Eating Away from Home: Influences on the Dietary Quality of Adolescents with Overweight or Obesity.
To examine the influence of peers and the source of meals and snacks on the dietary quality of adolescents seeking obesity treatment. Baseline surveys were completed by 173 adolescents with overweight or obesity (11-16 years old) enrolled in an e-health intervention in Vancouver, British Columbia. Dietary quality was assessed with three 24-h dietary recalls used to compute a Healthy Eating Index adapted to the Canadian context (HEI-C). Multiple linear regression examined associations between HEI-C scores and the frequency of: (i) meals prepared away from home, (ii) purchasing snacks from vending machines or stores, (iii) eating out with friends, and (iv) peers modeling healthy eating. Adolescents reported eating approximately 3 lunch or dinner meals prepared away from home and half purchased snacks from vending machines or stores per week. After adjusting for socio-demographics, less frequent purchases of snacks from vending machines or stores (b = -3.00, P = 0.03) was associated with higher HEI-C scores. More frequent dinner meals prepared away from home and eating out with friends were only associated with lower HEI-C scores in unadjusted models. Snack purchasing was associated with lower dietary quality among obesity treatment-seeking adolescents. Improving the healthfulness of foods obtained away from home may contribute to healthier diets among these adolescents.


Maintenance therapy in advanced non-small cell lung cancer.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the industrialized world, and survival rates for advanced disease remain low with standard platinum-based chemotherapy. One treatment strategy that has been investigated extensively in NSCLC is that of "maintenance" therapy. Options for maintenance include maintaining response to initial therapy by continuing the initial combination chemotherapy regimen, continuing only single agent chemotherapy, or by introducing a new agent. Treatments that have been studied in randomized trials to date include chemotherapy, molecularly targeted agents, and immunotherapy approaches. After the development of multiple new agents that show activity in NSCLC and have a tolerable side effect profile, there has been increasing interest recently in this treatment strategy. In this study, we examine the evolution of this strategy by reviewing trials investigating the main treatment paradigms used in maintenance therapy for NSCLC.


The effect of neurosphere culture conditions on the cellular metabolism of glioma cells.
Malignant gliomas, with an average survival time of 16-19 months after initial diagnosis, account for one of the most lethal tumours overall. Current standards in patient care provide only unsatisfying strategies in diagnostic and treatment for high-grade gliomas. Here we describe metabolic phenomena in the choline and glycine network associated with stem cell culture conditions in the classical glioma cell line U87. Using high-resolution proton magnetic resonance spectroscopy of cell culture metabolic extracts we compare the metabolic composition of U87 chronically propagated as adherent culture in medium supplemented with serum to serum-free neurosphere growth. We found that the switch to neurosphere growth, besides the increase of cells expressing the putative glioma stem cell marker CD133, modulated a number of intracellular metabolites including choline, creatine, glycine, and myo-inositol that have been previously reported as potential diagnostic markers in various tumours. These findings highlight the critical influence of culture conditions on glioma cell metabolism, and therefore particular caution should be drawn to the use of in vitro system research in order to investigate cancer metabolism.


Hamster female protein. A new Pentraxin structurally and functionally similar to C-reactive protein and amyloid P component.
Female protein (FP), a serum protein present in normal female hamsters was found to be similar to acute-phase reactant, C-reactive protein (CRP) and serum amyloid P component (SAP) in the following ways: (a) hamster FP complexed with phosphorylcholine (PC) in a Ca++-dependent fashion as shown by its isolation from serum by affinity chromatography with PC-Sepharose and selective elution with free PC or EDTA; (b) electron microscopy of FP indicated a pentameric structure similar in size and appearance to other pentraxins; (c) the parent molecule of FP (150,000 mol wt) was composed of five noncovalantly assembled subunits of 30,000 mol wt; and (d) the amino acid analysis and terminal NH2 sequence of FP clearly showed homology with SAP-CRP. Although FP evolved from an ancestral gene common to SAP and CRP, and shares functional, morphological and structural properties with these acute-phase proteins, the biological homology of FP appears quite diverse as this protein is a prominent serum constituent (1-2 mg/ml) of normal female hamsters and under hormonal control (testosterone suppression) in males.


Organic carbon burial is paced by a ~173-ka obliquity cycle in the middle to high latitudes.
Earth's climate system is complex and inherently nonlinear, which can induce some extraneous cycles in paleoclimatic proxies at orbital time scales. The paleoenvironmental consequences of these extraneous cycles are debated owing to their complex origin. Here, we compile high-resolution datasets of total organic carbon (TOC) and stable carbon isotope (δ13Corg) datasets to investigate organic carbon burial processes in middle to high latitudes. Our results document a robust cyclicity of ~173 thousand years (ka) in both TOC and δ13Corg The ~173-ka obliquity-related forcing signal was amplified by internal climate feedbacks of the carbon cycle under different geographic and climate conditions, which control a series of sensitive climatic processes. In addition, our new and compiled records from multiple proxies confirm the presence of the obliquity amplitude modulation (AM) cycle during the Mesozoic and Cenozoic and indicate the usefulness of the ~173-ka cycle as geochronometer and for paleoclimatic interpretation.


A Regional Outbreak of Clostridium difficile PCR-Ribotype 027 Infections in Southeastern France from a Single Long-Term Care Facility.
OBJECTIVE To describe and analyze a large outbreak of Clostridium difficile 027 (CD-027) infections. METHODS Confirmed CD-027 cases were defined as CD infection plus real-time polymerase chain reaction assay (PCR) positive for CD-027. Clinical and microbiological data on patients with CD-027 infection were collected from January 2013 to December 2015 in the Provence-Alpes-Côte-d'Azur region (southeastern France). RESULTS In total, 19 healthcare facilities reported 144 CD-027 infections (112 confirmed and 32 probable CD-027 infections) during a 22-month period outbreak. Although the incidence rate per 10,000 bed days was lower in long-term care facilities (LTCFs) than in acute care facilities (0.05 vs 0.14; P<.001), cases occurred mainly in LTCFs, one of which was the probable source of this outbreak. After centralization of CD testing, the rate of confirmed CD-027 cases from LTCFs or residential-care homes increased significantly (69% vs 92%; P<.001). Regarding confirmed CD-027 patients, the sex ratio and the median age were 0.53 and 84.2 years, respectively. The 30-day crude mortality rate was 31%. Most patients (96%) had received antibiotics within 3 months prior to the CD colitis diagnosis. During the study period, the rate of patients with CD-027 (compared with all patients tested in the point-of-care laboratories) decreased significantly (P=.03). CONCLUSIONS A large CD-027 outbreak occurred in southeastern France as a consequence of an initial cluster of cases in a single LTCF. Successful interventions included rapid isolation and testing of residents with potentially infectious diarrhea and cohorting of case patients in a specialized infectious diseases ward to optimize management. Infect Control Hosp Epidemiol 2016;1-5.


Safety and efficacy of transurethral resection of prostate glands up to 150 ml: a prospective comparative study with 1 year of followup.
We investigated the safety and efficacy of transurethral resection of the prostate (TURP) for prostate glands between 70 and 150 ml. We prospectively evaluated 113 patients treated with TURP for benign prostatic hyperplasia. A total of 57 patients with a prostate volume of less than 70 ml were assigned to group 1, while 56 with a prostate volume of between 70 and 150 ml were assigned to group 2. Preoperative parameters considered in each patient were prostate volume, International Prostate Symptom Score (I-PSS), urinary flow rate measurement (Qmax) and post-void residual urine volume (PVR). Operative time, resected tissue weight and all complications were recorded. All patients were evaluated 3 months and 1 year postoperatively. Preoperative, perioperative and postoperative data on the 2 groups were compared. Each group achieved significant improvement in I-PSS, Qmax and PVR. Operative time was significantly longer in group 2 but the complication rate was similar in the 2 groups. Group 2 resulted in better improvements in Qmax and I-PSS. At 1 year of followup PVR was significantly lower in group 1 than in group 2. Multivariate analysis revealed that only age was a significant independent predictor of complications, and only age and initial Qmax were independent predictive variables of outcome. TURP for large prostate glands is a safe procedure without showing a different complication rate compared with TURP for recommended volumes. Patients with a baseline prostate volume of greater than 70 ml seem to achieve better improvement in obstruction and symptoms.


An SH3 binding region in the epithelial Na+ channel (alpha rENaC) mediates its localization at the apical membrane.
The amiloride-sensitive Na+ channel constitutes the rate-limiting step for Na+ transport in epithelia. Immunolocalization and electrophysiological studies have demonstrated that this channel is localized at the apical membrane of polarized epithelial cells. This localization is essential for proper channel function in Na+ transporting epithelia. In addition, the channel has been shown to associate with the cytoskeletal proteins ankyrin and alpha-spectrin in renal epithelia. However, the molecular mechanisms underlying the cytoskeletal interactions and apical membrane localization of this channel are largely unknown. In this study we show that the putative pore forming subunit of the rat epithelial (amiloride-sensitive) Na+ channel (alpha ENaC) binds to alpha-spectrin in vivo, as determined by co-immunoprecipitation. This binding is mediated by the SH3 domain of alpha-spectrin which binds to a unique proline-rich sequence within the C-terminal region of alpha rENaC. Accordingly, the C-terminal region is sufficient to mediate binding to intact alpha-spectrin from alveolar epithelial cell lysate. When microinjected into the cytoplasm of polarized primary rat alveolar epithelial cells, a recombinant fusion protein containing the C-terminal proline-rich region of alpha rENaC localized exclusively to the apical area of the plasma membrane, as determined by confocal microscopy. This localization paralleled that of alpha-spectrin. In contrast, microinjected fusion protein containing the N-terminal (control) protein of alpha rENaC remained diffuse within the cytoplasm. These results suggest that an SH3 binding region in alpha rENaC mediates the apical localization of the Na+ channel. Thus, cytoskeletal interactions via SH3 domains may provide a novel mechanism for retaining proteins in specific membranes of polarized epithelial cells.


Bladder recurrence of primary upper tract urinary carcinoma following nephroureterectomy, and risk of upper urinary tract recurrence after ureteral stent positioning in patients with primary bladder cancer.
Upper tract urinary carcinoma (UTUC) and bladder cancer (BCa) share similar biological, histological and pathological characteristics. These resemblances could explain the high rate of synchronous and metachronous tumors affecting both upper urinary tract and bladder. In patients affected by primary UTUC bladder recurrence is quite common and it represents one of the major concerns during the follow-up of patients who underwent radical nephroureterectomy. Conversely, UTUC recurrence after primary non-muscular invasive BCa is a relatively rare event. Moreover, there is no clear evidence on whether the use of Double-J stenting as drainage in patients affected by BCa increases the risk of UTUC recurrence. The aim of the current study was to summarize the most recent evidence regarding the bladder recurrence after UTUC surgical treatment, and the UTUC recurrence after stent positioning in patients affected by primary BCa.


Culture and postpartum mood problems: similarities and differences in the experiences of first- and second-generation Canadian women.
Few studies have examined the role of culture in a woman's experience of postpartum mood problems (PPMP). This study explored differences and similarities in experiences of PPMP between first- and second-generation Canadian women. In this exploratory qualitative study, we interviewed nine first-generation and eight second-generation women who were clients of the Women's Health Centre at St. Joseph's Health Centre in Toronto, Canada. Using semistructured interviews, we explored how women perceived and experienced PPMP. Four themes reflected cultural issues: PPMP stigma, relationship with parents/in-laws, internalization of society's expectations of motherhood, and identity issues/relationship with self. The results of this study contribute to a limited literature on possible contributing factors to PPMP and can inform development of resources for delivering culturally appropriate mental health care for women dealing with PPMP.


Systematic determination of coupling constants in spin clusters from broken-symmetry mean-field solutions.
Quantum-chemical calculations aimed at deriving magnetic coupling constants in exchange-coupled spin clusters commonly utilize a broken-symmetry (BS) approach. This involves calculating several distinct collinear spin configurations, predominantly by density-functional theory. The energies of these configurations are interpreted in terms of the Heisenberg model, H̃=∑i<jJijs̃i⋅s̃j, to determine coupling constants Jij for spin pairs. However, this energy-based procedure has inherent limitations, primarily in its inability to provide information on isotropic spin interactions beyond those included in the Heisenberg model. Biquadratic exchange or multi-center terms, for example, are usually inaccessible and hence assumed to be negligible. The present work introduces a novel approach employing BS mean-field solutions, specifically Hartree-Fock wave functions, for the construction of effective spin Hamiltonians. This expanded method facilitates the extraction of a broader range of coupling parameters by considering not only the energies, but also Hamiltonian and overlap elements between different BS states. We demonstrate how comprehensive s=12 Hamiltonians, including multi-center terms, can be straightforwardly constructed from a complete set of BS solutions. The approach is exemplified for small clusters within the context of the half-filled single-band Hubbard model. This allows to contrast the current strategy against exact results, thereby offering an enriched understanding of the spin-Hamiltonian construction from BS solutions.


Proton transfer in the K-channel analog of B-type Cytochrome c oxidase from Thermus thermophilus.
A key enzyme in aerobic metabolism is cytochrome c oxidase (CcO), which catalyzes the reduction of molecular oxygen to water in the mitochondrial and bacterial membranes. Substrate electrons and protons are taken up from different sides of the membrane and protons are pumped across the membrane, thereby generating an electrochemical gradient. The well-studied A-type CcO uses two different entry channels for protons: the D-channel for all pumped and two consumed protons, and the K-channel for the other two consumed protons. In contrast, the B-type CcO uses only a single proton input channel for all consumed and pumped protons. It has the same location as the A-type K-channel (and thus is named the K-channel analog) without sharing any significant sequence homology. In this study, we performed molecular-dynamics simulations and electrostatic calculations to characterize the K-channel analog in terms of its energetic requirements and functionalities. The function of Glu-15B as a proton sink at the channel entrance is demonstrated by its rotational movement out of the channel when it is deprotonated and by its high pKA value when it points inside the channel. Tyr-244 in the middle of the channel is identified as the valve that ensures unidirectional proton transfer, as it moves inside the hydrogen-bond gap of the K-channel analog only while being deprotonated. The electrostatic energy landscape was calculated for all proton-transfer steps in the K-channel analog, which functions via proton-hole transfer. Overall, the K-channel analog has a very stable geometry without large energy barriers.


Optimal Allocation of Enterprise Resources Based on the Intelligent Algorithm from the Perspective of Multidimensional Dynamic Innovation.
Faced with the upsurge of digital technology, many small and medium-sized startups are aware of the opportunities and challenges it brings and are actively responding to digital transformation. Digital transformation is a type of strategic change with certain risks. On the one hand, this requires business leaders to have a sense of change, and on the other hand, it also requires certain resources to be invested. As a result, in the real world, not all small and medium-sized entrepreneurial firms have the ability or inclination to implement digital transformation. SMEs' digital transformation has become a key factor in promoting the national economy's transition from new and old kinetic energy and providing new prospects for development of small and medium firms. As a starting point, this study devises an index system for assessing the digital maturity of small and medium-sized businesses. Based on the AHP method in the multicriteria framework, a hierarchical structure is established for each index, a three-layer basic framework is established, and the weight of the evaluation index is calculated. Second, this work establishes a BP network model for digital transformation maturity assessment of startups based on AHP and establishes a three-layer BP network structure. This work aims to optimize BP network using the improved ISFLA algorithm. It improves the adaptive step size update formula in the SFLA algorithm by using the mutation operator and improves the evolution method of the worst individual of the frog to the simultaneous evolution of multiple poor individuals. The constructed ISFLA-BP algorithm is then used to evaluate the digital transformation maturity of small and medium-sized startups. Finally, systematic and comprehensive experiments are carried out to verify superiority as well as feasibility of the method.


High resolution computed tomography (HRCT) and new perspectives in functional radiology of the lung.
Computed Tomography (CT) with the advent of new techniques as high resolution computed tomography (HRTC) and spiral CT with 3D reconstructions (3D CT) allows a new morphologic-qualitative as well as functional-quantitative evaluation of pulmonary perfusion and ventilation. HRCT allows the identification of secondary lobule and a detailed morphologic and comparative analysis of minute distal anatomical structures with combined densitometric evaluation of lung parenchyma on perfusion. In particular, a new, more specific significance could be attributed to changes in density of lung parenchyma (mosaic pattern) with associated assessment of the vessel number, caliber and distribution, and a comparative evaluation of vessels and density between healthy and impaired areas. The "optical" HRCT evaluation on serial axial scans in inspiration and expiration allows the functional assessment of compartments which require spirometry and tests of respiratory function. Spiral CT allows volumetric acquisitions in a single breath which can be reconstructed and processed according to single requirements. 3D tailored reconstruction of spiral CT exam in maximum inspiration and expiration with a dedicated densitometric window (-1024/+ 100 HU) allows the calculation of total lung volume (TLV), of both lungs, of a single lung or selected sections. With the "air" densitometric window (-1024/-400 HU) the total lung capacity (TLC) and residual volume (RV) are calculated. The ratio between these values and the corresponding TLV represents the lung aeration index (LAI). 3D reconstruction with fixed densitometric value corresponding to median air density (peak of histogram) allows the scintigraphic-like "alveolographic" reconstruction of lung ventilation. Combined 3D CT and HRCT evaluation possibly from a single spiral CT exam, is used in the morphologic-functional diagnosis of respiratory pathophysiology.


Microbiological and immunological profile of patients with severe lupus flares related to bloodstream infections: a retrospective cohort study.
Background This study aimed to address whether bloodstream infections are a risk factor for the development of severe lupus flares, as well as clinical, immunological and microbiological features of patients with bloodstream infections that develop severe lupus flares. Methods We performed a retrospective cohort study comparing 87 systemic lupus erythematosus (SLE) patients with bloodstream infections and 87 hospitalized SLE patients without bloodstream infections as a comparison group. All patients were followed up for at least 3 months or until one of the primary outcomes was developed (severe SLE flare according to SELENA/SLEDAI score or death). Microbiological features of all bloodstream infections were recorded. The disease status at the end of follow up was registered. Results A total of 23 patients (13.2%) developed a severe flare during follow up; among them, 20 (87%) had an associated episode of bloodstream infection ( p < 0.001). The most frequent flares were renal (43.4%) and severe thrombocytopenia (26%). After multivariate analysis, baseline-independent factors associated with severe SLE flare were bloodstream infection [hazard ratio (HR) 7.3, 95% confidence interval (CI) 2.13-24.95; p = 0.002]. Among patients with bloodstream infections, low C4 levels (HR 2.43, 95% CI 1.04-5.69: p = 0.04) and Streptococcus pneumoniae were associated with severe SLE flare (HR 3.41, 95% CI 1.68-6.91; p = 0.012). Conclusions SLE patients with bloodstream infections, especially due to S. pneumoniae, and low C4 levels, are at higher risk for development of severe SLE flares.


Effect of education on ability of AI professionals and herd-owner inseminators to detect cows not in oestrus and its relation with progesterone concentration on day of re-insemination.
The effect of training background of persons performing artificial insemination (AI) (herd-owner inseminators (OWNER), AI technicians (AI-T), and fertility consultants (FC)) on pregnancy rate and their ability to detect cows not in oestrus were studied. A total of 1584 re-AI occasions on 754 dairy farms were included. Milk samples for progesterone (P4) analysis in all cases were collected, as were data on the herd, previous breeding attempts, oestrous signs, uterine tone, slipperiness of cervix, and co-operation of the cow. Further breeding attempts and next calving or culling date were sought from registers. The cases were distributed into three categories based on P4 concentrations; <6 nmol/l (no luteal activity, could be in oestrus), 6-10 nmol/l (some luteal activity), and >10 nmol/l (high luteal activity, not in oestrus). Of cows offered for re-AI 7.7% had P4 concentration >10 nmol/l, with no difference between OWNER farms and farms using AI service. OWNERs chose for AI more cows having intermediate P4 than farms using AI service (9.8% vs. 5.9%, p < 0.05). AI-Ts recommended no AI significantly less often than FCs (1.6% vs. 4.9%, p < 0.01). Both groups were equally right: 71% and 68% of cows that were recommended to have no AI had high P4 concentration. Due to courageous and correct rejection of cows with high P4, FCs inseminated proportionally more cows in low P4 and less cows in intermediate P4 than OWNERs (p < 0.05). Of cows finally inseminated, 36.7% became pregnant, with no difference between OWNER farms and farms using AI service. Fertility consultants had higher pregnancy rates than AI-Ts (39.6% vs. 32.6%, p < 0.05). Toneless uterus and sticky cervix at AI significantly correlated with AI occurring at the wrong time (p < 0.001). Behaviour of the cow at AI did not predict P4 concentration. In conclusion, 7.7% of cows offered for re-AI had high P4 concentration. Training of AI personnel increased their ability to detect and reject these cows.


Post-ERCP pancreatogastric fistula associated with an intraductal papillary-mucinous neoplasm of the pancreas--a case report and literature review.
Fistula formation has been reported in intraductal papillary-mucinous neoplasms (IPMNs) with or without invasion of the adjacent organs. The presence or absence of invasion is mostly determined by postoperative histological examination rather than by preoperative work-up. A 72 year-old Japanese woman showed remarkable dilatation of the main pancreatic duct (MPD) in the distal region of the pancreas. Subsequent ERCP also showed MPD dilatation, after which the patient suffered moderate pancreatitis. A subsequent gastroscopy revealed a small ulceration that had not been observed in a gastroscopy performed 3 months prior. Mucinous discharge from the ulceration suggested it might be the orifice of a fistula connected to the MPD. En bloc resection including the distal region of the pancreas, spleen, stomach and part of the transverse colon was performed under the pre- and intraoperative diagnosis of an invasive malignant IPMN. However, histopathology revealed the lesion to be of "borderline malignancy" without apparent invasion of the stomach. Light microscopy showed inflammatory cellular infiltrates (mainly neutrophils) around the pancreatogastric fistula, but there was no evidence of neoplastic epithelia lining the fistulous tract. This case highlights that a pancreatogastric fistula can develop after acute inflammation of the pancreas in the absence of cancer invasion. Further information regarding IPMN-associated fistulae is necessary to clarify the pathogenesis, diagnosis, appropriate surgical intervention and prognosis for this disorder.


[First Insights into Scope of Practice and Salary of Physician Assistants, A New Healthcare Profession, in Germany].
In 2010, the first government-approved physician assistant (PA) program was introduced at the Baden-Wuerttemberg Cooperative State University Karlsruhe (DHBW). There are not sufficient data regarding the scope of practice and salary of our graduates. Therefore, the aim of the present study was to obtain information regarding these. The survey included all graduates (2 classes, n=27). A specific questionnaire was developed, including 37 questions e. g. on the current employment status, scope of practice, salary and job satisfaction regarding the PA program and career. A descriptive analysis of the data was carried out using SPSS. 25 graduates participated in the survey (96.1%); the average age of participants was 32.2 years (25-53 years). 88% (n=22) were employed as a PA, most of them worked in internal medicine (n=11) or surgery (n=9). Responsibilities that are often or very often assigned to the PAs are preparing final documents, taking over a coordinating role in the therapeutic team, as well as participation in taking patient medical history and conducting physical examinations. In two-thirds of respondents, the gross monthly base salary (full-time position) was about 3000 euros. 77.3% (n=17) of graduates were generally satisfied or very satisfied with their current situation. It appears that graduates of the DHBW are well integrated into the staff structure of hospitals, as far as the scope of practice and average salary are concerned. Further studies on the integration of this new profession in Germany and on their extended scope of practice in comparison to established healthcare professions will be conducted.


Detection of ocular melanoma with 4-(3-dimethylaminopropylamino)-7-[123I]-iodoquinoline.
Iodine-123-labeled 4-(3-dimethylpropylamino)-7-iodoquinoline was evaluated in nine patients. By using a specially designed dual-pinhole ocular collimator, it was possible to obtain positive images at 2-6 hr for only 70% of the cases with subsequently proven ocular melanomas.


Blast-related traumatic brain injury.
A bomb blast may cause the full severity range of traumatic brain injury (TBI), from mild concussion to severe, penetrating injury. The pathophysiology of blast-related TBI is distinctive, with injury magnitude dependent on several factors, including blast energy and distance from the blast epicentre. The prevalence of blast-related mild TBI in modern war zones has varied widely, but detection is optimised by battlefield assessment of concussion and follow-up screening of all personnel with potential concussive events. There is substantial overlap between post-concussive syndrome and post-traumatic stress disorder, and blast-related mild TBI seems to increase the risk of post-traumatic stress disorder. Post-concussive syndrome, post-traumatic stress disorder, and chronic pain are a clinical triad in this patient group. Persistent impairment after blast-related mild TBI might be largely attributable to psychological factors, although a causative link between repeated mild TBIs caused by blasts and chronic traumatic encephalopathy has not been established. The application of advanced neuroimaging and the identification of specific molecular biomarkers in serum for diagnosis and prognosis are rapidly advancing, and might help to further categorise these injuries.


Cross-protection by B subunit-whole cell cholera vaccine against diarrhea associated with heat-labile toxin-producing enterotoxigenic Escherichia coli: results of a large-scale field trial.
The B subunit (BS) of cholera toxin and that of the heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli (ETEC) are antigenically similar. We therefore assessed whether a combined cholera toxin BS/whole-cell (BS-WC) oral vaccine against cholera conferred cross-protection against LT-producing ETEC (LT-ETEC) diarrhea in a randomized, double-blind field trial among rural Bangladeshi children and women. The 24,770 persons who ingested two or more doses of BS-WC vaccine were compared with 24,842 controls who took two or more doses of killed whole-cell (WC) oral cholera vaccine. Sixty-seven percent fewer episodes of LT-ETEC diarrhea were noted in the BS-WC group than in the WC group during short-term (three-month) follow-up (P less than .01), but no reduction was evident during the ensuing nine months. Short-term protection was particularly notable against LT-ETEC diarrhea causing life-threatening dehydration (protective efficacy, 86%; P less than .05).


Control of Glutamate Transport by Extracellular Potassium: Basis for a Negative Feedback on Synaptic Transmission.
Glutamate and K+, both released during neuronal firing, need to be tightly regulated to ensure accurate synaptic transmission. Extracellular glutamate and K+ ([K+]o) are rapidly taken up by glutamate transporters and K+-transporters or channels, respectively. Glutamate transport includes the exchange of one glutamate, 3 Na+, and one proton, in exchange for one K+. This K+ efflux allows the glutamate binding site to reorient in the outwardly facing position and start a new transport cycle. Here, we demonstrate the sensitivity of the transport process to [K+]o changes. Increasing [K+]o over the physiological range had an immediate and reversible inhibitory action on glutamate transporters. This K+-dependent transporter inhibition was revealed using microspectrofluorimetry in primary astrocytes, and whole-cell patch-clamp in acute brain slices and HEK293 cells expressing glutamate transporters. Previous studies demonstrated that pharmacological inhibition of glutamate transporters decreases neuronal transmission via extrasynaptic glutamate spillover and subsequent activation of metabotropic glutamate receptors (mGluRs). Here, we demonstrate that increasing [K+]o also causes a decrease in neuronal mEPSC frequency, which is prevented by group II mGluR inhibition. These findings highlight a novel, previously unreported physiological negative feedback mechanism in which [K+]o elevations inhibit glutamate transporters, unveiling a new mechanism for activity-dependent modulation of synaptic activity.


S-bacillithiolation protects against hypochlorite stress in Bacillus subtilis as revealed by transcriptomics and redox proteomics.
Protein S-thiolation is a post-translational thiol-modification that controls redox-sensing transcription factors and protects active site cysteine residues against irreversible oxidation. In Bacillus subtilis the MarR-type repressor OhrR was shown to sense organic hydroperoxides via formation of mixed disulfides with the redox buffer bacillithiol (Cys-GlcN-Malate, BSH), termed as S-bacillithiolation. Here we have studied changes in the transcriptome and redox proteome caused by the strong oxidant hypochloric acid in B. subtilis. The expression profile of NaOCl stress is indicative of disulfide stress as shown by the induction of the thiol- and oxidative stress-specific Spx, CtsR, and PerR regulons. Thiol redox proteomics identified only few cytoplasmic proteins with reversible thiol-oxidations in response to NaOCl stress that include GapA and MetE. Shotgun-liquid chromatography-tandem MS analyses revealed that GapA, Spx, and PerR are oxidized to intramolecular disulfides by NaOCl stress. Furthermore, we identified six S-bacillithiolated proteins in NaOCl-treated cells, including the OhrR repressor, two methionine synthases MetE and YxjG, the inorganic pyrophosphatase PpaC, the 3-D-phosphoglycerate dehydrogenase SerA, and the putative bacilliredoxin YphP. S-bacillithiolation of the OhrR repressor leads to up-regulation of the OhrA peroxiredoxin that confers together with BSH specific protection against NaOCl. S-bacillithiolation of MetE, YxjG, PpaC and SerA causes hypochlorite-induced methionine starvation as supported by the induction of the S-box regulon. The mechanism of S-glutathionylation of MetE has been described in Escherichia coli also leading to enzyme inactivation and methionine auxotrophy. In summary, our studies discover an important role of the bacillithiol redox buffer in protection against hypochloric acid by S-bacillithiolation of the redox-sensing regulator OhrR and of four enzymes of the methionine biosynthesis pathway.


Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism.
Long-term low-molecular-weight heparin (LMWH) is the current standard for treatment of venous thromboembolism (VTE) in cancer patients. Whether treatment strategies should vary according to individual risk of VTE recurrence remains unknown. We performed a retrospective cohort study and a validation study in patients with cancer-associated VTE to derive a clinical prediction rule that stratifies VTE recurrence risk. The cohort study of 543 patients determined the model with the best classification performance included 4 independent predictors (sex, primary tumor site, stage, and prior VTE) with 100% sensitivity, a wide separation of recurrence rates, 98.1% negative predictive value, and a negative likelihood ratio of 0.16. In this model, the score sum ranged between -3 and 3 score points. Patients with a score ≤ 0 had low risk (≤ 4.5%) for recurrence and patients with a score >1 had a high risk (≥ 19%) for VTE recurrence. Subsequently, we applied and validated the rule in an independent set of 819 patients from 2 randomized, controlled trials comparing low-molecular-weight heparin to coumarin treatment in cancer patients. By identifying VTE recurrence risk in cancer patients with VTE, we may be able to tailor treatment, improving clinical outcomes while minimizing costs.


MR arthrography of the ankle: indications and technique.
MR arthrography has become an important tool for the assessment of a variety of ankle disorders. MR arthrography permits more sensitive imaging of suspected intra-articular pathology in cases in which conventional MR imaging is either insufficient or inadequate for diagnosis or treatment planning. The main indications for MR arthrography are the evaluation of ligamentous injuries, impingement syndromes, cartilage lesions, osteochondral lesions of the talus, loose bodies, and several synovial joint disorders. Indirect MR arthrography can be a useful adjunct to conventional MR imaging and may be preferable to direct MR arthrography in those cases in which an invasive procedure is contraindicated or image guidance is not available.


Multicolor imaging findings in torpedo maculopathy.
We describe the multicolor imaging findings in two cases of Torpedo maculopathy (TM). Multicolor imaging can be a useful tool in identifying the level of retinal and choroidal layer involvement in TM. This imaging modality further confirms the hypothesis that TM is a localized congenital abnormality of retinal pigment epithelium pigmentation which leads to outer retinal and inner choroidal degeneration.


Risk factor analysis of locoregional recurrence after sublobar resection in patients with clinical stage IA non-small cell lung cancer.
Although lobectomy is the standard surgical procedure for operable non-small cell lung cancer (NSCLC), sublobar resection also has been undertaken for various reasons. The aim of this study was to identify risk factors of locoregional recurrence and poor disease-specific survival in patients with clinical stage IA NSCLC undergoing sublobar resection. We retrospectively reviewed 328 patients with clinical stage IA NSCLC who underwent segmentectomy or wedge resection. Demographic, clinical, and pathologic factors were analyzed using the log-rank test as univariate analyses, and all factors were entered into a Cox proportional hazards regression model for multivariate analyses to identify independent predictors of locoregional recurrence and poor disease-specific survival. The 5- and 10-year locoregional recurrence-free probabilities were 84.8% and 83.6%, respectively, and the 5- and 10-year disease-specific survivals were 83.6% and 73.6%, respectively. Four independent predictors of locoregional recurrence were identified: wedge resection (hazard ratio [HR], 5.787), microscopic positive surgical margin (HR, 3.888), visceral pleural invasion (HR, 2.272), and lymphatic permeation (HR, 3.824). Independent predictors of poor disease-specific survival were identified as follows: smoking status (Brinkman Index; HR, 1.001), wedge resection (HR, 3.183), microscopic positive surgical margin (HR, 3.211), visceral pleural invasion (HR, 2.553), and lymphatic permeation (HR, 3.223). All 4 predictors of locoregional recurrence also were identified as independent predictors of poor disease-specific survival. Segmentectomy should be the surgical procedure of first choice in patients with clinical stage IA NSCLC who are being considered for sublobar resection. Patients having tumors presenting with no suspicious of pleural involvement would be suitable candidates for sublobar resection.


Do healthier lifestyles lead to less utilization of healthcare resources?
Governments are urged to determine methods to control the use of medical resources and curb the rise of healthcare costs. The question is, do health behaviors have an impact on the use of medical resources? This study aims to identify and understand the difference in the number of outpatient visits and health examinations based on various health behaviors and to determine whether patients seek medical care for illness from the same physicians. This study used the dataset derived from the Department of Budget, Accounting and Statistics of Kaohsiung, Taiwan in 2005. Persons older than 15 years were surveyed using an on-site questionnaire. A total of 2911 persons were enrolled in this study. Independent t-tests, chi-square tests, one-way ANOVA, multiple linear regression and binominal logistic regression were used in the data analysis. The regression model for the frequency of doctor visits, health examinations, and whether the same physician is sought for medical care has demonstrated significant correlations with gender, age and education-level variables. Four health behaviors (i.e., exercise habits, dietary habits, regular blood pressure measurement, drinking habits) exhibited a significant correlation with healthcare utilization (P <0.05). Healthy lifestyles lead to an increase in the utilization of preventive health services. However, there is not much significantly reducing the number of outpatient visits in people with health behaviors. Specifically, people with regular exercise habits and who take their blood pressure measurement regularly have an increased number of outpatient visits. It is suggested that more available and accessible health consultation services be provided to inculcate in the general public the importance of maintaining a healthy lifestyle.


Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome.
We investigated 4 European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome, a connective tissue disorder. The kittens were sired by the same tomcat but were born by 3 different mothers. The kittens had easily torn skin resulting in nonhealing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All 4 affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect cosegregation with the autosomal recessive Ehlers-Danlos syndrome phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of Ehlers-Danlos syndrome in humans, mice, dogs, cattle, and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allows to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed Ehlers-Danlos syndrome.


Hematologic reference values for African American children and adolescents.
Anemia is prevalent among African American children. When evaluating pediatric patients for anemia, clinicians refer to the normative hematological reference values in reference textbooks. These reference values are used in spite of evidence that healthy African American people of all ages have average hemoglobin concentrations from 0.5 to 0.73 g/dl below those of Whites. In an earlier study, using samples from 2,161 healthy African American children from 2 to 18 years old, we found a statistically significant difference (P < 0.0001) in the mean hemoglobin value for each age group as compared to reference normative mean hemoglobin values. Here we present the results of a comparative analysis of the data set from our previous study and the data set from the National Health and Nutrition Examination Surveys III (NHANES III) 1988-1994. We found no statistically significant difference between these data sets with respect to the hemoglobin values for any age or sex group, confirming that African American children and adolescents have lower mean hemoglobin values than do Whites. Use of the reference hemoglobin values presented here will help prevent the misdiagnosis of anemia in African American children and thereby minimize unnecessary hematological workups and treatment.


Flexibility in the ambrosia symbiosis of Xyleborus bispinatus.
Ambrosia beetles maintain strict associations with specific lineages of fungi. However, anthropogenic introductions of ambrosia beetles into new ecosystems can result in the lateral transfer of their symbionts to other ambrosia beetles. The ability of a Florida endemic ambrosia beetle, Xyleborus bispinatus, to feed and establish persistent associations with two of its known symbionts (Raffaelea subfusca and Raffaelea arxii) and two other fungi (Harringtonia lauricola and Fusarium sp. nov.), which are primary symbionts of invasive ambrosia beetles, was investigated. The stability of these mutualisms and their effect on the beetle's fitness were monitored over five consecutive generations. Surface-disinfested pupae with non-developed mycangia were reared separately on one of the four fungal symbionts. Non-treated beetles (i.e., lab colony) with previously colonized mycangia were used as a control group. Xyleborus bispinatus could exchange its fungal symbionts, survive, and reproduce on different fungal diets, including known fungal associates and phylogenetically distant fungi, which are plant pathogens and primary symbionts of other invasive ambrosia beetles. These changes in fungal diets resulted in persistent mutualisms, and some symbionts even increased the beetle's reproduction. Females that developed on Fusarium sp. nov. had a significantly greater number of female offspring than non-treated beetles. Females that fed solely on Harringtonia or Raffaelea symbionts produced fewer female offspring. Even though some ambrosia beetles like X. bispinatus can partner with different ambrosia fungi, their symbiosis under natural conditions is modulated by their mycangium and possibly other environmental factors. However, exposure to symbionts of invasive beetles can result in stable partnerships with these fungi and affect the population dynamics of ambrosia beetles and their symbionts.


Chemical Topic Modeling: Exploring Molecular Data Sets Using a Common Text-Mining Approach.
Big data is one of the key transformative factors which increasingly influences all aspects of modern life. Although this transformation brings vast opportunities it also generates novel challenges, not the least of which is organizing and searching this data deluge. The field of medicinal chemistry is not different: more and more data are being generated, for instance, by technologies such as DNA encoded libraries, peptide libraries, text mining of large literature corpora, and new in silico enumeration methods. Handling those huge sets of molecules effectively is quite challenging and requires compromises that often come at the expense of the interpretability of the results. In order to find an intuitive and meaningful approach to organizing large molecular data sets, we adopted a probabilistic framework called "topic modeling" from the text-mining field. Here we present the first chemistry-related implementation of this method, which allows large molecule sets to be assigned to "chemical topics" and investigating the relationships between those. In this first study, we thoroughly evaluate this novel method in different experiments and discuss both its disadvantages and advantages. We show very promising results in reproducing human-assigned concepts using the approach to identify and retrieve chemical series from sets of molecules. We have also created an intuitive visualization of the chemical topics output by the algorithm. This is a huge benefit compared to other unsupervised machine-learning methods, like clustering, which are commonly used to group sets of molecules. Finally, we applied the new method to the 1.6 million molecules of the ChEMBL22 data set to test its robustness and efficiency. In about 1 h we built a 100-topic model of this large data set in which we could identify interesting topics like "proteins", "DNA", or "steroids". Along with this publication we provide our data sets and an open-source implementation of the new method (CheTo) which will be part of an upcoming version of the open-source cheminformatics toolkit RDKit.


Migration and regional population aging in the Philippines.
There is a growing realization that developing countries will be affected in the future by the problems associated with population aging. Although internal migration could exacerbate the problems of aging at subnational levels, there remains a paucity of research on the role of migration in elderly population change for the developing countries of the world. This study uses 1980 census data for the Philippines to explore the spatial and temporal dynamics of the country's elderly population. Through examination of internal migration patterns among the thirteen regions of the country and population projections, this paper demonstrates the potentially large role that migration plays in determining local patterns of aging.The National Capital Region, which is a primary destination of labor force migrants, exhibits the greatest projected increase in the share of the nation's elderly population, while the centrally located Visayas regions show rapid reductions in the future. The Visayas regions, however, may be expected to have the highest concentrations of elderly in their populations. Such findings suggest that labor force migration patterns, with subsequent aging-in-place, will most strongly influence near future distributions and concentrations of the elderly, and that national planning for the future's elderly population should incorporate regional examinations as a means of appropriately distributing financial and service related support.


In Vitro Comparison of Cone Beam Computed Tomography with Digital Periapical Radiography for Detection of Vertical Root Fracture in Posterior Teeth.
The diagnosis of vertical root fracture (VRF) is a challenging task. This in vitro study compared cone beam computed tomography (CBCT) imaging with digital periapical radiography (DPR) made by three different horizontal angels (20°mesial, 0° and 20° distal) for accurate diagnosis of VRF. Among 120 posterior teeth included in this study, 60 were vertically fractured. Fractured and non-fractured teeth were randomly distributed into three groups defined as group 1 with no filling in the root canal, group 2 with gutta-percha in the canal, and group 3 with the intracanal post. All samples were placed in a dry mandible and imaged with CBCT and DPR techniques. Two blind observers investigated the images. CBCT had higher sensitivity but lower specificity compared with DPR, except for the intracanal post group in which the sensitivity of DPR was higher; though the chi-square test showed the differences to be statistically insignificant. The sensitivity, specificity, and accuracy of CBCT and DPR were reduced in the cases that gutta-percha or post were present in the canal. Inter-observer agreement was higher for CBCT. A set of three DPRs with different horizontal angels were significantly more sensitive for VRF recognition than a single orthogonal DPR. Based on our results, there was no significant difference between CBCT and a set of three DPRs with different angulations for VRF detection in posterior teeth. Therefore, it is suggested to consider DPRs with three different horizontal angels (20°mesial, 0° and 20° distal) for radiographic evaluation before CBCT examination.


Levels of house dust mite allergen in cars.
This small study investigated house dust mite (HDM) allergen levels in cars and their owners' homes in north-east Scotland. Dust samples from twelve households and cars were collected in a standardised manner. The dust samples were extracted and measured for the Dermatophagoides group 2 allergens (Der p 2 and Der f 2) and total soluble protein. Allergen levels at homes tended to be higher than in the cars, but not significantly. However, they significantly correlated with paired car dust samples expressed either per unit weight of dust or soluble protein (rho=0.657; p=0.02 and 0.769; p=0.003, respectively). This points to house-to-car allergen transfer, with the car allergen levels largely reflecting levels in the owner's home. Car HDM allergen levels were lower than those reported in Brazil and the USA. Twenty-five percent of the houses and none of the cars had allergen levels in dust greater than 2000 ng g(-1). This value is often quoted as a threshold for the risk of sensitisation, although a number of studies report increased risk of sensitisation at lower levels. This small study does not allow for characterisation of the distribution of HDM allergen in vehicles in this geographic area, or of the likely levels in other warmer and more humid areas of the UK. Cars and other vehicles are an under-investigated micro-environment for exposure to allergenic material.


DNA-Histone Cross-Link Formation via Hole Trapping in Nucleosome Core Particles.
Radical cations (holes) produced in DNA by ionizing radiation and other oxidants yield DNA-protein cross-links (DPCs). Detailed studies of DPC formation in chromatin via this process are lacking. We describe here a comprehensive examination of DPC formation within nucleosome core particles (NCPs), which are the monomeric component of chromatin. DNA holes are introduced at defined sites within NCPs that are constructed from the bottom-up. DPCs form at DNA holes in yields comparable to those of alkali-labile DNA lesions that result from water trapping. DPC-forming efficiency and site preference within the NCP are dependent on translational and rotational positioning. Mass spectrometry and the use of mutant histones reveal that lysine residues in histone N-terminal tails and amino termini are responsible for the DPC formation. These studies are corroborated by computational simulation at the microsecond time scale, showing a wide range of interactions that can precede DPC formation. Three consecutive dGs, which are pervasive in the human genome, including G-quadruplex-forming sequences, are sufficient to produce DPCs that could impact gene expression.


Synthesis of nanometer-sized rod-coil block copolymers.
We present the solid-supported synthesis of a linear rigid rod-like tetradeca(p-benzamide) nanorod as well as a pentadeca( p -benzamide) nanorod carrying an amide N-hexyl side chain at the center of the rod (on the 8(th) amino acid of the molecule). These nanorods were conjugated with solubilizing poly(ethylene glycol) chains and their solution aggregation was investigated. Both rod-coil block copolymers form soluble aggregates even in polar aprotic solvents such as DMF and DMSO. We show that sequence-controlled nanometer-sized shape persistent aramide scaffolds can readily be prepared using solid-supported synthesis.


Enhanced efficacy of pluronic copolymer micelle encapsulated SCR7 against cancer cell proliferation.
5,6-Bis(benzylideneamino)-2-mercaptopyrimidin-4-ol (SCR7) is a new anti cancer molecule having capability to selectively inhibit non-homologous end joining (NHEJ), one of the DNA double strand break (DSB) repair pathways inside the cells. In spite of the promising potential as an anticancer agent, hydrophobicity of SCR7 decreases its bioavailability. Herein the entrapment of SCR7 in Pluronic copolymer is reported. The size of the aggregates was determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS) which yields an average diameter of 23 nm. SCR7 encapsulated micelles (ES) were also characterized by small-angle neutron scattering (SANS). Evaluation of its biological properties by using a variety of techniques, including Trypan blue, MTT and Live-dead cell assays, reveal that encapsulated SCR7 can induce cytotoxicity in cancer cell lines, being more effective in breast cancer cell line. Encapsulated SCR7 treatment resulted in accumulation of DNA breaks within the cells, resulting in cell cycle arrest at G1 phase and activation of apoptosis. More importantly, we found ≈ 5 fold increase in cell death, when encapsulated SCR7 was used in comparison with SCR7 alone.


Uncontrolled sarcomere shortening increases intracellular Ca2+ transient in rat cardiac trabeculae.
Isolated cardiac muscle preparations suffer from damaged-end compliance that allows for substantial shortening of central sarcomeres during contractions in which the overall length of muscle is kept constant. The impact of uncontrolled sarcomere shortening during a twitch on the intracellular calcium transient in myocardium is unknown. Accordingly, in the present study we developed an iterative laser-diffraction feedback system that allowed for the accurate control of central-segment sarcomere length and simultaneous measurement of iontophoretically injected fura 2 fluorescence in isolated cardiac trabeculae. We compared fura 2 fluorescence signals recorded during regular twitches with twitches in which central sarcomere length (SL) was held constant by feedback control ("SL clamp" twitches). We found that uncontrolled sarcomere shortening was associated with a significant (P = 0.005) increase in the peak of the calcium transient and that the amount of this increase was directly correlated to the extent of central-segment sarcomere shortening (r2 = 0.92; P < 0.01). The time course of the calcium transient, however, was unaffected by the mode of contraction (P = 0.64). These findings have important implications for the interpretation of studies of myocardial calcium handling in which uncontrolled sarcomere shortening takes place during the twitch.


Three strategies to promote sustainability of CEMOPLAF clinics in Ecuador. Céntros Médicos de Orientación y Planificación Familiar.
The continuing trend of donor attention and resources away from Latin America threatens the sustainability of nongovernmental family planning organizations in that region. Managers can improve sustainability through cost control, cost recovery, and income generation. The Population Council's INOPAL II and INOPAL III projects and Family Health International assisted CEMOPLAF, an Ecuadoran private voluntary organization, in carrying out operations research in each of these areas. Studies included cost-savings analysis from altering IUD revisit norms (cost control), an ability-to-pay study that showed potential gains from increased prices for reproductive health services (cost recovery), and a feasibility study to estimate income from ultrasound services (income generation). Results indicate that any one intervention will probably have a limited impact, and that managers likely will need to undertake several initiatives simultaneously to make significant progress toward sustainability.


Home Non-Invasive Ventilation for COPD: How, Who and When?
Patients with chronic obstructive pulmonary disease (COPD) and chronic respiratory failure have high levels of morbidity and mortality. The clinical efficacy of long term home oxygen therapy has been well documented in this patient group but despite the efficacy of non-invasive ventilation (NIV) during acute decompensated respiratory failure the addition of home NIV has been associated with equivocal results. The physiological efficacy of home NIV to improve gas exchange in chronic stable hypercapnic respiratory failure has been proven in small studies but larger clinical trials failed to translate this into clinical efficacy. Criticisms of early clinical trials include the use of marginally hypercapnic patients and failure to demonstrate effective delivery of home NIV. When considering recent trial data it is important to clearly evaluate the patient phenotype and timing and delivery of NIV. Recent data supports the delivery of home NIV in patients with chronic hypercapnia (PaCO2>7kPa or 50mmHg) and the frequent or infrequent exacerbator phenotype. Importantly in the frequent exacerbator the timing of the assessment needs to be in the recovery phase, 2-4 weeks after resolution of acute acidosis, to delineate transient from persistent hypercapnia. In patient with persistent hypercapnia NIV must be titrated to achieve control of sleep disordered breathing with the aim of improving daytime respiratory failure. Furthermore there are observational data to support the use of home positive airway pressure therapy (NIV or continuous positive airway pressure; CPAP) in patients with COPD and obstructive sleep apnoea (OSA) both with and without hypercapnia.


Thwarting predators? A three-dimensional perspective of morphological alterations in the freshwater crustacean Daphnia.
Predation is a major selective agent, so that many taxa evolved phenotypically plastic defensive mechanisms. Among them are many species of the microcrustacean genus Daphnia, which respond to an increased predation risk by developing inducible morphological alterations. Some of these features are obvious and easily recognized, e.g., crests in D. longicephala, while others are rather hidden, such as the bulkier shape of D. magna induced by the presence of the tadpole shrimp Triops. In this study we investigated the extraordinary diversity of morphological adaptations in the presence of predators with different foraging strategies in six predator-prey systems. For the first time we were able to analyze the unexposed and predator-exposed morphs comprehensively using three-dimensional scanning and reconstruction. We show that morphological changes are manifold in appearance between species and predators, and go beyond what has been known from previous 2D analyses. This further demonstrates the enormous trait flexibility of Daphnia. Interestingly, we found that among this variety some species share morphological strategies to counter a predator, while others use a different strategy against the same predator. Based on these intra- and interspecific comparisons, we discuss the mechanisms by which the respective defense might operate. These data therefore contribute to a deeper understanding of the inducible defenses' morphology as well as their diversified modes of operation in Daphnia, being a cornerstone for subsequent investigations, including the determination of costs associated with morphological change.


Electrochemistry of the Silicon Oxide Dielectric Layer: Principles, Electrochemical Reactions, and Perspectives.
Electrochemistry of the silicon oxide dielectric layer, a notable insulator often used as a gate oxide, is counterintuitive, but addresses fundamental questions to yield novel scientific discoveries. In this minireview, the fundamental electron transfer mechanism of silicon oxide in the electrolyte solution is elucidated. The possible electrochemical reactions to date are discussed in detail, providing numerous potential areas of application which are elaborated and justified. This minireview not only provides background but also guides future research.


Breast-feeding initiation in women with pregestational diabetes mellitus.
To examine feeding practices and factors associated with breast-feeding initiation (BFI) in women with pregestational diabetes mellitus (PGDM) and their infants. In all, 392 PGDM (135 late preterm and 257 term) pregnancies were studied. Infant feeding preference was ascertained on admission. After birth, 166 (42%) of the infants received well-baby care, whereas 226 (58%) were admitted to the newborn intensive care unit (NICU). Hypoglycemia (blood glucose <40 mg/dL), which occurred in 128 (33%) of all infants, did not influence BFI. Of 257 women who intended to BF, 55% initiated BF. Also, 5% of 105 women who intended to feed formula and 13% of the 30 undecided later initiated BF. The BFI rate for women with PGDM is remarkably low even among those who intended to BF. Factors associated with BFI failure in this population were primiparity, African American race, lower education, smoking, lack of intention to BF, and NICU admission.


Effects of different stimulus manipulations of the acquisition of word recognition in trainable mentally retarded children.
The present study was designed to assess the efficacy of different procedures for establishing transfer of stimulus control from pictorial representations to printed words in trainable mentally retarded school children. The study consisted of two experiments. In experiment 1, four training conditions were used, i.e. two conditions (stimulus shaping and stimulus connected prompt fading) in which the subjects' attention was guided to the training stimuli, and two conditions (stimulus disconnected prompt fading and no fading) in which the subjects were allowed to respond only to the prompts. The results showed that stimulus shaping and stimulus connected prompt fading were far more effective than either one of the other procedures. Subsequent analyses revealed that 1 the stimulus control of the trained words was restricted to one or two letters, and 2 in case it was restricted to one letter, this was frequently a letter other than the one used for training. Furthermore, it was noted that the learned discriminations deteriorated as time or training progressed. Experiment 2 was designed to replicate some of the findings of experiment 1, and to control for one of the variables contributing to the superior efficiency of stimulus shaping over stimulus connected prompt fading. In general, the results of this experiment confirmed those obtained in experiment 1.


Keeping Medicaid viable. Interview by Terese Hudson Thrall.
As the Medicaid program enters its fourth decade, it remains a safety net for Americans in need and for the nation itself, says Barbara Lyons, deputy director of the Kaiser Family Foundation's Commission on Medicaid and the Uninsured. In a question-and-answer interview, Lyons discusses whether it can stay that way--and why it must.


[Restoring phenotype of dedifferentiated normal nucleus pulposus cells by resveratrol].
To investigate the effects of in-vitro monolayer culture and three-dimensional (3-D) alginate microsphere culture on the differentiation of normal human nucleus pulposus cells (NPCs), and to discuss the regulatory mechanism of restoring the phenotype of dedifferentiated NPCs by culturing resveratrol (RES) in 3-D alginate microsphere. Normal human nucleus pulposus tissues were harvested for culture and identification of NPCs from 6 patients with burst lumbar vertebra fracture. NPCs at passages 1, 3, 5, and 7 in the in-vitro monolayer culture were harvested to observe the morphology, cell aging, and proteoglycan expression. The cell proliferation rates of NPCs at passage 1 in-vitro in monolayer culture and in 3-D alginate microsphere culture were detected. NPCs at passage 7 were randomly divided into 3-D alginate microsphere control group (group A), RES group (group B), silent mating type information regulation 2 homolog 1 (SIRT1)- small interfering RNA (siRNA) + RES group (group C), and negative control-siRNA + RES group (group D); and NPCs in the in-vitro monolayer culture was monolayer control group (group E). After corresponding treatment, Western blot was used for determining the protein expressions of SIRT1, Aggrecan, and collagen type II; real-time fluorescence quantitative PCR was used for detecting SIRT1 mRNA expression. The cultured cells were identified to be NPCs. Morphological observation, senescence-associated P-galactosidase (SA-P-gal) staining, and toluidine blue staining showed that dedifferentiation of normal NPCs tended to occur under continuous in-vitro monolayer culture, which was more obvious with increase of passage number. NPCs in 3-D alginate microsphere culture showed significantly lower proliferation rate than NPCs in the in-vitro monolayer culture (P < 0.05), but it could significantly improve the protein expressions of collagen type II and Aggrecan in dedifferentiated NPCs, showing significantly difference between groups E and A (P < 0.05). The protein expressions of SIRT1, collagen type II, and Aggrecan in group B were significantly improved when compared with that in group A (P < 0.05). Real-time fluorescence quantitative PCR and Western blot showed that the expressions of SIRT1 mRNA and proteins in group C were significantly inhibited after transfected with SIRT1-siRNA when compared with those in groups B and D (P < 0.05), and the protein expressions of collagen type II and Aggrecan in group C were significantly lower than those in groups B and D (P < 0.05). Continuous in-vitro monolayer culture could efficiently cultivate numerous seeding NPCs, but it is liable to dedifferentiate. In 3-D alginate microsphere culture, RES could restore the phenotype of dedifferentiated NPCs and synthesize more extracellular matrix, which is related to the regulation of SIRT1.


Management of the colorectal polyp referred for resection: A case-matched comparison of advanced endoscopic surgery and laparoscopic colectomy.
Colonoscopy is the gold standard for colorectal screening and surveillance. Advanced endoscopic polypectomy techniques such as endoscopic submucosal dissection (ESD) have been introduced to remove large colorectal polyps. Our aim was to compare the outcomes of patients who underwent ESD with those of who underwent laparoscopic colectomy for benign colorectal polyps. Patients with a preoperative diagnosis of benign colorectal polyp who underwent ESD or colectomy between 2011 and 2016 were case matched for age, sex, body mass index, American Society of Anesthesiologists status, polyp size, and location. Outcomes and cost data were analyzed. Polyps proximal to the splenic flexure were grouped as right-sided polyps, and polyps distal to the splenic flexure were grouped as left-sided polyps. We identified 144 patients in the laparoscopic resection group and 111 patients in the ESD group; 48 patients met the matching criteria. Of the 48 patients in the ESD group, 5 required operative resection. Mean duration of stay in laparoscopic resection group and the ESD group was 5.2 ± 2.4 days vs 1.5 ± 1.4 (P < .001). Mean operative time was no different (136 ± 45 vs 133 ± 72.7 minutes, respectively). Six patients had follow-up colonoscopy within a year in the laparoscopic resection group versus 22 patients in the ESD group. The laparoscopic group had 21% complication rate versus 15% for the ESD group (P > .05). ESD had a 43% cost-reduction advantage over laparoscopic colectomy, with a 44% and 39% cost advantage for right- and left-sided lesions, respectively. ESD is more cost effective than conventional segmental resection. With an experienced endoscopist, ESD can be offered as a colon-preserving procedure.


Disrupted Topological Organization of Functional Networks in Asymptomatic Carotid Plaque Without Significant Carotid Stenosis: A Resting-State fMRI Study.
Purpose: Previous studies have found that there are significant changes in functional network properties for patients with moderate to severe carotid artery stenosis. Our study aimed to explore the topology properties of brain functional network in asymptomatic patients with carotid plaque without significant stenosis. Methods: A total of 61 asymptomatic patients with carotid plaque (mean age 61.79 ± 7.35 years) and 25 healthy control subjects (HC; 58.12 ± 6.79 years) were recruited. General data collection, carotid ultrasound examination and resting state functional magnetic resonance imaging were performed on all subjects. Graph-theory was applied to examine the differences in the brain functional network topological properties between two groups. Results: In the plaque group, Eloc(P = 0.03), γ (P = 0.01), and σ (P = 0.01) were significantly higher than in the HC group. The degree centrality of left middle frontal gyrus and the nodal efficiency of left middle frontal gyrus and right inferior parietal angular gyrus were significantly higher in the plaque group than in HC. The degree centrality and betweenness centrality of right middle temporal gyrus, as well as the nodal efficiency of right middle temporal gyrus, were significantly lower in the plaque group than in HC. Conclusions: The brain functional networks of patients with carotid plaques differ from those of healthy controls. Asymptomatic patients with carotid plaques exhibit increased local and global connectivity, which may reflect subtle reorganizations in response to early brain damage.


Comparison of spindle and chromosome configuration in in vitro- and in vivo-matured mouse oocytes after vitrification.
To compare the cytogenetic changes in in vitro- and in vivo-matured oocytes after vitrification. In vitro experiments using murine model. Animal model study in university laboratory. CD-1 mice. In vitro maturation and vitrification of oocytes. Post-warming survival, analysis of spindle and chromosome configurations, aneuploidy screening of parthenogenetically activated oocytes, extent of DNA fragmentation, and early embryonic development after IVF. Eighty percent of germinal vesicle-stage oocytes matured after in vitro maturation and were cryopreserved by vitrification (n = 354). There was no significant difference in the post-warming survival of in vitro- and in vivo-matured oocytes (94.1% vs. 91.8%, respectively). The majority of in vitro- and in vivo-matured oocytes maintained normal meiotic spindle morphology and chromosome alignment (88.2% vs. 86.9%, respectively) after vitrification and the incidence of aneuploidy was not increased (11.5% vs. 9.3%). However, in vitro-matured oocytes showed a higher rate of DNA fragmentation after vitrification compared to in vivo-matured oocytes. After vitrification, the cleavage and blastocyst formation rates of in vitro-matured oocytes were significantly lower than those of in vivo-matured oocytes (37.0% vs. 60.0% and 5.4% vs. 18.9%, respectively). Vitrification of in vitro-matured mouse oocytes results in high survival rates, normal meiotic spindle and chromosome alignment, and no increased incidence of aneuploidy. A possible cause of the reduced developmental competence of in vitro-matured and vitrified oocytes may be due to DNA fragmentation.


Highlighting the use of micro and nanoparticles based-drug delivery systems for the treatment of Helicobacter pylori infections.
Due to the high adaptability of Helicobacter pylori and the low targeting specificity of the drugs normally used in pharmacological therapy, the strains are becoming increasingly resistant to these drugs, making it difficult to eradicate the infection. Thus, the search for new therapeutic approaches has been considered urgent. The incorporation of drugs in advanced drug delivery systems, such as nano and microparticles, would allow the improvement of the retention time in the stomach and the prolongation of drug release rates at the target site. Because of this, the present review article aims to highlight the use of micro and nanoparticles as important technological tools for the treatment of H. pylori infections, focussing on the main nanotechnological systems, including nanostructured lipid carriers, liposomes, nanoemulsion, metallic nanoparticles, and polymeric nanoparticles, as well as microtechnological systems such as gastroretentive dosage forms, among them mucoadhesive, magnetic and floating systems were highlighted.


Post-ischemic alterations in [3H]FK506 binding in the gerbil and rat brains.
We investigated post-ischemic changes in FK506 binding protein (FKBP) in the brain after transient global ischemia in gerbils or transient focal ischemia in rats. [3H]FK506 was used to label FKBP as a immunophilin. In transient global ischemia, [3H]FK506 binding showed a transient reduction in the frontal cortex only 1 h after recirculation. In the striatum, the dorsolateral part exhibited a significant increase in [3H]FK506 binding 5, 24 and 48 h after ischemia. However, the ventromedial part showed a transient elevation in [3H]FK506 binding 24 h after ischemia. Thereafter, the ventromedial part showed no conspicuous change in [3H]FK506 binding up to 7 days after ischemia. The dorsolateral part also showed no significant change in [3H]FK506 binding 7 days after ischemia. In the hippocampus and thalamus, [3H]FK506 binding was unchanged in the stratum radiatum of the hippocampal CA1 sector, hippocampal CA3 sector, dentate gyrus and thalamus up to 7 days after ischemia. However, the stratum oriens of the hippocampal CA1 sector showed a significant reduction in [3H]FK506 binding 48 h and 7 days after ischemia. A histological study showed that transient cerebral ischemia caused a severe damage in the striatum and hippocampal CA1 sector. In a model of transient focal ischemia, a marked increase in [3H]FK506 binding was also found in the striatum and cerebral cortex where severe infarctions were observed. These results demonstrate that post-ischemic change in [3H]FK506 binding between the striatum and hippocampus may be produced by different mechanisms. Furthermore, our findings suggest that immunophilins may play some role in the pathogenesis of ischemic diseases.


Invariant heart beat span versus variant heart beat intervals and its application to fetal ECG extraction.
The fundamental assumptions for various kinds of fetal electrocardiogram (fECG) extraction methods are not consistent with each other, which is a very important problem needed to be ascertained. Based on two public databases, the regularity on ECG wave durations for normal sinus rhythm is investigated statistically. Taking the ascertained regularity as an assumption, a new fECG extraction algorithm is proposed, called Partial R-R interval Resampling (PRR). Both synthetic and real abdominal ECG signals are used to test the algorithm. The results indicate that the PRR algorithm has better performance over the whole R-R interval resampling based comb filtering method (RR) and linear template method (LP), which takes advantages of both LP and RR. The final drawn conclusion is: (1) the proposition should be true that the individual's heart beat span is invariable for normal sinus rhythm; (2) the proposed PRR fetal ECG extraction algorithm can estimate the maternal ECG (mECG) more accurately and stably even in the condition of large HRV, finally resulting in better fetal ECG extraction.


Clustering and gelation of hard spheres induced by the Pickering effect.
A mixture of hard-sphere particles and model emulsion droplets is studied with a Brownian dynamics simulation. We find that the addition of nonwetting emulsion droplets to a suspension of pure hard spheres can lead to both gas-liquid and fluid-solid phase separations. Furthermore, we find a stable fluid of hard-sphere clusters. The stability is due to the saturation of the attraction that occurs when the surface of the droplets is completely covered with colloidal particles. At larger emulsion droplet densities a percolation transition is observed. The resulting networks of colloidal particles show dynamical and mechanical properties typical of a colloidal gel. The results of the model are in good qualitative agreement with recent experimental findings [E. Koos and N. Willenbacher, Science 331, 897 (2011)] in a mixture of colloidal particles and two immiscible fluids.


Proliferating effect of radiolytically depolymerized carrageenan on physiological attributes, plant water relation parameters, essential oil production and active constituents of Cymbopogon flexuosus Steud. under drought stress.
Carrageenan has been proved as potent growth promoting substance in its depolymerized form. However, relatively little is known about its role in counteracting the adverse effects of drought stress on plants. In a pot experiment, lemongrass (Cymbopogon flexuosus Steud.), grown under different water stress regimes [(100% field capacity (FC), 80% FC and 60% FC)], was sprayed with 40, 80 and 120 mg L-1 of gamma irradiated carrageenan (ICA). Foliar application of ICA mitigated the harmful effects of drought stress to various extents and improved the biochemical characteristics, quality attributes and active constituents (citral and geraniol) of lemongrass significantly. Among the applied treatments, ICA-80 mg L-1 proved the best in alleviating detrimental effects of drought. However, drought stress (80 and 60% FC), irrespective of the growth stages, had an adverse impact on most of the studied attributes. Generally, 60% FC proved more deleterious than 80% FC. At 80% FC, application of ICA-80 mg L-1 elevated the essential oil (EO) content by 18.9 and 25%, citral content by 7.33 and 8.19% and geraniol content by 9.2 and 8.9% at 90 and 120 days after planting (DAP), respectively, as compared to the deionized-water (DW) spray treatment (80% FC+ DW). Whereas, at 60% FC, foliar application of 80 mg L-1 ICA significantly augmented the EO content by 15.4 and 17.8% and active constituents viz. citral and geraniol, by 5.01 and 5.62% and by 6.06 and 5.61% at 90 and 120 DAP, respectively, as compared to the control (water-spray treatment).


Awakening arterial blood and end-tidal concentrations of isoflurane in female surgical patients.
Delayed extubation occurs after isoflurane anesthesia, especially following prolonged surgical duration. We aimed to determine the arterial blood concentrations of isoflurane and the correlation with end-tidal concentrations for predicting emergence from general anesthesia.Thirty-four American Society of Anesthesiologists physical status class I-II gynecologic patients were included. General anesthesia was maintained with a fixed 2% inspiratory isoflurane in 6 L/minute oxygen, which was discontinued after surgery. One milliliter of arterial blood was obtained for the determination of isoflurane concentration by gas chromatography at 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuation, in addition to the time of eye opening to verbal command, defined as awakening. Inspiratory and end-tidal concentrations were simultaneously detected by an infrared analyzer.The mean awakening arterial blood concentration of isoflurane was 0.20%, which was lower than the simultaneous end-tidal concentration 0.23%. The differences between arterial and end-tidal concentrations during emergence fell into an acceptable range (±1.96 standard deviation). After receiving a mean time of 108-minute general anesthesia, the time to eye opening after discontinuing isoflurane was 18.5 minutes (range 11-30, median 18 minutes), without statistical significance with anesthesia duration (P = 0.078) and body mass index (P = 0.170).We demonstrated the awakening arterial blood concentration of isoflurane in female patients as 0.20%. With well-assisted ventilation, the end-tidal concentration could be an indicator for the arterial blood concentration to predict emergence from shorter duration of isoflurane anesthesia.


Transcortin as an indicator of estrogenic potency in oral contraceptives.
Serum cortisol-binding globulin (CBG) was measured before, during and following a 21-day application period of 5 oral contraceptives used in the GDR. In a second group of patients determinations were carried out at the end of a 24-month treatment period and the end of the first post-treatment cycle. From a third group of volunteers blood samples were taken at the end of the first, second and third treatment cycles. All the drugs tested produced a marked increase of CBG in serum, reaching its maximum at the end of the second treatment cycle. Within four weeks following termination of application the level fell to the control range. There were no significant differences between the various contraceptives.


Revealing the role of regulatory T cells in the tumor microenvironment of lung adenocarcinoma: a novel prognostic and immunotherapeutic signature.
Regulatory T cells (Tregs), are a key class of cell types in the immune system. In the tumor microenvironment (TME), the presence of Tregs has important implications for immune response and tumor development. Relatively little is known about the role of Tregs in lung adenocarcinoma (LUAD). Tregs were identified using but single-cell RNA sequencing (scRNA-seq) analysis and interactions between Tregs and other cells in the TME were investigated. Next, we used multiple bulk RNA-seq datasets to construct risk models based on marker genes of Tregs and explored differences in prognosis, mutational landscape, immune cell infiltration and immunotherapy between high- and low-risk groups, and finally, qRT-PCR and cell function experiments were performed to validate the model genes. The cellchat analysis showed that MIF-(CD74+CXCR4) pairs play a key role in the interaction of Tregs with other cell subpopulations, and the Tregs-associated signatures (TRAS) could well classify multiple LUAD cohorts into high- and low-risk groups. Immunotherapy may offer greater potential benefits to the low-risk group, as indicated by their superior survival, increased infiltration of immune cells, and heightened expression of immune checkpoints. Finally, the experiment verified that the model genes LTB and PTTG1 were relatively highly expressed in cancer tissues, while PTPRC was relatively highly expressed in paracancerous tissues. Colony Formation assay confirmed that knockdown of PTTG1 reduced the proliferation ability of LUAD cells. TRAS were constructed using scRNA-seq and bulk RNA-seq to distinguish patient risk subgroups, which may provide assistance in the clinical management of LUAD patients.


[A combination of multiple cartilaginous exostoses and enchondromatosis of bone in a family].
Four cases of multiple cartilaginous exostoses in a family (mother and three children) are described. In two children the exostoses are combined with enchondromatosis of the large tubular bones. At some phalanges of these children the changes show the roentgenologic signs of solitary enchondromas and ecchondromas and in one of the cases with cartilaginous exostoses osteochondroma-like changes were found. The combination of the described symptoms seems to indicate a close relationship between enchondromatosis and the cartilaginous exostoses, as well as between these chondrodysplasias and the cartilaginous tumours.


Determinants of Patient's Adherence to Hypertension Medications: Application of Health Belief Model Among Rural Patients.
Hypertension is a major health problem in developing and developed countries, and its increasing epidemy is a serious warning to take more attention to this silent disease. This study was aimed to determine the factors of adherence to hypertension medication based on health belief model (HBM). A cross-sectional study was conducted in a rural area of the Ardabil city in 2013. This study was carried out using a pre-structured and validated questionnaire. The questionnaire included information on demographic characteristics, lifestyle habits, HBM constructs and adherence to hypertension medication (Morisky 4-Item Self-Report Measure of Medication-taking Behavior [Morisky Medication Adherence Scale]). Data were analyzed with the use of SPSS version 18. P < 0.05 was considered as statistically significant. A total of 671 hypertensive patients participated in the study (169 were males and 502 were females). The prevalence of adherence was 24% (161/671)% in the study population. Respondents with regular physical activity and nonsmokers were more adherent to hypertension medication when compared to respondents with sedentary lifestyle and smoking (P < 0.01). Based on HBM constructs, the respondents who perceived high susceptibility, severity, benefit had better adherence compared to moderate and low susceptibility, severity, and benefit. The prevalence of adherence to hypertension management was low in study population, this due to inadequate perceived susceptibility, perceived, severity, perceived benefit and poor lifestyle factors. Improving adherence in hypertension patients need to recognize the value and importance of patient perceptions medications.


High preoperative serum alanine transferase levels: effect on the risk of liver resection in Child grade A cirrhotic patients.
Despite careful selection of cirrhotic patients with hepatocellular carcinoma (HCC), liver resection remains associated with a greater risk than in patients without underlying liver disease. In this study we assessed by multivariate analysis parameters associated with in-hospital mortality and morbidity in a selected group of 108 Child-Pugh A cirrhotic patients undergoing liver resection of HCC. The overall incidences of in-hospital deaths and postoperative complications were 8.3% and 48.1%, respectively. By univariate analysis, the preoperative serum alanine transferase (ALT) level (p = 0.001) and intraoperative transfusions (p = 0.01) were significantly associated with in-hospital death; however, only the serum ALT concentration was an independent risk factor. In-hospital mortality rates in patients whose serum ALT was below 2N (twofold the upper limit of the normal value), between 2N and 4N, and more than 4N were 3.9%, 13.0%, and 37.5%, respectively. An ALT level greater than 2N was predominantly observed in patients with a hepatitis C virus infection and significantly associated with histologic features of superimposed active hepatitis. Patients with an ALT level greater than 2N experienced an increased incidence of postoperative ascites (58% versus 32%, p = 0.01), kidney failure (16% versus 0%, p = 0.0003), and upper gastrointestinal bleeding (6.4% versus 0%, p = 0.02). These results indicate that the preoperative ALT level is a reliable predictor of in-hospital mortality and morbidity following liver resection in Child-Pugh A cirrhotic patients. Cirrhotic patients with ALT > 2N should undergo only a limited resection; if a larger resection is required, those patients should be considered for nonsurgical therapy or liver transplantation.


Comparative mRNA Expression Profiles of Riboflavin Biosynthesis Genes in Lactobacilli Isolated from Human Feces and Fermented Bamboo Shoots.
With the aim to bioprospect potent riboflavin producing lactobacilli, the present study was carried out to evaluate the relative mRNA expression of riboflavin biosynthesis genes namely Rib 1, Rib 2, Rib 3, and Rib 4 from potent riboflavin producers obtained from our previous studies. All the four genes were successfully cloned and sequenced for further analysis by in silico procedures. As studied by non-denaturing Polyacrylamide gel electrophoresis, no difference in size of all the four genes among those of various lactobacilli was observed. The relative fold increase in mRNA expression in Rib 1, Rib 2, Rib 3, and Rib 4 genes has been observed to be 10-, 1-, 0.7-, and 8.5-fold, respectively. Due to increase in relative mRNA expression for all the Rib genes as well as phenotypic production attribute, KTLF1 strain was used further for expression studies in milk and whey. The fold increase in mRNA expression for all the four Rib genes was higher at 12 and 18 h in milk and whey respectively. After exposure to roseoflavin, resistant variant of KTLF1 showed considerable increase in expression of all the targets genes. This is the first ever study to compare the mRNA expression of riboflavin biosynthesis pathway genes in lactobacilli and it also under lines the effect of media and harvesting time which significantly affect the expression of rib genes. The use of roseoflavin-resistant strains capable of synthesizing riboflavin in milk and whey paves a way for an exciting and economically viable biotechnological approach to develop novel riboflavin bio-enriched functional foods.


[Long-acting carteolol hydrochloride 2% ophthalmic solution phase IV study--investigation of the effectiveness, safety and plasma concentration].
We investigated the effectiveness, safety and plasma concentration of long-acting carteolol hydrochloride 2% ophthalmic solution (LA) as compared with the original carteolol hydrochloride 2% ophthalmic solution(CA). Patients with primary open angle glaucoma and ocular hypertension were randomized to 62 patients of LA group (LA once a day) and 62 patients of CA group (CA twice a day) in this multicenter, open-label trial. The intraocular pressure (IOP), pulse rate, blood pressure and plasma concentration were examined for 8 weeks. The IOP reduction and reduction rate were not significant at any point between the two groups. Systolic blood pressure decreased significantly in both groups, however, diastolic blood pressure decreased only in the CA group. The plasma concentration of the LA group was significantly lower than that of the CA group. The IOP reduction effect of the LA group was the same as the CA group. This study suggests that long-acting treatment with alginic acid can be useful for reducing systemic side effects.


The middle half genome of interferon-inducing porcine reproductive and respiratory syndrome virus strain A2MC2 is essential for interferon induction.
Porcine reproductive and respiratory syndrome virus (PRRSV) is known to antagonize the innate immune response. An atypical PRRSV strain A2MC2 is capable of inducing synthesis of type I interferons (IFNs) in cultured cells. Here, we show that the middle half of the A2MC2 genome is needed for triggering the IFN synthesis. First, a cDNA infectious clone of this atypical strain was constructed as a DNA-launched version. Virus recovery was achieved from the infectious clone and the recovered virus, rA2MC2, was characterized. The rA2MC2 retained the feature of IFN induction in cultured cells. Infection of pigs with the rA2MC2 virus caused viremia similar to that of the wild-type virus. Chimeric infectious clones were constructed by swapping genomic fragments with a cDNA clone of a moderately virulent strain VR-2385 that antagonizes IFN induction. Analysis of the rescued chimeric viruses demonstrated that the middle two fragments, ranging from nt4545 to nt12709 of the A2MC2 genome, were needed for the IFN induction, whereas the chimeric viruses containing any one of the two A2MC2 fragments failed to do so. The results and the cDNA infectious clone of the IFN-inducing A2MC2 will facilitate further study of its biology, ultimately leading towards the development of an improved vaccine against PRRS.


[ORO-DENTO-FACIAL MANIFESTATIONS IN PATIENTS WITH FAMILIAL DYSAUTONOMIA].
The oro-dento-facial features and dysfunctions of children with hereditary sensory and autonomic neuropathy type III (HSAN III), known as familial dysautonomia (FD) or Riley-Day syndrome, were first described in the scientific literature in 1949. They include: dental trauma, dental and soft tissue selfmutilation, normal dental age, normal sequence and timing of eruption and exfoliation of teeth, smaller tooth size, different and disproportional tooth components, normal alveolar bone height, small jaws, mild crowding and malocclusion. These individuals have different craniofacial morphology from accepted norms, but resemble norms of their ethnic origin. The subjects often display gray, pale, shiny faces with an asymmetric suffering expression; frontal bossing, with eventual hypertelorism and narrow lips; a low dental caries rate; drooling, and genuine hypersalivation. They may have changes in salivary composition and content, which influence plaque and calculus accumulation and increase the risk of gingival and periodontal diseases. They also have difficulty in controlling oral muscles, a progressive decrease in the number of tongue fungiform papillae, accompanied by a reduced number of taste buds and specific dysgeusia, but a normal sense of smell.


Cyclin A is essential for the p53-modulated inhibition from benzo(a)pyrene toxicity in A549 cells.
Benzo(a)pyrene (B(a)P) is an environment carcinogen that can enhance cell proliferation by disturbing the signal transduction pathways in cell cycle regulation. The p53 tumor suppressor as a cell cycle check-point determinant plays a critical role in cell proliferation. However, the mechanism of p53 that accounts for the remarkable toxicity of B(a)P remains elusive. Here we reported that exposure of B(a)P to A549 cells caused G1 to S and G2/M phase transition along with increased expression of p53, cyclin D1, Cdk2, Cdk4, p21 and decreased expression of cyclin E, but no change in cyclin A and p27 expression. Up-regulation of p53 expression via transfection caused G1 phase arrest with decreased expression of cyclin A, E, Cdk2 and Cdk4, and increased expression of p21, when the expression of cyclin D1 and p27 were not significant changed. While B(a)P exposure to A549 cells following p53 transfection, up-regulation of p53 significantly attenuated the B(a)P-induced enhancement of cell proliferation and cell arrest, with increased expression of cyclin D1, Cdk2 and Cdk4, and with declined expression of cyclin A, cyclin E and p21, and p27 were not significant changed. Compared to the untreated cells, cylin A expression reduced in p53-transfected cells and in the B(a)P-treated cells following p53 transfection, but showed no change in the only B(a)P-treated cells. These results indicated that cyclin A is regulated by p53, not by B(a)P, and it is essential in the p53-modulated inhibition from benzo(a)pyrene toxicity in A549 cells, cyclin E and p21 also as downstream genes of p53 involved it, which is p27-independent.


A "sweet" hydrothorax in a child on peritoneal dialysis.
Peritoneal dialysis (PD) is an established, effective long term renal replacement treatment modality for children with end stage renal disease (ESRD). A rarely reported complication of PD in children is the development of hydrothorax1. We report the case of an 8-year-old boy that developed a right-sided pleural effusion during automated PD (APD), in order to raise awareness amongst paediatricians; we also review the diversity of clinical presentation and the available diagnostic tools, discuss theories regarding aetiology and highlight the available treatment options.