Causality in epidemiological research.
The article presents short historical review of the concepts of causality. Then it deals with contemporary concepts of causal dependence with special reference to epidemiological studies. In particular Lewis counterfactuals theory and contemporary probabilistic theories were analyzed including applications of DAG's (directed acyclic graphs), which in the last decade are frequently applied for presentation of complicated study designs in epidemiology. Authors high appreciation explanatory role of graphic presentation of relationships between variables and the role of conditional probability of events respecting Markov conditions and Bayesian premises, does not change his opinion, that statistical methods are insufficient for final assessment of causal dependence and some subjective element of learned judgment of the scientist has to be always present. In Authors opinion causal approach to associations between are crucial as a base for therapeutic approach and for public health interventions. This is why he is against consequent indeterministic approach.


Radiotoxicity of Auger electron-emitting estrogens in MCF-7 spheroids: a potential treatment for estrogen receptor-positive tumors.
To approach treatment of micrometastases of steroid receptor-rich cancers using estrogen receptor-directed therapy with Auger electrons, multicellular spheroids of the estrogen receptor-rich human breast cancer cell line, MCF-7, were prepared and exposed to a range of concentrations of an Auger electron-emitting estrogen, E-17alpha-[123I]-iodovinyl-11beta-methoxyestradiol, [123I]IVME2, in vitro. After washing, the treated spheroids were dissociated to single cells and plated for assay of colony survival, whereby we observed a dose-dependent reduction in survival that was inhibited by inclusion of an excess of unlabeled estradiol in the initial incubation with [123I]IVME2. Spheroids of a range of sizes from 40 to 280 microm showed similar sensitivity to the Auger electron-emitting estrogen. The mean lethal dose was approximately 700 decays per cell and corresponded to an initial [123I]IVME2 concentration of less than 0.5 nM. If the control and treated spheroids were not trypsinized but rather were allowed to grow intact, there was not only a significant reduction in the growth of the treated spheroids, but in 18 days nearly half became necrotic, while few control spheroids were necrotic. Considering the low concentrations of Auger electron-emitting estrogen required for a significant reduction in survival, we believe this approach has merit to pursue in vivo, especially in cases where it may be possible to target the steroid receptor-rich micrometastases directly, such as ovarian cancer.


Improvement of magnetic resonance imaging using a wireless radiofrequency resonator array.
In recent years, new human magnetic resonance imaging systems operating at static magnetic fields strengths of 7 Tesla or higher have become available, providing better signal sensitivity compared with lower field strengths. However, imaging human-sized objects at such high field strength and associated precession frequencies is limited due to the technical challenges associated with the wavelength effect, which substantially disturb the transmit field uniformity over the human body when conventional coils are used. Here we report a novel passive inductively-coupled radiofrequency resonator array design with a simple structure that works in conjunction with conventional coils and requires only to be tuned to the scanner's operating frequency. We show that inductive-coupling between the resonator array and the coil improves the transmit efficiency and signal sensitivity in the targeted region. The simple structure, flexibility, and cost-efficiency make the proposed array design an attractive approach for altering the transmit field distribution specially at high field systems, where the wavelength is comparable with the tissue size.


Validating the analytical methodologies for determining some important trace elements in food consumed in India.
This paper reports on the development, standardization, and application of instrumental as well as radiochemical neutron activation analysis (INAA and RNAA) techniques for determining the concentrations of iron, zinc, cobalt, cesium, strontium, selenium, thorium, and calcium in food consumed in India. Based on the analysis of 20 diet samples, prepared as per the data on dietary intake patterns of an adult in four provinces of India and that of an average adult Indian, the geometric mean (GM) intake of various elements for the reference Indian man was estimated to be 15.9 (10.7-34.4) mg for iron, 8.6 (5.1-15.6) mg for zinc, 17.0 (8.3-31.4) micrograms for cobalt, 4.76 (2.8-11.8) micrograms for cesium, 1.46 (0.79-2.96) mg for strontium, 52.4 (35.0-130.8) micrograms for selenium, 0.75 (0.44-1.75) micrograms for thorium, and 0.35 (0.17-0.67) mg for calcium. A comparison of the daily dietary intakes of these trace elements by the reference Indian man was made with that of the International Commission on Radiological Protection (ICRP) reference man and also with the world average compiled by the International Atomic Energy Agency (IAEA). When compared with the ICRP reference man data, the daily dietary intakes of all the eight elements by the reference Indian man were considerably lower by factors ranging from 1.4 for strontium to as much as 18.0 for cobalt. However, when compared with the world average, daily dietary intakes by the reference Indian man were comparable for iron and lower by factors 1.2 to 1.9 for zinc, selenium, and calcium.


Evaluation of four phloem-specific promoters in vegetative tissues of transgenic citrus plants.
'Mexican' lime (Citrus aurantifolia Swingle) was transformed with constructs that contained chimeric promoter-gus gene fusions of phloem-specific rolC promoter of Agrobacterium rhizogenes, Arabidopsis thaliana sucrose-H(+) symporter (AtSUC2) gene promoter of Arabidopsis thaliana, rice tungro bacilliform virus (RTBV) promoter and sucrose synthase l (RSs1) gene promoter of Oryza sativa (rice). Histochemical β-glucuronidase (GUS) analysis revealed vascular-specific expression of the GUS protein in citrus. The RTBV promoter was the most efficient promoter in this study while the RSs1 promoter could drive low levels of gus gene expression in citrus. These results were further validated by reverse transcription real-time polymerase chain reaction and northern blotting. Southern blot analysis confirmed stable transgene integration, which ranged from a single insertion to four copies per genome. The use of phloem-specific promoters in citrus will allow targeted transgene expression of antibacterial constructs designed to battle huanglongbing disease (HLB or citrus greening disease), associated with a phloem-limited Gram-negative bacterium.


Involvement of NpdA, a Putative 2-Nitropropane Dioxygenase, in the T3SS Expression and Full Virulence in Ralstonia solanacearum OE1-1.
Previously, we isolated several genes that potentially affected the expression of type III secretion system (T3SS) in Ralstonia solanacearum OE1-1. Here, we focused on the rsp0316, which encodes a putative 2-nitropropane dioxygenase (hereafter designated NpdA). The deletion of npdA substantially reduced the T3SS expression and virulence in OE1-1, and the complementation with functional NpdA could completely restore its reduced T3SS expression and virulence to that of wild type. The NpdA was highly conserved among diverse R. solanacearum species and the NpdA-dependent expression of T3SS was not specific to OE1-1 strain, but not the virulence. The NpdA was important for the T3SS expression in planta, while it was not required for the bacterial growth in planta. Moreover, the NpdA was not required for the elicitation of hypersensitive response (HR) of R. solanacearum strains in tobacco leaves. The T3SS in R. solanacearum is directly controlled by the AraC-type transcriptional regulator HrpB and regulated by a complex regulation network. The NpdA affected the T3SS expression mediated with HrpB but through some novel pathway. All these results from genetic studies demonstrate that NpdA is a novel factor for the T3SS expression in diverse R. solanacearum species in medium, but specifically for the T3SS expression in strain OE1-1 in planta. And the NpdA-dependent expression of T3SS in planta plays an important role in pathogenicity of R. solanacearum OE1-1 in host plants.


Iron oxide nanoparticles modulate the interaction of different antibiotics with cellular membranes.
The interaction of nanomaterials with cells and lipid bilayers is critical in many applications such as phototherapy, imaging and drug/gene delivery. These applications require a firm control over nanoparticle-cell interactions, which are mainly dictated by surface properties of the nanoparticles. The aim of this study was to investigate the interaction of Fe3O4 nanoparticles functionalized with several wide use antibiotics with opossum kidney (OK) cellular membranes in order to reveal changes in the membrane organization at different temperatures. We also investigated the in vivo biodistribution of the tested nanoparticles in a mouse model. Our results showed that, at low temperatures (31-35°C), plain Fe3O4 nanoparticles induced a drop of the membrane fluidity, while at physiological or higher temperatures (37-39°C) the membrane fluidity was increased. On the other hand, when nanoparticles functionalized with the tested antibiotics were used, we observed that the effect was opposite as compared to control Fe3O4 nanoparticles. Although most of antibiotics, used as plain solutions or linked on magnetite nanoparticles, proved heterogeneous effect on in vitro OK cells membrane fluidity, the aminoglycosides streptomycin and neomycin, used both as plain solutions and also combined with nanoparticles kept the same effect in all experimental conditions, increasing the membrane fluidity of OK cells plasma membrane. In vivo results showed that the antibiotic functionalized nanoparticles have a similar biodistribution pattern within the mouse body, being transported through the blood flow and entering the macrophages through endocytosis. Functionalized magnetite nanoparticles manifested a preferential biodistribution pattern, clustering within the lungs and spleen of treated mice. These results demonstrate that antibiotics manifest a different effect on plasma membrane fluidity depending on their type and temperature. Magnetite nanoparticles may interfere with antibiotic-cellular interactions by changing the plasma membrane fluidity. The fact that the antibiotic functionalized magnetite nanoparticles have a similar biodistribution pattern, are transported through the blood flow, and they increase the cellular uptake of the drug, suggest that they may be used for further studies aiming to develop personalized targeted delivery and controlled release nanoshuttles for treating localized and systemic infections.


High frequency jet ventilation through the laryngeal mask airway in a critically obstructed airway.
A 72 year-old man with an anticipated difficult airway secondary to a large, obstructing supraglottic tumour was scheduled for a panendoscopy. An elective pre-induction transtracheal catheter was placed to allow oxygenation if airway maintenance proved difficult. Following induction of anaesthesia, tracheal intubation was impossible and ventilation via both a facepiece and a laryngeal mask airway became progressively more difficult. An emergency tracheostomy was attempted whilst oxygenation was maintained with transtracheal jet ventilation, but the position of the transtracheal catheter made tracheostomy impossible. The catheter was removed and high frequency jet ventilation was then used via the laryngeal mask airway to maintain oxygenation. To our knowledge, the use of high frequency jet ventilation through the laryngeal mask airway in a critically obstructed airway has not been described before.


[Prognosis in 75 cases of chronic lymphocytic leukemia and second malignancies].
Clinical prognosis and analysis of causes of death of 75 CLL cases were evaluated. Median survival was 43.7 months. Major causes of death were infection (36%), primary CLL (16%), secondary malignancies (16%), cardiac failure (8%), brain hemorrhage (7%) and so on. There were 10 deaths (13%) with second or double cancers and 2 deaths with malignant lymphomas. In terms of deaths from CLL complicated by cancer, there were 4 deaths from stomach cancer, 3 from lung cancer, 1 from liver, pancreas, or prostata cancer. Cancer risk, which did not vary according to initial treatment category, was also constant across all time intervals after CLL diagnosis.


Diacylglycerol Kinase A Is Essential for Polymyxin Resistance Provided by EptA, MCR-1, and Other Lipid A Phosphoethanolamine Transferases.
Gram-negative bacteria utilize glycerophospholipids (GPLs) as phospho-form donors to modify various surface structures. These modifications play important roles in bacterial fitness in diverse environments influencing cell motility, recognition by the host during infection, and antimicrobial resistance. A well-known example is the modification of the lipid A component of lipopolysaccharide by the phosphoethanolamine (pEtN) transferase EptA that utilizes phosphatidyethanoalmine (PE) as the phospho-form donor. Addition of pEtN to lipid A promotes resistance to cationic antimicrobial peptides (CAMPs), including the polymyxin antibiotics like colistin. A consequence of pEtN modification is the production of diacylglycerol (DAG) that must be recycled back into GPL synthesis via the diacylglycerol kinase A (DgkA). DgkA phosphorylates DAG forming phosphatidic acid, the precursor for GPL synthesis. Here we report that deletion of dgkA in polymyxin-resistant E. coli results in a severe reduction of pEtN modification and loss of antibiotic resistance. We demonstrate that inhibition of EptA is regulated posttranscriptionally and is not due to EptA degradation during DAG accumulation. We also show that the inhibition of lipid A modification by DAG is a conserved feature of different Gram-negative pEtN transferases. Altogether, our data suggests that inhibition of EptA activity during DAG accumulation likely prevents disruption of GPL synthesis helping to maintain cell envelope homeostasis. IMPORTANCE For Gram-negative bacteria, modification of a key surface structure known as lipopolysaccharide (LPS) is critical for resistance to cationic antimicrobial peptides, including the last-resort antibiotic polymyxin. One key enzyme that is critical for resistance is EptA that adds a positively charged residue to LPS, preventing polymyxin binding. Here we show that EptA can be posttranscriptionally regulated by a key cell envelope lipid leading to changes in antibiotic resistance.


Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance.
ABCG2 is an efflux transporter conferring multidrug resistance (MDR) on cancer cells. However, the initial molecular events leading to its up-regulation in MDR tumor cells are poorly understood. Herein, we explored the impact of drug treatment on the methylation status of the ABCG2 promoter and consequent reactivation of ABCG2 gene expression in parental tumor cell lines and their MDR sublines. We demonstrate that ABCG2 promoter methylation is common in T-cell acute lymphoblastic leukemia (T-ALL) lines, also present in primary T-ALL lymphoblast specimens. Furthermore, drug selection with sulfasalazine and topotecan induced a complete demethylation of the ABCG2 promoter in the T-ALL and ovarian carcinoma model cell lines CCRF-CEM and IGROV1, respectively. This resulted in a dramatic induction of ABCG2 messenger RNA levels (235- and 743-fold, respectively) and consequent acquisition of an ABCG2-dependent MDR phenotype. Quantitative genomic polymerase chain reaction and ABCG2 promoter-luciferase reporter assay did not reveal ABCG2 gene amplification or differential transcriptional trans-activation, which could account for ABCG2 up-regulation in these MDR cells. Remarkably, mimicking cytotoxic bolus drug treatment through 12- to 24-hour pulse exposure of ABCG2-silenced leukemia cells, to clinically relevant concentrations of the chemotherapeutic agents daunorubicin and mitoxantrone, resulted in a marked transcriptional up-regulation of ABCG2. Our findings establish that antitumor drug-induced epigenetic reactivation of ABCG2 gene expression in cancer cells is an early molecular event leading to MDR. These findings have important implications for the emergence, clonal selection, and expansion of malignant cells with the MDR phenotype during chemotherapy.


Bicycle injuries in children: an analysis based on demographic density.
The purpose of this study was to investigate the characteristics and the outcome of bicycle injuries in paediatric patients according to the living environment, and to create guidelines for injury prevention. The evaluation was performed in part based on hospital database of 1803 in- and out-patient children treated at the Paediatric Surgical Department of Pécs/Hungary between 2000 and 2006, and at the Department of Paediatric Surgery at the Heim Pal Hospital Budapest between 2004 and 2006. Additionally questionnaires were mailed to the patients' families to gain follow-up information. We analysed three groups according to demographic density (village, midsize town and large town). We found, that poor road quality played an important role as a contributing factor of injuries in villages. The number of bicycle spoke-injuries was higher in villages (13%), than in midsize towns (4.6%) and the large town (9.9%). In villages, 5% of children injured wore a helmet; this rate was 9% in midsize towns and 9.1% in the large town. Head injury was more common in villages, while in midsize towns and the large town arm injuries proved to be predominant. Prevention strategies targeting bicycle injuries in children should take into account the population density. This analysis revealed a substantial difference in the use of safety devices, and in the characteristics of injuries occurring in villages, indicating that there is a need for special attention regarding this higher risk population.


A new experimental model: the vascular pedicled cutaneous flap over the mid-dorsum of the rat.
The cutaneous vascular anatomy of the mid-dorsum in the rat and its role in flap design was studied in the rat. The investigation consisted of anatomic dissection, methylene blue injection into the axial artery, and flap harvesting in live animals. Dissection and injection revealed that the mid-dorsum of the rat derives its blood supply largely from the 10th intercostal artery, here referred to as the middle dorsal artery, which originates from the lateral aspect of the thoracic aorta. The cutaneous vascular territory of the middle dorsal artery was defined as follows: the medial border, midline of the dorsum; the lateral border, midaxillary line; the cephalic border, a line joining the medial and lateral borders midway between the level of the axilla proximally and 1 cm above the base of the rib cage distally; and the caudal border, a line drawn midway between the latter point proximally and the anterior superior iliac spine distally. Both unilateral and bilateral vascular pedicled island cutaneous flaps were harvested in living rats based on and exceeding the vascular territory delimited by methylene blue injection. Flaps limited to this territory with intact middle dorsal arteries showed total survival, while oversized flaps underwent partial necrosis peripherally. Because of its simplicity, reliability, and consistent vascularity, this flap has potential applications in the study of flap hemodynamics.


Effects of annual mass treatment with ivermectin for onchocerciasis on the prevalence of intestinal helminths.
We evaluated the effect of annual ivermectin (IV) distribution for onchocerciasis on the prevalence of soil transmitted helminth (STH) infections in school-aged (SAC) and preschool-aged (PAC) children by comparing children in villages that had received treatment for 13 years to those from socioeconomically similar villages in untreated areas. We enrolled 1,031 SAC and 211 PAC for Kato Katz examinations. Treated areas had a lower prevalence of Ascaris (SAC: 3% versus 12%, P < 0.0001; PAC: 3% versus 10%, P < 0.051) and Trichuris (SAC: 6% versus 10%, P = 0.012; PAC: 1% versus 8%, P = 0.019), but not hookworm (SAC: 38% versus 42%, P = 0.20; PAC: 21% versus 27%, P = 0.30). The prevalence of Ascaris or Trichuris in treated areas was below the WHO threshold for mass antihelminthic treatment (MDA), but not for hookworm. We conclude that benzimidazole MDA in IV treatment areas is indicated to effectively control hookworm.


Optimum Mixed-State Discrimination for Noisy Entanglement-Enhanced Sensing.
Quantum metrology utilizes nonclassical resources, such as entanglement or squeezed light, to realize sensors whose performance exceeds that afforded by classical-state systems. Environmental loss and noise, however, easily destroy nonclassical resources and, thus, nullify the performance advantages of most quantum-enhanced sensors. Quantum illumination (QI) is different. It is a robust entanglement-enhanced sensing scheme whose 6 dB performance advantage over a coherent-state sensor of the same average transmitted photon number survives the initial entanglement's eradication by loss and noise. Unfortunately, an implementation of the optimum quantum receiver that would reap QI's full performance advantage has remained elusive, owing to its having to deal with a huge number of very noisy optical modes. We show how sum-frequency generation (SFG) can be fruitfully applied to optimum multimode Gaussian-mixed-state discrimination. Applied to QI, our analysis and numerical evaluations demonstrate that our SFG receiver saturates QI's quantum Chernoff bound. Moreover, augmenting our SFG receiver with a feedforward (FF) mechanism pushes its performance to the Helstrom bound in the limit of low signal brightness. The FF-SFG receiver, thus, opens the door to optimum quantum-enhanced imaging, radar detection, state and channel tomography, and communication in practical Gaussian-state situations.


Behavior and Health Indicators to Assess Cull Cow's Welfare in Livestock Markets.
The welfare status of cull cows going through livestock markets was assessed in 12 premises in Chile, using behavioral and health indicators observed during unloading, auction, and loading (once in winter and once in summer). Groups of cows were observed by the same observer and the following indicators were recorded at each stage: slips, falls, balks, turns, jumps, and vocalizations of cows were considered as behavioral events and a proportion was calculated based on the number of observed events per group divided by the number of cows per group to give a behavioral event index (BEI). Health status of the cows was assessed during auction by recording the proportion of cows with low body condition, lameness, udder problems, tegumentary lesions, and tail abnormalities. Handler behavior was assessed using a count of negative tactile interactions (NTI) with the cows, like blows/hits, kicks, and pokes with the devices used to drive them, then a NTI index (NTII) was calculated as for BEI. Using the groups of cows as the statistical unit, statistical models were built and used to identify how NTII, some facilities features and comingling were associated with BEI registered during unloading, auction, and loading and also to calculate if the selling price was associated with the different health problems of cows, using the software MLwiN 3.03. A total of 1,103 groups of cows (n = 3,963 cows) were observed, finding a high percentage of slips and balks, whereas hitting and poking were frequent NTI. The highest mean BEI was observed during unloading in winter (1.10), whilst the lowest one was found during auction in summer (0.34). There was an increase of 0.11 in BEI for every extra unit increase in the NTII by the handlers. The BEI was negatively affected by the winter season compared to summer. Of 1,608 cows, 49.8% had a low body condition, 28.3% had udder problems, 24% were lame, 8.7% presented tegumentary lesions, and 3.1% tail abnormalities. It can be concluded that the health of the cull cows is already compromised when leaving the farms; cow behavior and handler tactile interactions with the cows are useful indicators to assess the welfare of cull cows at livestock markets.


[Experimental morphological basis of the application of microsurgical intestinal suture under the conditions of inflammatory pathology of gastro-intestinal tract organs].
Experimental study of morphological peculiarities of intestinal wall and common bile duct wall healing using microsurgical sutures under the condition of peritonitis and cholangitis, was performed in 112 dogs. It was shown that the microsurgical suturing of intestinal wall and common bile duct wall affected by the inflammatory process, created the favorable conditions for wound healing. During the recovery period, the thickness of all the layers of the intestinal wall decreased, the disturbances of the normal fibrous structure and the vascular reaction of the submucosa were reduced. Connective tissue capsule was formed around the threads. The structure of the suture zone was not different from that of the neighboring areas of the intestine.


[Bronchoscopic diagnosis of pneumonia with quantitative microbial count determination].
Micro-organism counts of bronchoalveolar lavage (BAL) and microbrush swabs were obtained from 40 immunocompetent (group A) and 23 immunosuppressed (group B) patients with nosocomial pneumonia, and a control group consisting of 40 patients with noninfectious pulmonary infiltrates. The sensitivity of BAL was high: 77.5% for group A and 85% for group B, while microbrush swabs gave many false-negative results. Microorganism counts were at or above 10(5) cfu/ml in 32 of 44 examinations (bacterial or mycotic pneumonia), but in only one case of the control group. Lower counts were obtained with localized infection and microorganisms difficult to culture (Aspergilla and Legionella). Granulocytosis in the lavage fluid was demonstrated in 38 of 41 patients with bacterial pneumonia and thus proved useful in the differential diagnosis. In 16 of 40 immunocompetent and 13 of 23 immunosuppressed patients with pneumonia the results were therapeutically of importance. Thus, invasive diagnosis is indicated especially in complicated or treatment-resistant nosocomial infections.


Target-specific PET probes for neurodegenerative disorders related to dementia.
Dementia is a highly prevalent problem causing considerable disability and mortality and exacting great costs to individuals, their families, and society. The 4 most common neurodegenerative disorders that cause dementia-Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and dementia in Parkinson disease-have different underlying etiologies and pathogenetic mechanisms. There is a great need for early diagnostic markers; functional brain imaging may therefore assist in the detection and differential diagnosis of dementia due to neurodegenerative diseases. Functional imaging such as PET allows in vivo imaging of functional brain activity indicating cerebral blood flow and cerebral glucose metabolism, and PET allows imaging of neurotransmitter activity, including that of the cholinergic, dopaminergic, and serotonergic systems. New PET neuroimaging tracers are being developed for detecting pathologic parameters such as amyloid plaque and microglial activity. The development of molecular imaging is important for early diagnosis of dementia, selection of patients for therapies, and evaluation of therapies.


[Multidisciplinary approach in urology. Clinical aspects].
A solving diagnostic and therapeutic problems in patients with various urologic diseases often requires a cooperation between different specialists which emphasizes the interdisciplinarity of our discipline. A number of clinical manifestations and diseases that urologists have to deal with and in which they definitely need a timely assistance from other specialists are described in the article. Determining the connecting links in the work of different specialists, we tried to recall the main " intersection points" and draw attention to the necessary cooperation.


Temporal Associations Between Depression and Hostility in the Context of a Divorce Intervention.
Divorce interventions have been found to be effective in reducing negative outcomes for newly divorced people, including depression and hostility. Typically, divorce interventions cover a variety of issues that may influence people's level of depression and hostility. However, it is unclear whether the interventions differentially affect the outcomes. That is, it may be that intervention participation leads to a reduction in depression, which is associated with a prospective reduction in hostility-or vice versa. The current study used a sample of 1,856 recently divorced Danes, who completed questionnaires at baseline, 3-, 6-, and 12-month post-divorce. Structural equation modeling revealed that while depression and hostility were concurrently associated, there were no prospective associations, except for baseline depression predicting 3-month hostility. Moreover, the associations did not differ by gender. The results suggest that the intervention content may have influenced both depression and hostility. These findings may be useful in guiding future divorce intervention developments.


A theoretical discussion of the impact of stigma on psychological adjustment to having a sexually transmissible infection.
This paper provides a discussion of the utility of stigma theory as a conceptual framework for the interpretation and analysis of the psychological impact of contracting a sexually transmissible infection (STI). Most particularly, it focuses on those viral infections that cannot be medically cured, such as genital herpes and genital human papilloma virus. Recent research in the area of STIs suggests that the stigma associated with these conditions can hinder psychosocial and sexual adjustment post-diagnosis, and provides support for the use of stigma theory as a conceptual framework with which to analyse these experiences. This paper defines the concept of stigma and presents a theoretical overview of the process of stigmatisation. Three dimensions of stigma relevant to the experience of having a STI are then presented: the degree of concealability of the condition including the social consequences of concealing a condition; the origin of the condition; and the degree of peril presented by the condition. An overview of the way in which the presence of a stigmatising condition such as a STI may affect a person's feelings of self and his/her intimate relationships is then presented. Finally, the implications of stigma theory as a conceptual framework for guiding future research in the area of personal and interpersonal reactions to STIs is discussed.


Validation of the scale of assessment of self-care behaviours for arteriovenous fistula in patients ongoing haemodialysis in Turkey.
Several guidelines recommend that patients with chronic kidney disease treated by haemodialysis (HD) take care of their own arteriovenous fistula (AVF). The dialysis nurse plays an important role in the development of such self-care behaviours. A very small number of instruments are available to assess self-care behaviours with AVF in Turkey. Cultural adaptation and psychometric testing of the Turkish version of the scale of assessment of self-care behaviours with arteriovenous fistula in haemodialysis (ASBHD-AVF) patients. Cross-sectional validation study. This study was conducted involving 160 patients in the Bolu region in Turkey. The guidelines provided by Sousa and Rojjanasrirat were taken into account in the scale translation, adaptation and validation process. Validity was analysed through content validity and construct validity. The latter was measured through principal component analysis with varimax rotation, considering only factor loadings of 0.30 or larger. Reliability analysis was based on internal consistency measured by Cronbach's α. A two-factor structure was extracted explaining 59.01% of the total variance. Cronbach's α was 0.91, 0.85 and 0.84 for the overall scale, the self-care in prevention of complications subscale and the self-care in management of signs and symptoms subscale, respectively. The Turkish version of the scale of ASBHD-AVF patients is a reliable and valid instrument and can therefore be used.


Analysis of molecular ligand functionalization process in nano-molecular electronic devices containing densely packed nano-particle functionalization shells.
Molecular electronic devices based on few and single-molecules have the advantage that the electronic signature of the device is directly dependent on the electronic structure of the molecules as well as of the electrode-molecule junction. In this work, we use a two-step approach to synthesise functionalized nanomolecular electronic devices (nanoMoED). In first step we apply an organic solvent-based gold nanoparticle (AuNP) synthesis method to form either a 1-dodecanethiol or a mixed 1-dodecanethiol/ω-tetraphenyl ether substituted 1-dodecanethiol ligand shell. The functionalization of these AuNPs is tuned in a second step by a ligand functionalization process where biphenyldithiol (BPDT) molecules are introduced as bridging ligands into the shell of the AuNPs. From subsequent structural analysis and electrical measurements, we could observe a successful molecular functionalization in nanoMoED devices as well as we could deduce that differences in electrical properties between two different device types are related to the differences in the molecular functionalization process for the two different AuNPs synthesized in first step. The same devices yielded successful NO2gas sensing. This opens the pathway for a simplified synthesis/fabrication of molecular electronic devices with application potential.


Repellent Activity of the Essential Oil from the Heartwood of Pilgerodendron uviferum (D. Don) Florin against Aegorhinus superciliosus (Coleoptera: Curculionidae).
The weevil Aegorhinus superciliosus Guérin (Coleoptera: Curculionidae), which is endemic to Central-Southern Chile and Argentina, is one of the major berry pests in Chile and the most important pest in the La Araucanía Region (38°44'9″S, 72°35'25″W). Due to the poor effectiveness and problems surrounding the implementation of the traditional control methods using organophosphate and carbamate insecticides, new strategies for controlling this pest are needed. In this communication, we evaluated the behavioral responses of male and female A. superciliosus to volatile compounds released from the essential oil (EO) obtained from the heartwood of Pilgerodendron uviferum (D. Don) Florin using olfactometric bioassays. The composition of the EO was analyzed using gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). According to these analyses, δ-cadinol (24.16%), cubenol (22.64%), 15-copaenol (15.46%) and δ-cadinene (10.81%) were the principal components of the EO. The Pilgerodendron uviferum EO, which is almost exclusively composed of sesquiterpenes (99.5%), exhibited a repellent effect against A. superciliosus adults, regardless of the sex or concentration used (56.6 mg/cm³ and 1.58 × 10(-2) mg/cm³). The EO has low volatility and greater persistence than the EOs composed of monoterpenes and is considered a good model in the search for raspberry weevil repellents.


[The Montreal model: the challenges of a partnership relationship between patients and healthcare professionals].
A promising approach to improve the population's health and the quality of care and services provided by the health system consists of patient engagement at all levels of the health system together with training of health professionals. Since 2010, a new rational model based on the partnership between patients and healthcare professionals has been developed at the University of Montreal's Faculty of Medicine. This patient partnership model is based on the recognition of the patient's experiential knowledge gained from living with a disease, which is complementary to the healthcare professional's scientific knowledge. This partnership is part of a continuum of patient engagement and can be applied in healthcare, professional training, education and research settings. This article describes the theoretical basisfor patient partnerships and how this new model can be implemented in clinical, organizational and systemic levels, as well as the success factors in both patients and healthcare professionals. The Montreal Model provides relevant outlooks for chronic disease management by making patients essential partners in all decisions affecting them and by treating them as experts in the organisation of care. This model should have a significant impact on the population's health by improving physical, psychological health, as well as the patient's well-being. As part of this new framework, several research programs are currently underway to evaluate the impact of this model.


Therapeutic effects of combined oxaliplatin and S-1 in older patients with advanced gastric cardiac adenocarcinoma.
To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m² po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m² iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeated for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed. The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ² = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ² = 0.032 and P = 0.857). Efficacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ² = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05). The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.


The Unseen Global Burden of Disease.
Due to geographic-specific patient and institutional-related barriers to care, data extrapolation and expert opinion on global burden of disease in otolaryngology-head and neck surgery may under- or overestimate the presence and effect of common head and neck conditions. The group of conditions that fail to present to local physicians and/or missed in data extrapolation methods is the unseen burden of disease. This article presents opinions from otolaryngology-head and neck surgery physicians in high- and low/middle-income countries to help explain the contributing factors and ultimately how to use this unseen burden of disease.


Sonographically guided aspiration of cerebrospinal fluid pseudocysts in children and adolescents.
Cerebrospinal fluid (CSF) pseudocyst formation is an uncommon cause of ventriculoperitoneal shunt malfunction in children. Traditional staged treatment consists of shunt externalization, antibiotics, and later shunt revision and internalization. We sought to evaluate whether sonographically guided pseudocyst aspiration to alleviate acute symptoms and to exclude CSF infection could obviate shunt externalization and expedite the care of these patients. Sonographically guided CSF pseudocyst aspiration is an effective technique, allowing exclusion or confirmation of infection and providing relief of abdominal symptoms. In patients with sterile collections, staged surgical revision with shunt externalization can be avoided, speeding and simplifying treatment.


Lactation and gestation in dairy cows: flexibility avoids nutritional extremes.
The modern dairy cow has been selectively bred to produce large amounts of milk. Partly as a result, food consumption is considerably less than milk energy output in early lactation. It is only at 2 months or more postpartum that intake increases to the point where positive energy balance is regained, the initial production being achieved by a substantial mobilisation of body reserves. These reserves are laid down before parturition, but it is certainly not the case that the pregnant cow will accumulate adipose tissue recklessly; in the last third of pregnancy well-fed cows in good body condition exhibit reduced, not increased, appetite. There is a fine balancing act to perform. Excessive body condition at parturition quickly leads to metabolic problems such as ketosis, but cows who subsequently become too thin have increased risk of metabolic diseases such as mastitis and lameness. The biological mechanisms regulating output of milk are reasonably well understood, those controlling appetite less well so, and there has been little attempt at systematic integration of the two. The transition from pregnancy to lactation represents a major challenge to homeostasis, made more complicated in multiparous cows by the fact that much of gestation is concurrent with lactation. Herein lies the potential for nutritionally-entrained flexibility. In the wild, concurrent pregnancy and lactation only occur when nutritional conditions are favourable. If conditions are poor, rebreeding will be delayed and lactation will continue, at an energetically-sustainable level, for much longer than its 'normal' duration. In this way the twin energetic burdens of pregnancy and lactation are separated, and extremes are avoided. Given the increasing public concern about stresses suffered by intensively-managed dairy cows, this case may be one where commercial dairying could learn useful lessons from nature.


Granisetron: a review of pharmacokinetics and clinical experience in chemotherapy induced - nausea and vomiting.
Chemotherapy induced nausea and vomiting (CINV) are major side effects of chemotherapy and a great burden to patients' quality of life. Serotonin and substance P are the major neurotransmitters involved in the pathophysiology of CINV, but in spite of new antiemetics no completely effective regime exists for its prevention or treatment. Areas covered: In this review the authors provide a detailed description of granisetron's chemistry pharmacokinetics, pharmacodynamics, toxicity and a brief review of clinical trials involving granisetron and the management of CINV. We searched reviews, meta-analysis and randomized controlled trials (Medline, Embase and article reference lists). Expert opinion: According to current literature, granisetron 2 mg orally or 0,01mg/kg (1 mg) intravenously per day, co-administered with dexamethasone and NK-1 antagonists is the recommended regime for highly emetogenic chemotherapy. In the future the role of transdermal and subcutaneous formulations against delayed CINV will be clarified and probably enhance patients' convenience.


Evidence that a simpático self-schema accounts for differences in the self-concepts and social behavior of Latinos versus Whites (and Blacks).
On the basis of the assumption that Latino Americans use a simpático self-schema more than White Americans do, the authors predicted that the effects of this difference would be evident in the participants' self-concepts and social behavior. As predicted, Studies 1 and 2 revealed that Latino participants reported significantly more simpático-related terms in their spontaneous self-concepts than did White participants. Complementing these findings, Study 3a revealed that the level of interactional involvement and the perceived quality of initial same-sex interactions was significantly enhanced by the presence of Latino dyad members. Study 3b tested the prediction that the content of the dyad members' thoughts and feelings would reveal a greater use of the simpático self-schema by the Latino participants. This prediction was confirmed, and follow-up analyses indicated that a simpático self-schema plays an important mediating role in the subjective experience and social behavior of Latino individuals.


Neuroanatomical and neuropsychological features of euthymic patients with bipolar disorder.
Previous studies reported that the severity of cognitive deficits in euthymic patients with bipolar disorder (BD) increases with the duration of illness and postulated that progressive neuronal loss or shrinkage and white matter changes may be at the origin of this phenomenon. To explore this issue, the authors performed a case-control study including detailed neuropsychological and magnetic resonance imaging analyses in 17 euthymic elderly patients with BD and 17 healthy individuals. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal cortex, and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. Periventricular and deep white matter were assessed semiquantitatively. Differences in cognitive performances and structural data between BD and comparison groups were analyzed using paired t-test or analysis of variance. Wilcoxon test was used in the absence of normal distribution. Compared with healthy individuals, patients with BD obtained significantly lower performances in processing speed, working memory, and episodic memory but not in executive functions. Morphometric analyses did not show significant volumetric or white matter differences between the two groups. Our results revealed impairment in verbal memory, working memory, and processing speed in euthymic older adults with BD. These cognitive deficits are comparable both in terms of affected functions and size effects to those previously reported in younger cohorts with BD. Both this observation and the absence of structural brain abnormalities in our cohort do not support a progressively evolving neurotoxic effect in BD.


Efficacy of ossein-hydroxyapatite complex compared with calcium carbonate to prevent bone loss: a meta-analysis.
There is increasing evidence to suggest that ossein-hydroxyapatite complex (OHC) is more effective than calcium supplements in maintaining bone mass. The aim of this meta-analysis was to determine whether OHC has a different clinical effect on bone mineral density (BMD) compared with calcium carbonate (CC). A meta-analysis of randomized controlled clinical trials was carried out to evaluate the efficacy of OHC versus CC on trabecular BMD. We identified publications on clinical trials by a search of electronic databases, including MEDLINE (1966-November 2008), EMBASE (1974-November 2008), and the Cochrane Controlled Clinical Trials Register.The primary endpoint was percent change in BMD from baseline. Data were pooled in a random-effects model, and the weighted mean difference was calculated. A sensitivity analysis that excluded trials without full data was performed. Of the 18 controlled trials initially identified, 6 were included in the meta-analysis. There was no significant heterogeneity among the included trials. The percent change in BMD significantly favored the OHC group (1.02% [95% CI, 0.63-1.41], P < 0.00001). These results were confirmed in the sensitivity analysis. OHC is significantly more effective in preventing bone loss than CC.


The history of nursing in the home: revealing the significance of place in the expression of moral agency.
The history of nursing in the home: revealing the significance of place in the expression of moral agency The relationship between place and moral agency in home care nursing is explored in this paper. The notion of place is argued to have relevance to moral agency beyond moral context. This argument is theoretically located in feminist ethics and human geography and is supported through an examination of historical documents (1900-33) that describe the experiences and insights of American home care/private duty nurses or that are related to nursing ethics. Specifically, the role of place in inhibiting and enhancing care, justice, good relationships, and power in the practice of private duty nurses is explored. Several implications for current nursing ethics come out of this analysis. (i) The moral agency of nurses is highly nuanced. It is not only structured by nurses' relationships to patients and health professionals, i.e. moral context, it is also structured by the place of nursing care. (ii) Place has the potential to limit and enhance the power of nurses. (iii) Some aspects of nursing's conception of the good, such as what constitutes a good nurse-patient relationship, are historically and geographically relative.


False-negative urine latex particle agglutination testing in neonates with group B streptococcal bacteremia. A function of improper test implementation?
Although blood cultures remain the most specific indicator of Group B streptococcus (GBS) sepsis, a potentially life-threatening infection in neonates, test results may not be available for 24 to 48 hours. Detection of GBS antigen in the urine by latex particle agglutination (LPA) may speed diagnosis. This study analyzed the sensitivity of the GBS urine LPA assay under clinical conditions. The urine of neonates with early-onset GBS bacteremia was analyzed for GBS antigen over a three-year period at six military medical centers. Overall, 53.5% (38/71) of infants with positive blood cultures had a positive urine LPA test. Only one medical center routinely followed manufacturer's recommendations to concentrate urine specimens before testing. These data suggest that the sensitivity for the urine LPA assay, when performed on unconcentrated urine, is lower than previously reported. Clinicians should insist that the laboratory maximize sensitivity by concentrating urine prior to GBS LPA testing.


Effects of lisofylline on hyperoxia-induced lung injury.
Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] decreases lipid peroxidation in vitro and in vivo suppresses proinflammatory cytokine expression in models of lung injury due to sepsis, blood loss, and oxidative damage. In the present experiments, we used a murine hyperoxia model to examine the effects of lisofylline on the activation of nuclear transcriptional regulatory factors [nuclear factor-kappaB and cAMP response element binding protein (CREB)], the expression of proinflammatory cytokines in the lungs, and the circulating levels of oxidized free fatty acids as well as on hyperoxia-induced lung injury and mortality. Treatment with lisofylline inhibited hyperoxia-associated increases in tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in the lungs as well as decreased the levels of hyperoxia-induced serum-oxidized free fatty acids. Although hyperoxic exposure produced activation of both nuclear factor-kappaB and CREB in lung cell populations, only CREB activation was reduced in the mice treated with lisofylline. Lisofylline diminished hyperoxia-associated increases in lung wet-to-dry weight ratios and improved survival in animals exposed to hyperoxia. These results suggest that lisofylline ameliorates hyperoxia-induced lung injury and mortality through inhibiting CREB activation, membrane oxidation, and proinflammatory cytokine expression in the lungs.


Primary fallopian tube carcinoma arising in the setting of chronic pelvic inflammatory disease.
Primary fallopian tube cancer (PFTC) is a rare gynaecological malignancy, clinically often mistaken for pelvic inflammatory disease or ovarian cancer. Three primary fallopian tube carcinomas, arising in a background of chronic pelvic inflammatory disease (PID), are presented. The possible association between chronic PID and PFTC is discussed and a hypothesies linking these cancers with chronic inflammation is proposed.


Rate of community methadone treatment reporting at jail reentry following a methadone increased dose quality improvement effort.
The Rikers Island Key Extended Entry Program (KEEP) has offered methadone treatment for opioid dependent inmates incarcerated in New York City's jails since 1986. In response to a trend toward low-dose methadone maintenance prescribing, a quality improvement (QI) protocol trained KEEP counselors, physicians, and pharmacists in the evidence base supporting moderate-to-high methadone maintenance doses in order to maximize therapeutic effects and rates of successful reporting to community methadone treatment programs (MTPs) post release. Discharge dose level and length of incarceration data were analyzed for 2 groups of KEEP patients discharged pre/post-QI. Among patients incarcerated for 21 or more days, the proportion of those on moderate-to-high doses of methadone increased significantly. Patients who reached a moderate-to-high methadone dose demonstrated higher rates of reporting to community MTP versus lower doses, both pre- and post-QI. Overall, a higher proportion of all patients reported to community MTP post-QI.


The effect of stenosis rate and Reynolds number on local flow characteristics and plaque formation around the atherosclerotic stenosis.
Atherosclerosis causes plaque to build-up in arteries. Effect of the specific local hemodynamic environment around an atherosclerotic plaque on the thrombosis formation does not remain quite clear but is believed to be crucial. The aim of this study is to uncover the flow effects on plaques formation. To study the mechanically regulated plaque formation, the flow fields in artery blood vessels with different stenosis rates at various Reynolds numbers were simulated numerically with the two-dimensional axisymmetric models, and the hemodynamic characteristics around the plaque were scaled with stenosis rate and Reynolds number. The results showed that increases of both Reynolds number and stenosis rate facilitated the occurrence of flow separation phenomenon, extended recirculation zone, and upregulated the maximum normalized wall shear stress near the plaque throat section while downregulated the minimal normalized wall shear stress at the front shoulder of plaque, as it should be; in the atherosclerotic plaque leeside of the recirculation zone, an obvious catch bond region of wall shear stress might exist especially under low Reynolds number with stenosis rate smaller than 30%. This catch bond region in the plaque leeside might be responsible for the LBF (low blood flow)-enhanced formation of the atherosclerotic plaque. This work may provide a novel insight into understanding the biomechanical effects behind the formation and damage of atherosclerotic plaques and propose a new strategy for preventing atherosclerotic diseases.


15-Deoxyspergualin hinders physical interaction between basic residues of transit peptide in PfENR and Hsp70-1.
The apicoplast of Plasmodium harbors several metabolic pathways. The enzymes required to perform these reactions are all nuclearly encoded and apicoplast targeted (NEAT) proteins. Plasmodium falciparum Enoyl-ACP Reductase (PfENR) is one such NEAT protein. The NEAT proteins have a transit peptide which is required for crossing the membranes of apicoplast. We studied the importance of basic residues like Arginine and Lysine within the transit peptide. Previous studies have suggested that all basic residues are essential for apicoplast trafficking. In this study, we demonstrate that only some of these residues are essential (K44, R48, K51, and R52), whereas others are dispensable (R40, K42, and K49). On mutating these specific residues, PfENR is not imported into the apicoplast and is mislocalized to the cytoplasm. We also demonstrate that these residues are also crucial for interaction with Hsp70-1, implying that interactions of Lysine 44, Arginine 48, Lysine 51, and Arginine 52 of the transit peptide with PfHsp70-1 are required for apicoplast trafficking. 15-Deoxyspergualin, which has earlier been proposed to interact with EEVD motif of PfHsp70-1 hinders the physical interaction between these cationic residues of PfENR and Hsp70-1. Hence, we propose that in the transport competent state of NEAT proteins some specific positively charged amino acids in the transit peptide interact with PfHsp70-1, and this interaction is essential for apicoplast targeting.


THE PICNIC GAME: PRESENTATION OF A SITUATION OF OBSERVATION TO ASSESS FAMILY INTERACTIONS.
The aim of this article is to present a situation of observation designed for the assessment of family interactions: The PicNic Game (PNG). In this situation, families are invited to play at having a picnic together. This can be done with any number of children, aged from a few weeks to adolescence. A companion assessment tool, the Revised-Picnic Assessment Scale (Re-PAS), allows evaluation of interactions in the family on several dimensions. This article presents the PNG and a preliminary study of the validation of the Re-PAS dimensions in a sample of families (N = 67) with 18-month-old infants and their siblings. The PNG was well-received by the families. Construct validity of the Re-PAS was tested, first against self-reported data by mothers and fathers regarding marital satisfaction, coparenting behavior, and division of household tasks, and then against observed maternal and paternal sensitivity and controlling behaviors assessed during free-play. Results show satisfactory preliminary reliability and validity. Two contrasting cases are presented to illustrate the different interactions highlighted in the PNG. This situation is useful for researchers and clinicians, particularly as a basis for video-feedback work with the family.


Notions and treatment of guinea worm in northern Ghana.
Dracunculiasis, infection with Dracunculus medinensis or guinea worm, is widespread in the Northern Region of Ghana, where rural people drink from unprotected water sources such as ponds and small-scale dams. This paper discusses the results of an anthropological study of beliefs and practices concerning commonly occurring illnesses, such as infection with guinea worm (nierifu), in two rural Dagomba communities in the Northern Region of Ghana. The importance of knowing about local perceptions and treatment of guinea worm is stressed. Guinea worm is not attributed to water. The general understanding is that guinea worm is an innate part of human anatomy. It is not seen as an alien presence in the body. Guinea worm is rather said to be 'in people's blood', and sooner or later to 'stand up'. Guinea worm is considered an 'inevitable' feature of living. After a description of the background to the study, the methods are characterized. Brief background information on the people, their environment and their water sources are given. The central portion of the paper focuses on local perceptions of illness and notions of guinea worm ('guinea worm is in the human blood'), which are very different from those of biomedicine ('guinea worm is a disease'). Attention is also given to perceptions of water ('bitter' vs 'sweet') and the prevention of guinea worm. The social limitations to the filter technology are addressed. People's choice of therapy and the role of medicines (herbs and Western pharmaceuticals) in treatment of guinea worm are also considered. The paper concludes with a discussion of health education and stresses the importance of showing respect for the local view of guinea worm, which is said to be 'in the blood'. It is suggested that, since people are not adverse to the use of Western pharmaceuticals, the use of Western medicines to treat guinea worm should be further promoted. The social constraints on filtering must also be appreciated. These relate to the organization of labour within the household and the dominant role of the 'senior wife'.


The intriguing dose-dependent effect of selected amphiphilic compounds on insulin amyloid aggregation: Focus on a cholesterol-based detergent, Chobimalt.
The amyloidogenic self-assembly of many peptides and proteins largely depends on external conditions. Among amyloid-prone proteins, insulin attracts attention because of its physiological and therapeutic importance. In the present work, the amyloid aggregation of insulin is studied in the presence of cholesterol-based detergent, Chobimalt. The strategy to elucidate the Chobimalt-induced effect on insulin fibrillogenesis is based on performing the concentration- and time-dependent analysis using a combination of different experimental techniques, such as ThT fluorescence assay, CD, AFM, SANS, and SAXS. While at the lowest Chobimalt concentration (0.1 µM; insulin to Chobimalt molar ratio of 1:0.004) the formation of insulin fibrils was not affected, the gradual increase of Chobimalt concentration (up to 100 µM; molar ratio of 1:4) led to a significant increase in ThT fluorescence, and the maximal ThT fluorescence was 3-4-fold higher than the control insulin fibril's ThT fluorescence intensity. Kinetic studies confirm the dose-dependent experimental results. Depending on the concentration of Chobimalt, either (i) no effect is observed, or (ii) significantly, ∼10-times prolonged lag-phases accompanied by the substantial, ∼ 3-fold higher relative ThT fluorescence intensities at the steady-state phase are recorded. In addition, at certain concentrations of Chobimalt, changes in the elongation-phase are noticed. An increase in the Chobimalt concentrations also triggers the formation of insulin fibrils with sharply altered morphological appearance. The fibrils appear to be more flexible and wavy-like with a tendency to form circles. SANS and SAXS data also revealed the morphology changes of amyloid fibrils in the presence of Chobimalt. Amyloid aggregation requires the formation of unfolded intermediates, which subsequently generate amyloidogenic nuclei. We hypothesize that the different morphology of the formed insulin fibrils is the result of the gradual binding of Chobimalt to different binding sites on unfolded insulin. A similar explanation and the existence of such binding sites with different binding energies was shown previously for the nonionic detergent. Thus, the data also emphasize the importance of a protein partially-unfolded state which undergoes the process of fibrils formation; i.e., certain experimental conditions or the presence of additives may dramatically change not only kinetics but also the morphology of fibrillar aggregates.


[Progress of researches on approaches for estimating the burden of vector-borne diseases].
The burden of vector-borne diseases refers to the loss and impact of healthy life and social economy due to disability and early death caused by vector-borne diseases, including economic burden and family burden. Disability-adjusted life year (DALY) is a comprehensive measure of the burden of disease. The economic burden of disease is classified into direct economic burden, indirect economic burden and intangible economic burden. Currently, the estimates of direct economic burdens include micro-cost and macro-cost models, and the estimates of indirecteconomic burdens include human resources and friction cost methods, while the intangible economic burden is generally estimated by willingness to pay. The currently available health economics approaches mainly include cost-utility analysis, cost-benefit analysis and cost-effectiveness analysis. This review summarizes the approaches for estimating the burden of malaria and other vector-borne diseases.


[State of the coronary arteries and assessment of the role of hormone replacement therapy in patients with coronary heart disease against the background of primary manifest hypothyroidism].
Aim To study features of coronary damage and incidence of different types of acute coronary syndrome (ACS) in history associated with primary symptomatic hypothyroidism in patients with ischemic heart disease (IHD) and possible associations of replacement hormonal therapy with lipidogram indexes.Material and methods This retrospective study included 344 patients with IHD and functional class I-III stable angina (ССS, 1976). Of them 100 patients had primary symptomatic hypothyroidism and 244 had no hypothyroidism. Coronary angiography was performed for all patients included into this study. Routine laboratory, instrumental and clinical indexes were analyzed. Hypothyroidism was confirmed by levels of thyrotropic hormone, free triiodothyronine, and thyroxine. Comparative analysis was performed for the incidence of ACS types in history, types of coronary injury, and laboratory, instrumental and clinical indexes with assessment of potential interrelations. Statistically significant results were reported. Type of data distribution was evaluated with the Kolmogorov-Smirnov test. Quantitative data with normal (Gaussian) distribution were presented as mean (M) and standard deviation (SD). Data with attributes of non-normal distribution were presented as median (Me) with maximum and minimum values (min; max). Statistical significance of differences between means was assessed with the Mann-Whitney test. Logistic regression analysis was used in parallel for evaluating dependence of a quantitative variable on values of two or more quantitative or qualitative variables (factors). Significance level for testing of statistical hypotheses was р<0.05.Results Incidence of ST segment elevation ACS (STEACS) was significantly higher in IHD patients with hypothyroidism than in the group without hypothyroidism (61.6 and 35.6 %, р=0.03) and also with three-vessel coronary artery disease (60.6 and 30.6 %, р=0.001). In the IHD group with hypothyroidism, levels of total cholesterol, triglycerides, and low- and very low-density lipoproteins were significantly increased compared to the respective values in patients without hypothyroidism (р<0.0001). An inverse correlation was found between lipidogram indexes and L-thyroxine (р<0.0001).Conclusion The incidence of STEACS associated with primary symptomatic hypothyroidism in history was significantly higher in the patient group with IHD on the background of primary symptomatic hypothyroidism compared to the comparison group. Also, the incidence of three-vessel coronary disease was significantly greater than in the IHD patient group without hypothyroidism. A significant association was found between the replacement hormonal therapy and the best lipidogram indexes. The authors suggested that the key factor for prevention of adverse cardiovascular events in IHD with hypothyroidism is achieving control of clinical manifestations of hypothyroidism with replacement hormonal therapy.


[Effects of methyl tertiary-butyl ether on hepatic lipid peroxidation in mice].
The effect of one-shot or repeated treatment with methyl tertiary-butyl ether (MTBE) on lipid peroxidation and cytochrome P-450 in mouse liver was examined. One-shot treatment at the 500 mg/kg dose level caused a transient decrease in leukocyte number after 24 h. An increased level of lipid peroxide was observed in the liver homogenates 24 h after one-shot treatment and four weeks of repeated 200 mg/kg treatment. The hepatic cytochrome P-450 content increased after one and four weeks of repeated treatment (50, 200 mg/kg). On the other hand, the treatment did not affect glutathione content and glutathione-S-transferase activity. These results indicate that MTBE treatment caused lipid peroxidation in the liver homogenate and induction of hepatic microsomal cytochrome P-450 content.


[Research of relationship between thyroid-stimulating hormone level after surgery and hypercholesterolemia in female patients with differentiated thyroid cancer].
Objective:To evaluate changes of postoperative thyroid-stimulating hormone(TSH) and total cholesterol(TC) levels in serum, and to analyze the risk of hypercholesterolemia in female patients with differentiated thyroid cancer(DTC) receiving levothyroxine after total thyroidectomy. Method:Female patients with DTC in the first affiliated hospital of hebei north university, who underwent total thyroidectomy, were analyzed retrospectively. All patients were divided into four groups according to follow-up TSH levels:<0.03 mIU/L, 0.03-0.29 mIU/L, 0.30-4.20 mIU/L and>4.20 mIU/L. Changes in TC levels before and after surgery were compared and the occurrence of hypercholesterolemia was analyzed. Result:The lower postoperative TSH level groups had higher preoperative TC levels than the higher TSH level groups. Compared with preoperative level, the TC levels remained unchanged in 0.03-0.29 mIU/L group, but decreased in <0.03 mIU/L group, and markedly increased in greater than 0.3 mIU/Lgroups with TSH levels after surgery. The preoperative-to-follow-up change in TC levels had positive correlation with follow-up TSH level. Compared with those with TSH levels of 0.03-0.29 mIU/L, the risk of TC marginal elevation and hypercholesterolemia in the patients with TSH of 0.30-4.20 mIU/L was found to be 1.16 times and 1.91 times higher, respectively. For patients with TSH levels of >4.2 mIU/L, the risk of TC marginal elevation and hypercholesterolemia was 1.29 times and 3 times, respectively. The increase in TSH was consistent with the increase in the incidence of hypercholesterolemia (P for trend=0.003). Conclusion:Women with DTC who are using levothyroxine to maintain TSH after surgery should be aware of the risk of hypercholesterolemia due to inadequate replacement.


Factors Affecting Undergraduates' Participation in Medical Research in Lagos.
The current situation regarding the scope and contribution of undergraduate medical research to the health space in Nigeria is still largely unreported in formal literature. This study examined the knowledge, attitudes, and the perceived barriers faced by medical students in Lagos toward research. A cross-sectional study design was conducted among all medical students in 200-600 levels of study at the College of Medicine, University of Lagos. With the aid of Self-administered questionnaires, we examined their knowledge of research and the analytical tools used in research, their attitudes and the perceived barriers to their participation in research. The data were obtained from 221 medical students, of whom 52.9% had prior involvement in research and 14.0% and 6.3% had presented or published their research, respectively. The overall knowledge of medical research was low (21.3%) and reported barriers included lack of funding for research' (79.6%), "lack of research and biostatistics curriculum" (76.0%), "inadequate training in research methodology" (74.7%), "insufficient time allocation to undergraduate research" (73.3%), "lack of professional supervisors and proper mentoring" (58.8%), and "lack of equipped laboratory facilities to conduct research" (77.8%). Our results highlight the need for more mentored supervision and training to improve their knowledge of the principles and techniques of clinical research to increase involvement.


Insomnia treatment: a new multitasking natural compound based on melatonin and cannabis extracts.
Our main aim was to investigate the short-term thera-peutic effects, safety/tolerability of natural compound, composed of melatonin (1,5 mg) and cannabis extracts (2.5 mg CBD) in patients with sleep disorders. In this spontaneous, anecdotal, retrospective, "compas-sionate-use," observational, open-label study, 20 patients (age 43-96 years) were appealed to our "Second Opinion Medical Consulting Net-work" (Modena, Italy), because of a variable pattern of sleep disorders and anxiety and were instructed to take sublingually the compound (20 drops) overnight for 3 months of treatment. Tolerability and adverse effects were assessed monthly during the treatment period through direct contact (email or telephone) or visit if required. PSQUI and HAM-A scores evidenced reduction in mood alterations, including anxiety, panic, paranoia, depression (P < 0.03), in pain (P < 0.02) and good general health perceptions. These data suggest that the formula CBD-melatonin could be competitive with the classic hypnotic synthetic drugs, the antioxidant activity of melatonin offers a further benefit to the brain network, restoring the biological clock functions, while CBD, redu-cing chronic pain perception, helps to complete the neuromuscular relaxation and to relieve anxiety fulfilling a very balanced sensation of wellbeing during the sleep.


Bilateral Renal Vein Thrombosis due to Elevated Factor VIII Levels.
Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use.


Regulation of formation of the intracellular beta-galactosidase activity of Aspergillus nidulans.
The regulation of formation of the single intracellular beta-galactosidase activity of Aspergillus nidulans was investigated. beta-Galactosidase was not formed during growth on glucose or glycerol, but was rapidly induced during growth on lactose or D-galactose. L-Arabinose, and -- with lower efficacy -- D-xylose also induced beta-galactosidase activity. Addition of glucose to cultures growing on lactose led to a rapid decrease in beta-galactosidase activity. In contrast, in cultures growing on D-galactose, addition of glucose decreased the activity of beta-galactosidase only slightly. Glucose inhibited the uptake of lactose, but not of D-galactose, and required the carbon catabolite repressor CreA for this. In addition, CreA also repressed the formation of basal levels of beta-galactosidase and partially interfered with the induction of beta-galactosidase by D-galactose, L-arabinose, and D-xylose. D-Galactose phosphorylation was not necessary for beta-galactosidase induction, since induction by D-galactose occurred in an A. nidulans mutant defective in galactose kinase, and by the non-metabolizable D-galactose analogue fucose in the wild-type strain. Interestingly, a mutant in galactose-1-phosphate uridylyl transferase produced beta-galactosidase at a low, constitutive level even on glucose and glycerol and was no longer inducible by D-galactose, whereas it was still inducible by L-arabinose. We conclude that biosynthesis of the intracellular beta-galactosidase of A. nidulans is regulated by CreA, partially repressed by galactose-1-phosphate uridylyl transferase, and induced by D-galactose and L-arabinose in independent ways.


Interplay of Sp1 and Egr-1 in the proximal platelet-derived growth factor A-chain promoter in cultured vascular endothelial cells.
The platelet-derived growth factor (PDGF) A-chain has been implicated in the initiation and progression of vascular occlusive lesions. The elements in the human PDGF-A promoter that mediate increased expression of the gene in vascular endothelial cells have not been identified. A potent inducer of PDGF-A expression in endothelial cells is phorbol 12-myristate 13-acetate (PMA). 5'-Deletion and transfection analysis revealed that a G+C-rich region in the proximal PDGF-A promoter is required for PMA-inducible gene expression. This region bears overlapping consensus recognition sequences for Sp1 and Egr-1. PMA induces Egr-1 mRNA expression within 1 h, whereas PDGF-A transcript levels increase after 2-4 h. Constitutive levels of Sp1 are not altered over 24 h. A specific nucleoprotein complex is formed when an oligonucleotide bearing the G+C-rich element is incubated with nuclear extracts from PMA-treated cells. The temporal appearance of this complex is consistent with the transient increase in Egr-1 transcripts. Antibodies to Egr-1 completely supershift the PMA-induced complex. Interestingly, increased nuclear levels of Egr-1 attenuate the ability of Sp1 to interact with the oligonucleotide, implicating competition between Egr-1 and Sp1 for the G+C-rich element. Binding studies with recombinant proteins demonstrate that Egr-1 can displace Sp1 from this region. Insertion of the G+C-rich element into a hybrid promoter-reporter construct confers PMA inducibility on the construct. Mutations that abolish Egr-1 binding also abrogate expression induced by PMA or overexpressed Egr-1. These findings demonstrate that PMA-induced Egr-1 displaces Sp1 from the G+C-rich element and activates expression driven by the PDGF-A proximal promoter in endothelial cells. The Sp1/Egr-1 displacement mechanism may be an important regulatory circuit in the control of inducible gene expression in vascular endothelial cells.


The spindle checkpoint in the dinoflagellate Crypthecodinium cohnii.
Dinoflagellates are a major group of organisms with an extranuclear spindle. As the purpose of the spindle checkpoint is to ensure proper alignment of the chromosomes on the spindle, dinoflagellate cell cycle control may be compromised to accomodate the extranuclear spindle. In the present study, we demonstrated that nocodazole reversibly prolonged the G2 + M phase of the dinoflagellate cell cycle, in both metaphase and anaphase. The regulation of the spindle checkpoint involves the activation and inhibition of the anaphase promoting complex (APC), which in turn degrades specific cell cycle regulators in the metaphase to anaphase transition. In Crypthecodinium cohnii, nocodazole was also able to induce a prolongation of the degradation of mitotic cyclins and a delay in the inactivation of p13(suc1)-associated histone kinase activities. In addition, cell extracts prepared from C. cohnii in G1 phase and G2/M phase (or nocodazole treated) were able to activate and inhibit, respectively, the degradation of exogenous human cyclin B1 in vitro. The present study thus demonstrated the presence of the spindle checkpoint and APC-mediated cyclin degradation in dinoflagellates. This is discussed in relation to a possible role of the nuclear membrane in mitosis in dinoflagellates.


Orientation of Transverse Acetabular Ligament With Reference to Anterior Pelvic Plane.
Transverse acetabular ligament (TAL) is a 3-dimensional structure which cannot be defined by a single plane. Therefore, we aimed at describing the orientation of different parts of TAL with respect to anterior pelvic plane (APP) and correlate it with gender, body mass index (BMI), and Lewinnek's safe zone. A total of 109 consecutive patients undergoing imageless navigated THA were prospectively studied. Computer navigation was used as the measurement tool. APP was registered for navigation. After excision of osteophytes, a trial component matching the size of unreamed acetabular cavity was aligned with acetabular rim, outer and inner margins, and middle of TAL to record cup orientation with computer tracker. Ninety-nine patients (41 males and 58 females, mean BMI of 28.8kg/m2) were studied after applying exclusion criteria. Mean acetabular inclination was 55.15°, 53.00°, 47.70°, and 42.60° respectively, for acetabular rim, outer, middle, and inner margins of the TAL. Corresponding mean acetabular anteversion was 6.63°, 7.41°, 11.23° and 14.90°respectively. Overall, 17.17%, 28.28%, 47.47% and 71.71% of cup orientation corresponding to acetabular rim, outer, middle, and inner margin of TAL respectively, were within Lewinnek's safe zone. No association was established between BMI and acetabular orientation. Males had overall lesser anteversion than females. We describe orientation of outer, middle, and inner margins of TAL, as reference planes for TAL, in relation to APP. The anteversion differs significantly with gender. A knowledge about these will assist surgeon in component placement during THA, with inner margin of TAL providing the best chance of orientation out of the studied landmarks.


Feed Intake of Growing Dairy Heifers Raised under Tropical Conditions: A Model Evaluation Using Meta-Analysis.
Several models for predicting dry matter intake (DMI) of replacement dairy heifers have been developed; however, only a few have been evaluated using data from heifers of different breeds raised under tropical conditions. Thus, the objective of this study was to evaluate the DMI equations for dairy heifers managed under tropical conditions. A total of 230 treatment means from 61 studies using dairy heifers (n = 1513 heifers, average body weight = 246 kg) were used. The animals were grouped into two groups based on their genetics: (1) Bos taurus (Holstein, Jersey, Brown Swiss, and Holstein × Jersey) and (2) crossbred (Bos taurus × Bos indicus). Seven previously published DMI equations (HH, HHJ, QUI, STA, 2001 NRC, OFLin, and OFNLin) for heifers were evaluated using mean bias, slope bias, mean squared prediction errors (MSPE) and its decomposition, and other model evaluation statistics. For Bos taurus heifers, our results indicated that OFNLin and HHJ had lower mean bias (0.13 and 0.16 kg/d, respectively) than other models. There was no significant slope or mean bias for HHJ and OFNLin (p > 0.05), indicating agreement between the observed and predicted DMI values. All other models had a significant mean bias (p < 0.05), whereas the QUI model also presented a significant slope bias (p < 0.02). For crossbred heifers, the STA equation was the only one that did not present mean and slope bias significance (p > 0.05). All other DMI models had significant mean bias when evaluated using crossbred data (p < 0.04), and QUI, OFLin, and OFNLin also presented significant slope bias (p < 0.01). Based on our results, predictions from OFNLin and HHJ best represented the observed DMI of Bos taurus heifers (MSPE ≤ 1.25 kg2/d2, mean bias ≤ 0.16 kg/d), whereas STA was the best model for crossbred heifers (MSPE = 1.25 kg2/d2, mean bias = 0.09 kg/d). These findings indicate that not all available models are adequate for estimating the DMI of dairy heifers managed under a tropical climate, with HHJ and OFNLin for Bos taurus and STA for crossbreds being the most suitable models for DMI prediction. There is evidence that models from Bos taurus heifers could be used to estimate the DMI of heifers under tropical conditions. For heifer ration formulation is necessary to consider that DMI is influenced by breed, diet, management, and climate. Future work should also include animal genetic and environmental variables for the prediction of DMI in dairy heifers.


The Relative Impact of Urinary and Sexual Function vs Bother on Health Utility for Men With Prostate Cancer.
Function and bother are related but distinct aspects of health-related quality of life. The objective of this study was to compare quantitatively the relative impacts of function and bother in urinary, sexual, and bowel outcomes on health utility as a reflection of health-related quality of life in men with prostate cancer. Our analysis included participants in the Cancer of the Prostate Strategic Urologic Research Endeavor utility supplementary study, with a final cohort of 1617 men. Linear regression on the patients' function and bother summary scores (0-100) from the University of California, Los Angeles Prostate Cancer Index was performed to predict bias-corrected health utilities. Urinary and sexual bother were associated with each health utility, and their coefficients were 3.7 and 20.8 times greater, respectively, than those of the corresponding function. To our knowledge, our study provides the first quantitative and direct comparison of the impacts of function vs bother on health utility.


[Palmar lunate dislocation].
Palmar lunate dislocation as the end stage of a perilunate dislocation is a very uncommon injury. Having treated 19,534 hospitalized patients between 1 January 1986 and 1 October 2001 the diagnosis was recorded in four male trauma patients (33, 36, 37 and 62 years old). Among the operatively treated carpal dislocations and carpal fracture dislocations those of the lunate were seen in five per cent. The dislocation was caused in by an acute hyperextension injury resulting of falls from heights in three cases, and of a motorcycle accident in a further case. In two of these cases a complete palmar lunate dislocation was analysed that were produced by fall from seven meters heights of a young craftsman and by accident of a motorcyclist. First using a longitudinal palmar approach in both cases a revision of the hemorrhagic carpal canal was performed urgently, the largely denuded lunate was reduced and the repair of identified ligamentous structures was performed by means of sutures respectively suture anchors. Reduction was stabilized with Kirschner wires. Afterwards performed computed tomography identified the result of reduction and associated defects (subluxation distal radioulnar joint). In one patient a soft tissue infection prevented the dorsal ligamentous repair. In spite of a consequent after-treatment and a good functional result a scapho-lunate dissociation was proved. An avascular defect of the lunate could be excluded by magnetic resonance imaging. In case of a secondary performed dorsal repair a persisting carpal stabilization with a satisfactory functional result could achieved. At second hand an advanced carpal collapse was proved. If reduction cannot be achieved by closed manipulation or a loss of reduction is shown, open reduction is indicated first by a palmar approach. An additional dorsal ligamentous repair seems to be necessary. Transfixation by Kirschner wires and suture anchors stabilize the restored anatomic relationships. Wrist immobilization in a cast for at least eight weeks is recommended. Although ligamentous insufficiency, osteoarthrosis and avascular necrosis are often proved, functional results are satisfactory.


Aberrant Patterns of Sensory-Evoked Activity in the Olfactory Bulb of LRRK2 Knockout Mice.
The LRRK2 gene is the major genetic determinant of familiar Parkinson's disease (PD). Leucine-rich repeat kinase 2 (LRRK2) is a multidomain protein involved in several intracellular signaling pathways. A wealth of evidence indicates that LRRK2 is enriched at the presynaptic compartment where it regulates vesicle trafficking and neurotransmitter release. However, whether the role of LRRK2 affects neuronal networks dynamic at systems level remains unknown. Addressing this question is critical to unravel the impact of LRRK2 on brain function. Here, combining behavioral tests, electrophysiological recordings, and functional imaging, we investigated neuronal network dynamics, in vivo, in the olfactory bulb of mice carrying a null mutation in LRRK2 gene (LRRK2 knockout, LRRK2 KO, mice). We found that LRRK2 KO mice exhibit olfactory behavioral deficits. At the circuit level, the lack of LRRK2 expression results in altered gamma rhythms and odorant-evoked activity with significant impairments, while the spontaneous activity exhibited limited alterations. Overall, our data in the olfactory bulb suggest that the multifaced role of LRRK2 has a strong impact at system level when the network is engaged in active sensory processing.


Effects of Levothyroxine and thyroid stimulating hormone on bone loss in patients with primary hypothyroidism.
Previous studies on bone mineral density (BMD) abnormalities associated with hypothyroidism are scarce and not conclusive. The effect of thyroid hormone therapy on BMD has shown mixed results. The aim of the present study was to determine the severities of osteoporosis in female patients with hypothyroidism in comparison to healthy women. This cross-sectional descriptive study was performed on 150 women aged over 50 years. Totally, 100 patients with primary hypothyroidism and 50 healthy subjects were enrolled in this study and divided into three groups. Group A, which consisted the patients who had been recently diagnosed with primary hypothyroidism. The second group of patients diagnosed with primary hypothyroidism for at least 2 years and was treated with levothyroxine (Group B). The third group of healthy individuals was selected as a control group (Group C). Blood samples were taken for the measurements of thyroid stimulating hormone (TSH), and bone densitometry was performed to determine the BMD reported as T-score in order to measure the severity of osteoporosis. T-score of the lumbar vertebra (L2-L4) and femoral neck were measured with dual energy X-ray absorptiometry and were compared between the three groups. Data were analyzed by SPSS using regression analysis and Mann-Whitney, Kruskal-Wallis, or analysis of variances statistical tests. The statistical significance was set at a P < 0.05. The average age of patients and baseline serum TSH levels in Group B was significantly different from the other two groups (P < 0.001). T-score of the lumbar spine (L2-L4) in Group B was significantly lower than the other groups (P = 0.01). The linear regression between serum TSH levels and BMD categories were not clearly associated. However, after removing the effect of the baseline TSH level in Group B, bone loss was significantly greater than the other two groups (P = 0.01). According to the present study, it seems that the treatment of hypothyroidism with thyroid hormones reduces both serum levels of TSH and bone density. Hence, proper control of this risk factor can be an effective way in prevention of osteoporosis.


Identification of bioactive compounds of Bacillus velezensis HNA3 that contribute to its dual effects as plant growth promoter and biocontrol against post-harvested fungi.
The current study is an extension to our previous work on the plant growth-promoting rhizobacteria (PGPR) Bacillus velezensis HNA3 strain, which comes to confirm and reveals the huge stock of active secondary metabolites produced by HNA3. HNA3-emitted volatile organic compounds (VOCs) have demonstrated the capacity to impede the growth of phytopathogens affecting some fruits and vegetables, even in the absence of direct contact. Additionally, these volatiles enhanced soybean seed germination by breaking seed dormancy and inducing root system development. Furthermore, they promoted seedling growth, giving it prominence in soybean cultivation. The relevance of active volatiles derives from the fact that they can be developed as natural-safe biocontrol agents and plant promoters. This research validates the remarkable bioactivities exhibited by the Bacillus velezensis HNA3 and their potential applications in agriculture as an inoculant, encompassing biocontrol, plant growth promotion, and seed germination activities, thereby offering a safer alternative to hazardous chemicals.


The role of vitamin D supplementation in the risk of developing pneumonia: three independent case-control studies.
Vitamin D plays a role in host defence against infection. Vitamin D deficiency has been associated with an increased risk of respiratory tract infections in children and adults. This study aimed to examine whether vitamin D supplementation is associated with a lower pneumonia risk in adults. Three independent case-control studies were performed including a total of 33 726 cases with pneumonia in different settings with respect to hospitalisation status and a total of 105 243 controls. Cases and controls were matched by year of birth, gender and index date. The major outcome measure was exposure to vitamin D supplementation at the time of pneumonia diagnosis. Conditional logistic regression was used to compute ORs for the association between vitamin D supplementation and occurrence of pneumonia. Vitamin D supplementation was not associated with a lower risk of pneumonia. In studies 1 and 2, adjustment for confounding resulted in non-significant ORs of 1.814 (95% CI 0.865 to 3.803) and 1.007 (95% CI 0.888 to 1.142), respectively. In study 3, after adjustment for confounding, the risk of pneumonia remained significantly higher among vitamin D users (OR 1.496, 95% CI 1.208 to 1.853). Additional analyses showed significant modification of the association through co-use of corticosteroids and drugs that affect bone mineralisation. For patients using these drugs, ORs below one were found combined with higher ORs for patients not using these drugs. This study showed no preventive association between vitamin D supplementation and the risk of pneumonia in adults.


GPR30 Activation Promotes the Progression of Gastric Cancer and Plays a Significant Role in the Anti-GC Effect of Huaier.
Gastric cancer (GC) is one of the most common types of cancer. The n-butanol extract of Huaier (NEH) is the alcohol-soluble part extracted by the systematic solvent method, which is effective against gastric cancer (GC). However, the mechanism of action of NEH remains unclear. In this study, we aim to evaluate the clinical relevance of GPR30 expression in GC patients and the role of the GPR30/PI3K/AKT signalling pathway in the anti-GC effect of NEH. The expression of GPR30 was examined using immunohistochemistry. Cell counting kit 8 (CCK-8) assay, wound healing, and transwell experiments were used to investigate the viability, migration, and invasion of gastric cancer cells. Western blotting was used to detect the expression of GPR30 and its downstream signalling molecules of the PI3K/AKT signalling pathway. Gastric cancer patient-derived xenografts (PDX) mouse model was used to evaluate the antitumor effect of NEH in vivo. In addition, the graded doses and the maximum tolerated dose of NEH were administered intraperitoneally into the mice for acute toxicity test. We demonstrate that GPR30 expression in GC tissues was significantly higher than that in corresponding adjacent noncancerous tissues and the expression of GPR30 was correlated with a poor prognosis in GC patients. Moreover, GPR30 expression was involved in the migration and invasion of GC cells in vitro. Additionally, we found that NEH can suppress the growth of GC in patient-derived xenograft tumors in vivo. Furthermore, NEH inhibited the proliferation, migration, and invasion in GC cells in a concentration-dependent manner through inhibiting the GPR30-mediated PI3K/AKT signalling pathway in vitro. Acute toxicity test showed that NEH caused no toxic reaction or death and the maximum tolerated dose of NEH in mice was greater than 1600 mg/kg. Our results demonstrate that the high expression of GPR30 is an independent factor of poor prognosis in patients with GC and NEH could be a new agent for the treatment of gastric cancer.


Active and Protected: Developing a "Safer Sex" Handout for Adolescents and Young Adults with Cancer.
There is a critical need to engage adolescents and young adults (AYAs) with cancer in conversations regarding "safer" sexual activity during treatment. Many providers, however, report lacking the knowledge and/or tools to engage in these discussions. This article describes the experience of one pediatric institution in assessing and addressing provider barriers to safer sexual activity discussions among AYAs with cancer. Feedback from patients and providers resulted in an educational handout detailing recommendations regarding safer sex practices for AYAs with cancer. Handout adoption, acceptability, appropriateness, and feasibility are described alongside barriers to assist other institutions seeking to develop similar interventions.


A New Rabbit Model of Chronic Dry Eye Disease Induced by Complete Surgical Dacryoadenectomy.
Purpose/Aim: Dry eye disease (DED), common and suboptimally treated, is in need of novel animal models to understand its pathophysiology and assess the efficacy and other parameters of new pharmacological agents for its treatment. The more than 10 rabbit models of DED described to date have significant limitations including induction of mild disease, lack of consistency, and off-target effects when chemical agents are used for disease induction. Our aim was to develop a new model of chronic DED in rabbits that overcomes the limitations of existing models. We performed a complete surgical resection of all orbital lacrimal glands (LGs; dacryoadenectomy) in normal adult New Zealand White rabbits. One week after removal of the nictitating membrane, we surgically removed the orbital superior LG, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Surgery was performed under anesthesia, required about 1 h/eye, and was well-tolerated. Dacryoadenectomy induced severe DED, evidenced by >90% reduction in the tear break up time test, 50% reduction in the Schirmer tear test, 10% increase in tear osmolarity, and a marked increase in the rose bengal staining score. DED was sustained and essentially unchanged for the eight weeks of observation. Sham-operated rabbits showed no such changes, with the exception of a non-significant and transient reduction in the tear break up time test, a response to ocular surgery. This model of stable, chronic, predominantly aqueous-deficient DED recapitulates key clinical and histological features of human DED and is suitable for the study of ocular surface homeostasis, of the pathophysiology of DED, and of the efficacy of candidate drugs for DED treatment.


Early evaluation and value-based pricing of regenerative medicine technologies.
Since the first pioneering scientists explored the potential of using human cells for therapeutic purposes the branch of regenerative medicine has evolved to become a mature industry. The focus has switched from 'what can be done' to 'what can be commercialized'. Timely health economic evaluation supports successful marketing by establishing the value of a product from a healthcare system perspective. This article reports results from a research project on early health economic evaluation in collaboration with developers, clinicians and manufacturers. We present an approach to determine an early value-based price for a new treatment of cartilage defects of the knee from the area of regenerative medicine. Examples of using evaluation results for the purpose of business planning, market entry, preparing the coverage decision and managed entry are discussed.