Fenticonazole cream once daily in dermatomycosis, a double-blind controlled trial versus bifonazole.
A randomized, double-blind clinical trial was undertaken in 41 patients with dermatomycosis to compare topical 2% fenticonazole cream (group A: 21 patients) with topical 1% bifonazole cream (group B: 20 patients). Treatment was performed as a once daily application. Mycological and clinical parameters were assessed before treatment and after 7, 14, 21 and 28 days. At the control visits the clinical investigator also expressed an overall judgement on the patient's state of disease. This parameter was based on a combined clinical and mycological assessment by the physician; laboratory screening investigations were undertaken before and at the end of treatments. All patients were checked for their state of disease 3-4 weeks after the end of treatment. All assessment criteria showed fenticonazole to be at least as efficacious as bifonazole. Several trends in favor of fenticonazole were also found: fenticonazole achieved superior results in the overall clinical evaluation, and after 3 weeks of treatment 15 patients out of 21 on fenticonazole were cured in mycological and clinical terms, whereas treatment with bifonazole resulted in complete healing of only 7 patients out of 20. This difference is statistically significant (p = 0.021) and indicates a more rapid therapeutic activity of fenticonazole. At the posttreatment rechecks no recurrent disease was registered, irrespective of whether patients had received fenticonazole or bifonazole. Laboratory screening investigations revealed no evidence of significant treatment-related changes or abnormalities in both treatments. No adverse events were noted for either treatment.


Pituitary calcium channel modulation and regulation of prolactin gene expression.
The dihydropyridine Ca2+ channel modulators (-) Bay K 8644 (R5417) and nimodipine were used to study the role of voltage-gated Ca2+ channels in the regulation of PRL gene transcription in GH3 cells. Fusion constructs containing 5'-flanking sequences from the rat PRL gene linked to either the bacterial chloramphenicol acetyltransferase (CAT) gene or the firefly luciferase gene were transiently expressed in GH3 cells and the transcriptional response to Ca2+ channel modulators was assessed. The Ca2+ channel agonist R5417 enhanced the transcription of a PRL-CAT fusion gene containing 2.5 kilobase (kb) pairs of the 5'-flanking sequence. This response was completely blocked by the Ca2+ channel blocker nimodipine demonstrating that sequences in the PRL 5'-flanking region confer response to Ca2+. Transfection with PRL-CAT constructs containing 2.5 kb to 0.6 kb pairs of 5'-flanking sequence were responsive to Ca2+, although those which contained the distal enhancer region (positions-1765 to -1495) had much higher basal expression. The possibility that the distal enhancer might contain Ca2(+)-responsive elements was tested by comparing the response to R5417 and TRH for both the proximal enhancer region (approximately first 300 base pair of the 5'-flanking sequence) and distal enhancer regions linked to the thymidine kinase promoter and CAT. The results demonstrate that these two regions contribute to the overall transcriptional response to Ca2+ and TRH. The distal region does not confer a response to phorbol ester, while the proximal region is responsive to that treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Purification and biochemical characterization of four iron superoxide dismutases in Trypanosoma cruzi.
Four superoxide dismutase (SOD) activities (SOD I, II, III, and IV) have been characterized in the epimastigote form of Trypanosoma cruzi. The total extract was subjected to two successive ammonium sulphate additions between 35 and 85%, and the resulting fraction was purified using two continuous chromatography processes (ion exchange and filtration). Enzymes were insensitive to cyanide but sensitive to hydrogen peroxide, properties characteristic of iron-containing SODs. The molecular masses of the different SODs were 20 kDa (SOD I), 60 kDa (SOD II), 50 kDa (SOD III) and 25 kDa (SOD IV), whereas the isoelectric points were 6.9, 6.8, 5.2 and 3.8, respectively. Subcellular location and digitonin experiments have shown that these SODs are mainly cytosolic, with small amounts in the low-mass organelles (SOD II and SOD I) and the mitochondrion (SOD III), where these enzymes play an important role in minimizing oxidative damage.


24-hour profiles of adrenocorticotropin, cortisol, and growth hormone in major depressive illness: effect of antidepressant treatment.
Plasma ACTH, cortisol, and GH concentrations were measured at 15-min intervals for 24 h in 11 men suffering from major depressive illness during an acute episode of depression and during clinical remission following antidepressant treatment with either electroconvulsive therapy or amitriptyline. Seven age-matched normal men also were studied. During the acute phase of the illness, the patients had abnormally short rapid eye movement sleep latencies, hypercortisolism, early timing of the nadirs of the ACTH-cortisol rhythms, and shorter nocturnal periods of quiescent cortisol secretion. GH was hypersecreted during wakefulness, and a major pulse occurred before, rather than after, sleep onset. After treatment, rapid eye movement sleep latencies were lengthened, and cortisol levels returned to normal due to a decrease in the magnitude of episodic pulses. Moreover, the timing of the circadian rhythms of ACTH and cortisol as well as the duration of the quiescent period of cortisol secretion were normalized. The amount of GH secreted during wakefulness decreased to normal values, with fewer significant GH pulses. The major elevation of GH secretion in the early part of the night occurred later than that during the depressive episode. These results demonstrate that a disorder of circadian rhythmicity characterizes acute episodes of major depressive illness and that this chronobiological abnormality as well as the hypersecretion of ACTH, cortisol, and GH are state rather than trait dependent.


Multi-level coupled cluster theory.
We present a general formalism where different levels of coupled cluster theory can be applied to different parts of the molecular system. The system is partitioned into subsystems by Cholesky decomposition of the one-electron Hartree-Fock density matrix. In this way the system can be divided across chemical bonds without discontinuities arising. The coupled cluster wave function is defined in terms of cluster operators for each part and these are determined from a set of coupled equations. The total wave function fulfills the Pauli-principle across all borders and levels of electron correlation. We develop the associated response theory for this multi-level coupled cluster theory and present proof of principle applications. The formalism is an essential tool in order to obtain size-intensive complexity in the calculation of local molecular properties.


Diversity of culturable nocardioform actinomycetes from wastewater treatment plants in Spain and their role in the biodegradability of aromatic compounds.
Currently, municipal and industrial wastewater treatment plants (WWTPs) are mainly focusing on reduction of biological oxygen demand and on the removal of nutrients. However, there are microorganisms that interfere with the process. In this environment, there is a large diversity of microorganisms that have not been studied in detail and that could provide real and practical solutions to the foaming problems. Among such microorganisms, Gram-positive actinomycete bacteria are of special interest because they are known for producing secondary metabolites as well as chemically diverse compounds and for their capacity to degrade recalcitrant pollutants. Three different media were chosen to isolate actinomycetes from 28 WWTPs in Spain. A total of 189 activated sludge samples were collected; 126 strains were isolated and identified to belong to 1 suborder, i.e. Corynebacterineae, and 7 genera, i.e. Corynebacterium, Dietzia, Gordonia, Mycobacterium, Rhodococcus, Tsukamurella and Williamsia. Furthermore, 71 strains were capable of biodegrading at least 1 aromatic product, and that 27 of them amplified for catA gene. The results of this research help us understand the complexity of the foam-forming microbial populations in Spain and it shows that WWTPs can be a good source of microorganisms that can degrade phenol or naphthalene.


Adenovirus HSV-TK construct with thyroid-specific promoter: enhancement of activity and specificity with histone deacetylase inhibitors and agents modulating the camp pathway.
The successful use of tissue- or tumor-selective promoters in targeted gene therapy for cancer depends on high and selective activity. Tg is a thyroid-specific protein that is expressed in the normal thyroid and a majority of thyroid tumors. In the present study, we show, using a luciferase reporter assay, that a construct containing the putative Tg promoter and enhancer is active in 4 thyroid carcinoma cell lines (including 2 anaplastic thyroid carcinoma cell lines) and not in 5 cancer cell lines arising from nonthyroid tissues. Furthermore, both the activity and the specificity of this construct were increased by pretreatment with 8-Br-cAMP and the histone deacetylase inhibitor depsipeptide (FR901228). Expression of thymidine kinase in thyroid cancer cells infected with a recombinant adenovirus (Ad) carrying a Tg enhancer/promoter-thymidine kinase expression cassette (AdTg enhancer/promoter-TK) correlated with the level of Tg enhancer/promoter activity in these cells. Under similar conditions, TK expression was not observed in cancer cell lines arising from nonthyroid tissues. Cells infected with AdTg enhancer/promoter-TK demonstrated preferential GCV sensitivity, with up to a 100,000-fold increase in GCV sensitivity in thyroid cancer cell lines compared to cancer cell lines of nonthyroid origin. The construct described herein can be used to selectively target thyroid cancer cells, and its expression can be modulated to further increase its specificity and selectivity, especially in anaplastic thyroid carcinoma cells, using 8-Br-cAMP and depsipeptide.


Fenofibrate-induced renal dysfunction, yes or no?
In the treatment process of hypertriglyceridemia and diabetic nephropathy in type 2 diabetes, fenofibrate (FEN) is a well-known medication. FEN is from fibrate class drugs that using orally; however, as a side effect, it is associated with serum creatinine level increasing. The aim of this review was to determine the real effect of FEN therapy on renal functions based on both experimental and clinical studies. For this review, using the keywords of "fenofibrate" and "renal" and "function," a variety of sources of information banks, including PubMed, Google Scholar, and Scopus, were used, and the published articles were considered and interpreted. Followed by searching in databases, 45 articles were collected. After screening these articles, based on the study source, they were devided into two parts: 23 articles on animal experiments and 22 articles clinical experiments. Based on this information, it seems that the protective mechanism of FEN is related to vascular endothelial functions. The increased creatinine by FEN is related to different sensitivities to FEN effects caused by a polymorphism in different patients. In patients with normal renal function, follow-up of serum creatinine would be necessary after FEN, but the discontinuation of FEN is not recommended. In addition, in diabetic patients with hypertriglyceridemia, FEN treatment would be suggested for protecting the kidney from diabetes-induced renal injury.


Comparative Study of Probiotic Ice Cream and Probiotic Drink on Salivary Streptococcus mutans Levels in 6-12 Years Age Group Children.
Dental caries is one of the most common health problems in the world. Probiotics are one the various preventive methods to reduce dental caries. The aim of this study is to compare the effectiveness of probiotic ice cream and drink on salivary Streptococcus mutans levels in children of 6-12 years age group. A three phase study was carried out in children (n = 50) of 6-12 years age with zero decayed missing filled teeth (dmft)/DMFT. They were randomly divided into two equal groups. Saliva samples were collected before the consumptions of probiotic ice cream and probiotic drink. Colony count obtained was recorded as baseline data. For both groups probiotic ice cream and drink was given randomly for 7 days and a washout period of 90 days were given and then the saliva samples were collected and colony counting was done. Statistical analysis was performed using Student's paired t-test and multiple comparisons by Tukey's honest significant difference test which showed, there is a significant reduction in salivary S. mutans level in both groups after 7 days period. However, after washout period only probiotic ice cream showed reduction whereas drink did not. Also, there was no significant difference between probiotic ice cream and drink. Probiotic organisms definitely have a role in reducing the salivary S. mutans level and ice cream would be a better choice than drink. However, the prolonged use of the agents and their effects on caries is still to be determined.


[Effect of Sishen Pills and its split prescriptions on Tfr/Tfh9/Tfh17 cells in colitis mice].
This study aims to investigate the regulatory effect of Sishen Pills(SSP) and its split prescriptions Ershen Pills(EP) and Wuweizi Powder(WP) on T follicular helper(Tfh) cell subset in the dextran sodium sulfate(DSS)-induced colitis mice and the mechanism. A total of 60 male SPF BALB/c mice were used, 10 of which were randomly selected as the normal group. The rest 50 were induced with 3% DSS solution for colitis modeling. After modeling, they were randomized into 5 groups: model group, SSP group, EP group, WP group, and mesalazine group. Body mass, colon mass, colon mass index, colon length, and unit colon mass index in each group were observed. After hematoxylin-eosin(HE) staining, the pathological injury of colon tissue was scored. The expression levels of molecules related to the STAT/SOCS signaling pathway in colon tissues were analyzed by Western blot. Differentiation levels of Tfh cells such as CD4~+CXCR5~+IL-9~+(Tfh9), CD4~+CXCR5~+IL-17~+(Tfh17), and CD4~+CXCR5~+Foxp3~+(Tfr) in peripheral blood of mice were detected by flow cytometry. The results showed each treatment group demonstrated significant increase in body mass and colon length, decrease in colon mass, colon mass index, unit colon mass index, and histopathological score(P<0.05, P<0.01), reduction of the expression of p-STAT3, STAT3, p-STAT6, and STAT6(P<0.05, P<0.01), rise of the expression of SOCS1 and SOCS3(P<0.05, P<0.01), decrease of Tfh9 and Tfh17 cells, and increase of Tfr cells(P<0.05, P<0.01) compared with the model group. These results indicated that SSP and the split EP and WP may alleviate ulcerative colitis by inhibiting the activation of STAT/SOCS signaling pathway and regulating the balance of Tfr/Tfh9/Tfh17 cells.


[Lasers in urology].
The objective of this article is to quote under the form of a document the opinions expressed by the participants of the round table "Lasers in Urology Today" (january 2006). The material and method used is the compilation of critical and updated notions on the usefulness of lasers in urology, supplemented by bibliographic references, a limited iconography. The results achieved by lasers today enable us to state that: Holmium laser is the choice treatment for in situ lithotripsy; however, it has not significantly improved previous results when treating urologic tumours and stenoses. Nowadays we have two types of lasers: KTP and HoL, which obtain results similar to surgery regarding BPH, but with reduced morbidity. The usefulness of laser in laparoscopic surgery is still under development. Lasers in Urology Today play an active role in in situ lithotripsy (HoL), and a competitive one in BPH surgery (KTP and HoL). Regarding the rest of indications, i.e. tumours, stenoses, laparoscopic surgery, etc., further studies and enough follow-up times are still needed.


eIF4A2 targets developmental potency and histone H3.3 transcripts for translational control of stem cell pluripotency.
Translational control has emerged as a fundamental regulatory layer of proteome complexity that governs cellular identity and functions. As initiation is the rate-limiting step of translation, we carried out an RNA interference screen for key translation initiation factors required to maintain embryonic stem cell (ESC) identity. We identified eukaryotic translation initiation factor 4A2 (eIF4A2) and defined its mechanistic action through ribosomal protein S26-independent and -dependent ribosomes in translation initiation activation of messenger RNAs (mRNAs) encoding pluripotency factors and the histone variant H3.3 with demonstrated roles in maintaining stem cell pluripotency. eIF4A2 also mediates translation initiation activation of Ddx6, which acts together with eIF4A2 to restrict the totipotent two-cell transcription program in ESCs through Zscan4 mRNA degradation and translation repression. Accordingly, knockdown of eIF4A2 disrupts ESC proteome, causing the loss of ESC identity. Collectively, we establish a translational paradigm of the protein synthesis of pluripotency transcription factors and epigenetic regulators imposed on their established roles in controlling pluripotency.


Evaluating the effectiveness and cost-effectiveness of a digital, app-based intervention for depression (VMood) in community-based settings in Vietnam: Protocol for a stepped-wedge randomized controlled trial.
The COVID-19 pandemic has amplified mental health problems and highlighted inequitable gaps in care worldwide. In response there has been an explosion of digital interventions such as smartphone applications ("apps") to extend care. The objective of this trial is to evaluate the effectiveness and cost-effectiveness of a digital depression intervention (VMood), delivered via a smartphone app. VMood is adapted from an in-person intervention that was delivered by non-specialist providers and shown to be effective in the Vietnamese context in our previous trial (2016-2019). A stepped-wedge, randomized controlled trial will be conducted across eight provinces in Vietnam. Adults aged 18 years and over will be recruited through community-based primary care centres and screened for depression using the embedded Patient Health Questionnaire-9 (primary outcome measure). Participants scoring 10-19, indicating depression caseness, will be randomly allocated to the intervention or control group until the target of 336 is reached. Secondary outcome measures will examine the effect of the intervention on commonly co-occuring anxiety, quality of life and work productivity, along with use of alcohol and tobacco products. Assessments will be administered through an online survey platform (REDCap) at baseline, and at every 3 months until 3 months post-intervention. Intervention-group participants will receive VMood for a 3-month period, with online support provided by social workers. Control-group participants will receive a limited version of the app until they cross into the intervention group. Generalized Linear Mixed-effect Models for clustered measures will be used for all outcomes data. We will conduct a cost-effectiveness analysis alongside the trial to capture VMood's costs and benefits. This trial will provide evidence on the effectiveness and cost-effectiveness of a digital mental health intervention adapted from an in-person intervention. This trial will also contribute important information to the growing and promising field of digital mental health. Trail regulation. Registered at ClinicalTrials.gov, identifier [NCT05783531].


Smart implants: 4D-printed shape-morphing scaffolds for medical implantation.
Biomedical implants have recently shown excellent application potential in tissue repair and replacement. Applying three-dimensional (3D) printing to implant scaffold fabrication can help to address individual needs more precisely. Fourdimensional (4D) printing emerges rapidly based on the development of shape-responsive materials and design methods, which makes the production of dynamic functional implants possible. Smart implants can be pre-designed to respond to endogenous or exogenous stimuli and perform seamless integration with regular/ irregular tissue defects, defect-luminal organs, or curved structures via programmed shape morphing. At the same time, they offer great advantages in minimally invasive surgery due to the small-to-large volume transition. In addition, 4D-printed cellular scaffolds can generate extracellular matrix (ECM)-mimetic structures that interact with the contacting cells, expanding the possible sources of tissue/organ grafts and substitutes. This review summarizes the typical technologies and materials of 4D-printed scaffolds, and the programming designs and applications of these scaffolds are further highlighted. Finally, we propose the prospects and outlook of 4D-printed shape-morphing implants.


Photoacoustic imaging to assess pixel-based sO2 distributions in experimental prostate tumors.
A protocol for photoacoustic imaging (PAI) has been developed to assess pixel-based oxygen saturation (sO2) distributions of experimental tumor models. The protocol was applied to evaluate the dependence of PAI results on measurement settings, reproducibility of PAI, and for the characterization of the oxygenation status of experimental prostate tumor sublines (Dunning R3327-H, -HI, -AT1) implanted subcutaneously in male Copenhagen rats. The three-dimensional (3-D) PA data employing two wavelengths were used to estimate sO2 distributions. If the PA signal was sufficiently strong, the distributions were independent from signal gain, threshold, and positioning of animals. Reproducibility of sO2 distributions with respect to shape and median values was demonstrated over several days. The three tumor sublines were characterized by the shapes of their sO2 distributions and their temporal response after external changes of the oxygen supply (100% O2 or air breathing and clamping of tumor-supplying artery). The established protocol showed to be suitable for detecting temporal changes in tumor oxygenation as well as differences in oxygenation between tumor sublines. PA results were in accordance with histology for hypoxia, perfusion, and vasculature. The presented protocol for the assessment of pixel-based sO2 distributions provides more detailed information as compared to conventional region-of-interest-based analysis of PAI, especially with respect to the detection of temporal changes and tumor heterogeneity.


[Problems of the current theory of polymorphonuclear leukocytes].
Neutrophil is an effector cell capable of intra- and extracellular secretion of biologically active substances which produce a variety of effects on the course of inflammation, stop or inhibit multiplication of bacteria, fungi, viruses, transformed or affected cells of the macroorganism. A wide spectrum of neutrophil functions, recorded both in aerobic and anaerobic conditions, is furnished by previously synthesized and accumulated substances which provide the neutrophil with functionally essential components as early as its entrance into tissues from blood. Being a potent killer of biological objects, neutrophil acts with rapid loss of component substances and eventually destroys itself. Enhanced RNA synthesis proceeding in affected cells and thought to provide their reparative capacity, in neutrophils is denied of this compensatory function for reasons still awaiting clarification. Once stimulated for a specific function, neutrophil reduces or loses its capacity for response to additional stimuli.


Adenoviral gene therapy, radiation, and prostate cancer.
Viral gene therapy has exceptional potential as a specifically tailored cancer treatment. However, enthusiasm for cancer gene therapy has varied over the years, partly owing to safety concerns after the death of a young volunteer in a clinical trial for a genetic disease. Since this singular tragedy, results from numerous clinical trials over the past 10 years have restored the excellent safety profile of adenoviral vectors. These vectors have been extensively studied in phase I and II trials as intraprostatically administered agents for patients with locally recurrent and high-risk local prostate cancer. Promising therapeutic responses have been reported in several studies with both oncolytic and suicide gene therapy strategies. The additional benefit of combining gene therapy with radiation therapy has also been realized; replicating adenoviruses inhibit DNA repair pathways, resulting in a synergistic sensitization to radiation. Other, nonreplicating suicide gene therapy strategies are also significantly enhanced with radiation. Combined radiation/gene therapy is currently being studied in phase I and II clinical trials and will likely be the first adenoviral gene therapy mechanism to become available to urologists in the clinic. Systemic gene therapy for metastatic disease is also a major goal of the field, and clinical trials are currently under way for hormone-resistant metastatic prostate cancer. Second- and third-generation "re-targeted" viral vectors, currently being developed in the laboratory, are likely to further improve these systemic trials.


Huanglongbing: An overview of a complex pathosystem ravaging the world's citrus.
Citrus huanglongbing (HLB) has become a major disease and limiting factor of production in citrus areas that have become infected. The destruction to the affected citrus industries has resulted in a tremendous increase to support research that in return has resulted in significant information on both applied and basic knowledge concerning this important disease to the global citrus industry. Recent research indicates the relationship between citrus and the causal agent of HLB is shaped by multiple elements, in which host defense responses may also play an important role. This review is intended to provide an overview of the importance of HLB to a wider audience of plant biologists. Recent advances on host-pathogen interactions, population genetics and vectoring of the causal agent are discussed.


[Treatment of splenic injuries in children].
Most children with blunt splenic trauma are treated non-operatively. Controversy exists regarding the minimal hospital stay, follow-up imaging and length of activity restriction required after discharge. To evaluate outcome for this group of patients, a review was performed of children (age below 14) with blunt splenic injuries treated between January 2000 and December 2003. Fifteen children were admitted with blunt splenic trauma, all were successfully treated non-operatively. Four patients were excluded from further analysis because of multiple injuries that prolonged their hospital stay or they were transferred to our institution more than six days after the accident. Median age was 8 years (range, 1-12). Median length of stay was 5 days (range, 3-8) including 0 days (range, 0-4) in the intensive care unit. Median numbers of follow-up ultrasound examinations were 2 (range, 0-4) with no influence on treatment. Reduced activity after discharge was advised for a median of 4 weeks (3-6). All patients had an uneventful recovery. Haemodynamically stable children with blunt splenic injuries can be treated non-operatively with short hospital stay and a few weeks of restricted activity after discharge. Routine follow-up imaging seems unnecessary.


Relationships between affiliative social behavior and hair cortisol concentrations in semi-free ranging rhesus monkeys.
Sociality is a fundamental aspect of human behavior and health. One benefit of affiliative social relationships is reduced short-term levels of glucocorticoids (GCs), which are indicative of physiological stress. Less is known, however, about chronic GC production in relation to affiliative social behavior. To address this issue, we studied a semi-free ranging troop of rhesus macaques (Macaca mulatta) and collected hair samples to measure hair cortisol concentrations (HCCs), as a measure of chronic GC production, during routine biannual exams. We collected social behavior (both aggressive and affiliative) and hair samples for 32 adult female rhesus macaques over one year (Experiment 1). Our results indicated that adult females who initiated higher levels of social affiliation had significantly lower levels of HCCs. Neither the initiation nor the receipt of aggression were significantly related to HCCs in this study. In a second experiment we studied 28 mother-infant dyads for the first 90days postpartum to examine mother-infant facial interactions (i.e. mutual gazing). We analyzed HCCs during weaning approximately one year later, which is a major transitional period. We found that infants that engaged in higher levels of mutual gazing in the first 90days postpartum had significantly lower levels of HCCs during weaning. Finally, we studied 17 infant rhesus macaques (13 males) to examine whether social behavior (such as play) in the first five months of life correlated with infant HCCs over those months (Experiment 3). We found that infant males that engaged in more social play had significantly lower levels of HCCs. By relying on an animal model, our study shows that affiliative social traits are associated with lower long-term GC production. Future research should address the complex interactions between social behavior, chronic GC production, and mental and physical health.


An approach to classifying human resources constraints to attaining health-related Millennium Development Goals.
BACKGROUND: For any wide-ranging effort to scale up health-related priority interventions, human resources for health (HRH) are likely to be a key to success. This study explores constraints related to human resources in the health sector for achieving the Millennium Development Goals (MDGs) in low-income countries. METHODS AND FRAMEWORK: The analysis drew on information from a variety of publicly-available sources and principally on data presented in published papers in peer-reviewed journals. For classifying HRH constraints an analytical framework was used that considers constraints at five levels: individual characteristics, the health service delivery level, the health sector level, training capacities and the sociopolitical and economic context of a country. RESULTS AND DISCUSSION: At individual level, the decision to enter, remain and serve in the health sector workforce is influenced by a series of social, economic, cultural and gender-related determinants. For example, to cover the health needs of the poorest it is necessary to employ personnel with specific social, ethnic and cultural characteristics. At health-service level, the commitment of health staff is determined by a number of organizational and management factors. The workplace environment has a great impact not only on health worker performance, but also on the comprehensiveness and efficiency of health service delivery. At health-sector level, the use of monetary and nonmonetary incentives is of crucial importance for having the accurate skill mix at the appropriate place. Scaling up of priority interventions is likely to require significant investments in initial and continuous training. Given the lead time required to produce new health workers, such investments must occur in the early phases of scaling up. At the same time coherent national HRH policies are required for giving direction on HRH development and linking HRH into health-sector reform issues, the scaling-up of priority interventions, poverty reduction strategies, and training approaches. Multisectoral collaboration and the sociopolitical and economic context of a country determine health sector workforce development and potential emigration. CONCLUSIONS: Key determinants of success for achieving international development goals are closely related to human-resource development.


EXPANDED PHENOTYPE OF TMEM67 GENE MUTATION (CASE REPORT).
Human ciliopathies are a class of multi-organ genetic disorders caused by defects of proteins expressed at the primary cilium, an organelle present on the cell surface of almost all cell types. Thus far, dozens of causative genes for ciliopathies have been identified and many of them are known to cause allelic disease. Of particular interest is the TMEM67 gene, encoding the transmembrane protein meckelin. The involvement of the mutant TMEM67 gene is known to be associated with a broad range of clinical presentations, namely Joubert syndrome 6 (JBTS6), nephronophthisis 11 (NPHP11), Bardet-Biedel syndrome (BBS), COACH syndrome, and lethal Meckel syndrome type 3 (MKS3). Here we present a case of a 3-year-old boy with compound heterozygous missense mutations in the TMEM67 gene manifesting features of both JBTS and NPHP syndromes, with neonatal onset of end-stage renal disease (ESRD) and associated microcephaly. Such a phenotype has not been reported to date, thus highlighting the diversity of ciliopathies and expanding the phenotype of the TMEM67 gene.


[Effect of modification of the N-terminal region of molecule on the expression of neotropic effect of semax analogues].
A comparative study of neotropic activity of semax (MEHFPGP), an analogue of the ACTH(4-10), and some of its derivatives in which the N-terminal methionine was modified or substituted with other amino acid residues was performed. The effect of these peptides on learning of albino rats in tests with positive (alimentary) and negative (pain) reinforcement was studied. In the case of modification of methionine by attachment of the gluconic-acid residue or substitution of methionine with lysine, the neotropic effect of the peptide was retained. The substitution of methionine with tryptophan or serine resulted in a decrease in the neotropic activity. The substitution of methionine with glycine, threonine, or alanine caused a complete loss of the neotropic activity of the peptide. Therefore, the amino acid residue located at position 1 of the heptapeptide analogue semax, plays a key role in retaining the neotropic effects of the peptide and determines the degree of their expression.


Characterization of sea cucumber (stichopus japonicus) ovum hydrolysates: calcium chelation, solubility and absorption into intestinal epithelial cells.
Sea cucumber (Stichopus japonicus) ovum hydrolysates (SCOHs) chelated with calcium were produced to investigate the characteristics of calcium binding and solubility, as well as to study any effects on calcium absorption by human intestinal epithelial cells. The results of the present study show that the calcium-binding capacity of SCOHs depended greatly on the type of proteases. The maximum level of Ca binding (0.38 mmol L-1 ) occurred when trypsin was used, with a peptide yield of 85.7%. Investigation of the possible chelating modes between SCOHs and calcium ions indicated that calcium ions bound to SCOHs primarily via interactions with carboxyl oxygen and amino nitrogen atoms of Glu and Asp and also that the phosphoserine residues might be also responsible for SCOH-calcium chelation. Moreover, SCOH-calcium complexes maintained the solubility of calcium under simulated gastrointestinal digestion, regardless of the presence of dietary components such as oxalate. Furthermore, SCOH-Ca led to higher peak intracellular [Ca2+ ]i in both Caco-2 cells (338.3 nmol L-1 versus 269.6 nmol L-1 ) and HT-29 cells (373.9 nmol L-1 versus 271.7 nmol L-1 ) than casein phosphopeptide-Ca. Carboxyl oxygen and amino nitrogen atoms in the SCOHs could bind calcium ions, forming SCOH-calcium complexes. These complexes improved calcium solubility under simulated gastrointestinal digestion and also promoted calcium absorption in Caco-2 and HT-29 cells. © 2017 Society of Chemical Industry.


Quantification of the 2-deoxyribonolactone and nucleoside 5'-aldehyde products of 2-deoxyribose oxidation in DNA and cells by isotope-dilution gas chromatography mass spectrometry: differential effects of gamma-radiation and Fe2+-EDTA.
The oxidation of 2-deoxyribose in DNA has emerged as a critical determinant of the cellular toxicity of oxidative damage to DNA, with oxidation of each carbon producing a unique spectrum of electrophilic products. We have developed and validated an isotope-dilution gas chromatography-coupled mass spectrometry (GC-MS) method for the rigorous quantification of two major 2-deoxyribose oxidation products: the 2-deoxyribonolactone abasic site of 1'-oxidation and the nucleoside 5'-aldehyde of 5'-oxidation chemistry. The method entails elimination of these products as 5-methylene-2(5H)-furanone (5MF) and furfural, respectively, followed by derivatization with pentafluorophenylhydrazine (PFPH), addition of isotopically labeled PFPH derivatives as internal standards, extraction of the derivatives, and quantification by GC-MS analysis. The precision and accuracy of the method were validated with oligodeoxynucleotides containing the 2-deoxyribonolactone and nucleoside 5'-aldehyde lesions. Further, the well-defined 2-deoxyribose oxidation chemistry of the enediyne antibiotics, neocarzinostatin and calicheamicin gamma(1)(I), was exploited in control studies, with neocarzinostatin producing 10 2-deoxyribonolactone and 300 nucleoside 5'-aldehyde per 10(6) nt per microM in accord with its established minor 1'- and major 5'-oxidation chemistry. Calicheamicin unexpectedly caused 1'-oxidation at a low level of 10 2-deoxyribonolactone per 10(6) nt per microM in addition to the expected predominance of 5'-oxidation at 560 nucleoside 5'-aldehyde per 10(6) nt per microM. The two hydroxyl radical-mediated DNA oxidants, gamma-radiation and Fe(2+)-EDTA, produced nucleoside 5'-aldehyde at a frequency of 57 per 10(6) nt per Gy (G-value 74 nmol/J) and 3.5 per 10(6) nt per microM, respectively, which amounted to 40% and 35%, respectively, of total 2-deoxyribose oxidation as measured by a plasmid nicking assay. However, gamma-radiation and Fe(2+)-EDTA produced different proportions of 2-deoxyribonolactone at 7% and 24% of total 2-deoxyribose oxidation, respectively, with frequencies of 10 lesions per 10(6) nt per Gy (G-value, 13 nmol/J) and 2.4 lesions per 10(6) nt per microM. Studies in TK6 human lymphoblastoid cells, in which the analytical data were corrected for losses sustained during DNA isolation, revealed background levels of 2-deoxyribonolactone and nucleoside 5'-aldehyde of 9.7 and 73 lesions per 10(6) nt, respectively. Gamma-irradiation of the cells caused increases of 0.045 and 0.22 lesions per 10(6) nt per Gy, respectively, which represents a approximately 250-fold quenching effect of the cellular environment similar to that observed in previous studies. The proportions of the various 2-deoxyribose oxidation products generated by gamma-radiation are similar for purified DNA and cells. These results are consistent with solvent exposure as a major determinant of hydroxyl radical reactivity with 2-deoxyribose in DNA, but the large differences between gamma-radiation and Fe(2+)-EDTA suggest that factors other than hydroxyl radical reactivity govern DNA oxidation chemistry.


Concentrations of tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid in canine amniotic membranes cryopreserved for different time points and its effects in dogs with complicated corneal ulcers.
To determine the concentrations of total protein (TP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and hyaluronic acid (HA) in amniotic membranes (AMs) harvested from placentas of bitches of different ages and cryopreserved for different time points. The outcomes of complicated corneal defects of dogs repaired with AMs stored for the same time points were also evaluated. Ten cryopreserved canine AMs were stored for short term (2-50 days), middle term (92-210 days), or long term (256-357 days). TP was quantified by Bradford's test, whereas TIMP-1 and HA were quantified by ELISA. Twenty-one dogs that had an AM transplantation to restore deep or perforating corneal wounds were selected. TIMP-1 levels were lower in AMs cryopreserved for middle term (p = .02) and long term (p = .0009), when compared to AMs stored for short term. TP (p = .39) and HA (p = .18) concentrations in AMs did not differ among the storage time. TIMP-1 concentration in AMs correlated with storage time (R = -.65, p < .0001), while TP (R = -.33, p = .07) and HA concentrations did not (R = -.15, p = .41). The age of donors did not correlate with the components evaluated in the AMs. Corneal defects repaired with AMs stored for short term healed sooner than the ones repaired with AMs stored for middle (p < .01) and long term (p = .02). Additionally, TIMP-1 levels in AMs correlated negatively with the epithelization time (R = -.62, p = .002). Graft opacity was severe in 55% of cases. However, the HA levels in AMs correlated negatively with the opacification score (R = -.47, p = .03). Vision was observed in more patients who presented deep ulcers and descemetoceles, than in the ones with perforations (p = .004). TIMP-1 concentration in canine AMs significantly decreased over a year storage time, while TP and HA concentrations did not change during the same period. The age of donors did not correlate with the components evaluated in the AMs. Complicated corneal defects repaired with AMs cryopreserved for short term healed sooner and tended to be less opaque; however, satisfactory to optimal outcomes were achieved even in the eyes repaired with AMs stored for up to a year.


Effectiveness of a dental gel to reduce plaque in beagle dogs.
Tooth brushing is considered a superior technique for reducing plaque accumulation. Chemical agents may be used to reduce plaque accumulation on tooth surfaces since many owners may not be willing or able to brush their dog's teeth. Following a professional teeth cleaning procedure, a dental gel containing chlorhexidine was applied in 11 dogs BID for 7-days, while 11 other dogs received a control dental gel applied in the same manner. Dogs in the treatment group had significantly less plaque accumulation during the trial period compared with dogs in the control group. The dental gel applied in the study reported here decreases plaque accumulation in the short-term and may be beneficial in reducing the severity of gingivitis and associated periodontal disease if provided on a long-term basis.


Knowledge, attitudes, and practices associated with bioterrorism preparedness in healthcare workers: a systematic review.
Bioterrorism is an important issue in the field of biosecurity, and effectively dealing with bioterrorism has become an urgent task worldwide. Healthcare workers are considered bioterrorism first responders, who shoulder essential responsibilities and must be equipped to deal with bioterrorism. This study aims to extract and summarize the main research components of the bioterrorism knowledge, attitude, and practice dimensions among healthcare workers. This study utilized a systematic review research design based on the PRISMA 2020 guidelines. A literature search was conducted in the PubMed, Web of Science, and Scopus databases for peer-reviewed literature, and the Mixed Methods Appraisal Tool (MMAT) version 2018 was used to assess the quality of the literature. A total of 16 studies were included in the final selection. Through the analysis and summary of the included studies, three main aspects and 14 subaspects of the knowledge dimension, three main aspects and 10 subaspects of the attitude dimension, and two main aspects and six subaspects of the practice dimension were extracted. This study conducted a literature review on bioterrorism knowledge, attitudes, and practices for healthcare workers based on the PRISMA 2020 guidelines. The findings can guide improvements in health literacy and provide beneficial information to professional organizations that need to respond effectively to bioterrorism.


Internal Ca2+ mobilization and secretion in bovine adrenal chromaffin cells.
Since secretion from intact bovine adrenal chromaffin cells in response to depolarization by nicotine is triggered by a rise in the concentration of intracellular Ca2+ ([Ca2+]i) to about 200-300 nM above basal, it has been assumed that the failure of the inositol 1,4,5-trisphosphate (InsP3)-mobilizing muscarinic agonists to induce secretion reflects the fact that the 50 nM rise in [Ca2+]i they elicit is insufficient to trigger the exocytotic machinery. A recent report, however, has demonstrated that some of the nicotine-induced rise in [Ca2+]i could originate from the InsP3-releasable Ca2+ store. The role of this Ca2+ store in secretion from bovine adrenal chromaffin cells is therefore unclear. In order to investigate in more detail the role of the InsP3-sensitive Ca2+ store in secretion from these cells, we have used a combination of an InsP3-mobilizing muscarinic agonist and the sesquiterpene lactone thapsigargin (TG), which releases internal Ca2+ without concomitant breakdown of inositol lipids or protein kinase C activation, to examine the events which follow depletion of the releasable Ca2+ store in these cells. Monitoring [Ca2+]i using Fura-2 demonstrated that TG released Ca2+ from the InsP3-sensitive store and, additionally, that the Ca2+ response to TG was composed of two distinct, temporally separated, components: a) a slow (1 min) increase in [Ca2+]i to approximately 50 nM above basal that was independent of extracellular Ca2+ and b) the maintenance of this level at a new steady-state that was dependent on the continual entry of extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)


Direct and social genetic effects on body weight at 270 days and carcass and ham quality traits in heavy pigs.
The aims of this study were to estimate covariance components for BW at 270 d (BW270) and carcass and ham quality traits in heavy pigs using models accounting for social effects and to compare the ability of such models to fit the data relative to models ignoring social interactions. Phenotypic records were from 9,871 pigs sired by 293 purebred boars mated to 456 crossbred sows. Piglets were born and reared at the same farm and randomly assigned at 60 d of age to groups (6.1 pigs per group on average) housed in finishing pens, each having an area of 6 m(2). The average additive genetic relationship among group mates was 0.11. Pigs were slaughtered at 277 ± 3 d of age and 169.7 ± 13.9 kg BW in groups of nearly 70 animals each. Four univariate animal models were compared: a basic model (M1) including only direct additive genetic effects, a model (M2) with nonheritable social group (pen) effects in addition to effects in M1, a model (M3) accounting for litter effects in addition to M2, and a model (M4) accounting for social genetic effects in addition to effects in M3. Restricted maximum likelihood estimates of covariance components were obtained for BW270; carcass backfat depth; carcass lean meat content (CLM); iodine number (IOD); and linoleic acid content (LIA) of raw ham subcutaneous fat; subcutaneous fat depth in the proximity of semimembranosus muscle (SFD1) and quadriceps femoris muscle (SFD2); and linear scores for ham round shape (RS), subcutaneous fat (SF), and marbling. Likelihood ratio tests indicated that, for all traits, M2 fit the data better than M1 and that M3 was superior to M2 except for SFD1 and SFD2. Model M4 was significantly better than M3 for BW270 (P < 0.001) and CLM, IOD, RS, and SF (P < 0.05). The contribution of social genetic effects to the total heritable variance was large for CLM and BW270, ranging from 33.2 to 35%, whereas the one for ham quality traits ranged from 6.8 (RS) to 11.2% (SF). Direct and social genetic effects on BW270 were uncorrelated, whereas there was a negative genetic covariance between direct and social effects on CLM, IOD, RS, and SF, which reduced the total heritable variance. This variance, measured relative to phenotypic variance, ranged from 21 (CLM) to 54% (BW270). Results indicate that social genetic effects affect variation in traits relevant for heavy pigs used in dry-cured hams manufacturing. Such effects should be exploited and taken into account in design of breeding programs for heavy pigs.


Delta and gamma oscillations in operculo-insular cortex underlie innocuous cold thermosensation.
Cold-sensitive and nociceptive neural pathways interact to shape the quality and intensity of thermal and pain perception. Yet the central processing of cold thermosensation in the human brain has not been extensively studied. Here, we used magnetoencephalography and EEG in healthy volunteers to investigate the time course (evoked fields and potentials) and oscillatory activity associated with the perception of cold temperature changes. Nonnoxious cold stimuli consisting of Δ3°C and Δ5°C decrements from an adapting temperature of 35°C were delivered on the dorsum of the left hand via a contact thermode. Cold-evoked fields peaked at around 240 and 500 ms, at peak latencies similar to the N1 and P2 cold-evoked potentials. Importantly, cold-related changes in oscillatory power indicated that innocuous thermosensation is mediated by oscillatory activity in the range of delta (1-4 Hz) and gamma (55-90 Hz) rhythms, originating in operculo-insular cortical regions. We suggest that delta rhythms coordinate functional integration between operculo-insular and frontoparietal regions, while gamma rhythms reflect local sensory processing in operculo-insular areas.NEW & NOTEWORTHY Using magnetoencephalography, we identified spatiotemporal features of central cold processing, with respect to the time course, oscillatory profile, and neural generators of cold-evoked responses in healthy human volunteers. Cold thermosensation was associated with low- and high-frequency oscillatory rhythms, both originating in operculo-insular regions. These results support further investigations of central cold processing using magnetoencephalography or EEG and the clinical utility of cold-evoked potentials for neurophysiological assessment of cold-related small-fiber function and damage.


Postharvest Calcium Chloride Treatment Strengthens Cell Wall Structure to Maintain Litchi Fruit Quality.
Litchi (Litchi chinensis Sonn.) fruit deterioration occurs rapidly after harvest and is characterized by pericarp browning, pulp softening, and decay. In this study, we found that calcium chloride (CaCl2) treatment (5 g L-1 CaCl2 solution vacuum infiltration for 5 min) affected the cell wall component contents and cell wall-degrading enzyme activities of litchi fruit during storage at room temperature. CaCl2 treatment significantly increased the contents of Ca2+ and cellulose, while it decreased the water-soluble pectin content, and the activities of polygalacturonase, β-galactosidase, and cellulase in the litchi pericarp. Meanwhile, the treatment resulted in significantly increased contents of Ca2+, water-soluble pectin, ionic-soluble pectin, covalent-soluble pectin and hemicellulose, and upregulated activities of pectinesterase and β-galactosidase, while significantly decreasing the activities of polygalacturonase and cellulase in litchi pulp. The above results indicate that CaCl2 treatment strengthened the cell wall structure of litchi fruit. More importantly, the enzymatic browning of the pericarp, softening of the pulp, and disease incidence were delayed. The treatment had a more pronounced effect on the pericarp than on the pulp. We consider CaCl2 treatment to be a safe and effective treatment for maintaining the postharvest quality of litchi fruit.


Potential--energy surfaces for excited states in extended systems.
With a simple and physically intuitive method, first-principles calculations of potential-energy surfaces are performed for excited states in a number of illustrative systems, including dimers (H(2) and NaCl) and gas-surface systems [Cl-Na(100) and Cl(2)-Na(100)]. It is based on density-functional theory and is a generalization of the Delta self-consistent field (DeltaSCF) method, where electron-hole pairs are introduced in order to model excited states, corresponding to internal electron transfers in the considered system. The desired excitations are identified by analysis of calculated electron orbitals, local densities of states, and charge densities. For extended systems, where reliable first-principles methods to account for electronically excited states have so far been scarce, our method is very promising. Calculated results, such as the chemiluminescence of halogen molecules impinging on a alkali-metal surface, and the vertical (5 sigma-->2 pi(*)) excitation within the adsorbed CO molecule on the Pd(111) surface, are in working agreement with those of other studies and experiments.


Concentrations, Trends, and Air-Water Exchange of PAHs and PBDEs Derived from Passive Samplers in Lake Superior in 2011.
Polycyclic aromatic hydrocarbons (PAHs) and polybrominated diphenylethers (PBDEs) are both currently released into the environment from anthropogenic activity. Both are hence primarily associated with populated or industrial areas, although wildfires can be an important source of PAHs, as well. Polyethylene passive samplers (PEs) were simultaneously deployed in surface water and near surface atmosphere to determine spatial trends and air-water gaseous exchange of 21 PAHs and 11 PBDEs at 19 sites across Lake Superior in 2011. Surface water and atmospheric PAH concentrations were greatest at urban sites (up to 65 ng L(-1) and 140 ng m(-3), respectively, averaged from June to October). Near populated regions, PAHs displayed net air-to-water deposition, but were near equilibrium off-shore. Retene, probably depositing following major wildfires in the region, dominated dissolved PAH concentrations at most Lake Superior sites. Atmospheric and dissolved PBDEs were greatest near urban and populated sites (up to 6.8 pg L(-1) and 15 pg m(-3), respectively, averaged from June to October), dominated by BDE-47. At most coastal sites, there was net gaseous deposition of BDE-47, with less brominated congeners contributing to Sault Ste. Marie and eastern open lake fluxes. Conversely, the central open lake and Eagle Harbor sites generally displayed volatilization of PBDEs into the atmosphere, mainly BDE-47.


Colonization-induced protection against invasive pneumococcal disease in mice is independent of CD103 driven adaptive immune responses.
Nasopharyngeal colonization with Streptococcus pneumoniae (the pneumococcus) is known to mount protective adaptive immune responses in rodents and humans. However, the cellular response of the nasopharyngeal compartment to pneumococcal colonization and its importance for the ensuing adaptive immune response is only partially defined. Here we show that nasopharyngeal colonization with S. pneumoniae triggered substantial expansion of both integrin αE (CD103) positive dendritic cells (DC) and T lymphocytes in nasopharynx, nasal-associated lymphoid tissue (NALT) and cervical lymph nodes (CLN) of WT mice. However, nasopharyngeal de-colonization and pneumococcus-specific antibody responses were similar between WT and CD103 KO mice or Batf3 KO mice. Also, naïve WT mice passively immunized with antiserum from previously colonized WT and CD103 KO mice were similarly protected against invasive pneumococcal disease (IPD). In summary, the data show that CD103 is dispensable for pneumococcal colonization-induced adaptive immune responses in mice.


Choice between single and multiple reinforcers in concurrent-chains schedules.
Pigeons responded on concurrent-chains schedules with equal variable-interval schedules as initial links. One terminal link delivered a single reinforcer after a fixed delay, and the other terminal link delivered either three or five reinforcers, each preceded by a fixed delay. Some conditions included a postreinforcer delay after the single reinforcer to equate the total durations of the two terminal links, but other conditions did not include such a postreinforcer delay. With short initial links, preference for the single-reinforcer alternative decreased when a postreinforcer delay was present, but with long initial links, the postreinforcer delays had no significant effect on preference. In conditions with a postreinforcer delay, preference for the single-reinforcer alternative frequently switched from above 50% to below 50% as the initial links were lengthened. This pattern of results was consistent with delay-reduction theory (Squires & Fantino, 1971), but not with the contextual-choice model (Grace, 1994) or the hyperbolic value-added model (Mazur, 2001) as they have usually been applied. However, the hyperbolic value-added model could account for the results if its calculations were expanded to include reinforcers delivered in later terminal links. The implications of these findings for models of concurrent-chains performance are discussed.


Preliminary Results: Can Dual-Energy Computed Tomography Help Distinguish Cardiogenic Pulmonary Edema and Acute Interstitial Lung Disease?
We compared iodine concentration in pulmonary ground-glass opacity on iodine density images of contrast-enhanced chest dual-energy computed tomography (DECT) between patients with cardiogenic pulmonary edema (CPE) and acute interstitial lung disease (AILD). Five of 12 patients who underwent contrast-enhanced chest DECT to exclude pulmonary embolism were clinically diagnosed with CPE and 7, with AILD. We compared the mean CT value on monochromatic images at 65 keV and iodine concentration on iodine density images between the affected and normal areas. The mean iodine concentrations were comparable between the affected and normal areas (P = 0.3048) in patients with CPE and were significantly higher in the affected than in the normal areas in those with AILD (P < 0.0001). Measurement of iodine concentration in pulmonary ground-glass opacity of contrast-enhanced chest DECT has the potential to help distinguish CPE and AILD.


Current-Density Calculations on Zn-Porphyrin40 Nanorings.
Two porphyrinoid nanorings have been studied computationally. They were built by linking 40 Zn-porphyrin units with butadiyne bridges. The molecular structures belonging to the D40h point group were fully optimized with the Turbomole program at the density functional theory (DFT) level using the B3LYP functional and the def2-SVP basis sets. The aromatic character was studied at the DFT level by calculating the magnetically induced current-density (MICD) susceptibility using the GIMIC program. The neutral molecules are globally non-aromatic with aromatic Zn-porphyrin units. Charged nanorings could not be studied because almost degenerate frontier orbitals led to vanishing optical gaps for the cations. Since DFT calculations of the MICD are computationally expensive, we also calculated the MICD using three pseudo-π models. Appropriate pseudo-π models were constructed by removing the outer hydrogen atoms and replacing all carbon and nitrogen atoms with hydrogen atoms. The central Zn atom was either replaced with a beryllium atom or with two inner hydrogen atoms. Calculations with the computationally inexpensive pseudo-π models yielded qualitatively the same magnetic response as obtained in the all-electron calculations.


Protocol for Compass: a randomised controlled trial of primary HPV testing versus cytology screening for cervical cancer in HPV-unvaccinated and vaccinated women aged 25-69 years living in Australia.
Australia's National Cervical Screening Program (NCSP) currently recommends 2-year cytology in women aged 18-69 years. Following a review of the NCSP prompted by the implementation of human papillomavirus (HPV) vaccination, the programme will transition in 2017 to 5-year primary HPV screening with partial genotyping for HPV16/18 in women aged 25-74 years. Compass is a sentinel experience for the renewed NCSP and the first prospectively randomised trial of primary HPV screening compared with cytology to be conducted in a population with high uptake of HPV vaccination. This protocol describes the main Compass trial, which commenced after a pilot study of ~5000 women completed recruitment. Women aged 25-69 years will be randomised at a 1:2 allocation to (1) 2.5-year image-read, liquid-based cytology (LBC) screening with HPV triage of low-grade smears (active control Arm A) or (2) 5-year HPV screening with partial genotyping and referral of HPV16/18-positive women to colposcopy (intervention Arm B). Women in Arm B positive for other oncogenic HPV (not 16/18) will undergo secondary randomisation at a 1:1 allocation to either LBC or dual-stained (p16INK4a and Ki-67) cytology testing (dual-stained cytology). The primary outcome is cumulative CIN3+ (CIN3, adenocarcinoma in situ and invasive cervical cancer) following a 5-year HPV exit testing round in both arms, in women randomised to the HPV arm versus women randomised to the LBC arm, based on an intention-to-treat analysis. The primary outcome will first be tested for non-inferiority and if declared, the primary outcome will be tested for superiority. A total of 36 300 women in birth cohorts not offered vaccination and 84 700 women in cohorts offered vaccination will be recruited, bringing the final sample size to 121 000. The trial is powered for the secondary outcome of cumulative CIN3+ in screen-negative women, adjusted for censoring after CIN2+ treatment and hysterectomy. Approved by the Bellberry Ethics Committee (2014-11-592). Findings will be reported in peer-reviewed journals and presented at scientific meetings. NCT02328872; Pre-results.


Cost-effective strategies for rural community outreach, Hawaii, 2010-2011.
Three strategies designed to maximize attendance at educational sessions on chronic disease medication safety in older adults in rural areas were implemented sequentially and compared for cost-effectiveness: 1) existing community groups and events, 2) formal advertisement, and 3) employer-based outreach. Cost-effectiveness was measured by comparing overall cost per attendee recruited and number of attendees per event. The overall cost per attendee was substantially higher for the formal advertising strategy, which produced the lowest number of attendees per event. Leveraging existing community events and employers in rural areas was more cost-effective than formal advertisement for recruiting rural community members.


Unprecedented formation of novel phosphonodithioate ligands from diferrocenyldithiadiphosphetane disulfide.
The reaction of the phosphetane disulfide, FcP(S)S 2P(S)Fc ( 1) (Fc = (eta (5)-C 5H 5)Fe(eta (5)-C 5H 4)), the ferrocenyl analogue of the Lawesson reagent, with gold and palladium complexes leads to the unprecedented formation of phosphonodithioate ligands upon coordination to the metal centers. The reaction of 1 with gold complexes such as [AuCl(PR 3)] affords the species [Au{S 2P(OH)Fc}(PR 3)] (PR 3 = PPh 3 ( 2), PPh 2Me ( 3)), in which the phosphonodithioate ligand Fc(OH)PS 2 (-) has been formed. The same ligand is present in the compound [Au 2{S 2P(OH)Fc} 2].[N(PPh 3) 2]Cl ( 4), obtained by reaction of 1 with [N(PPh 3) 2][AuCl 2]. It crystallizes with one molecule of [N(PPh 3) 2]Cl, whereby complex 4 acts as an anion receptor and forms strong hydrogen bonds between the chloro and the hydroxyl groups. The reaction with palladium derivatives is different; two complexes, [Pd 2(S 4OP 2Fc 2) 2] ( 5) and [Pd 4Cl 4(S 4OP 2Fc 2) 2] ( 6), are obtained in molar ratio 2:1 and 1:1, respectively. In these complexes a new phosphonodithioate ligand is present and probably arises from the condensation of two molecules of Fc(OH)PS 2 (-). Complex 5 has also been characterized by X-ray methods.


Laparoscopic versus inguinal (Ivanissevich) varicocelectomy.
To compare the postsurgical outcome of laparoscopic and open inguinal varicocelectomy. Quasi-experimental study. Department of Surgery, Liaquat University of Medical and Health Sciences, Jamshoro, from July 2003 to June 2007. One hundred seven patients underwent either open inguinal or laparoscopic varicocelectomy. Diagnosis was made by clinical examination and color Doppler scan in doubtful cases. Pre-operative semen analysis was done in all patients. Operative time, postoperative analgesic requirement in number of tablets, hospital stay in days, improvement in semen parameters in subfertile subjects, pain on visual analog score. and postoperative complications were recorded and compared between the two groups. There were 50 patients in each group, with age ranging from 12-50 years (26.9+/-7.67 in open inguinal and 26.2+/-7.08 in laparoscopic group). Average operative time was 34.8+/-7.89 minutes for open inguinal and 43.8+/-8.95 minutes for laparoscopic group. The analgesic requirement was 16.3+/-1.58 tablets in the open inguinal and 11.3+/-2.23 in the laparoscopic group. Postoperative pain was significantly less in the laparoscopic group. There was statistically significant (p < 0.001) improvement in sperm count as well as motility in both groups irrespective of procedure. The open inguinal (Ivanissevich) procedure and laparoscopic varicocelectomy had almost equivalent postoperative outcomes regarding improvement in semen parameters and postoperative complications. Open inguinal procedure had a shorter operating time while laparoscopic varicocelectomy had the advantage of less analgesic requirement and short hospital stay. On the whole, open inguinal (loupe magnified) varicocelectomy is an effective procedure where availability and costs of laparoscopic instruments are barriers.


[Role of functional rehabilitation in preventive and interceptive orthodontic management].
Orofacial dysfunction and parafunctions are responsible for many orthodontic abnormalities right from the stage of deciduous teeth.Incisor malocclusion, dental malposition and alveolar arch malformations are the most common abnormalities.Functional rehabilitation for prevention or as part of interceptive orthodontics significantly reduces the risk of appearance or progression of these abnormalities to more extensive malocclusions that are more difficult to manage.Functional rehabilitation consists of re-educating and restoring physiological orofacial functions, such as speech and swallowing, breathing and/or chewing disorders.


Effect of ochratoxin A on brush border enzymes of rat kidney.
Ochratoxin A was given orally at 60 microgram/kg body weight in neutral olive oil to Fischer rats for 30 days, at which time they were killed. Clinical state, weights of animals and of their organs and urea and creatinine concentrations were not affected during the exposure period. Significant increases in the activity of enzymes in urine were found: 60% increase in alanine aminopeptidase, 45% increase in gamma-glutamyl-transferase and 90% increase in alkaline phosphatase. These changes indicate early pathological changes in the kidney. Relatively small amounts of the toxin thus affect kidney membrane cells.


Comparison of nanoemulsion and non-emollient artificial tears on tear lipid layer thickness and symptoms.
Dry eye disease (DED) is often managed with over-the-counter eye drops. This study evaluated the diurnal effects of a single drop of two ocular lubricants (nanoemulsion vs. non-emollient) on tear film lipid layer thickness (LLT) and symptoms of ocular dryness. Subjects were also assessed after 1 month of nanoemulsion eye drop use. Part 1 was a cross-over comparison of a nanoemulsion and a non-emollient eye drop. LLT and dry eye symptoms were measured at baseline and at 15min, 1h, 2h, 4h and 6h after instillation of each drop. Part 2 was a 1-month observational study assessing LLT and symptoms after 30-day use of the nanoemulsion drop four times daily (qid). Total of 20 subjects completed the study (mean age=45.6±7.9, 15 female). Part 1 found a significant increase in average LLT 15min after nanoemulsion drop instillation in the overall and inferior third of the tear film for subjects with baseline LLT values <50nm. Average LLT values did not increase after use of the non-emollient. Symptoms of dryness improved up to 6h following instillation of both drops. Part 2 results found that using the nanoemulsion eye drop for 1 month improved symptoms reported on symptom surveys. Nanoemulsion eye drop use increased average LLT in subjects with low baseline levels. Statistically and clinically significant improvement in symptoms were found on symptom surveys after qid-use (four times a day) of the nanoemulsion drop. Results suggest that a nanoemulsion eye drop can benefit subjects with dry eye symptoms.


Higher PEDOT Molecular Weight Giving Rise to Higher Thermoelectric Property of PEDOT:PSS: A Comparative Study of Clevios P and Clevios PH1000.
Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is a promising candidate as the next-generation thermoelectric (TE) material. Its TE properties are strongly dependent on its chemical and electronic structures. In this paper, we investigated the effect of PEDOT molecular weight on the TE properties of PEDOT:PSS films by a comparative study on two commercial grades of PEDOT:PSS, Clevios P, and Clevios PH1000. Dynamic light scattering (DLS) and Raman spectra imply that the PEDOT of Clevios PH1000 possesses longer conjugated chains than that of Clevios P. The TE properties of both the Clevios P and Clevios PH1000 films can be significantly enhanced through various post treatments, including solvent treatment, germinal diol treatment, organic solution treatment, and acid treatment. After these treatments, the treated Clevios PH1000 films constantly show both superior Seebeck coefficients and electrical conductivities over the treated Clevios P films. It is attributed to the higher molecular weight of PEDOT for the former than the latter. For the treated Clevios PH1000, longer PEDOT chains result in large PEDOT domains, facilitating the charge conduction a semimetallic behavior. Tuning the oxidation level of PEDOT:PSS is a facile way to enhance their TE property. A base treatment with sodium hydroxide was subsequently performed on both the treated Clevios P and Clevios PH1000 films. The power factors of both grades of PEDOT:PSS films were remarkably increased by a factor of 1.2-3.6. Still, both the conductivity and the Seebeck coefficient of a based-treated Clevios PH1000 film are superior over those of a control Clevios P film. The highest power factor the former is 334 μW/(m K2) for the former while only 11.4 μW/(m K2) for the latter. They are different by a factor of about 30 times.


Recurrent endobronchial actinomycosis following an interventional procedure.
Actinomycosis is an indolent, slowly progressive infection caused by anaerobic or microaerophilic bacteria, primarily from the genus Actinomyces. Thoracic involvement is observed in approximately 15% of cases of infection with actinomycosis. Here, we present a case of a 61-year-old male who presented with recurrent endobronchial actinomycosis. The case is being presented because of its rarity on three counts - endobronchial involvement, which is uncommon, recurrence in different sites in the bronchial tree, which is even rarer and development of the disease following an endobronchial procedure.


Diagnostic pitfalls associated with a large true posterior communicating artery aneurysm: a case report.
True posterior communicating artery (PCoA) aneurysm is an aneurysm that originates from the PCoA, and large or giant true PCoA aneurysms are rare. We report a case of a large true PCoA aneurysm successfully clipped after anterior clinoidectomy and discuss the diagnostic pitfalls associated with this rare clinical entity.


Long-term Favorable Outcomes of Radiofrequency Ablation for Hepatocellular Carcinoma as an Initial Treatment: A Single-center Experience Over a 10-Year Period.
Radiofrequency ablation (RFA) is an alternative to hepatic resection and one of the major therapeutic options for hepatocellular carcinoma (HCC). Here, we investigated the long-term outcomes of RFA as an initial treatment for HCC. From January 2000 to December 2014, we treated 1,043 patients with RFA for HCC at the Kumamoto University Hospital; 327 of these patients (31.4%) were treated for primary HCC. After exclusion of 75 patients who underwent combined therapy, data for 252 patients were examined. We retrospectively analyzed the long-term outcomes of RFA and identified factors of poor prognosis. The median platelet count, prothrombin activity and indocyanine green retention rate at 15 min were 9.1×104/μl, 83% and 26%, respectively. The 5-year overall survival (OS) rate was 69% and the median survival time was 7.0 years. The 5-year recurrence-free survival (RFS) rate was 17%, and the median RFS was 2.0 years. A multivariate analysis revealed that age >80 years [hazard ratio (HR)=7.76, p=0.011], tumor diameter >2 cm (HR=1.68, p=0.047) and multiple tumors (HR=1.87, p=0.014) were independent prognostic factors for poor OS. For RFS, des-γ-carboxy prothrombin (DCP) ≥40 mAU/ml (HR=1.47, p=0.038) and multiple tumors (HR=1.63, p=0.0056) were independent prognostic factors. Local recurrence at the ablated site occurred in 33/252 patients (13%), and in 33/372 tumors (8.9%). Although our cohort included patients with relatively worse liver function, a favorable 5-year survival rate 69% was obtained by RFA. DCP ≥40 mAU/ml and multiple HCCs contribute to a higher risk of recurrence. Patients with these factors should therefore be followed-up intensively.


Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.
Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.


Elucidating the mechanism of a two-step spin transition in a nanoporous metal-organic framework.
The nanoporous metal-organic framework, Fe(bpe)2(NCS)2 x 3(acetone), SCOF-4(Ac) (where bpe is 1,2-bis(4'-pyridyl)ethane), displays a two-step spin crossover (SCO) transition (65-155 K) that is sensitive to the presence of acetone guest molecules. Structural analyses have revealed a structural phase transition, from tetragonal (P42(1)c) to orthorhombic (P2(1)2(1)2), associated with the spin transition that defines a checkerboard-like ordering of spin sites at the high-spin:low-spin plateau. The reversible desorption of the acetone guest species is accompanied by a complex series of structural phase transitions that describe a dramatic flexing of the structure. The thermal trapping of a metastable state with approximately 20-25% high-spin character was observed both magnetically and structurally upon rapid quenching of SCOF-4(Ac) to 10 and 25 K, respectively. The light-induced excited spin state trapping (LIESST) effects for SCOF-4(Ac) show a 55% excitation of a metastable HS state at 10 K and a characteristic T(LIESST) value of 52 K.


Combination therapies in oculofacial rejuvenation.
The oculo-facial surgeon's quest for non-invasive procedures is a response to increasing patient demands for enhanced results without any downtime. Technology has obliged us with multiple injectable and light therapeutic modalities that tighten skin, relax and fill in wrinkles, and improve skin dyspigmentation and texture. When these techniques are combined, the results are superior to the use of individual therapies alone. The foundation for combination therapies are: botulinum toxin, filling agents, chemical peels, intense pulsed light, non-ablative and ablative lasers.


The effects of excision of left ventricular scars on the electrocardiogram.
The effects of resection of post-ischemic ventricular scars on the electrocardiogram have been studied in 29 patients. No change occurred in atrial rhythm, P wave morphology, and A-V conduction. Fascicular blocks developed postoperatively in five patients. These were attributed to surgical trauma. Changes in mean frontal plane QRS axis were noted in 25 of 29 patients. There was no correlation between postoperative shifts in QRS axis and preoperative QRS axis, calculated scar size, or ventricular end-diastolic volume. No significant postoperative change was observed in Q waves or S-T segment deviation. It is concluded that electrocardiographic changes following scar resection occur randomly in a minority of patients. The presence of several unquantified factors makes it difficult to evaluate the post-resection electrocardiogram.


The frequency of antisperm antibodies in the cervical mucus of women with poor postcoital tests and their effect on pregnancy rates.
To determine the impact of the presence of antisperm antibodies (ASAs) in the cervical mucus of female partners in couples with unexplained poor postcoital tests (PCT). Furthermore, the efficacy of intrauterine insemination (IUI) in these same patients was determined by pregnancy rates (PRs). Pregnancy rates following IUI in patients with infertility and poor postcoital tests, whether the cervical mucus was positive or negative for ASAs, were evaluated. The 6-month PRs were similar in the ASA negative (40.5%) versus the positive (42.4%) group. It appears that the antifertility effect of ASA may be mainly the immobilization of sperm in the cervical mucus, and thus, performing IUI may effectively correct the problem.


[End inspiratory lung volumes as the limiting factor in PEEP ventilation].
In 17 patients requiring artificial ventilation expiratory pressure-volume curves (VPE) were plotted all over the inspiratory capacity (IC) between total lung capacity (TLC) and functional residual capacity (FRC). Then patients were ventilated with PEEP of 0, 5, 10 and 15 cmH2O for 30 min. The volume excursions with known PEEP were displayed graphically into the VPE to determine the position of end-inspiratory volume within the IC. The steep, quasi-linear part of each VPE was flattening exponentially against TLC in the upper part of the curve. This "overdistension range" was found to be identical with the upper 40% of IC. Heavy side-effects of PEEP ventilation were never seen before the inspiratory volume excursion had reached this upper 40% of IC. If this was the case, the following observations were made: 1. Static compliance (Cst) decreased by more than 10% in all cases. 2. Pulmonary vascular resistance (PVR) increased by more than 20% in 12 cases. 3. Cardiac index (CI) decreased by more than 15% in 12 cases. 4. The alterations observed in Cst, PVR and CI increased rapidly, when the lungs were further distended, and were well correlated parabolically to the position of end-inspiratory volume within IC. --5 patients failed to show important circulatory alterations. It is concluded that overdistension-related side-effects of PEEP on respiratory mechanics and circulation do not occur before the linear part of the pressure-volume curve has been exceeded by hyperinflation. For the first adjustment of controlled ventilation at least the upper third of IC should be avoided.


Prevention by polyhydroxysteroids and saponins of Asterina pectinifera of the desquamation of stratum corneum cells.
Two polyhydroxysteroids and three steroidal saponins (pectiniosides A, B and C) were isolated as bioactive substances from Asterina pectinifera. These compounds inhibited the release of guinea-pig skin stratum corneum cells by 48-67% (control, 0%) at 2 mg/ml. It is suggested that the bioactivity of these compounds is connected with the remedial and preventive effects of an aqueous extract of A. pectinifera on rough human skin.


Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria.
The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment.


Anti-HLA Antibody Levels Are Associated With the Risk of Graft Failure After Allogeneic Hematopoietic Stem Cell Transplant.
Allogeneic hematopoietic stem cell transplant provides a curative treatment for a considerable amount of hematologic diseases, and it is widely used today. Successful allogeneic stem cell transplant can be compromised by treatment-related toxicity, graft-versus-host disease, infectious complications, disease relapse, and graft failure. Primary graft failure is an important cause of hematopoietic stem cell transplant failure. Primary graft failure correlates with the level of complement-binding, donor-specific anti-HLA antibodies prior to transplant. We evaluated 15 patients who underwent hematopoietic stem cell transplant using peripheral blood stem cells in terms of graft failure and anti-HLA antibody levels before transplant. All were treated between January 2015 and June 2016. Pretreatment serum anti-HLA class I and anti-HLA class II antibody levels were measured in all patients. Anti-HLA class I antibodies were present in 7 patients (46.6%) and anti-HLA class II antibodies in 8 (53.3%). All three patients who developed primary graft failure were anti-HLA-positive. Anti-HLA antibodies are a significant cause of graft failure. It is a situation that must be understood with caution. Our results support the considerations that allogeneic hematopoietic stem cell transplant, especially when a fully compatible sibling donor is not present, should include screening of donor-specific antibodies of alternative donors and desensitization therapy for allosensitized patients before transplant.


Key features of the two-intron Saccharomyces cerevisiae gene SUS1 contribute to its alternative splicing.
Alternative pre-mRNA splicing allows dramatic expansion of the eukaryotic proteome and facilitates cellular response to changes in environmental conditions. The Saccharomyces cerevisiae gene SUS1, which encodes a protein involved in mRNA export and histone H2B deubiquitination, contains two introns; non-canonical sequences in the first intron contribute to its retention, a common form of alternative splicing in plants and fungi. Here we show that the pattern of SUS1 splicing changes in response to environmental change such as temperature elevation, and the retained intron product is subject to nonsense-mediated decay. The activities of different splicing factors determine the pattern of SUS1 splicing, including intron retention and exon skipping. Unexpectedly, removal of the 3' intron is affected by splicing of the upstream intron, suggesting that cross-exon interactions influence intron removal. Production of different SUS1 isoforms is important for cellular function, as we find that the temperature sensitivity and histone H2B deubiquitination defects observed in sus1Δ cells are only partially suppressed by SUS1 cDNA, but SUS1 that is able to undergo splicing complements these phenotypes. These data illustrate a role for S. cerevisiae alternative splicing in histone modification and cellular function and reveal important mechanisms for splicing of yeast genes containing multiple introns.


Classification of depressive disorders: a multiaxial approach.
Classification of depressive disorders can be performed following the Linnaean binomial nomenclature model by defining depression as a genus and the subtypes as species. A medical classification of depressive disorders would need to be jointly inclusive and mutually exclusive between subtypes, and to provide time of onset, severity of illness, pathological process, prognosis, and treatment indications. Etiologic, phenomenologic (clinical, descriptive), statistical, and biological approaches have been used to classify depression. A convergence of these various systems in different combinations has evolved, and a consensus approach using the multiaxial system, such as DSM-III, has advanced psychiatric nomenclature to provide clinical relevance and heuristic possibilities.


A retrospective evaluation of lomustine (CeeNU) in 32 treatment naïve cats with intermediate to large cell gastrointestinal lymphoma (2006-2013).
Multi-drug chemotherapy protocols for feline lymphoma have demonstrated variable efficacy and tolerability. In phase I trials, lomustine has demonstrated efficacy for cats with lymphoma though its use for treatment naïve feline intermediate/large cell gastrointestinal (GI) lymphoma remains unknown. This study evaluated the efficacy and tolerability of lomustine for the treatment of feline GI lymphoma. Thirty-two cats with histologically or cytologically confirmed intermediate/large cell GI lymphoma were evaluated retrospectively. Factors assessed included clinical signs, hematologic/biochemical parameters and use of l-asparaginase at induction. A response rate of 50% (16/32), with median duration of response of 302 days (range 64-1450 days), was found. Median progression-free interval was 132 days (range 31-1450 days), with overall median survival time of 108 days (range 4-1488 days). History of hyporexia, presence of anaemia and dose of lomustine were significantly associated with progression-free survival. Overall, lomustine is a well-tolerated and effective treatment for feline GI lymphoma.


Laparoscopic diaphragmatic hernia repair using expanded polytetrafluoroethylene (ePTFE) for delayed traumatic diaphragmatic hernia.
Traumatic diaphragmatic hernia (TDH) is an uncommon surgical problem, and diagnosis is often delayed. However, the mortality from bowel necrosis can reach 80%. Therefore, suspicion is needed and surgery is required to prevent complications. A 50-year-old man was transferred due to abdominal pain and vomiting. Chest X-ray and computed tomography (CT) scan showed herniation of the stomach through the left diaphragm. The patient had fallen down 15 months ago and CT scan at that time revealed a small defect of the diaphragm without herniation. We diagnosed delayed herniation of TDH and the patient underwent laparoscopic repair using an expanded polytetrafluoroethylene (ePTFE) mesh. Recovery was uneventful and the CT scan at 3 months after the operation showed no recurrence. We reported a delayed presenting TDH and considered a laparoscopic approach to be safe and feasible during elective surgery. Moreover, use of an ePTFE mesh for repair of large diaphragmatic hernia was also feasible.


A comparison of 4 methods of data presentation for lysosomal enzyme activity in gingival crevicular fluid.
In previous studies, we have emphasized the importance of considering the methods used for analysis of gingival crevicular fluid (GCF). This study evaluated 4 different approaches for data presentation of lysosomal enzyme activity in GCF. GCF was collected from patients displaying at least 2 mm of clinical attachment loss at a minimum of 3 sites in the mouth (DA), and patients who did not display clinical attachment loss of 2 mm or more at any site in the mouth (DI), during a 3-month interval following entry into a longitudinal trial. GCF was collected by the timed intrasulcular placement of precut filter paper strips. 16 to 28 individual GCF samples were collected from each patient. The lysosomal enzymes studied were B-glucuronidase (BG) and arylsulfatase. The mean values for the DA and DI groups at baseline and 3 months are reported. The results indicate that when the data is expressed as total enzyme activity (unit activity) per 30-s collection (UA) or UA x GCF volume (microliter) per mm of probing depth, the DA group demonstrated significantly greater mean values than the DI group at baseline and 3 months. In contrast, when the data was expressed as concentration (UA/microliter), or UA per mm of probing depth, differences between the DA and DI groups were observed only at the 3-month evaluation. The difficulty in using concentration when reporting GCF lysosomal enzyme activity is emphsized by comparison of the data from the DA group and the high and low enzyme activity subsets of the DI group.(ABSTRACT TRUNCATED AT 250 WORDS)


Diosgenin inhibits angiotensin II-induced extracellular matrix remodeling in cardiac fibroblasts through regulating the TGF‑β1/Smad3 signaling pathway.
The proliferation of cardiac fibroblasts (CFs) and deposition of extracellular matrix (ECM) proteins are pivotal in the development of cardiac fibrosis. Recent studies have indicated that diosgenin may inhibit high glucose‑induced renal tubular fibrosis; however, to the best of our knowledge, no studies have focused on the effects of diosgenin on cardiac fibrosis. Therefore, the present study aimed to explore the effects of diosgenin on angiotensin II (Ang II)‑induced ECM remodeling, and its possible mechanism in rat CFs. CFs were pre‑incubated with diosgenin (1, 5 and 10 µM) for 24 h and were then stimulated with Ang II (100 nM) for 24 h. Cell proliferation was estimated using the MTS assay. The expression levels of α‑SMA, fibronectin, collagen I, TGF‑β1, in addition to phosphorylation of Smad3 were detected by western blotting. The results demonstrated that diosgenin inhibited Ang II‑induced CF proliferation and the differentiation of CFs to myofibroblasts. In addition, diosgenin was able to inhibit Ang II‑induced ECM expression in rat CFs. Furthermore, diosgenin inhibited Ang II‑induced expression of transforming growth factor‑β1 (TGF‑β1) and Smad3 phosphorylation in CFs. Taken together, these results suggest that diosgenin may inhibit Ang II‑induced ECM remodeling by suppressing the TGF‑β1/Smad3 signaling pathway in rat CFs. Therefore, diosgenin may possess therapeutic potential for the treatment of cardiac fibrosis.


Basil polysaccharide inhibits hypoxia-induced hepatocellular carcinoma metastasis and progression through suppression of HIF-1α-mediated epithelial-mesenchymal transition.
Invasion and metastasis of cancerous cells affects the treatment and prognosis of hepatocellular carcinoma (HCC). HIF-1α-induced epithelial-mesenchymal transition (EMT) is a critical process associated with cancer metastasis. Basil polysaccharide (BPS), one of the major active ingredients isolated from Basil (Ocimum basilicum L.), has been identified to possess an antitumor activity for HCC. In our current study, BPS was obtained by water extraction and ethanol precipitation method and the characterization was analyzed through ultraviolet absorption spectra and Fourier-transform infrared spectrum. A CoCl2-induced hypoxia model and a HCC cell line-derived xenograft (CDX) model were used to explore the anti-metastasis efficacy and the mechanism that underlies the antitumor activity of BPS. The results showed that hypoxia could facilitate EMT and promote HCC cells migration and/or invasion. Conversely, BPS inhibited the progression and metastasis of tumor, as well as reversed EMT by causing cytoskeletal remodeling under hypoxic conditions. Moreover, BPS alleviated tumor hypoxia by targeting HIF1α, and the mesenchymal markers (β-catenin, N-cadherin and vimentin) were down-regulated, while the epithelial markers (E-cadherin, VMP1 and ZO-1) were up-regulated after BPS treatment under hypoxic conditions. Thus, these results suggested that BPS may be a valuable option for use in clinical treatment of HCC and other malignant tumors.


[Comparative analysis of Daoyintu (Physical and Breathing Exercise Graph) and Yinshu (Guidance Way)].
Daoyintu (Physical and Breathing Exercise Graph) and Yinshu (Guidance Way) were guiding technique which simultaneously prevailed in the early time of Western Han dynasty. One is a graph, the other is a text, which were combined harmoniously. Mutual corroboration and comparative analysis on their differences from four aspects: content characteristics, related diseases, guiding techniques in the style of animal movements and applied sports apparatus, in general revealed the overview of the guiding techniques and gymnastics of 2000 years ago, which can provide reference for the further study and practical application of health cultivation methods in the future.


Automatic attraction of visual attention by supraletter features of former target strings.
Observers were trained to search for a particular horizontal string of three capital letters presented among similar strings consisting of exactly the same letters in different orders. The training was followed by a test in which the observers searched for a new target that was identical to one of the former distractors. The new distractor set consisted of the remaining former distractors plus the former target. On each trial, three letter strings were displayed, which included the target string with a probability of 0.5. In Experiment 1, the strings were centered at different locations on the circumference of an imaginary circle around the fixation point. The training phase of Experiment 2 was similar, but in the test phase of the experiment, the strings were located in a vertical array centered on fixation, and in target-present arrays, the target always appeared at fixation. In both experiments, performance (d') degraded on trials in which former targets were present, suggesting that the former targets automatically drew processing resources away from the current targets. Apparently, the two experiments showed automatic attraction of visual attention by supraletter features of former target strings.


Multifrequency Oscillatory Ventilation in the Premature Lung: Effects on Gas Exchange, Mechanics, and Ventilation Distribution.
Despite the theoretical benefits of high-frequency oscillatory ventilation (HFOV) in preterm infants, systematic reviews of randomized clinical trials do not confirm improved outcomes. The authors hypothesized that oscillating a premature lung with multiple frequencies simultaneously would improve gas exchange compared with traditional single-frequency oscillatory ventilation (SFOV). The goal of this study was to develop a novel method for HFOV, termed "multifrequency oscillatory ventilation" (MFOV), which relies on a broadband flow waveform more suitable for the heterogeneous mechanics of the immature lung. Thirteen intubated preterm lambs were randomly assigned to either SFOV or MFOV for 1 h, followed by crossover to the alternative regimen for 1 h. The SFOV waveform consisted of a pure sinusoidal flow at 5 Hz, whereas the customized MFOV waveform consisted of a 5-Hz fundamental with additional energy at 10 and 15 Hz. Per standardized protocol, mean pressure at airway opening ((Equation is included in full-text article.)) and inspired oxygen fraction were adjusted as needed, and root mean square of the delivered oscillatory volume waveform (Vrms) was adjusted at 15-min intervals. A ventilatory cost function for SFOV and MFOV was defined as (Equation is included in full-text article.), where Wt denotes body weight. Averaged over all time points, MFOV resulted in significantly lower VC (246.9 ± 6.0 vs. 363.5 ± 15.9 ml mmHg kg) and (Equation is included in full-text article.)(12.8 ± 0.3 vs. 14.1 ± 0.5 cm H2O) compared with SFOV, suggesting more efficient gas exchange and enhanced lung recruitment at lower mean airway pressures. Oscillation with simultaneous multiple frequencies may be a more efficient ventilator modality in premature lungs compared with traditional single-frequency HFOV.


Association of TNF-α (-238 and -308) promoter polymorphisms with susceptibility of oral squamous cell carcinoma in North Indian population.
The pro-inflammatory cytokines play an essential role in immune response and are involved in a variety of inflammatory and infectious disease. Tumor necrosis factor alpha (TNF-α) gene polymorphism has been a potential determinant of susceptibility to various types of cancer. To evaluate the association of TNF-α gene promoter (-238) G/A and (-308) G/A polymorphisms with the susceptibility of OSCC patients in North Indian population. A total 272 patients with OSCC and 185 healthy volunteers were genotypes for the TNF-α (-238) G/A and (-308) G/A gene polymorphism. Genotypes were identified by polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP). Genotype frequencies were evaluated by Chi-square test and Odds ratio (OR) relative risk. TNF-α (-238) G/A polymorphism was significantly associated with OSCC patients as compared to healthy volunteers (GG vs. GA: OR=0.3500, 95% CI=0.1289-09502; p=0.036; G vs. A: OR=0.3589 1.477, 95% CI=0.1335-0.9652; p=0.0386). No significant association was found in TNF-α (-308) G/A gene polymorphism with OSCC patients and controls. We conclude that the TNF-α (-238) G/A polymorphism was significantly associated with OSCC however TNF-α (-308) G/A polymorphism was not associated in OSCC patients.