable and hence toxic ones. This study, in batch settings, investigated the influences of different types of washing agents (i.e. HCl, EDTA and H2O2) on metal (i.e. Cu and Zn) removal from contaminated river sediment, destroy or dissolution of sediment components, and transformation of metal fractions during chemical washing treatment. Additionally, bioavailability of these metals left in the washed sediment was assessed. Results showed that HCl obtained the highest Cu and Zn removal through destroying the reducible, oxidizable and residual sediment components. Meanwhile, it transformed metal fractions to acid extractable one, resulting in an increase in metal bioavailability. Thus, the feasibility of washing with HCl for sediment remediation shall be reconsidered due to the caused high metal bioavailability. EDTA was capable of removing metals via direct complexation of labile metal species and indirect dissolution of reducible and oxidizable sediment components, where the transformation of corresponding metal binding fraction may occur. H2O2 obtained the lowest total Cu and Zn removal, but it preferentially removed the oxidizable metal species by oxidizing sulfides in the sediment. The bioavailable levels of Cu and Zn in the sediment washed by EDTA or H2O2 seemed not increase. To maintain a good balance between labile metal species removal and avoiding increase of metal bioavailability, EDTA and H2O2 are promising additives for metal removal by sediment washing.


Effect of sucrose ester addition on nucleation and growth behavior of milk fat-sunflower oil blends.
The effects of addition of the sucrose esters (SE) P-1670, P-170, and S-170 to a high-melting fraction of milk fat (HMF) and its blends with sunflower oil (SFO) on nucleation and growth were studied by laser polarized light turbidimetry and polarized light microscopy (PLM). The three SE delayed nucleation of HMF at the temperatures selected. P-1670 did not modify average crystal size after 3 h at crystallization temperature (T(c)) or crystal size distribution and modified crystallization kinetics only slightly. P-170 and S-170, however, markedly diminished crystal size and narrowed crystal size distribution. Activation free energies of nucleation at equivalent supercooling, calculated using the Fisher-Turnbull equation, significantly increased with addition of SE. According to these results, among the mechanisms described in the literature for fats or emulsions, the cocrystallization hypothesis is the one that better described the effects of sucrose esters on crystallization behavior in these systems.


Expanded interaction fingerprint method for analyzing ligand binding modes in docking and structure-based drug design.
An expanded interaction fingerprint method has been developed for analyzing the binding modes of ligands in docking and structure-based design methods. Taking the basic premise of representing a ligand in terms of a binary string that denotes its interactions with a target protein, we have expanded the method to include additional interaction-specific information. By considering the hydrogen-bonding strength and/or accessibility of the hydrogen bonding groups within a binding site as well as their geometric arrangement we aim to provide a better representation of a ligand-protein interaction. These expanded methods have been applied to the postprocessing of binding poses generated in a docking study for 220 different proteins and to the analysis of ligands generated by an automated ligand-generation algorithm for the anthrax oedema factor. In the docking study, the application of the interaction fingerprint method as a postprocessing tool resulted in an increased success rate in identifying the crystallographic binding mode. In the analysis of the ligands generated for the anthrax oedema factor, the incorporation of additional interaction-specific information resulted in a more intuitive and comprehensive analysis of automated ligand-generation output.


Combined coronary bypass and liver transplantation: technical considerations.
Combined coronary artery bypass grafting and orthotopic liver transplantation was carried out successfully in a 58-year-old man with angina pectoris and end-stage liver disease. To date, only 2 similar cases have been documented worldwide whereby the transplantation was performed either during cardiopulmonary bypass or with femoral-to-axillary venovenous bypass initiated at the termination of cardiopulmonary bypass. In this report we describe our experience with a simplified one-exposure approach for the combined operation using cardiopulmonary bypass in tandem with percutaneous femoral-to-right atrial venovenous bypass.


Effect of nitrogen supply on frost resistance, nitrogen metabolism and carbohydrate content in white clover (Trifolium repens).
Effects of mineral nitrogen (2, 4, 6 and 8 mM NH4 NO3 ) and nodulation with Rhizobium on frost hardiness in seedlings of white clover (Trifolium repens) have been studied. Seedlings of a population from Bodø (67°N lat.) were grown in Leonard jars under controlled conditions in a phytotron. For induction of frost hardening, plants were first exposed to 12 h photoperiod conditions for 2 weeks at 18°C, then for 2 weeks at 6°C and finally for 2 weeks at 0.5°C. Frost hardiness after treatments at 6 and 0.5°C was significantly enhanced by increasing nitrogen supply and was positively correlated with total nitrogen content of the stolons. Frost hardiness of nodulated plants correlated to the tissue nitrogen concentration. Content of soluble proteins in stolons decreased during hardening at 6°C but did not change during treatment at 0.5°C. There were minor changes in total amount of free amino acids during hardening. Both absolute and relative amounts of proline and arginine increased, and those of asparagine decreased during hardening. Absolute amounts of all free amino acids increased with increasing nitrogen supply, but the changes during hardening were similar in all treatments. There was a significant increase in the content of soluble carbohydrates during hardening. However, this increase was inversely related to nitrogen supply.


Comparative lipidomics of four strains of Saccharomyces cerevisiae reveals different responses to furfural, phenol, and acetic acid.
To reveal differences between inhibitor-resistant Saccharomyces cerevisiae strains and their parental strain and to investigate the response of S. cerevisiae to furfural, phenol, and acetic acid, comparative lipidomics strategy was employed using an LC-ESI/MS(n) technique on four S. cerevisiae strains, which include an industrial strain (SC) and three tolerant strains screened by this laboratory by step adaptationa furfural-tolerant strain (SCF), a phenol-tolerant strain (SCP), and an acetic acid-tolerant strain (SCA). Lipidome data were then analyzed using wavelet transform-principal component analysis (WT-PCA). Results revealed that phosphatidylcholines (PCs), phosphatidylinositols (PIs), and phosphatidic acids (PAs) were biomarkers for discriminating SC from SCF, SCP, and SCA, respectively. PIs were believed to be extraordinarily important in all inhibitor-tolerant processes because they were the biomarkers responsible for the discrimination of all four different strains. Further analysis of the distribution of different hydrocarbon chains revealed that both the saturation and the length of the chains helped in maintaining proper fluidity of membranes.


Modification of the mycobacteriophage Ms6 attP core allows the integration of multiple vectors into different tRNAala T-loops in slow- and fast-growing mycobacteria.
Mycobacteriophage Ms6 integrates into Mycobacterium smegmatis and M. bovis BCG chromosome at the 3' end of tRNAala genes. Homologous recombination occurs between the phage attP core and the attB site located in the T-loop. Integration-proficient vectors derived from Ms6 are useful genetic tools, but their insertion sites in the BCG chromosome remain poorly defined. The primary objective of this study was to identify Ms6 target genes in M. smegmatis and BCG. We then aimed to modify the attP site in Ms6-derived vectors, to switch integration to other tRNAala loci. This provided the basis for the development of recombinant M. bovis BCG strains expressing several reporter genes inserted into different tRNAala genes. The three tRNAala genes are highly conserved in M. smegmatis and BCG. However, in the T-loop of tRNAalaU and tRNAalaV containing the attB site, a single base difference was observed between the two species. We observed that the tRNAalaU gene was the only site into which Ms6-derived integration-proficient vectors integrated in M. smegmatis, whereas in BCG, the tRNAalaV gene was used as the target. No integration occurred in the BCG tRNAalaU T-loop, despite a difference of only one base from the 26-base Ms6 attP core. We mutated the attP core to give a perfect match with the other tRNAala T-loops from M. smegmatis and BCG. Modification of the seven-base T-loop decreased integration efficiency, identifying this site as a possible site of strand exchange. Finally, two Ms6 vectors were constructed to integrate two reporter genes into the tRNAalaU and tRNAalaV T-loops of the same BCG chromosome. Small changes in the 7 bp T-loop attP site of Ms6 made it possible to use another attB site, albeit with a lower integration efficiency. These molecular studies on BCG tRNAala genes made it possible to create valuable tools for the site-directed insertion of several genes in the same BCG strain. These tools will be useful for the development of novel multivalent vaccines and genetic studies.


Anticoagulation for renal replacement therapy for patients with acute kidney injury.
Patients with acute kidney injury are generally prothrombotic, and as such prone to increased risk of clotting in extracorporeal renal replacement therapy (RRT) circuits. Although some patients may be adequately treated by intermittent RRT, however due to cardiovascular instability many patients are treated by continuous renal replacement therapy (CCRT) or prolonged intermittent renal replacement therapy (PIRRT). Clotting in the RRT circuit not only reduces the efficiency of solute clearances, affects fluid balance, but also has economic health care costs. The longer duration RRT modes, CRRT and PIRRT are more prone to clotting, and more dependent on adequate anticoagulation. This review will compare the currently available systemic and regional anticoagulation options for CRRT and PIRRT for the patient with acute kidney injury.


Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information.
This paper presents a new computer method for folding an RNA molecule that finds a conformation of minimum free energy using published values of stacking and destabilizing energies. It is based on a dynamic programming algorithm from applied mathematics, and is much more efficient, faster, and can fold larger molecules than procedures which have appeared up to now in the biological literature. Its power is demonstrated in the folding of a 459 nucleotide immunoglobulin gamma 1 heavy chain messenger RNA fragment. We go beyond the basic method to show how to incorporate additional information into the algorithm. This includes data on chemical reactivity and enzyme susceptibility. We illustrate this with the folding of two large fragments from the 16S ribosomal RNA of Escherichia coli.


The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment.
Recent investigations of the tumor microenvironment have shown that many tumors are infiltrated by inflammatory and lymphocytic cells. Increasing evidence suggests that the number, type and location of these tumor-infiltrating lymphocytes in primary tumors has prognostic value, and this has led to the development of an 'immunoscore. As well as providing useful prognostic information, the immunoscore concept also has the potential to help predict response to treatment, thereby improving decision- making with regard to choice of therapy. This predictive aspect of the tumor microenvironment forms the basis for the concept of immunoprofiling, which can be described as 'using an individual's immune system signature (or profile) to predict that patient's response to therapy' The immunoprofile of an individual can be genetically determined or tumor-induced (and therefore dynamic). Ipilimumab is the first in a series of immunomodulating antibodies and has been shown to be associated with improved overall survival in patients with advanced melanoma. Other immunotherapies in development include anti-programmed death 1 protein (nivolumab), anti-PD-ligand 1, anti-CD137 (urelumab), and anti-OX40. Biomarkers that can be used as predictive factors for these treatments have not yet been clinically validated. However, there is already evidence that the tumor microenvironment can have a predictive role, with clinical activity of ipilimumab related to high baseline expression of the immune-related genes FoxP3 and indoleamine 2,3-dioxygenase and an increase in tumor-infiltrating lymphocytes. These biomarkers could represent the first potential proposal for an immunoprofiling panel in patients for whom anti-CTLA-4 therapy is being considered, although prospective data are required. In conclusion, the evaluation of systemic and local immunological biomarkers could offer useful prognostic information and facilitate clinical decision making. The challenge will be to identify the individual immunoprofile of each patient and the consequent choice of optimal therapy or combination of therapies to be used.


[Prenatal diagnosis and obstetric management of a case of Klippel-Trenaunay-Weber syndrome].
A description is given of a case of Klippel-Trenaunay-Weber syndrome diagnosed by sonography in the 28th week of pregnancy. The ultrasound findings established in the course of pregnancy are presented. Whereas minor variants of this syndrome normally do not represent a birth hindrance, a cesarean section was indicated in the present case on the basis of the size of the deformation--especially at the hip--an in order to save the child.


Optical images of dose distributions in Gel-Fricke: dosimetric performances of the gel.
The purpose of this work was to examine the dosimetric performances of the radiochromic Fricke-Agarose-Xylenol Orange gel by optical measurements in order to perform dose reconstructions, in view of a future development for 3-D maps. Optical images and dose-response curves of the gel were obtained by a CCD-based device, originally designed for reading radiochromic films, that was modified to meet the optical properties of the dosemeter. With a resolution of 0.18 x 0.18 mm the optimum range of doses in which per cent uncertainty is lower than 2% was 3-10 Gy. The minimum detectable dose, estimated as the absorbed dose corresponding to 3 SD above background, was 0.1 Gy. With a resolution of 1.98 x 1.98 mm the optimum range of doses in which per cent uncertainty is lower than 2% was 0.3-10 Gy. The minimum detectable dose, estimated as the absorbed dose corresponding to 3 SD above background, was 0.015 Gy. The comparison with alanine dosemeters in the dose range 7-10 Gy showed agreement within a few per cent and the same agreement was observed for the comparison with TLD in the range 1-3 Gy.


Mothers' decision-making during times of stress as a lone parent: a qualitative study.
Little empirical evidence exists to identify the impact that a partner's absence or presence has on the mother's decision-making and her consequential help-seeking behaviour when her child is unwell. This study used a qualitative design in three phases using focus groups and interviews to explore Army mothers' help-seeking behaviour as a lone parent when their child was unwell during the out-of-hours period. Thirty-one parents from a British Army garrison were interviewed. The findings demonstrated that Army life created a combination of stressors for Army mothers, which altered their help-seeking behaviour when their child was unwell. When their partner was available, mothers contacted health services as a last resort, once all other avenues had been exhausted. However, in contrast, in their partners' absence, they were contacted as a first resort. An algorithm was generated from the findings, which illustrates the importance of ascertaining whether the mother is alone at the time of the consultation. Increased emotional vulnerability intensified the need for reassurance and affected a mother's decision-making ability. Primary healthcare staff should ascertain whether mothers are currently lone parents at an early stage of their assessment, as this may influence the entire consultation.


Lead Speciation in Microorganisms.
The biogeochemical cycles of lead (Pb) have been largely affected by anthropogenic activities as a result of its high natural abundance and use over the centuries [1]. At sites more strongly impacted by urbanization [2] and mining [3], Pb is found at high nano to low micromolar concentrations in surface waters, and can be significantly higher in soil and sediment [4]. Microorganisms are found everywhere and their responses to Pb exposure can range from resistant to highly sensitive [5, 6]. These varying levels of toxicity can be attributed to the cellular handling of Pb, making it important to understand the role of intracellular Pb speciation for more accurate toxicity predictions.


Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy.
Retinopathy of prematurity (ROP) remains a leading cause of childhood blindness, affecting infants born prematurely. ROP is characterized by the onset of delayed physiological retinal vascular development (PRVD) and followed by pathologic neovascularization into the vitreous instead of the retina, called intravitreal neovascularization (IVNV). Therefore, the therapeutic strategy for treating ROP is to promote PRVD and inhibit or prevent IVNV. Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of ROP. There is a growing body of studies testing the use of anti-VEGF agents as a treatment for ROP. Intravitreal anti-VEGF treatment for ROP has potential advantages compared with laser photocoagulation, the gold standard for the treatment of severe ROP; however, intravitreal anti-VEGF treatment has been associated with reactivation of ROP and suppression of systemic VEGF that may affect body growth and organ development in preterm infants. Therefore, it is important to understand the role of VEGF in PRVD and IVNV. This review includes the current knowledge of anti-VEGF treatment for ROP from animal models of oxygen-induced retinopathy (OIR), highlighting the importance of VEGF inhibition by targeting retinal Müller cells, which inhibits IVNV and permits PRVD. The signaling events involved in mediating VEGF expression and promoting VEGF-mediated angiogenesis, including hypoxia-dependent signaling, erythropoietin/erythropoietin receptor-, oxidative stress-, beta-adrenergic receptor-, integrin-, Notch/Delta-like ligand 4- and exon guidance molecules-mediated signaling pathways, are also discussed.


Fecundity in Thai and European regions: results based on waiting time to pregnancy.
Very little is known about the frequency of subfecundity in different cultures, ethnic groups and regions. To fill this gap, the European Study Group on Infertility and Subfecundity established data on the prevalence of infertility and subfecundity in five European regions. In this study, a comparison of fecundity was made between 4035 Caucasian women from five European countries and 1496 Asian women from southern Thailand. Fecundity was measured using 'time to pregnancy', i.e. the time women took to conceive after stopping contraceptive methods. The Thai primigravid women had a shorter time to pregnancy than European women, whereas time to pregnancy was found to be longer among Thai multigravidae, although this was not statistically significant. This study has illustrated that cross-culture comparison of subfecundity is difficult despite using a common protocol and questionnaire because of differences in the use of contraceptive methods and a different concept of pregnancy planning. The distribution of time to pregnancy for the Thai women was not outside the variation found within the European samples.


Use of laboratory markers and the audit questionnaire by primary care physicians to detect alcohol abuse by patients.
To evaluate how often laboratory markers [Mean corpuscular volume (MCV), Gamma-glutamyl transferase, Aspartate aminotransferase, Alanine aminotransferase, or Carbohydrate-deficient transferrin (CDT)] and the Alcohol Use Disorders Identification Test (AUDIT) are used to detect alcohol abuse in primary health care. Cross-sectional self-administered questionnaire survey to all 3193 primary health care physicians in Finland. Response rate was (65.7%). CDT was used at least occasionally by 43.4% of the physicians. Corresponding figures were 53.4% for conventional alcohol laboratory markers (MCV, transaminases) and 67.0% for AUDIT. Almost all the respondents used some laboratory marker to detect alcohol abuse. The use of brief alcohol intervention was associated with the greater likelihood that a physician uses different methods to detect alcohol abuse. The data also indicates that gender, age, and having a specialist licence influence activity in using different methods. Considering the ambivalences in relation to alcohol issues in health care, the use of CDT and AUDIT are reasonably frequent. This may indicate that tools to facilitate the work may also help in adapting new activities.


Aging test and dynamic fatigue test of apatite-wollastonite-containing glass ceramics and dense hydroxyapatite.
The purpose of this study is to examine the changes in mechanical strength of two bioactive ceramics in living tissue. An aging test and dynamic fatigue test were performed using apatite-wollastonite-containing glass ceramics (A X W-GC) and dense hydroxyapatite (HA). Specimens (5 mm X 5 mm X 25 mm, abraded with No. 2000 Al2O3 powder) were implanted into subcutaneous tissue of rats for varying periods of time. The bending strength of aged samples was measured by the three-point loading method. The bending strength of A X W-GC was greater than that of HA (P less than 0.001). There was no reduction in bending strength for both A X W-GC and HA in living tissue. The n value of both A X W-GC and HA did not decrease significantly after implantation as assessed by the results of the dynamic fatigue test according to analysis of covariance. SEM-EPMA showed that Si and Mg contents decreased, Ca content did not change, while P content increased in the surface of A X W-GC. The area where x-ray intensity changed increased moderately after implantation. There were no changes in Ca and P at the interface between HA and soft tissue. In macroscopic and microscopic observations, specimens were found to be encapsulated with a thin layer of connective tissue. Foreign body giant cells, osteoblasts, or osteoclasts were not observed in the soft tissue. There was no bonding between ceramics and soft tissue.


[Hereditary vitreous degeneration muddy: report of ten cases].
Hereditary vitreous degeneration muddy is rare in clinic. Here we report ten cases (thirteen eyes) of hereditary vitreous degeneration muddy from two families. All patients presented with vitreous opacity, and the textures appeared tough and tensile. Two cases had concurrent detachment of rhegmatogenous retina. HE staining showed red changeableness, and methyl violet staining appeared purple. All patients received vitrectomy with traditional Chinese medicine treatment, and got satisfactory efficacy.


Hypoxic training increases maximal oxygen consumption in Thoroughbred horses well-trained in normoxia.
Hypoxic training is effective for improving athletic performance in humans. It increases maximal oxygen consumption (V̇O2max) more than normoxic training in untrained horses. However, the effects of hypoxic training on well-trained horses are unclear. We measured the effects of hypoxic training on V̇O2max of 5 well-trained horses in which V̇O2max had not increased over 3 consecutive weeks of supramaximal treadmill training in normoxia which was performed twice a week. The horses trained with hypoxia (15% inspired O2) twice a week. Cardiorespiratory valuables were analyzed with analysis of variance between before and after 3 weeks of hypoxic training. Mass-specific V̇O2max increased after 3 weeks of hypoxic training (178 ± 10 vs. 194 ± 12.3 ml O2 (STPD)/(kg × min), P<0.05) even though all-out training in normoxia had not increased V̇O2max. Absolute V̇O2max also increased after hypoxic training (86.6 ± 6.2 vs. 93.6 ± 6.6 l O2 (STPD)/min, P<0.05). Total running distance after hypoxic training increased 12% compared to that before hypoxic training; however, the difference was not significant. There were no significant differences between pre- and post-hypoxic training for end-run plasma lactate concentrations or packed cell volumes. Hypoxic training may increase V̇O2max even though it is not increased by normoxic training in well-trained horses, at least for the durations of time evaluated in this study. Training while breathing hypoxic gas may have the potential to enhance normoxic performance of Thoroughbred horses.


Sorption and Release of Natural Phenolic Antioxidants in Different Cyclodextrin Polymers.
The sorption and release of tyrosol and caffeic acid, two biophenolic antioxidants with known health benefits, in different insoluble cyclodextrin polymers have been studied. Cyclodextrin polymers were synthesized by cross-linking β-cyclodextrin or 50:50 w/w nominal mixtures of α- and β-cyclodextrins using either epichlorohydrin (EP) or toluene-2,4-diisocyanate (TDI) as cross-linking agents. An analogous sucrose polymer was prepared using EP as cross-linking reagent. Freundlich isotherms and isosteric heats of sorption for tyrosol and caffeic acid in the insoluble β-cyclodextrin polymer cross-linked with epichlorohydrin at 50 °C were obtained and discussed. Finally, the release of tyrosol and caffeic acid has been studied from loaded polymer disks, the microstructures of which were characterized by mercury intrusion porosimetry. Caffeic acid shows greater affinity than tyrosol for the polymeric matrices as it presents a higher sorption and a lower and slower release. However, tyrosol has a higher isosteric heat of sorption for low coverages.


Hepatic arterial infusion of oxaliplatin, 5-fluorouracil and leucovorin in patients with liver metastases from colorectal carcinoma.
Limited data are available regarding the efficacy of hepatic arterial infusion (HAI) of oxaliplatin in patients with liver metastases from colorectal carcinoma (CRC). The aim of the present study was to evaluate the results of HAI of oxaliplatin combined with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with such metastases. A retrospective analysis of 22 CRC patients treated with HAI of combination of oxaliplatin and 5-FU and LV was performed. Partial response (PR) was observed in 4 (18%) patients and stable disease (SD) in 7, with an overall disease control rate of 50%. The median progression-free (PFS) and overall survival (OS) were 7 and 11 months, respectively. Two patients treated with first-line treatment underwent subsequent liver resection. In 2 patients, HAI of oxaliplatin, 5-FU and LV was combined with systemic administration of bevacizumab. Our data demonstrate reasonable efficacy of HAI with oxaliplatin, 5-FU and LV in patients with liver metastases from CRC.


Kirigami-Inspired Structures for Smart Adhesion.
Spatially controlled layouts of elasticity can provide enhanced adhesion over homogeneous systems. Emerging techniques in kirigami, where designed cuts in materials impart highly tunable stiffness and geometry, offer an intriguing approach to create well-defined layouts of prescribed elastic regions. Here, we show that kirigami-inspired structures at interfaces provide a new mechanism to spatially control and enhance adhesion strength while providing directional characteristics for smart interfaces. We use kirigami-inspired cuts to define stiff and compliant regions, where above a critical, material-defined length scale, bending rigidity and contact width can be tuned to enhance adhesive force capacity by a factor of ∼100 across a spatially patterned adhesive sheet. The directional nature of these designs also imparts anisotropic responses, where peeling in different directions results in anisotropic adhesion ratios of ∼10. Experimental results are well-supported by theoretical predictions in which the bending rigidity and contact width of kirigami-inspired structures and interconnects control the adhesive capacity. These new interfacial structures and design criteria provide diverse routes for advanced adhesive functionality, including spatially controlled systems, wearable kirigami-inspired electronics, and anisotropic kirigami-inspired bandages that enable strong adhesive capacity while maintaining easy release.