Multidrug-Resistant Organisms Detected More Than 48 Hours After Hospital Admission Are Not Necessarily Hospital-Acquired.
BACKGROUND Infections and colonization with multidrug-resistant organisms (MDROs) identified >48 hours after hospital admission are considered healthcare-acquired according to the definition of the Centers for Disease Control and Prevention (CDC). Some may originate from delayed diagnosis rather than true acquisition in the hospital, potentially diluting the impact of infection control programs. In addition, such infections are not necessarily reimbursed in a healthcare system based on the diagnosis-related groups (DRGs). OBJECTIVE The goal of the study was to estimate the preventable proportion of healthcare-acquired infections in a tertiary care hospital in Switzerland by analyzing patients colonized or infected with MDROs. METHODS All hospitalized patients with healthcare-acquired MDRO infection or colonization (HAMIC) or according to the CDC definition (CDC-HAMIC) were prospectively assessed from 2002 to 2011 to determine whether there was evidence for nosocomial transmission. We utilized an additional work-up with epidemiological, microbiological, and molecular typing data to determine the true preventable proportion of HAMICs. RESULTS Overall, 1,190 cases with infection or colonization with MDROs were analyzed; 274 (23.0%) were classified as CDC-HAMICs. Only 51.8% of CDC-HAMICs had confirmed evidence of hospital-acquisition and were considered preventable. Specifically, 57% of MRSA infections, 83.3% of VRE infections, 43.9% of ESBL infections, and 74.1% of non-ESBL MDRO infections were preventable HAMICs. CONCLUSIONS The CDC definition overestimates the preventable proportion of HAMICs with MDROs by more than 50%. Relying only on the CDC definition of HAMICs may lead to inaccurate measurement of the impact of infection control interventions and to inadequate reimbursement under the DRG system. Infect. Control Hosp. Epidemiol. 2016;1-6.


Increasing phosphorus supply is not the mechanism by which arbuscular mycorrhiza increase attractiveness of bean (Vicia faba) to aphids.
Arbuscular mycorrhizal (AM) fungi, important plant mutualists, provide plants with nutrients such as phosphorus (P) in return for carbon. AM fungi also enhance the attractiveness of plants to aphids via effects on emissions of plant volatiles used in aphid host location. We tested whether increased P uptake by plants is the mechanism through which AM fungi alter the volatile profile of plants and aphid behavioural responses by manipulating the availability of P and AM fungi to broad beans (Vicia faba L.) in a multi-factorial design. If AM fungi affect plant volatiles only via increased P acquisition, we predicted that the emission of volatiles and the attractiveness of mycorrhizal beans to aphids would be similar to those of non-mycorrhizal beans supplied with additional P. AM fungi and P addition increased leaf P concentrations by 40 and 24%, respectively. The production of naphthalene was less in mycorrhizal plants, regardless of P addition. By contrast, production of (S)-linalool, (E)-caryophyllene and (R)-germacrene D was less in plants colonized by AM fungi but only in the absence of P additions. The attractiveness of plants to pea aphids (Acyrthosiphon pisum Harris) was positively affected by AM fungi and correlated with the extent of root colonization; however, attractiveness was neither affected by P treatment nor correlated with leaf P concentration. These findings suggest that increased P uptake is not the main mechanism by which mycorrhiza increase the attractiveness of plants to aphids. Instead, the mechanism is likely to operate via AM fungi-induced plant systemic signalling.


Overproduction of SecA suppresses the export defect caused by a mutation in the gene encoding the Escherichia coli export chaperone secB.
SecB is a cytosolic protein required for rapid and efficient export of particular periplasmic and outer membrane proteins in Escherichia coli. SecB promotes export by stabilizing newly synthesized precursor proteins in a nonnative conformation and by targeting the precursors to the inner membrane. Biochemical studies suggest that SecB facilitates precursor targeting by binding to the SecA protein, a component of the membrane-embedded translocation apparatus. To gain more insight into the functional interaction of SecB and SecA, in vivo, mutations in the secA locus that compensate for the export defect caused by the secB missense mutation secBL75Q were isolated. Two suppressors were isolated, both of which led to the overproduction of wild-type SecA protein. In vivo studies demonstrated that the SecBL75Q mutant protein releases precursor proteins at a lower rate than does wild-type SecB. Increasing the level of SecA protein in the cell was found to reverse this slow-release defect, indicating that overproduction of SecA stimulates the turnover of SecBL75Q-precursor complexes. These findings lend additional support to the proposed pathway for precursor targeting in which SecB promotes targeting to the translocation apparatus by binding to the SecA protein.


Perception of Quality of Life among People with Diabetes.
Diabetes is a chronic disease that affects a patient's quality of life. This cross-sectional study aimed to determine the socio-demographic and disease profile factors associated with poor quality of life among patients with diabetes. The study was conducted at a primary health care clinic in Kuching between August to November 2010. Short Form - 36 (SF - 36) questionnaire was used to assess the quality of life of diabetic patients aged ≥ 18. A total of 142 respondents participated in the survey. After adjusting for age, those with no education scored lower at vitality (p=0.043) and emotional health (p=0.033) compared with those who have tertiary education. Those working in the private sector scored better for physical functioning (p=0.042) compared with pensioners and the unemployed. Patients with uncontrolled diabetes scored lower in the role-emotional domain (p=0.003). Participants who were on <3 (p=0.014) and ≥3 (p=0.024) oral medications had better score for role-physical than those on insulin. Those on insulin had worse score for bodily pain than those on oral medication only (vs <3 oral drugs, p=0.026; vs ≥3 oral drugs, p=0.001). Various socio-demographic factors, uncontrolled diabetes and insulin usage were found to have negative impact on a diabetic patient's quality of life. Programmes addressing the physical and emotional needs of diabetic patients at the primary health care setting are essential to help improve their quality of life.


The effects of extra virgin olive oil or butter on cardiovascular biomarkers in European and Chinese males in the UK: A pilot randomised crossover trial.
Purpose: No dietary interventional studies have reported the impact of olive oil on cardiovascular risk markers in groups of different ethnic origins. We report a pilot randomised controlled trial of an intervention supplementing extra virgin olive oil (EVOO) on markers of cardiovascular risk among East Asian Chinese, and European Caucasian individuals. Methods: A cross-over, randomised controlled dietary intervention for 2 weeks was undertaken. Thirty-two adults, healthy, individuals of Chinese and European origin took part in this study. 24-h ambulatory systolic and diastolic blood pressure (SBP, DBP), and blood lipids, were assessed. Results: Positive benefits of EVOO consumption were observed in all participants. Lower 24-h ambulatory SBP (-4.3 mmHg; p = 0.020), and day-time SBP (5.528 mmHg; p = 0.008), night-time DBP (-3.784 mmHg; p = 0.008) and night-time MAP (-3.747 mmHg; p = 0.007) were seen in all participants independently of covariates. In addition, total cholesterol (7.9 mg/dL; p = 0.017) and LDL-cholesterol (6.5 mg/dL; p = 0.028) were increased with butter but not with olive oil. No significant difference in other cardiovascular risk factors were observed. However, differences were observed between Caucasians and East Asian individuals in the absence of significant differences in lifestyle. Conclusion: This pilot study suggests that consumption of EVOO should be advocated as a healthier dietary fat and recommended to replace butter as a dietary strategy to improve cardiovascular health in both Caucasians and East Asian individuals.


Hypopituitarism in Wilson's disease resolved after copper-chelating therapy.
Wilson's disease (WD) is a rare disorder of copper metabolism usually presenting with variable liver damage and neuropsychiatric symptoms. Here we report a 39-year-old Taiwanese female with late manifestation of WD presenting with gonadotroph, thyreotroph and corticotroph hypopituitarism. Molecular genetic testing revealed compound heterozygosity for two mutations in exons 12 and 14 (c.2828G>A and c.3140A>T). Copper-chelating therapy with D-penicillamine and zinc was initiated along with supplementation of hydrocortisone and L-thyroxine. Hypopituitarism resolved when urinary copper excretion returned to normal levels under copper chelation. This case should raise awareness of pituitary function in WD patients. Hypopituitarism can complicate Wilson's disease (WD) and endocrinologists should be aware of it when caring for hypopituitary patients. Hepatologists should consider endocrinologic testing for hypopituitarism when WD patients present with symptoms of adrenal insufficiency, thyroid or gonadal dysfunction. Copper-chelating treatment is mandatory and may lead to the recovery of pituitary function in such patients.


The association of financial difficulties and out-of-pocket payments with health-related quality of life among breast, prostate and colorectal cancer patients.
Objectives: Financial difficulties experienced by cancer patients may affect their health-related quality of life (HRQoL). This study assessed the direct economic burden that out-of-pocket (OOP) payments cause and explored how they and financial difficulties are associated with HRQoL. Methods: This is a cross-sectional registry and survey study of 1978 cancer patients having either prostate (630), breast (840) or colorectal cancer (508) treated in Finland. The patients were divided into five groups according to the stage of their disease: primary treatment, rehabilitation, remission, metastatic disease and palliative care. The cost data and OOP payments were retrieved from primary and secondary healthcare registries, the Social Insurance Institution of Finland, and a patient questionnaire. HRQoL was measured by 15D, EQ-5D-3L and by EORTC-QLQ-C30. Financial difficulties were evaluated based on patients' self-assessment in the EORTC-QLQ-C30 four-level question about financial difficulties. A path analysis was used to explore the relationship between clinical and demographic factors, HRQoL, OOP payments and financial difficulties. Results: The highest OOP payments were caused by outpatient medication. Total costs and OOP payments were highest in the palliative care group in which the OOP payments consisted mostly of outpatient medication and public sector specialist care. Private sector health care was an important item of OOP payments in the early stages of cancer. Financial difficulties increased together with OOP payments. HRQoL deteriorated the more a person had financial difficulties. In the path analysis, financial difficulties had a major negative direct and total effect on the HRQoL. Factors that attenuated financial difficulties were age, cohabiting and higher education and factors that increased them were OOP payments, total costs of healthcare use, and unemployment. Conclusions: High OOP payments are related to financial difficulties, which have a negative effect on HRQoL. Outpatient medication was a major driver of OOP payments. Among palliative patients, the economic burden was highest and associated with impaired HRQoL.


Mini-Mental State Exam performance of older African Americans: effect of age, gender, education, hypertension, diabetes, and the inclusion of serial 7s subtraction versus "world" backward on score.
The Mini-Mental State Exam (MMSE) is a clinically ubiquitous yet incompletely standardized instrument. Though the test offers considerable examiner leeway, little data exist on the normative consequences of common administration variations. We sought to: (a) determine the effects of education, age, gender, health status, and a common administration variation (serial 7s subtraction vs. "world" spelled backward) on MMSE score within a minority sample, (b) provide normative data stratified on the most empirically relevant bases, and (c) briefly address item failure rates. African American citizens (N = 298) aged 55-87 living independently in the community were recruited by advertisement, community recruitment, and word of mouth. Total score with "world" spelled backward exceeded total score with serial 7s subtraction across all levels of education, replicating findings in Caucasian samples. Education is the primary source of variance on MMSE score, followed by age. In this cohort, women out-performed men when "world" spelled backward was included, but there was no gender effect when serial 7s subtraction was included in MMSE total score. To ensure an appropriate interpretation of MMSE scores, reports, whether clinical or in publications of research findings, should be explicit regarding the administration method. Stratified normative data are provided.


Proteomic Profiling Reveals Specific Molecular Hallmarks of the Pig Claustrum.
The present study, employing a comparative proteomic approach, analyzes the protein profile of pig claustrum (CLA), putamen (PU), and insula (IN). Pig brain is an interesting model whose key translational features are its similarities with cortical and subcortical structures of human brain. A greater difference in protein spot expression was observed in CLA vs PU as compared to CLA vs IN. The deregulated proteins identified in CLA resulted to be deeply implicated in neurodegenerative (i.e., sirtuin 2, protein disulfide-isomerase 3, transketolase) and psychiatric (i.e., copine 3 and myelin basic protein) disorders in humans. Metascape analysis of differentially expressed proteins in CLA vs PU comparison suggested activation of the α-synuclein pathway and L1 recycling pathway corroborating the involvement of these anatomical structures in neurodegenerative diseases. The expression of calcium/calmodulin-dependent protein kinase and dihydropyrimidinase like 2, which are linked to these pathways, was validated using western blot analysis. Moreover, the protein data set of CLA vs PU comparison was analyzed by Ingenuity Pathways Analysis to obtain a prediction of most significant canonical pathways, upstream regulators, human diseases, and biological functions. Interestingly, inhibition of presenilin 1 (PSEN1) upstream regulator and activation of endocannabinoid neuronal synapse pathway were observed. In conclusion, this is the first study presenting an extensive proteomic analysis of pig CLA in comparison with adjacent areas, IN and PUT. These results reinforce the common origin of CLA and IN and suggest an interesting involvement of CLA in endocannabinoid circuitry, neurodegenerative, and psychiatric disorders in humans.


The effect of rate control on speech rate and intelligibility of dysarthric speech.
This study investigated the effect of rate control methods (RCMs) on speaking rate (SR), articulation rate (AR), and intelligibility in dysarthric speakers. Nineteen dysarthric patients (7 unilateral upper motor neuron dysarthria, 6 hypokinetic, 3 flaccid, 3 ataxic) participated. SR, AR and intelligibility ratings were determined on the basis of 1-min recorded reading passages. Seven RCMs were applied: voluntary rate control, hand tapping, alphabet board, pacing board and delayed auditory feedback with a delay of 50, 100 and 150 ms. Almost all methods resulted in lower mean SRs and ARs (p < 0.05). Rate control did not improve overall intelligibility of the dysarthric population. However, a meaningful increase of intelligibility was found in 5 participants. This study indicates that the effect of rate control on intelligibility is independent of habitual speech rate and type of dysarthria. Degree of intelligibility may be an influencing factor. The most effective methods are: voluntary rate control, alphabet board, hand tapping and pacing board. RCMs do result in lower speech rates. Some dysarthric individuals do benefit from one or more RCMs, but rate control may also have an inverse effect on intelligibility.


What are the active carbon species during graphene chemical vapor deposition growth?
The dissociation of carbon feedstock is a crucial step for understanding the mechanism of graphene chemical vapor deposition (CVD) growth. Using first-principles calculations, we performed a comprehensive theoretical study for the population of various active carbon species, including carbon monomers and various radicals, CHi (i = 1, 2, 3, 4), on four representative transition-metal surfaces, Cu(111), Ni(111), Ir(111) and Rh(111), under different experimental conditions. On the Cu surface, which is less active, the population of CH and C monomers at the subsurface is found to be very high and thus they are the most important precursors for graphene CVD growth. On the Ni surface, which is more active than Cu, C monomers at the subsurface dominate graphene CVD growth under most experimental conditions. In contrast, on the active Ir and Rh surfaces, C monomers on the surfaces are found to be very stable and thus are the main precursors for graphene growth. This study shows that the mechanism of graphene CVD growth depends on the activity of catalyst surfaces and the detailed graphene growth process at the atomic level can be controlled by varying the temperature or partial pressure of hydrogen.


A Novel Dual-Phase Activation-Dependent Foot-Switch Mechanism for Surgical Energy Devices as an Asset in Early Surgical Training: A Proof of Concept Study.
Introduction. Many processes exist that limit or eliminate the incidence of adverse events in general surgery including the World Health Organization safety checklist. Technology and device advancement has a potentially expanding role in the context of surgical safety. Materials and Methods. A dual controlled accessory electrical diathermy footswitch (Permissive diathermy foot switch device or PDf) device concept was developed in an effort to improve patient safety in theatre and enhance opportunities in training. Electrical diathermy is only activated if the senior supervising surgeon and the novice surgeon simultaneously activate their interconnected footswitches. The activation of the PDf accessory footswitch device allows a senior surgeon to exert control on "initiation" of activation of diathermy devices operated by a novice surgeon (foot on pedal) as well as when desiring to deactivate the device (foot off pedal). Results. A process of designing and prototyping was initiated to define the purpose and the functionality of the PDf device up till the stage of a fully functioning prototype. The PDf device was constructed as a final working and tested prototype in association with the local medical engineering department at the Cumberland Infirmary in Carlisle. The device was on a nonbiological model to determine efficacy and safety and passed its laboratory testing phase and was deemed ready for clinical use. Conclusion. We demonstrated the feasibility and functionality of the PDf device and propose a positive role in surgical training in the context of early surgical training and specific circumstances where more control is needed.


Prognostic Significance of Tumor-associated Stroma in Nasopharyngeal Carcinoma: A Multicenter Study.
Assessment of tumor-associated stroma has shown a reliable prognostic value in recent research. We evaluated the prognostic value of tumor-stroma ratio (TSR) in a large multicenter cohort of nasopharyngeal carcinoma (NPC). We used the conventional hematoxylin and eosin-stained slides of 115 cases of NPC to assess TSR as described in recent guidelines. The amount of tumor-associated stroma was assessed as a percentage and then tumors were classified as stroma-high (>50%) or stroma-low (≤50%). Kaplan-Meier curves, χ2 test, and Cox regression univariable and multivariable analyses were carried out. A total of 48 (41.7%) tumors were stroma-high and 67 (58.3%) tumors were stroma-low. In the Cox regression multivariable analysis, the tumors categorized as stroma-high were associated with a worse overall survival with a hazard ratio of 2.30 (95% CI: 1.27-4.15, P=0.006) and with poor disease-specific survival (hazard ratio=1.87, 95% CI: 1.07-3.28, P=0.029). The assessment of TSR in NPC is simple and cost-effective, and it has a significant prognostic value. TSR can aid in risk stratification and clinical decision-making in NPC.


Use of concomitant aspirin in patients with atrial fibrillation: Findings from the ROCKET AF trial.
We aimed to investigate the relationship between aspirin use and clinical outcomes in patients enrolled in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), in particular, those with known coronary artery disease (CAD). Patients in ROCKET AF, comparing rivaroxaban and warfarin, were analyzed. Aspirin use was assessed at baseline. Stroke and systemic embolism, myocardial infarction, death, and major or nonmajor clinically relevant (NMCR) bleeding were compared between groups. Multivariable modeling was done adjusting for baseline risk factors. A total of 5,205 (36.5%) patients were receiving aspirin at baseline (mean dose 99.2mg); 30.6% of those had known CAD. Patients receiving aspirin were more likely to have prior myocardial infarction (22% vs 14%; P<.001) and heart failure (68% vs 59%; P<.001). Relative efficacy of rivaroxaban versus warfarin was similar with and without aspirin use for both stroke/systemic embolism (P=.95 for interaction), and major or NMCR bleeding (P=.76 for interaction). After adjustment, aspirin use was associated with similar rates of stroke/systemic embolism (hazard ratio [HR] 1.16, 95% CI 0.98-1.37; P=.094) but higher rates of all-cause death (HR 1.27, 95% CI 1.13-1.42; P<.0001) and major or NMCR bleeding (HR 1.32, 95% CI 1.21-1.43; P<.0001). There was a significant interaction between no CAD at baseline and aspirin for all-cause death (P=.009). Aspirin use at baseline was associated with an increased risk for bleeding and all-cause death in ROCKET AF, a risk most pronounced in patients without known CAD. Although these findings may reflect unmeasured clinical factors, further investigation is warranted to determine optimal aspirin use in patients with AF.


Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke.
Previous studies have shown that stroke is a potential first sign of neoplasia, but the relationship between stroke and cancer remains unclear. As a complex brain disease, ischemic stroke involves cell death and immunity. Thus, it is necessary to investigate the association of the tumor immune microenvironment and cell death with ischemic stroke. We established a photothrombosis-induced ischemic injury model in mouse brain and skull. Subsequently, we sequenced the whole transcriptome of the injured mouse brain and skull and analyzed the expression profiles. To investigate the association of stroke with cell death and cancer, we systematically performed gene set enrichment analysis in pan-cell death (i.e., apoptosis, cuproptosis, ferroptosis, necroptosis, and pyroptosis) and the cancer hallmark pathways. The time-dependent immune cell abundance variations after ischemic injury were estimated. Furthermore, pan-cancer genomic and prognostic analyses of the ischemic injury-related gene sets were also performed. In this study, we found that there exist temporal and spatial differences in the gene expression patterns of both the brain and skull with ischemic injury. The skull ischemic injury-induced changes in the brain transcriptome were particularly great, but could recover in a short period, while the skull transcriptome variation resulting from brain ischemic injury was long-lasting. In addition, the expression of the genes related to ischemic injury was also associated with pan-cell death and the cancer hallmark pathways. The changes in the abundance of immune cells indicate that brain ischemic injury may disrupt the immune microenvironment for a longer time, while the skull can balance the stability of the immune microenvironment better. Moreover, the brain ischemic injury-related gene sets were highly correlated with a variety of tumors, particularly glioblastoma multiforme (GBM), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and uveal melanoma (UVM), which carry a greater mortality risk after stroke. This systematic analysis not only helps in the understanding of the changes in the gene expression profiles of both the brain and skull with ischemic injury but also reveals the association of the tumor immune microenvironment and cell death with ischemic stroke.


Surface roughness modulates the response of MG63 osteoblast-like cells to 1,25-(OH)(2)D(3) through regulation of phospholipase A(2) activity and activation of protein kinase A.
Implant surface roughness influences osteoblast proliferation, differentiation, and local factor production. Moreover, the responsiveness of osteoblasts to systemic hormones such as 1, 25-(OH)(2)D(3) is altered by the effects of surface roughness; on the roughest Ti surfaces the effects of roughness and 1, 25-(OH)(2)D(3) are synergistic. Prostaglandin E(2) (PGE(2)) appears to be involved in mediating the effects of surface roughness on the cells, as well as in the response to 1,25-(OH)(2)D(3). However, it is not yet known through which signaling pathways surface roughness exerts its effects on the response of osteoblasts to 1, 25-(OH)(2)D(3). The present study examined the potential role of protein kinase A (PKA), phospholipase A(2)(PLA(2)), and protein kinase C (PKC) in this process. MG63 osteoblast-like human osteosarcoma cells were cultured on cpTi disks with R(a) values of 0. 54 microm (PT), 4.14 microm (SLA), or 4.92 microm (TPS). PKA was inhibited by adding H8 to the cultures; similarly, PLA(2) was inhibited with quinacrine or activated with melittin, and PKC was inhibited with chelerythrine. Inhibitors or activators were included in the culture media through the entire culture period or for the last 24 h of culture. In addition, cultures were treated for 24 h with inhibitors or activators in the presence of 1,25-(OH)(2)D(3). The effects on cell number and alkaline phosphatase specific activity were determined after 24 h; PKC activity was determined after 9 min and at 24 h. Cell number was reduced on rough surfaces, and alkaline phosphatase activity was increased. 1,25-(OH)(2)D(3) had a synergistic effect with surface roughness on alkaline phosphatase. However, neither surface roughness nor 1,25-(OH)(2)D(3) had an effect on PKC. H8 treatment for 24 h inhibited cell number and alkaline phosphatase on all surfaces; however, when it was present throughout the culture period, the PKA inhibitor had no effect on cell number, but decreased alkaline phosphatase-specific activity. H8 reduced the 1,25-(OH)(2)D(3)-mediated effect on cell number and alkaline phosphatase. Quinacrine inhibited cell proliferation and alkaline phosphatase on all surfaces and further reduced the 1,25-(OH)(2)D(3)-dependent decreases in both parameters. Melittin had no effect when applied for 24 h and did not modify the 1,25-(OH)(2)D(3) effect; however, when present throughout the culture period, it caused a decrease in proliferation and an increase in enzyme activity. Chelerythrine, the PKC inhibitor, only inhibited cell proliferation when it was present throughout the entire culture period. However, it decreased alkaline phosphatase in cultures treated for 24 h, but increased enzyme activity when it was present for the entire culture period. The results indicate that surface roughness and 1,25-(OH)(2)D(3) both mediate their effects through PLA(2) which catalyzes the rate-limiting step in PGE(2) production. Further downstream, PGE(2) activates PKA. Surface roughness-dependent effects are also mediated through PKC, but only after the cells have reached confluence and are undergoing phenotypic maturation. The effect of surface roughness on responsiveness to 1,25-(OH)(2)D(3) is mediated through PLA(2)/PKA and not through PKC.


[Agricultural land use impacts on aquatic macroinvertebrates in small streams from La Vieja river (Valle del Cauca, Colombia].
The expansion of the agricultural frontier in Colombia has exerted significant pressure on its aquatic ecosystems during the last few decades. In order to determine the impacts of different agricultural land uses on the biotic and abiotic characteristics of first and second order streams of La Vieja river watershed, we evaluated 21 streams located between 1,060 and 1,534 m asl in the municipalities of Alcalá, Ulloa, and Cartago (Valle del Cauca, Colombia). Seven streams were protected by native vegetation buffers, eight had influence of coffee and plantain crops, and six were influenced by cattle ranching. Habitat conditions, channel dimensions, water quality, and aquatic macroinvertebrates were studied in each stream. Streams draining cattle ranching areas had significantly higher dissolved solids, higher phosphorus, higher alkalinity, higher conductivity, and lower dissolved oxygen than those covered by cropland and forests. Coarse substrates and diversity of flow regimes were significantly higher in cropland and protected streams when compared to streams affected by cattle ranching, whereas the percent of silt and slow currents was significantly higher in the latter. A total of 26,777 macroinvertebrates belonging to 17 orders, 72 families and 95 genera were collected. The most abundant groups were Diptera 62.8%, (Chironomidae 49.6%, Ceratopogonidae 6.7%), Mollusca 18.8% (Hydrobiidae 7.2%, Sphaeriidae 9.6%) and Trichoptera 5.7% (Hydropsychidae 3.7%). The Ephemeroptera, Trichoptera, and Plecoptera orders, known for their low tolerance to habitat perturbation, had high abundance in cropland and forested streams, whereas Diptera and Mollusca were more abundant in those impacted by cattle ranching. Results indicate that streams draining forests and croplands have better physical and biological conditions than those draining pastures, and highlight the need to implement protective measures to restore the latter.


Examination of the Effects of Heterogeneous Organization of RyR Clusters, Myofibrils and Mitochondria on Ca2+ Release Patterns in Cardiomyocytes.
Spatio-temporal dynamics of intracellular calcium, [Ca2+]i, regulate the contractile function of cardiac muscle cells. Measuring [Ca2+]i flux is central to the study of mechanisms that underlie both normal cardiac function and calcium-dependent etiologies in heart disease. However, current imaging techniques are limited in the spatial resolution to which changes in [Ca2+]i can be detected. Using spatial point process statistics techniques we developed a novel method to simulate the spatial distribution of RyR clusters, which act as the major mediators of contractile Ca2+ release, upon a physiologically-realistic cellular landscape composed of tightly-packed mitochondria and myofibrils. We applied this method to computationally combine confocal-scale (~ 200 nm) data of RyR clusters with 3D electron microscopy data (~ 30 nm) of myofibrils and mitochondria, both collected from adult rat left ventricular myocytes. Using this hybrid-scale spatial model, we simulated reaction-diffusion of [Ca2+]i during the rising phase of the transient (first 30 ms after initiation). At 30 ms, the average peak of the simulated [Ca2+]i transient and of the simulated fluorescence intensity signal, F/F0, reached values similar to that found in the literature ([Ca2+]i ≈1 μM; F/F0≈5.5). However, our model predicted the variation in [Ca2+]i to be between 0.3 and 12.7 μM (~3 to 100 fold from resting value of 0.1 μM) and the corresponding F/F0 signal ranging from 3 to 9.5. We demonstrate in this study that: (i) heterogeneities in the [Ca2+]i transient are due not only to heterogeneous distribution and clustering of mitochondria; (ii) but also to heterogeneous local densities of RyR clusters. Further, we show that: (iii) these structure-induced heterogeneities in [Ca2+]i can appear in line scan data. Finally, using our unique method for generating RyR cluster distributions, we demonstrate the robustness in the [Ca2+]i transient to differences in RyR cluster distributions measured between rat and human cardiomyocytes.


Properties of a Ca(2+)-activated large conductance K(+) channel with ATP sensitivity in human renal proximal tubule cells.
The properties of a native Ca(2+)-activated large conductance K(+) channel (BK channel) present in the surface membrane of cultured human renal proximal tubule epithelial cells (RPTECs) were investigated by using the patch-clamp technique. The slope conductance of the BK channel was about 295 pS, and the channel was selective to K(+) over Na(+), with a selectivity ratio of about 12.2. The activity of the channel was almost maximally enhanced by 10(-4 )M or more Ca(2+) in the cytoplasmic surface of the patch membrane and was markedly diminished by reducing the cytoplasmic Ca(2+) to 10(-6) M at the membrane potential of about 0 mV. The depolarization of the patch membrane also enhanced the channel activity, and hyperpolarization lowered it. K(+) channel blockers, Ba(2+) (0.1-1 mM), tetraethylammonium (1 mM), and charybdotoxin (100 nM), were effective for the suppression of channel activity. A significant feature of the K(+) channel was that channel activity maintained by 10(-5)-10(-4 )M Ca(2+) in inside-out patches was inhibited by the addition of ATP (1-10 mM) to the bath solution. ATPgammaS, and a nonhydrolyzable ATP analogue, 5'-adenylylimidodiphosphate (AMP-PNP), also had inhibitory effects on channel activity. However, an inhibitor of ATP-sensitive K(+) channels, glibenclamide (0.1 mM), induced no appreciable change in channel activity from both intra- and extracellular sides. These results suggest that besides the common natures of the BK channel family such as regulation by cytoplasmic Ca(2+) and membrane potential, the BK channel in RPTECs is directly inhibited by intracellular ATP independent of phosphorylation processes and sulfonylurea receptor.


Human leukocyte antigen subtype analysis in patients with advanced adenocarcinoma of the prostate.
Human leukocyte antigens (HLA) are cell surface glycoproteins that have a significant role in the immune system. In some cancers, changes in major histocompatibility complex (MHC) class I and II expression, usually a reduction or loss of these molecules, appear to provide a mechanism whereby tumor cells may escape host immunity. HLA analysis in patients with advanced adenocarcinoma of the prostate revealed the antigens with the highest relative risk factors as DRw52, DRw53, Bw73, DR2, and B5(51). As a result, determination of HLA haplotypes may prove to be useful in determining the men with a higher risk of developing prostate cancer.


Ugly ducklings-the dark side of plastic materials in contact with potable water.
Bath toys pose an interesting link between flexible plastic materials, potable water, external microbial and nutrient contamination, and potentially vulnerable end-users. Here, we characterized biofilm communities inside 19 bath toys used under real conditions. In addition, some determinants for biofilm formation were assessed, using six identical bath toys under controlled conditions with either clean water prior to bathing or dirty water after bathing. All examined bath toys revealed notable biofilms on their inner surface, with average total bacterial numbers of 5.5 × 106 cells/cm2 (clean water controls), 9.5 × 106 cells/cm2 (real bath toys), and 7.3 × 107 cells/cm2 (dirty water controls). Bacterial community compositions were diverse, showing many rare taxa in real bath toys and rather distinct communities in control bath toys, with a noticeable difference between clean and dirty water control biofilms. Fungi were identified in 58% of all real bath toys and in all dirty water control toys. Based on the comparison of clean water and dirty water control bath toys, we argue that bath toy biofilms are influenced by (1) the organic carbon leaching from the flexible plastic material, (2) the chemical and biological tap water quality, (3) additional nutrients from care products and human body fluids in the bath water, as well as, (4) additional bacteria from dirt and/or the end-users' microbiome. The present study gives a detailed characterization of bath toy biofilms and a better understanding of determinants for biofilm formation and development in systems comprising plastic materials in contact with potable water.


[Anthropometrical measurements of the height of the upper lip and length of the philtrum].
indirect anthropometrical measurements of the height of the upper lip and length of the philtrum. to describe the measurements of the height of the upper lip and length of the philtrum, extracted from video x-rays, in children with mixed dentition, relating these measurements to facial typology--medium and long-, to occlusion--Angle's class I and II--and to the rest position of the lips--with and without lip seal. verification of 123 x-rays, in lateral norm, of children with ages between 7:7 and 11:10 years, 56 male and 67 female, extracted from archives of orthodontical documentation prior to treatment. the T-Student test, with a significance level of 5%, was used for the statistical analyses and the obtained results were: for the height of the upper lip no statistical difference was found considering the variables of face typology, occlusion and gender; there was no statistical difference for the measurements of the philtrum considering the variables of face typology and occlusion, but a statistically significant difference was found for the variable gender: a statistically significant difference was found for the height of the upper lip and length of the philtrum considering the variable rest position of the lips--with and without lip seal--being this a determinant factor for the measurements. This finding suggests that a direction of structural modifications may exist. the mean value for the height of the upper lip was established at 21mm; the mean value for the length of the philtrum was established at 12mm. It is important to consider the rest posture of the lips, during assessment and therapy, when taking the measurements of the height of the upper lip and length of the philtrum.


Abnormal hyperexcitability of hippocampal slices from kindled rats is transient.
The anatomic substrates and mechanisms responsible for the development and permanence of kindling remain to be determined. One region believed to play an important role in kindling development is the hippocampus. Epileptiform activity (K+-induced spontaneous bursting) was recently shown to be enhanced in hippocampal slices from kindled rats studied 1 day after kindling from the lateral entorhinal cortex (LEC). Identical results one month after kindling raised the possibility that hippocampal excitability might be permanently increased in kindled animals. One goal of the present study was to confirm this finding, and also to extend it in terms of both the anatomic extent and the duration of this excitability increase. Stimulus train-induced bursting (STIB) is an in vitro model of hippocampal epileptogenesis. Parallels between STIB and kindling suggested STIB might prove useful for studying mechanisms underlying kindling. To strengthen the relation of STIB to kindling, we examined whether slices from kindled animals would behave as if they had undergone STIB during kindling. K+-induced bursting and STIB were studied in hippocampal slices from control and kindled rats one day and about 3 months after completion of kindling from the right LEC. Both K+-induced bursting and STIB development were enhanced one day after kindling. The enhancement of K+-induced bursting was present in both temporal and septal slices from both the ipsilateral and the contralateral hippocampus. Neither of these proepileptic changes was detected 3 months after kindling.(ABSTRACT TRUNCATED AT 250 WORDS)


Short (35-cm) versus long (60-cm) flexible sigmoidoscopy: a comparison of findings and tolerance in asymptomatic patients screened for colorectal neoplasia.
The purpose of this study was to compare the utility of the 35-cm versus the 60-cm flexible sigmoidoscope in screening asymptomatic patients for colorectal neoplasia. Two hundred fifty-eight patients 45 years of age or older were examined in a randomized fashion with both the 35-cm and 60-cm instruments. Fifteen percent (39/258) of patients had a total of 50 polypoid lesions 3 mm or greater in diameter (including one carcinoma). Of all polypoid lesions, 76% were detected with the 35-cm instrument compared to 98% with the 60-cm sigmoidoscope. Eighty-four percent of all polyps occurred within the distal 35 cm of colon. The mean time required to complete the examination was significantly less with the 35-cm sigmoidoscope than with the 60-cm sigmoidoscope (2.5 vs. 5.7 min). Moderate to severe discomfort was experienced by 69% of patients with the 60-cm instrument compared to only 29% with the 35-cm sigmoidoscope. Seventy-two percent of patients preferred examination with the shorter instrument compared with 7% for the longer sigmoidoscope, while 21% of patients expressed no preference. The 35-cm flexible sigmoidoscope fulfills many criteria of an effective screening test for colorectal neoplasia including rapidity of examination, safety, good sensitivity, and excellent patient acceptance.


One-session treatment compared with multisession CBT in children aged 7-16 years with specific phobias: the ASPECT non-inferiority RCT.
Up to 10% of children and young people have a specific phobia that can significantly affect their mental health, development and daily functioning. Cognitive-behavioural therapy-based interventions remain the dominant treatment, but limitations to their provision warrant investigation into low-intensity alternatives. One-session treatment is one such alternative that shares cognitive-behavioural therapy principles but has a shorter treatment period. This research investigated the non-inferiority of one-session treatment to cognitive-behavioural therapy for treating specific phobias in children and young people. The acceptability and cost-effectiveness of one-session treatment were examined. A pragmatic, multicentre, non-inferiority randomised controlled trial, with embedded economic and qualitative evaluations. There were 26 sites, including 12 NHS trusts. Participants were aged 7-16 years and had a specific phobia defined in accordance with established international clinical criteria. Participants were randomised 1 : 1 to receive one-session treatment or usual-care cognitive-behavioural therapy, and were stratified according to age and phobia severity. Outcome assessors remained blind to treatment allocation. The primary outcome measure was the Behavioural Avoidance Task at 6 months' follow-up. Secondary outcomes included the Anxiety Disorder Interview Schedule, Child Anxiety Impact Scale, Revised Children's Anxiety and Depression Scale, a goal-based outcome measure, Child Health Utility 9D, EuroQol-5 Dimensions Youth version and resource usage. Treatment fidelity was assessed using the Cognitive Behaviour Therapy Scale for Children and Young People and the One-Session Treatment Rating Scale. A total of 274 participants were recruited, with 268 participants randomised to one-session treatment (n = 134) or cognitive-behavioural therapy (n = 134). A total of 197 participants contributed some data, with 149 participants in the intention-to-treat analysis and 113 in the per-protocol analysis. Mean Behavioural Avoidance Task scores at 6 months were similar across treatment groups when both intention-to-treat and per-protocol analyses were applied [cognitive-behavioural therapy: 7.1 (intention to treat), 7.4 (per protocol); one-session treatment: 7.4 (intention to treat), 7.6 (per protocol); on the standardised scale adjusted mean difference for cognitive-behavioural therapy compared with one-session treatment -0.123, 95% confidence interval -0.449 to 0.202 (intention to treat), mean difference -0.204, 95% confidence interval -0.579 to 0.171 (per protocol)]. These findings were wholly below the standardised non-inferiority limit of 0.4, which suggests that one-session treatment is non-inferior to cognitive-behavioural therapy. No between-group differences in secondary outcome measures were found. The health economics evaluation suggested that, compared with cognitive-behavioural therapy, one-session treatment marginally decreased the mean service use costs and maintained similar mean quality-adjusted life-year improvement. Nested qualitative evaluation found one-session treatment to be considered acceptable by those who received it, their parents/guardians and clinicians. No adverse events occurred as a result of phobia treatment. The COVID-19 pandemic meant that 48 children and young people could not complete the primary outcome measure. Service waiting times resulted in some participants not starting therapy before follow-up. One-session treatment for specific phobia in UK-based child mental health treatment centres is as clinically effective as multisession cognitive-behavioural therapy and highly likely to be cost-saving. Future work could involve improving the implementation of one-session treatment through training and commissioning of improved care pathways. This trial is registered as ISRCTN19883421. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 42. See the NIHR Journals Library website for further project information.


Phenotypic selection on an ornamental trait is not modulated by breeding density in a pied flycatcher population.
Most studies of phenotypic selection in the wild have focussed on morphological and life-history traits and looked at abiotic (climatic) variation as the main driver of selection. Consequently, our knowledge of the effects of biotic environmental variation on phenotypic selection on sexual traits is scarce. Population density can be considered a proxy for the intensity of intrasexual and intersexual competition and could therefore be a key factor influencing the covariation between individual fitness and the expression of sexual traits. Here, we used an individual-based data set from a population of pied flycatchers (Ficedula hypoleuca) monitored over 24 years to analyze the effect of breeding density on phenotypic selection on dorsal plumage colouration, a heritable and sexually selected ornament in males of this species. Using the number of recruits as a fitness proxy, our results showed overall stabilizing selection on male dorsal colouration, with intermediate phenotypes being favoured over extremely dark and dull individuals. However, our results did not support the hypothesis that breeding density mediates phenotypic selection on this sexual trait. We discuss the possible role of other biotic factors influencing selection on ornamental plumage.


Work disability in inflammatory bowel disease patients 10 years after disease onset: results from the IBSEN Study.
To compare the work disability (WD) rate in inflammatory bowel disease (IBD) patients 10 years after disease onset, with the WD rate in the background population,and to assess whether clinical or demographic factors in the early disease course could predict WD after 10 years disease. A large, population-based inception cohort (the Inflammatory Bowel in South Eastern Norway cohort) was prospectively followed up at 1, 5 and 10 years after diagnosis. At the 10-year follow-up data on WD were collected. Data on disability pension (DP) in the background population were retrieved from public databases. We calculated overall and age-standardised relative risks (RR) for DP. Logistic regression analysis was used to examine predictive factors. A total of 518 patients completed the 10-year follow-up (response rate 83.5%). The overall disability rate in the IBD population was 18.8%, and the RR was 1.8 (95% CI 1.4 to 2.3) for ulcerative colitis (UC) and 2.0 (95% CI 1.4 to 2.7) for Crohn's disease (CD). The RR for DP was highest in patients aged below 40 years while patients aged over 60 years had no increased RR. Steroid treatment at the 1-year follow-up predicted WD after 10 years disease in both CD and UC. In UC, increased C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) at diagnosis, early colectomy, and more than two relapses during the first year of the disease also predicted WD. Ten years after disease onset IBD patients had an increased RR for DP as compared with the background population. The youngest patients had the highest RR. Markers of severe disease course predicted WD.


Gemcitabine and arabinosylcytosin pharmacogenomics: genome-wide association and drug response biomarkers.
Cancer patients show large individual variation in their response to chemotherapeutic agents. Gemcitabine (dFdC) and AraC, two cytidine analogues, have shown significant activity against a variety of tumors. We previously used expression data from a lymphoblastoid cell line-based model system to identify genes that might be important for the two drug cytotoxicity. In the present study, we used that same model system to perform a genome-wide association (GWA) study to test the hypothesis that common genetic variation might influence both gene expression and response to the two drugs. Specifically, genome-wide single nucleotide polymorphisms (SNPs) and mRNA expression data were obtained using the Illumina 550K(R) HumanHap550 SNP Chip and Affymetrix U133 Plus 2.0 GeneChip, respectively, for 174 ethnically-defined "Human Variation Panel" lymphoblastoid cell lines. Gemcitabine and AraC cytotoxicity assays were performed to obtain IC(50) values for the cell lines. We then performed GWA studies with SNPs, gene expression and IC(50) of these two drugs. This approach identified SNPs that were associated with gemcitabine or AraC IC(50) values and with the expression regulation for 29 genes or 30 genes, respectively. One SNP in IQGAP2 (rs3797418) was significantly associated with variation in both the expression of multiple genes and gemcitabine and AraC IC(50). A second SNP in TGM3 (rs6082527) was also significantly associated with multiple gene expression and gemcitabine IC50. To confirm the association results, we performed siRNA knock down of selected genes with expression that was associated with rs3797418 and rs6082527 in tumor cell and the knock down altered gemcitabine or AraC sensitivity, confirming our association study results. These results suggest that the application of GWA approaches using cell-based model systems, when combined with complementary functional validation, can provide insights into mechanisms responsible for variation in cytidine analogue response.


Effect of Nasal Submucosal Injection of Low-concentration Epinephrine on Visual Field Visualization in Endoscopic Sinus Surgery: A Systematic Review and Meta-analysis.
Objective: To determine whether nasal submucosal injection of low-concentration epinephrine improved the surgical field visualization and physician satisfaction compared to placebo or without intervention. Methods: A literature search of PubMed, Scopus, Web of Science, Cochrane library, China National Knowledge Infrastructure, and Wanfang Database was conducted from inception to January 10, 2023. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Meta-analyses were performed using Review Manager (RevMan version 5.3; the Cochrane Collaboration). Quality was assessed by 2 reviewers using the Cochrane Risk of Bias Tool. And we used funnel plots to visually assess the risk of publication bias. Results: We included a total of 11 studies with 492 patients, all of which were randomized controlled trials. Among the studies, 4 had a low risk of bias, 4 had a moderate risk of bias, and 3 had a high risk of bias. Five studies reported visual bleeding grade in the surgical field (P = 0.07) and total blood loss (P = 0.16), 8 studies reported preoperative baseline heart rate (P = 0.58) and baseline mean arterial pressure (MAP) (P = 0.78), and 9 studies reported intraoperative heart rate (P = 0.27) and MAP (P = 0.56), which showed no significant differences in these parameters between the 2 groups. None of these outcomes were statistically significant between the epinephrine group and the control group. Conclusion: There is insufficient evidence to support the nasal submucosal application of low-concentration epinephrine to improve surgical field dryness and reduce total surgical bleeding.


[Characteristics of group b streptococcus vertical transmission].
The goal of this study was to compare the characteristics of group B streptococcus (GBS) or Streptococcus agalactiae vertical transmission in woman, receiving or not intrapartum. antimicrobial prophylaxis, at risk of delivering an infant with GRS disease. The study included 330 women, with risk factors for delivering an infant with GBS disease. The vaginal GBS colonization was studied by conventional culture. A clinical and microbiological follow-up was done in both women and neonates. GHS was detected in 37 women (11.2%). Among these, 21 (56.8%) received intrapartum antibiotics and 16 (43.2%) did not. Forty-one neonates were born from these 37 women. Of these, 11 showed signs of infection (3 with positive blood culture and 8 with blood culture negative for GBS) and 2 presented an asymptomatic bacteremia A GBS neonatal infection (with positive blood culture) was produced in 4.8% of newborns from mothers who received intrapartum antibiotics versus 25% of newborns from mothers who did not receive intrapartum antibiotics. However, this difference was not significant nor was the difference between external colonization by GBS between these two groups of newborns. On the contrary, significant differences were found in the percentage of clinically suspected sepsis (with negative blood cultures), which was more frequent among newborns from mothers without intrapartum antibiotics (30.4% vs 5.6%). A good correlation between the intensity of vaginal colonization and the incidence of microbiologically demonstrated sepsis, suspected sepsis an asymptomatic bacteremia in the newborn was found. In conclusion, in order to minimize the vertical transmission of GBS, the most efficient strategy seems to be to offer antibiotic prophylaxis to women identified as GBS carriers, since the antibiotic administration to women with "obstetric risks" often means that it is impossible that two hours elapse between antibiotic administration and delivery, resulting in the loss of efficacy of this second strategy.


Functional outcome of implant removal following fracture fixation below the level of the knee: a prospective cohort study.
The aim of this study was to evaluate the functional outcome in patients undergoing implant removal (IR) after fracture fixation below the level of the knee. All adult patients (18 to 75 years) undergoing IR after fracture fixation below the level of the knee between November 2014 and September 2016 were included as part of the WIFI (Wound Infections Following Implant Removal Below the Knee) trial, performed in 17 teaching hospitals and two university hospitals in The Netherlands. In this multicentre prospective cohort, the primary outcome was the difference in functional status before and after IR, measured by the Lower Extremity Functional Scale (LEFS), with a minimal clinically important difference of nine points. A total of 179 patients were included with a median age of 50 years (interquartile range (IQR) 37 to 60), of whom 71 patients (39.7%) were male. With a median score of 60 before IR (IQR 45 to 72) and 66 after IR (IQR 51 to 76) on the LEFS, there was a statistically significant improvement in functional outcome (p < 0 .001). A total of 31 surgical site infections (17.3%) occurred. Although IR led to a statistically significant improvement of functional outcome, the minimal clinically important difference was not reached. In conclusion, this study shows that IR does not result in a clinically relevant improvement in functional outcome. These results, in combination with the high complication rate, highlight the importance of carefully reviewing the indication for IR. Cite this article: Bone Joint J 2019;101-B:447-453.


Analysis of pulsatile pressures and flows in glomerular filtration.
Previous mathematical models of glomerular filtration have ignored the pulsatility of the glomerular capillary pressure, using only steady-state equations and time-averaged pressures and flows. Because the actual pressure pulses are rapid and of large amplitude and because the governing equations are nonlinear, it is questionable whether the effects of the pressure pulses average out in the manner that has been assumed. We have developed a model that includes sinusoidal variations in the glomerular transcapillary hydraulic pressure (delta P) and the afferent arteriolar plasma flow rate over each cardiac cycle. The analysis suggests that the previously ignored time derivatives in the luminal mass balance equations are not negligible. The amplitude of the oscillations in delta P was found to be sufficient to reverse the direction of the transmural fluxes over part of each cardiac cycle, at the more efferent locations in a capillary. However, the time-averaged values of single-nephron glomerular filtration rate and sieving coefficients for macro-molecules from the pulsatile model differed from that for a steady-state formulation by less than 0.1 and less than or equal to 10%, respectively. We conclude that use of the usual steady-state assumption introduces negligible errors in calculating glomerular membrane parameters from experimental data.


Rosmarinic acid influences collagen, MMPs, TIMPs, glycosylation and MUC1 in CRL-1739 gastric cancer cell line.
Rosmarinic acid (RA) is a natural phenylpropanoid with numerous pharmacological activities. Because of limited studies of the effects of RA action in gastric cancer cells we examined how 100 and 200 μM acid influences MMPs, TIMPs, collagen, MUC1 and specific sugar antigens in gastric adenocarcinoma CRL-1739 cells. We revealed inhibitory effect of RA on MMP-9 activity what was correlated with increased collagen type I expression, main ECM substrate degraded by MMPs. Tissue inhibitor of MMPs, TIMP-1 but not TIMP-2 was significantly decreased on the protein level and increased on mRNA level by RA action what can suggest TIMP-1 independent inhibitory action of an acid on MMP-9 activity. Glycosylation of gastric cancer proteins was also effected by RA. ELISA tests revealed inhibitory effect of an acid on Tn antigen in cell lysates and culture supernatant and on T antigen in cell lysates. RA inhibited also sialylated Tn antigen in protein of culture supernatant and sialyl T in cell lysates. Extracellular domain of MUC1 mucin, main carrier of Tn and T antigens was significantly inhibited by higher dose of RA. The data suggest potential usefulness of RA as a complementary agent supporting chemotherapy in cancer treatment.


Tracheoesophageal puncture in the office setting with local anesthesia.
Tracheoesophageal puncture (TEP) with voice prosthesis placement is currently the method of choice for vocal rehabilitation of patients who have undergone total laryngectomy. Occasionally, secondary TEP needs to be performed. We have used a TEP technique that is performed in the clinic setting with local anesthesia and no sedation. The purpose of this study was to review our technique and experience and to evaluate results, complications, and patients' acceptance of the procedure. We performed a retrospective chart review of the records of 14 patients who had undergone total laryngectomy and secondary TEP placement in the clinic setting. The procedure was well tolerated. The voice results were fair to good in 11 of 12 patients. There was 1 complication, a false passage between the trachea and the esophagus. Voicing was immediate in 12 of the 14 cases. We conclude that TEP can be performed in the office setting with local anesthesia. The voice results are excellent, and the procedure is well tolerated by the patient. Proper patient selection and regular follow-up by a speech-language pathologist are important.


Extracellular vesicles as a potential source of tumor-derived DNA in advanced pancreatic cancer.
Tumor-derived extracellular vesicles (EVs) are reported to contain nucleic acids, including DNA. Several studies have highlighted the potential of EV-derived DNA (evDNA) as a circulating biomarker, even demonstrating that evDNA can outperform cell-free DNA (cfDNA) in terms of sensitivity. Here, we evaluated EVs as a potential source of tumor-derived DNA in patients with advanced pancreatic cancer. evDNA from both DNase-treated and untreated EV samples was analyzed to determine whether the DNA was primarily located internally or outside (surface-bound) the EVs. To assess whether methodology affected the results, we isolated EVs using four different methods for small EV isolation and differential centrifugation for isolating large EVs. Our results indicated that the DNA content of EVs was significantly less than the cfDNA content isolated from the same plasma volume (p < 0.001). Most of the detected evDNA was also located on the outside of the vesicles. Furthermore, the fraction of tumor-derived DNA in EVs was similar to that found in cfDNA. In conclusion, our results suggest that quantification of evDNA, as a source of tumor-derived DNA, does not add information to that obtained with cfDNA, at least not in patients with advanced pancreatic cancer.


Removal of fluoride from fluoride contaminated industrial waste water by electrolysis.
Wastewater containing fluoride are generally treated with lime or calcium salt supplemented with aluminium salts. Wastewater generated from different industries does not always behave in the same way due to the presence of interfering contaminants. A number of techniques have been developed and studied for the removal of excessive fluoride. Most of these are based on use of aluminium salt. In alum coagulation the sorption properties of product of hydrolysis of aluminium salts and capacity of fluoride for complex formation plays a very important role. These hydrolysis products of aluminium can be produced by passing direct current through aluminium electrode. The text presented in the paper deals with the various aspect of removal of fluoride by electrolysis using aluminium electrode from fluoride chemical based industrial wastewater.


Neurophysiology of perceptual and motor aspects of interception.
The interception of moving targets is a complex activity that involves a dynamic interplay of several perceptual and motor processes and therefore involves a rich interaction among several brain areas. Although the behavioral aspects of interception have been studied for the past three decades, it is only during the past decade that neural studies have been focused on this problem. In addition to the interception itself, several neural studies have explored, within that context, the underlying mechanisms concerning perceptual aspects of moving stimuli, such as optic flow and apparent motion. In this review, we discuss the wealth of knowledge that has accumulated on this topic with an emphasis on the results of neural studies in behaving monkeys.


Cryopreserved versus freshly isolated lymphocytes in human biomonitoring: endogenous and induced DNA damage, antioxidant status and repair capability.
Lymphocytes are routinely used in human biomonitoring to assess the potential toxic and cytoprotective effects of diet on both DNA damage and repair and, by implication, health. Logistically, samples may require to be cryopreserved and stored. How this affects cells used in human biomonitoring is often not considered. In this study we have evaluated the influence of cryopreservation on endogenous and induced DNA strand breakage, altered bases (oxidized purines, oxidized pyrimidines and misincorporated uracil), antioxidant capacity and DNA repair capability in human peripheral blood lymphocytes. Neither isolation nor freezing increased DNA strand breakage above endogenous levels found in freshly isolated human lymphocytes. Oxidized bases (both pyrimidines and purines) and misincorporated uracil, were similar for fresh and frozen lymphocytes. Fresh and frozen lymphocytes responded almost identically to hydrogen peroxide. Quercetin-mediated cytoprotection against hydrogen peroxide-induced strand breakage was maintained in cryopreserved lymphocytes after short-term (24 h) and longer term (2 months) storage compared with freshly isolated and treated cells. Hydrogen peroxide-induced DNA strand breakage was repaired in fresh lymphocytes. Cryopreserved lymphocytes were unable to repair oxidant-induced DNA strand breaks. Frozen human lymphocytes can therefore be successfully used for most aspects of DNA damage biomonitoring, but not for repair.


A Case Report of Glycogenic Hepatopathy.
Glycogenic hepatopathy is a rare condition that may be seen in patients with poorly controlled diabetes mellitus. This is a case presentation of a 15-year-old female with type 1 diabetes mellitus who was not fully adherent to her insulin regimen and presented in acute diabetic ketoacidosis. She had the associated symptom of two months of abdominal pain. The patient's ketoacidosis resolved during her hospitalization with insulin and intravenous fluid management; however, her lactic acid and liver transaminases remained persistently elevated. Abdominal ultrasound was consistent with parenchymal liver disease and a clinical diagnosis of glycogenic hepatopathy was made. Management consisted of tight glucose control. After discharge, the patient was followed closely by pediatric endocrinology and pediatric gastroenterology, and once her glucose was optimized, her transaminitis and lactic acidosis resolved. Although an uncommon condition, it is important to consider glycogenic hepatopathy in diabetic patients with poor glucose control, abdominal pain, transaminitis and lactic acidosis. Diabetic ketoacidosis, hepatopathy, lactic acidosis, transaminitis, glycogen, diabetes mellitus. Brown D, et al. A Case Report of Glycogenic Hepatopathy. JETem 2021. 6(3):V1-3.


Digression and Value Concatenation to Enable Privacy-Preserving Regression.
Regression techniques can be used not only for legitimate data analysis, but also to infer private information about individuals. In this paper, we demonstrate that regression trees, a popular data-analysis and data-mining technique, can be used to effectively reveal individuals' sensitive data. This problem, which we call a "regression attack," has not been addressed in the data privacy literature, and existing privacy-preserving techniques are not appropriate in coping with this problem. We propose a new approach to counter regression attacks. To protect against privacy disclosure, our approach introduces a novel measure, called digression, which assesses the sensitive value disclosure risk in the process of building a regression tree model. Specifically, we develop an algorithm that uses the measure for pruning the tree to limit disclosure of sensitive data. We also propose a dynamic value-concatenation method for anonymizing data, which better preserves data utility than a user-defined generalization scheme commonly used in existing approaches. Our approach can be used for anonymizing both numeric and categorical data. An experimental study is conducted using real-world financial, economic and healthcare data. The results of the experiments demonstrate that the proposed approach is very effective in protecting data privacy while preserving data quality for research and analysis.


Diversity and niche evolution along aridity gradients in north american lizards (phrynosomatidae).
Deserts occupy approximately 12% of the Earth's land surface, and are thought to have species poor but highly specialized biotas. However, few studies have examined the evolutionary origins of desert biotas and of diversity patterns along aridity gradients. Further, it is unclear if species occurring in more extreme conditions on a given niche axis (i.e., precipitation) are more specialized for those conditions (i.e., have narrower niche breadths). We address these questions here using a time-calibrated phylogeny and climatic data for 117 species of phrynosomatid lizards. Phrynosomatids are the most species-rich family of lizards in North America, and are found from deserts to rainforests. Surprisingly, we find that phrynosomatids have higher richness in more arid environments. This pattern occurs seemingly because they have been present in more arid habitats longer (~55 million years), and lineages in mesic environments are recently derived from more arid-dwelling ancestors. We find little support for the hypothesis that species in more extreme environments are more specialized. Instead, many desert-dwelling species are broadly distributed, and species in the most mesic environments have the broadest niche breadths. In summary, phrynosomatids offer a counterexample to the idea that arid regions are inhabited by a small number of recent and highly specialized lineages.


Voxelwise encoding models with non-spherical multivariate normal priors.
Predictive models for neural or fMRI data are often fit using regression methods that employ priors on the model parameters. One widely used method is ridge regression, which employs a spherical multivariate normal prior that assumes equal and independent variance for all parameters. However, a spherical prior is not always optimal or appropriate. There are many cases where expert knowledge or hypotheses about the structure of the model parameters could be used to construct a better prior. In these cases, non-spherical multivariate normal priors can be employed using a generalized form of ridge known as Tikhonov regression. Yet Tikhonov regression is only rarely used in neuroscience. In this paper we discuss the theoretical basis for Tikhonov regression, demonstrate a computationally efficient method for its application, and show several examples of how Tikhonov regression can improve predictive models for fMRI data. We also show that many earlier studies have implicitly used Tikhonov regression by linearly transforming the regressors before performing ridge regression.


Spatial/temporal correlation of BOLD and optical intrinsic signals in humans.
Comparing the BOLD signal with electrophysiological maps and other perfusion-dependent signals, such as the optical intrinsic signal (OIS), within subjects should provide insight into the etiology of the BOLD signal. Tongue activations were compared in five human subjects using BOLD fMRI, 610-nm OIS, and the electrocortical stimulation map (ESM). Robust fMRI activations centered on the lateral inferior aspect of the central sulcus and extended into pre- and post-central gyri, adjacent to ESM tongue loci. OIS and fMRI maps colocalized, although optical responses were spatially larger (P <.001 across multiple thresholds) and contained more gyral components. The timecourses of the fMRI and OIS signals were similar, appearing within 2.5 s and peaking 6-8 s after task onset. Although many processes contribute to increased 610-nm reflectance, optical spectroscopy and fluorescent dye imaging suggest that a significant part of this signal is due to a concomitant decrease in deoxyhemoglobin and increase in oxyhemoglobin concentrations. The spatial/temporal correlation of BOLD and the positive 610-nm response within subjects suggests that the two signals may share similar etiologies. The OIS/fMRI inconsistencies may be due to cell swelling and light-scattering contributions to OIS and fMRI sensitivity. This study also demonstrates that fMRI maps do not precisely colocalize with ESM, rather they emphasize changes in adjacent venous/sulcal structures.


How structural adaptability exists alongside HLA-A2 bias in the human αβ TCR repertoire.
How T-cell receptors (TCRs) can be intrinsically biased toward MHC proteins while simultaneously display the structural adaptability required to engage diverse ligands remains a controversial puzzle. We addressed this by examining αβ TCR sequences and structures for evidence of physicochemical compatibility with MHC proteins. We found that human TCRs are enriched in the capacity to engage a polymorphic, positively charged "hot-spot" region that is almost exclusive to the α1-helix of the common human class I MHC protein, HLA-A*0201 (HLA-A2). TCR binding necessitates hot-spot burial, yielding high energetic penalties that must be offset via complementary electrostatic interactions. Enrichment of negative charges in TCR binding loops, particularly the germ-line loops encoded by the TCR Vα and Vβ genes, provides this capacity and is correlated with restricted positioning of TCRs over HLA-A2. Notably, this enrichment is absent from antibody genes. The data suggest a built-in TCR compatibility with HLA-A2 that biases receptors toward, but does not compel, particular binding modes. Our findings provide an instructional example for how structurally pliant MHC biases can be encoded within TCRs.


Infrared surface polaritons on antimony.
The semimetal antimony, with a plasma frequency ~80 times less than that of gold, is potentially useful as a host for infrared surface polaritons (SPs). Relevant IR SP properties, including the frequency-dependent propagation length and penetration depths for fields into the media on either side of the interface, were determined from optical constants measured on optically-thick thermally-evaporated Sb films over the wavelength range 1 to 40 μm. Plasma and carrier relaxation frequencies were determined from Drude-model fits to these data. The real part of the permittivity is negative for wavelengths beyond 11 μm. Distinct resonant decreases in specular reflected intensity were observed for Sb lamellar gratings in the wavelength range of 6 to 11 μm, where the real part of the permittivity is positive. Both resonance angles and the angular reflectance spectral line shapes are in agreement with theory for excitation of bound surface electromagnetic waves (SPs). Finite element method (FEM) electrodynamic simulations indicate the existence of SP modes under conditions matching the experiments. FEM results also show that such waves depend on having a significant imaginary part of the permittivity, as has been noted earlier for the case of surface exciton polaritons.


Involvement of Notch signaling in initiation of prechondrogenic condensation and nodule formation in limb bud micromass cultures.
Notch signaling is an evolutionarily conserved mechanism that plays a critical role in the determination of multiple cellular differentiation pathways and morphogenesis during embryogenesis. The limb bud high-density culture is an established model that recapitulates mesenchymal condensation and chondrocyte differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) showed that Notch and its related genes were expressed in such cultures on day 1 and reached a peak between day 3 and day 5, when cell condensation and nodule formation were initiated. Immunohistochemical experiments revealed that the expression of Notch1 was initially localized within the nodules and shifted to their peripheral region as the cell differentiation progressed. We disrupted Notch signaling by using a gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), to analyze the function of Notch signaling in the culture system. The blocking of Notch signaling by DAPT apparently promoted the initiation of prechondrogenic condensation and fusion of the nodules, and such an effect was reversed by exogenous expression of the Notch cytoplasmic domain. DAPT treatment also induced chondrogenic markers and bone morphogenetic protein (BMP)-related molecules, including type II collagen, Sox9, GDF5, and Id1. These observations imply that the Notch signal may have an important role in chondrogenic differentiation by negatively regulating the initiation of prechondrogenic condensation and nodule formation.


[Electro-osmotic processes in the region of bilayer lipid membrane contact].
The influence of outer voltage on a contact of two bilayer lipid membranes has been revealed and investigated. The effect was due to the origination of an electro-osmotic water flow in the contact region.


Vascular outcome in patients with homocystinuria due to cystathionine beta-synthase deficiency treated chronically: a multicenter observational study.
An inborn error of metabolism, homocystinuria due to cystathionine beta-synthase deficiency, results in markedly elevated levels of circulating homocysteine. Premature vascular events are the main life-threatening complication. Half of all untreated patients have a vascular event by 30 years of age. We performed a multicenter observational study to assess the effectiveness of long-term homocysteine-lowering treatment in reducing vascular risk in 158 patients. Vascular outcomes were analyzed and effectiveness of treatment in reducing vascular risk was evaluated by comparison of actual to predicted number of vascular events, with the use of historical controls from a landmark study of 629 untreated patients with cystathionine beta-synthase deficiency. The 158 patients had a mean (range) age of 29.4 (4.5 to 70) years; 57 (36%) were more than 30 years old, and 10 (6%) were older than 50 years. There were 2822 patient-years of treatment, with an average of 17.9 years per patient. Plasma homocysteine levels were markedly reduced from pretreatment levels but usually remained moderately elevated. There were 17 vascular events in 12 patients at a mean (range) age of 42.5 (18 to 67) years: pulmonary embolism (n=3), myocardial infarction (n=2), deep venous thrombosis (n=5), cerebrovascular accident (n=3), transient ischemic attack (n=1), sagittal sinus thrombosis (n=1), and abdominal aortic aneurysm (n=2). Without treatment, 112 vascular events would have been expected, for a relative risk of 0.09 (95% CI 0.036 to 0.228; P<0.0001). Treatment regimens designed to lower plasma homocysteine significantly reduce cardiovascular risk in cystathionine beta-synthase deficiency despite imperfect biochemical control. These findings may be relevant to the significance of mild hyperhomocysteinemia that is commonly found in patients with vascular disease.


Phenotypic and genetic characterization of the bacteriophage abortive infection mechanism AbiK from Lactococcus lactis.
The natural plasmid pSRQ800 isolated from Lactococcus lactis subsp. lactis W1 conferred strong phage resistance against small isometric phages of the 936 and P335 species when introduced into phage-sensitive L. lactis strains. It had very limited effect on prolate phages of the c2 species. The phage resistance mechanism encoded on pSRQ800 is a temperature-sensitive abortive infection system (Abi). Plasmid pSRQ800 was mapped, and the Abi genetic determinant was localized on a 4.5-kb EcoRI fragment. Cloning and sequencing of the 4.5-kb fragment allowed the identification of two large open reading frames. Deletion mutants showed that only orf1 was needed to produce the Abi phenotype. orf1 (renamed abiK) coded for a predicted protein of 599 amino acids (AbiK) with an estimated molecular size of 71.4 kDa and a pI of 7.98. DNA and protein sequence alignment programs found no significant homology with databases. However, a database query based on amino acid composition suggested that AbiK might be in the same protein family as AbiA. No phage DNA replication nor phage structural protein production was detected in infected AbiK+ L. lactis cells. This system is believed to act at or prior to phage DNA replication. WHen cloned into a high-copy vector, AbiK efficiency increased 100-fold. AbiK provides another powerful tool that can be useful in controlling phages during lactococcal fermentations.


Automatic Outlier Detection in Laboratory Result Distributions Within a Real World Data Network.
Laboratory data must be interoperable to be able to accurately compare the results of a lab test between healthcare organizations. To achieve this, terminologies like LOINC (Logical Observation Identifiers, Names and Codes) provide unique identification codes for laboratory tests. Once standardized, the numeric results of laboratory tests can be aggregated and represented in histograms. Due to the characteristics of Real World Data (RWD), outliers and abnormal values are common, but these cases should be treated as exceptions, excluding them from possible analysis. The proposed work analyses two methods capable of automating the selection of histogram limits to sanitize the generated lab test result distributions, Tukey's box-plot method and a "Distance to Density" approach, within the TriNetX Real World Data Network. The generated limits using clinical RWD are generally wider for Tukey's method and narrower for the second method, both greatly dependent on the values used for the algorithm's parameters.


Investigation of keratinase digestion to improve steroid hormone extraction from diverse keratinous tissues.
Monitoring the physiology of wild populations presents many technical challenges. Blood samples, long the gold standard of wildlife endocrinology studies, cannot always be obtained. The validation and use of non-plasma samples to obtain hormone data have greatly improved access to more integrated information about an organism's physiological state. Keratinous tissues like skin, hair, nails, feathers, or baleen store steroid hormones in physiologically relevant concentrations, are stable across decades, and can be used to retrospectively infer physiological state at prior points in time. Most protocols for steroid extraction employ physical pulverization or cutting of the sample, followed by mixing with a solvent. Such methods do produce repeatable and useful data, but low hormone yield and detectability issues can complicate research on small or rare samples. We investigated the use of keratinase, an enzyme that breaks down keratin, to improve the extraction and yield of corticosterone from vertebrate keratin tissues. Corticosterone content of keratinase-digested extracts were compared to non-keratinase extracts for baleen from three species of whale (blue, Balaenoptera musculus; bowhead, Balaena mysticetus; southern right, SRW; Eubalaena australis), shed skin from two reptiles (tegu lizard, Salvator merianae; narrow-headed garter snake, Thamnophis rufipunctatus), hair from arctic ground squirrel (AGS; Urocitellus parryii), feathers from Purple Martins (PUMA; Progne subis), and spines from the short-beaked echidna (Tachyglossus aculeatus). We tested four starting masses (10, 25, 50, 100 mg) for each sample; digestion was most complete in the 10 and 25 mg samples. A corticosterone enzyme immunoassay (EIA) was validated for all keratinase-digested extracts. In all sample types except shed skin from reptiles, keratinase digestion improved hormone yield, with PUMA feathers and blue whale baleen having the greatest increase in apparent corticosterone content (100% and 66% more hormone, respectively). The reptilian shed skin samples did not benefit from keratinase digestion, actually yielding less hormone than controls. With further optimization and refinement, keratinase digestion could greatly improve yield of steroid hormones from various wildlife epidermal tissue types, allowing more efficient use of samples and ultimately improving understanding of the endocrine physiology of wild populations.


Changes in Color Stability and Surface Roughness of Teflon-Coated Arch Wires After Clinical Use.
Peeling of polytetrafluoroethylene (Teflon)-coated esthetic arch wires results in rough surfaces that may cause plaque accumulation, and the exposed core material may not meet the esthetic expectations of patients. The aim of this study was to evaluate the in-vivo surface roughness, Streptococcus mutans colonization, and color stability of Teflon-coated arch wires from 3 different manufacturers. Surface roughness and color data of 0.016-inch and 0.016 × 0.022-inch Teflon-coated arch wires from 3 different manufacturers were recorded as they were received (T0) and after 28 days of clinical exposure (retrieved) (T1) using an atomic force microscope and a spectrophotometer. The amount of S. mutans was assessed in terms of colony-forming units on the as-received and retrieved wires. The surface roughness increased significantly, and a clinically noticeable color change was observed in all groups after clinical use (P < .005). There was no statistically significant difference in the amount of S. mutans adhesion for most of the wires. No significant correlation was found between the amount of S. mutans adhesion and the surface roughness. All the arch wires showed increased surface roughness and clinically noticeable color change. The surface roughness values were not found to be correlated with the amount of S. mutans adhesion.


Renal venotomy for thrombectomy and kidney preservation in dogs with adrenal tumors and renal vein invasion.
To describe the surgical technique and report the outcomes of adrenalectomy and thrombus removal with kidney preservation by renal venotomy in a population of dogs with adrenal tumors and vascular invasion into the renal vein (RV) and caudal vena cava (CVC). Short case series. Five client-owned dogs that underwent adrenalectomy. Dogs with adrenal tumors and vascular invasion into the RV and CVC were retrospectively enrolled in this multi-institutional study. Renal venotomy was performed at the time of adrenalectomy for tumor thrombus removal. Recorded data included signalment, clinical signs and results of laboratory testing, physical examination findings, diagnostic imaging results, surgical technique, surgical time, surgical complications, and outcome. Tumor thrombus was removed by renal venotomy in five dogs. In one dog with an ectopic adrenal tumor located ventral to the left kidney, the thrombus was occluding 90% of caval flow, and a small caval venotomy was required to remove it. Kidney preservation was achieved in all dogs. No significant intraoperative or postoperative complications occurred, and all dogs were discharged 3 to 4 days postoperatively. Median surgical time was 125 minutes (range, 80-210). At the end of the study, four dogs were alive without signs of recurrence, while one dog died of a suspected pulmonary embolism at 510 days. Median follow-up was 510 days (range, 279-890). Renal venotomy is feasible for thrombectomy in dogs with adrenal tumors and RV invasion and allowed for the preservation of the kidney in this case series, thus limiting perioperative morbidity.


Neuronal mechanisms of developmental plasticity in the cat's visual system.
During early postnatal development various response properties of single neurones can be changed in the cat's visual system. These modifications must be based on changes of synaptic efficacy and depend on neuronal activity. Rearing kittens with artificial astigmatism creates meridional amblyopia demonstrable on different levels of investigation. Characteristic interdependencies of ocular dominance and orientation preference in visual cortex can be generated that demonstrate that synaptic changes involve a postsynaptic gating mechanism. The same conclusion can be drawn from the results of monocular strobe rearing, which has differential effects on cells in different cortical laminae. Connectivity changes can be induced by rather brief stimulation, but need time for consolidation, as can be shown by reverse occlusion experiments. Deprivation effects may also act across sensory modality borders: auditory neurones in superior colliculus are found much more frequently after visual deprivation. Judging from the number of bimodal cells, synaptic competition may be less powerful here than in visual cortex.


Intravenous cannulation: a different approach.
This article presents a different method of venous cannulation. It has been used successfully to teach dental residents working on pediatric and developmentally disabled patients. The technique includes using a syringe of 1% lidocaine hydrochloride attached to a 25-ga needle to produce a skin wheal by "jet injection." This is accomplished by placing the bevel of the needle downward and forcing the syringe in a downward and backward direction, with pressure being continuously exerted on the plunger. A 20-ga, 1 1/4-inch catheter is then attached to the syringe containing the remaining lidocaine hydrochloride. The catheter is bent, with its bevel up, approximately three-fourths of the way from the tip to form a gradually sloping bend of approximately 40 degrees to 45 degrees. The catheter is then inserted into the skin wheal and advanced into the vein. The advantages of this technique are that it (1) can eliminate the pain associated with a subcutaneous infiltration of a local anesthetic solution, (2) provides a method of venous cannulation that is easier to master by the novice, and (3) gives a visual check on successful catheterization of the vein.


Polymerase chain reaction amplification fails to detect aromatase cytochrome P450 transcripts in normal human endometrium or decidua.
It has been proposed that the biosynthesis of estrogens by the human endometrium may be of physiological significance during the menstrual cycle. Local estrogen production was also suggested to be important in the development of endometrial cancer; however, the presence or absence of aromatase enzyme activity in normal human endometrium is controversial. To address this issue, we used a sensitive technique capable of detecting mRNA transcripts present in only very low copy number. The polymerase chain reaction linked to reverse transcription (RT-PCR) was used to evaluate the presence or absence of aromatase cytochrome P450 (P450arom) transcripts in endometrial tissues (n = 7) and endometrial stromal cells (n = 9) under various culture conditions. RNA was isolated from four proliferative and three secretory tissue samples and from cultured endometrial stromal cells isolated from seven proliferative and two secretory endometria. Five sets of cultures were treated with medroxyprogesterone acetate (MPA), estradiol (E2), and forskolin. Additionally, RNA was isolated from decidualized endometrium obtained from a patient with tubal pregnancy. A single stranded cDNA was synthesized from total RNA using Moloney murine leukemia virus reverse transcriptase and a P450arom-specific oligonucleotide. The single stranded cDNA was used as a template for PCR and was amplified for 20-35 cycles using P450arom-specific primers. RNA from adipose tissue and placenta was amplified to provide positive controls, whereas myometrial RNA was used as a negative control. In two experiments involving two endometrial tissues and three sets of cells in culture, a rat P450arom cRNA was coamplified in each sample as an internal control to demonstrate that the remote possibility of RT-PCR failures in individual test samples cannot account for our negative results. By Southern or slot blot hybridization of the amplified fragments using human and rat P450arom-specific probes, we found no evidence for the presence of P450arom transcripts in normal endometrium, decidualized endometrium, or endometrial stromal cells in culture. In our hands, assay of aromatase activity using [3H]water release from [3H]androstenedione by endometrial stromal cells in culture treated with MPA and E2, did not reveal any detectable aromatase activity. The same cells responded to MPA plus E2 treatment by a significant increase in PRL secretion into the culture medium. Presently, RT-PCR is the most sensitive method available for the detection of specific mRNA species in low copy numbers. These findings are indicative of the absence of P450arom transcripts in normal human endometrium.


Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study.
In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P = 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r = 0.36 and 0.28, respectively, P < 0.001 each) but a negative correlation between apoA-V and LPL mass (r = -0.14 and -0.12 for men and women respectively, P < 0.001 each). The frequency of the c.56C>G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For -1131T>C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P = 0.047). The association of -1131T>C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V.


[Effects of students' work activities in autumn agricultural teams on their morbidity].
The authors used social studies, timing in order to assess organization and work conditions of manual cotton harvesting by students. Further analysis covered morbidity with transitory disablement among the participants of 8 agricultural teams. Manual cotton harvesting appeared to bring intensive physical strain, awkward working posture, long trips to carry heavy loads in excessive exposure to agrochemical agents. Those hazards induced the growing morbidity. Each third one of the examinees faced transitory disablement. The morbidity structure was opened by respiratory diseases (25.1% of all the cases and 16.9% of all the disablement days), then came gastrointestinal diseases (21.6% and 18.0% respectively), the third place was occupied by neurologic illnesses and disorders of sensory organs (12.8% and 10.1% respectively). The studies proved the activities estimated as an important hazard for the students' health.


Spectrum of Clinical and Associated MR Imaging Findings in Children with Olfactory Anomalies.
The olfactory apparatus, consisting of the bulb and tract, is readily identifiable on MR imaging. Anomalous development of the olfactory apparatus may be the harbinger of anomalies of the secondary olfactory cortex and associated structures. We report a large single-site series of associated MR imaging findings in patients with olfactory anomalies. A retrospective search of radiologic reports (2010 through 2014) was performed by using the keyword "olfactory"; MR imaging studies were reviewed for olfactory anomalies and intracranial and skull base malformations. Medical records were reviewed for clinical symptoms, neuroendocrine dysfunction, syndromic associations, and genetics. We identified 41 patients with olfactory anomalies (range, 0.03-18 years of age; M/F ratio, 19:22); olfactory anomalies were bilateral in 31 of 41 patients (76%) and absent olfactory bulbs and olfactory tracts were found in 56 of 82 (68%). Developmental delay was found in 24 (59%), and seizures, in 14 (34%). Pituitary dysfunction was present in 14 (34%), 8 had panhypopituitarism, and 2 had isolated hypogonadotropic hypogonadism. CNS anomalies, seen in 95% of patients, included hippocampal dysplasia in 26, cortical malformations in 15, malformed corpus callosum in 10, and optic pathway hypoplasia in 12. Infratentorial anomalies were seen in 15 (37%) patients and included an abnormal brain stem in 9 and an abnormal cerebellum in 3. Four patients had an abnormal membranous labyrinth. Genetic testing was performed in 23 (56%) and findings were abnormal in 11 (48%). Olfactory anomalies should prompt careful screening of the brain, skull base, and the pituitary gland for additional anomalies. Genetic testing should be considered.


Suicide Risk among Immigrants and Ethnic Minorities: A Literature Overview.
Recent studies have demonstrated that immigrants and ethnic minorities may be at higher risk of suicidal behaviour as compared to the general population. We conducted a literature search to identify studies in English from 1980 to 2017 related to suicide risk among immigrants and ethnic minorities. Six hundred and seventy-eight reports were screened, and 43 articles were included in the qualitative synthesis of the review. Some studies reported lower rates of suicide attempts, while other findings suggested higher rates of suicidal behaviour and deaths among immigrants as compared to the native population. Also, a positive correlation was found between suicidal behaviour and specific countries of origin. Non-European immigrant women were at the highest risk for suicide attempts, a group which included young women of South Asian and black African origin. Risk factors among migrants and ethnic minorities were found to be: language barriers, worrying about family back home, and separation from family. The lack of information on health care system, loss of status, loss of social network, and acculturation were identified as possible triggers for suicidal behaviour. Overall, results suggest that specific migrant populations and ethnic minorities present a higher risk of suicidal behaviour than native populations, as well as a higher risk of death by suicide.