The interplay between drug resistance and fitness in malaria parasites.
Controlling the spread of antimalarial drug resistance, especially resistance of Plasmodium falciparum to artemisinin-based combination therapies, is a high priority. Available data indicate that, as with other microorganisms, the spread of drug-resistant malaria parasites is limited by fitness costs that frequently accompany resistance. Resistance-mediating polymorphisms in malaria parasites have been identified in putative drug transporters and in target enzymes. The impacts of these polymorphisms on parasite fitness have been characterized in vitro and in animal models. Additional insights have come from analyses of samples from clinical studies, both evaluating parasites under different selective pressures and determining the clinical consequences of infection with different parasites. With some exceptions, resistance-mediating polymorphisms lead to malaria parasites that, compared with wild type, grow less well in culture and in animals, and are replaced by wild type when drug pressure diminishes in the clinical setting. In some cases, the fitness costs of resistance may be offset by compensatory mutations that increase virulence or changes that enhance malaria transmission. However, not enough is known about effects of resistance mediators on parasite fitness. A better appreciation of the costs of fitness-mediating mutations will facilitate the development of optimal guidelines for the treatment and prevention of malaria.


The mutation Ala677-->Val in the methylene tetrahydrofolate reductase gene: a risk factor for arterial disease and venous thrombosis.
Mild hyperhomocysteinemia has been identified as a risk factor for arterial disease and for venous thrombosis. Individuals homozygous for the thermolabile variant of the methylene tetrahydrofolate reductase gene (MTHFR) which results from a common mutation Ala677-->Val and is found in 5-15% of the general population, have significantly elevated plasma homocysteine levels and may account for one of the genetic risk factors in vascular disease. We have analyzed the prevalence of MTHFR-T homozygotes in patients with arterial disease or venous thrombosis. We studied 191 patients with arterial disease and 127 individuals with venous thrombosis and compared with 296 unmatched controls. The results showed that there was a high prevalence of homozygotes for the mutated MTHFR-T allele among a group of patients with arterial disease (19%) in the absence of hyperlipoproteinemia, hypertension, and diabetes mellitus when compared to controls (4%), odds ratio of 5.52 (95% C.I., 2.27 to 13.51). The prevalence of homozygotes among patients with venous thrombosis was 11%, odds ratio of 2l93 (95% C.I., 1.23 to 7.01). The risk of venous thrombosis remained high, odds ratio of 2.63, even after we excluded 27 patients with hereditary thrombophilia (e.g. factor V Leiden, dysfibrinogenemia, deficiency of protein C, protein S, antithrombin III, or factor XII) from the 127 overall cases with venous thrombosis. These data support the hypothesis that being a homozygote for the MTHFR-T is a risk factor for the development of arterial disease and also for venous thrombosis.


Quality of Life of Intermittent Urinary Catheterization Users and Their Caregivers: A Scoping Review.
This study aimed to examine and map the scientific evidences regarding quality of life in neurogenic bladder patients and consequently their caregivers by means of a scoping review. This is a scoping review proposal of the Joanna Briggs Institute. It was conducted to examine and map the scientific evidences about quality of life (QoL) in neurogenic bladder patients and their caregivers, to identify the meanings attributed to QoL and its relation with intermittent urinary catheterization. The following guiding question was: "What scientific evidence has been produced on the QoL of neurogenic bladder patients using intermittent urinary catheterization and their caregivers?" A total of 2945 research studies were identified using The Cochrane Library, CINAHL, LILACS, Academic Search Premier (via EBSCO platform), PubMed, SCOPUS, the platforms Web of Science, the b-on and Gray Literature. The keywords established were patient, intermittent urinary catheterization, neurogenic urinary bladder, quality of life and caregiver. From 2,945 studies, 13 studies were selected. Most of the selected studies that analyzed variables related to the patients' QoL were regarding the urinary catheterization technique, assessment of urinary incontinence, individual perceptions of the procedure and experiences with urinary catheter in childhood and adult life. The meanings attributed to QoL, when compared to adult and child individuals with normal bladder functioning, presented lower QoL scores. Concerning caregivers, the QoL of caregivers of children using intermittent urinary catheterization demonstrated low scores. The QoL of patient's who use intermittent urinary catheterization can be determined by improvement of urinary symptoms and self-confidence. Research related to QoL of patients who use urinary catheter indicates the importance of adequate professional support and appropriate health public policies.


Perceived dysphonia by the clinician's and patient's viewpoint.
To verify the relationship between the clinician's vocal evaluation and vocal self-assessment and voice-related quality of life. Participants were 96 individuals: 48 with vocal complaints and voice deviation (VCG), mean age of 51 years, with diagnosis and indication of voice therapy; and 48 with no vocal complaints and healthy voices (NVCG), mean age of 46 years. All participants answered the Voice-Related Quality of Life (V-RQOL) questionnaire, performed a vocal self-assessment and were submitted to auditory-perceptual analysis of voice. Mean V-RQOL scores were different between groups for all domains. Self-assessment results also showed differences between groups, which was not the case in the auditory-perceptual analysis of sustained vowel and connected speech, showing that the patient's perception was worse than the clinician's. There was correlation between the V-RQOL domains (Socio-emotional and Physical: 76.8%; Socio-emotional and Total: 90.8%; Physical and Total: 95.8%), as well as between the Socio-emotional (-52.9%), Physical (-43.1%) and Total (-52.2%) domains and the self-assessment. However, no correlation was found between auditory-perceptual analysis and self-assessment measures, except for a weak correlation between vocal self-assessment and auditory-perceptual analysis of the sustained vowel (33.3%). The clinician's perception does correspond to the individual's self-perception of his/her vocal quality and the impact of a voice deviation on his/her quality of life, but not directly. The individual's perception about his/her vocal quality and voice-related quality of life complements the clinician's perception regarding the overall degree of the voice deviation.


The molecular physiology of hepatic nuclear factor 3 in the regulation of gluconeogenesis.
Glucocorticoids stimulate gluconeogenesis by increasing the rate of transcription of genes that encode gluconeogenic enzymes such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase. Previous studies have shown that hepatic nuclear factor 3 (HNF3) is required as an accessory factor for several glucocorticoid-stimulated genes, including PEPCK. Here, we show that adenovirus-mediated expression of an HNF3beta protein with a deleted C-terminal transactivation domain (HNF3betaDeltaC) reduces the glucocorticoid-induced expression of the PEPCK and glucose-6-phosphatase genes in H4IIE hepatoma cells. Furthermore, expression of this truncated HNF3 protein results in a proportionate reduction of glucocorticoid-stimulated glucose production from lactate and pyruvate in these cells. The expression of HNF3betaDeltaN, in which the N-terminal transactivation domain is deleted, does not exhibit any of these effects. These results provide direct evidence that members of the HNF3 family are required for proper regulation of hepatic gluconeogenesis. Modulation of the function of the HNF3 family of proteins might be used to reduce the excessive hepatic production of glucose that is an important pathophysiologic feature of diabetes mellitus.


Survey of Naegleria fowleri in geothermal recreational waters of Guadeloupe (French West Indies).
In 2008 a fatal case of primary amoebic meningoencephalitis, due to the amoeboflagellate Naegleria fowleri, occurred in Guadeloupe, French West Indies, after a child swam in a bath fed with geothermal water. In order to improve the knowledge on free-living amoebae in this tropical part of France, we investigated on a monthly basis, the presence of Naegleria spp. in the recreational baths, and stream waters which feed them. A total of 73 water samples, 48 sediments and 54 swabs samples were collected from 6 sampling points between June 2011 and July 2012. The water samples were filtered and the filters transferred to non-nutrient agar plates seeded with a heat-killed suspension of Escherichia coli while sediment and swab samples were placed directly on these plates. The plates were incubated at 44°C for the selective isolation of thermophilic Naegleria. To identify the Naegleria isolates the internal transcribed spacers, including the 5.8S rDNA, were amplified by polymerase chain reaction and the sequence of the PCR products was determined. Thermophilic amoebae were present at nearly all collection sites. The pathogenic N. fowleri was the most frequently encountered thermophilic species followed by N. lovaniensis. The concentration of N. fowleri was rather low in most water samples, ranging from 0 to 22 per liter. Sequencing revealed that all N. fowleri isolates belonged to a common Euro-American genotype, the same as detected in the human case in Guadeloupe. These investigations need to be continued in order to counsel the health authorities about prevention measures, because these recreational thermal baths are used daily by local people and tourists.


Medication instruction design: younger and older adult schemas for taking medication.
We examined whether older and younger adults share a schema for taking medication and whether instructions are better recalled when they are organized to match this schema. Experiment 1 examined age difference in schema organization. Participants sorted medication items (e.g., purpose, dose, possible side effects) according to similarity and then ordered the items to create a preferred instruction set. Cluster analysis of the sort and order data showed that younger and older adults share a schema for taking medication. Secondary regression analyses found that verbal ability (i.e., vocabulary scores) predicted individual differences in schema organization. In Experiment 2 participants recalled instructions that were either compatible with this schema in terms of grouping and order of items or were presented in nonpreferred orders. Younger participants remembered more information than did older participants, but both age groups better remembered and preferred the more schema-compatible instructions. Secondary analyses showed that recall was also positively related to verbal ability. Along with our earlier research, this study suggests that older and younger adults possess a schema for taking medication and that instructions that are compatible with this schema provide an environmental support that improves memory for medication information.


What needs to be done for polio eradication in India?
Even if wild poliovirus persists in one country only, global polio eradication cannot be achieved, because of the risk of exportation of wild virus to other countries. Among the countries where polio cases are still occurring, India happens to be the largest country. India cannot become polio free unless Uttar Pradesh and Bihar become polio free. There was a quick decline in polio incidence in some states in India, while other states reported decline slowly, but, Uttar Pradesh and Bihar have never been polio free since the polio eradication programme was launched in 1995. Despite increase in number of pulse polio immunization (PPI) rounds since year 2000 and introduction of monovalent polio vaccine type 1 (mOPV1) and type 3 (mOPV3) in Uttar Pradesh in 2005, there has been no respite in polio incidence in Uttar Pradesh and Bihar. Lately, majority of polio cases being reported from other states are occurring in migrant population from Uttar Pradesh and Bihar, and also molecular study shows that polioviruses being detected in other states have origin in Uttar Pradesh or Bihar. Thus, there is an urgent need to develop a new vaccine or strategy specifically for Uttar Pradesh and Bihar.


Factors influencing engagement in online dual practice by public hospital doctors in three large cities: A mixed-methods study in China.
In the digital age, a rising number of public sector doctors are providing private telemedicine and telehealth services on online health care platforms. This novel practice pattern - termed online dual practice - may profoundly impact health system performance in both developed and developing countries. This study aims to understand the factors influencing doctors' engagement in online dual practice. Using a mixed-methods design, this study concurrently collects quantitative demographic and practice data (n = 71 944) and semi-structured interview data (n = 32) on secondary and tertiary public hospital doctors in three large Chinese cities: Beijing, Shanghai and Guangzhou. We use the quantitative data to examine the prevalence of the online dual practice and its associated factors via the binary logit regression model. The qualitative data are used to further explore associated factors of online dual practice via thematic analysis. The findings about associated factors from the two parts were merged using the categories of personal, professional, and organisational characteristics. Our quantitative analysis shows that at least 47.1% of public hospital doctors are involved in online dual practice. The shares in Beijing, Shanghai, and Guangzhou are 43.7%, 53.1%, and 44.8%, respectively. This practice is more prevalent among doctors who are male, senior, and non-managerial. Different specialties, hospital ownership, hospital levels, and locations are also significantly associated with this practice. The qualitative analysis further suggests that financial returns, perceived effectiveness of telemedicine, and hospital directors' attitude towards telemedicine may affect doctors' engagement with online dual practice. Online dual practice is prevalent among doctors at tertiary and secondary public hospitals in Beijing, Shanghai, and Guangzhou. Personal, professional, and organisational characteristics are all associated with doctors' choice to engage in online dual practice. The findings in this study provide implications for promoting telemedicine adoption and developing relevant regulatory policies in China and other countries.


Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines.
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines. We used a test-negative case-control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants. Vaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults. We observed limited waning in vaccine effectiveness against Covid-19-related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.


Childhood suppurative otitis media in Abakaliki: isolated microbes and in vitro antibiotic sensitivity pattern.
Suppurative otitis media (SOM) is the most common pediatric problem seen by otolaryngologists in Nigeria. Devising simple and effective ways of treating pediatric patients with suppurating ears, especially in situations without a specialist care, will help prevent chronicity. Our experience with som at the ebonyi state university teaching hospital (ebsuth), abakaliki, is reviewed in this study. it may serve as a guide in patient care. Determine the bacteriology of SOM in children in Abakaliki and ascertain their sensitivity to common antibiotics. A 2-year retrospective analysis of ear swabs culture results and case files of children aged 0-18 years with SOM managed in EBSUTH. Sixty-five patients with discharging ears were reviewed. Of these, 73% were ≤ 5 years, of which 41.5% were infants. About 83% had unilateral ear discharge. Acute suppuration was seen in 67%. Overall swab yield was 87.7%; Pseudomonas was (57.4%), Klebsiella (16.4%), and Proteus species (11.5%). Ciprofloxacin showed 60% sensitivity, Gentamicin (58%), and Ceftazidime (35%). Amoxicillin/Clavulanic acid, ceftriaxone, and cefuroxime showed sensitivity of 4.3%-9.7%. Treatment protocols of SOM in children should emphasize the use of Ciprofloxacin or Gentamicin, especially in situations with limited access to laboratory services or specialist care.


The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum.
To investigate the role of the KDEL receptor in the retrieval of protein toxins to the mammalian cell endoplasmic reticulum (ER), lysozyme variants containing AARL or KDEL C-terminal tags, or the human KDEL receptor, have been expressed in toxin-treated COS 7 and HeLa cells. Expression of the lysozyme variants and the KDEL receptor was confirmed by immunofluorescence. When such cells were challenged with diphtheria toxin (DT) or Escherichia coli Shiga-like toxin 1 (SLT-1), there was no observable difference in their sensitivities as compared to cells which did not express these exogenous proteins. By contrast, the cytotoxicity of Pseudomonas exotoxin A (PE) is reduced by expressing lysozyme-KDEL, which causes a redistribution of the KDEL receptor from the Golgi complex to the ER, and cells are sensitised to this toxin when they express additional KDEL receptors. These data suggest that, in contrast to SLT-1, PE can exploit the KDEL receptor in order to reach the ER lumen where it is believed that membrane transfer to the cytosol occurs. This contention was confirmed by microinjecting into Vero cells antibodies raised against the cytoplasmically exposed tail of the KDEL receptor. Immunofluorescence confirmed that these antibodies prevented the retrograde transport of the KDEL receptor from the Golgi complex to the ER, and this in turn reduced the cytotoxicity of PE, but not that of SLT-1, to these cells.


Microwave Imaging Based on a Subspace-based Two-step Iterative Shrinkage/Thresholding Method.
This paper presents a subspace-based two-step iterative shrinkage/thresholding method(S-TwIST) based on the Distorted Born iterative method (DBIM) to improve the performance of the original TwIST inverse algorithm. This method retrieves the deterministic part of the induced current from inhomogeneous Green's function operator leading to more accurate total field calculation at each iteration step than that of the original TwIST. Both inverse algorithms have been evaluated with a set of synthetic geometries with fine structures. Compared with TwIST, the results show that S-TwIST has superior accuracy in multiple objects profile (εerr=0.1454%) and 1/16λ resolution at 2GHz. Also, S-TwIST is more robust to initial guess, which means it is less likely to become unstable when the inversion procedure starts without initial guess.


Top-emitting white organic light-emitting devices with down-conversion phosphors: theory and experiment.
White top-emitting organic light-emitting devices (TEOLEDs) with down-conversion phosphors are investigated from theory and experiment. The theoretical simulation was described by combining the microcavity model with the down-conversion model. A White TEOLED by the combination of a blue TEOLED with organic down-conversion phosphor 3-(4-(diphenylamino)phenyl)-1-pheny1prop-2-en-1-one was fabricated to validate the simulated results. It is shown that this approach permits the generation of white light in TEOLEDs. The efficiency of the white TEOLED is twice over the corresponding blue TEOLED. The feasible methods to improve the performance of such white TEOLEDs are discussed.


Serodiagnosis of whooping cough in Belgium: results of the National Reference Centre for Bordetella pertussis anno 2013.
Report on the pitfalls of serodiagnosis of pertussis in Belgium for 2013 by the NRC Bordetella. Determine cases of acute infection using an anti-pertussis toxin (PT) IgG antibody ELISA. A total of 2471 serum samples were received. Clinical information on the duration of cough (at moment of blood sampling) is essential for a reliable interpretation of the results. In order to avoid false negative results, 213 samples for which this information was lacking were not tested. For a total of 2179 patients tested, 520 (23.9%) had antibody levels indicative of an acute infection, 261 (12%) samples were diagnosed as positive (indicative of a pertussis infection or vaccination during the last year), 143 (6.7%) samples were classified as doubtful and 752 (34,5%) (35.5%) were diagnosed as negative. The serodiagnosis of pertussis has limited value for the early diagnosis of the disease and PCR analysis on nasopharyngeal swabs is the method of choice during the first 2 weeks and always for young children <1 year old. For sera collected during the first 2 weeks with anti-PT levels below the threshold for acute infection, a second sample collected 2-3 weeks later is needed a definitive diagnosis. For 503 (23.0%) early samples, a second serum sample was requested but not provided. For 85 patients, for whom a second sample was received, 12.9% were eventually diagnosed as having an acute infection. In order to generate reliable serodiagnostic results for pertussis, serum samples should preferentially be collected 3 weeks after onset of symptoms.


Factors affecting the efficacy of repetitive transcranial magnetic stimulation for patients with Alzheimer's disease.
Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive technique. In recent years, many studies have demonstrated that rTMS can improve cognitive function in Alzheimer's disease (AD) patients and has potential as a therapeutic method for AD. However, the efficacy varies greatly with different rTMS treatment regimens, which is related to the frequency, type, location, duration, intensity and focusing power of stimulation. Recent studies have shown that high-frequency stimulation is superior to low-frequency stimulation; efficacy of intermittent theta burst stimulation (iTBS) is similar to that of conventional rTMS, but iTBS treatment session is shorter and might be more acceptable for AD patients; rTMS stimulation sites targeting AD-damaged brain regions or associated networks would be more effective; short-term intensive treatment combined with long-term maintenance treatment can gain long-term efficacy; dynamic adjustment of stimulus intensity combined with the degree of cognitive impairment can enhance the efficacy; functional connection based on functional magnetic resonance imaging may improve the focusing power of rTMS. In this article, we review the factors related to the efficacy of rTMS, to provide reference for feasible rTMS therapeutic regimens of AD.


Role of E-cadherin in antimigratory and antiinvasive efficacy of silibinin in prostate cancer cells.
The epithelial-to-mesenchymal transition (EMT) in prostate cancer (PCA) cells is considered prerequisite for acquiring migratory/invasive phenotype, and subsequent metastasis. We hypothesized that promoting the E-cadherin expression in PCA cells by using nontoxic phytochemicals, like silibinin, would prevent EMT and consequently invasiveness. Our results showed that silibinin treatment (5-90 μmol/L) significantly inhibits migratory and invasive potential of advance human PCA PC3, PC3MM2, and C4-2B cells in in vitro assays. Importantly, the antimigratory/antiinvasive efficacy of silibinin was not due to its cytotoxicity toward PCA cells. Molecular analyses showed that silibinin increases E-cadherin level that was localized mainly at cellular membrane as evidenced by subcellular fractional and confocal analyses in PC3 cells, which might be responsible for morphologically observed shift toward epithelial character. Silibinin also decreased the levels of Slug, Snail, phospho-Akt(ser(473)), nuclear β-catenin, phospho-Src(tyr(419)) and Hakai; together they play an important role in regulating E-cadherin expression/function and EMT. Similar silibinin effects on E-cadherin, β-catenin, phospho-Src(tyr(419)), and Hakai levels were also observed in PC3MM2 and C4-2B PCA cells. Selective Src inhibition by dasatinib also showed increased E-cadherin expression in PC3 cells suggesting a possible involvement of Src inhibition in silibinin-caused increase in E-cadherin level. Additional studies in PC3 cells with stable knock-down of E-cadherin expression revealed that antimigratory/antiinvasive efficacy of silibinin is in-part dependent on E-cadherin expression. Together, our results showing antimigratory/antiinvasive effects of silibinin and associated mechanisms suggest that silibinin should be tested further in clinically relevant animal models toward exploiting its potential benefits against metastatic PCA.


Effect of a carbohydrase mixture on ileal amino acid digestibility in extruded full-fat soybeans fed to finishing pigs.
Extrusion technology has been used successfully to improve the nutritive value of full-fat oilseeds via shear force and heat applied during passage through the extruder, exposing more peptide bonds to enzymatic hydrolysis. However, the fibrous portion of the seeds is largely intact after extrusion. Therefore, application of carbohydrase mixtures targeting nonstarch polysaccharides might further improve the nutritive value of extruded full-fat oilseeds. This hypothesis was investigated in a study involving 6 ileal-cannulated barrows (average initial BW = 75.0 kg) fed extruded full-fat, soybean- (FFSB) based diets, without or with a carbohydrase mixture (CM) to determine apparent ileal digestibility (AID) of energy and standardized ileal digestibility (SID) of AA. The CM supplement provided 500, 50, 400, 1200, 450, and 45 units of pectinase, cellulase, mannanase, xylanase, glucanase, and galactanase, respectively, per kilogram of diet. A basal diet was formulated to contain FFSB as the sole source of AA, whereas the CM diet was formulated by supplementing the basal diet with CM. Diets contained titanium dioxide as an indigestible marker. Diets were fed in a 2-period crossover design to give 6 observations per diet. Each experimental period lasted 7 d, including a 5-d adaptation period and 2-d ileal digesta collection period. The SID of N and AA were calculated using published values for ileal endogenous N and AA losses from our laboratory. Enzyme supplementation increased (P < 0.01) AID values of DM (68.7 vs. 65.7%), GE (74.6 vs. 70.5%), and N (64.2 vs. 58.5%). Greater (P < 0.05) AID values were recorded for Leu, Met + Cys, Thr, Cys, Ser, and Tyr in the CM diet compared with the basal diet. Compared with the basal diet, the CM diet had greater SID values for N (73.7 vs. 68.6%; P < 0.01), Met + Cys (59.9 vs. 52.2%; P < 0.05), and Thr (66.3 vs. 61.2%; P < 0.05). The average SID for indispensable and total AA increased by 3.4% and 3.8% units, respectively, after enzyme supplementation. In conclusion, enzyme supplementation increased the nutritive value of extruded FFSB for finishing pigs.


Plasma endothelin-1 levels after exercise in patients with congenital heart disease.
We have previously reported that plasma endothelin-1 (ET-1) levels were significantly increased after exercise in healthy athletes. In the present study, venous plasma ET-1 levels were measured to investigate whether the role of ET-1 during exercise differs between healthy athletes and patients with congenital heart disease. Seven patients (mean age 13 years) performed symptom-limited treadmill exercise (Bruce protocol). All patients were in class I of the NYHA functional classification. The mean end-exercise O2 utilization was 32 ml/min/kg (166% of ventilatory threshold). Blood sampling was carried out in the seated position. The plasma ET-1 level was 1.21 pg/ml before exercise and did not alter immediately after or 30 min after exercise. The plasma level of norepinephrine was markedly elevated immediately after exercise and returned to the basal level 30 min after exercise. The present study demonstrated that exercise failed to alter plasma ET-1 levels in patients with congenital heart disease.


The experience and self-management of fatigue in patients on hemodialysis.
Fatigue is a common and debilitating symptom for adult patients with end stage renal disease on hemodialysis, and has been associated with decreased survival and quality of life. Patients on hemodialysis must find ways to manage their fatigue and mitigate its effects on their lives. The purpose of this qualitative descriptive work was to describe the experience and self-management of fatigue in patients on incenter hemodialysis. Several themes were identified which included the nature of fatigue, management of fatigue, consequences of fatigue, and factors associated with fatigue. This information will be valuable to nephrology nurses as they continue to care for and educate patients on hemodialysis.


Relative adrenal insufficiency in post-transplant lymphoproliferative disorder.
Post-transplant lymphoproliferative disorder is treated with rapid decrement of immunosuppressive therapy. This cannot be achieved with ease in patients on long-term glucocorticoid therapy, as chronically suppressed adrenal glands may not be capable of mounting adequate response to stress. A 52-year-old Caucasian male presented with fever, orthostatic hypotension, lymphadenopathy and hyponatraemia. Serum cortisol levels were within normal levels with a sub optimal response to stimulation by ACTH. Hyponatraemia and orthostasis responded poorly to fluid restriction, saline and salt repletion but corrected after increasing the steroid dose. The normal baseline cortisol levels represented a stimulated adrenal gland, however, the ACTH stimulation had inadequate response. This sub optimal stimulation and a good response to increased steroids suggest the presence of relative or occult adrenal insufficiency. Relative adrenal insufficiency must be considered in patients who have received prolonged glucocorticoid therapy and have symptoms such as hypotension and/or hyponatraemia.


Development of Bioglass/PEEK Composite Coating by Cold Gas Spray for Orthopedic Implants.
Cold gas spray (CGS) technology has allowed the development of biofunctional coatings composed of 45S5 and polyetheretherketone (PEEK). The combination of a bioactive glass material embedded in a polymeric matrix makes this composite an interesting material for orthopedic applications since this composite meets the biomechanical and biological requirements of an implant. In the present study, blends of bioactive glass 45S5 and PEEK powder with different granulometry and 45S5/PEEK ratio have been prepared. These mixtures of powders have been deposited onto PEEK substrates by CGS with the goal of incorporating a bioactive additive to the biocompatible polymer, which can improve the bone-implant interaction of PEEK. The deposition efficiency (DE) of the coatings has been evaluated, and from the results obtained, it was possible to conclude that DE is significantly affected by the granulometry and by the 45S5/PEEK ratio of the blends. By scanning electron microscopy (SEM) inspection, it was observed that the use of blends with high 45S5/PEEK ratio lead to the deposition of coatings with high content of 45S5. Finally, the friction behavior of the coatings was analyzed performing ball-on-disk tests and these experiments showed that the presence of glass particles has a beneficial role in the wear resistance.


How do we engage people in testing for COVID-19? A rapid qualitative evaluation of a testing programme in schools, GP surgeries and a university.
The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly community RT-LAMP (Reverse transcription loop-mediated isothermal amplification) testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. The insights generated and informed the design and modification of the Southampton COVID-19 Saliva Testing Programme and the next phase of community-testing. Discussions revealed that high levels of communication, trust and convenience were necessary to ensure people's engagement with the programme. Participants felt reassured by and pride in taking part in this novel programme. They suggested modifications to reduce the programme's environmental impact and overcome cultural barriers to participation. Participants' and stakeholders' motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary. Community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise engagement.


[Responsibility of ENT specialists in rendering medical care in present-day social-economic conditions].
The article contains basic legal and standard acts on regulating law in health service, rights and responsibilities of patients and doctors. Knowledge of the regulation raises responsibility of otorhinolaryngologists in rendering medical care and must improve quality of ENT service.


Early Pregnancy Serum Metabolite Profiles Associated with Hypertensive Disorders of Pregnancy in African American Women: A Pilot Study.
Hypertensive disorders of pregnancy (HDP) are the most common cardiometabolic complications of pregnancy, affecting nearly 10% of US pregnancies and contributing substantially to maternal and infant morbidity and mortality. In the US, women of African American race are at increased risk for HDP. Early biomarkers that reliably identify women at risk for HDP remain elusive, yet are essential for the early identification and targeting of interventions to improve maternal and infant outcomes. We employed high-resolution metabolomics (HRM) to identify metabolites and metabolic pathways that were altered in early (8-14 weeks) gestation serum samples of pregnant African American women who developed HDP after 20 weeks' gestation (n = 20)-either preeclampsia (PE; n = 11) or gestational hypertension (gHTN; n = 9)-compared to those who delivered full term without complications (n = 80). We found four metabolic pathways that were significantly (p < 0.05) altered in women who developed PE and five pathways that were significantly (p < 0.05) altered in women who developed gHTN compared to women who delivered full term without complications. We also found that four specific metabolites (p < 0.05) were distinctly upregulated (retinoate, kynurenine) or downregulated (SN-glycero-3-phosphocholine, 2'4'-dihydroxyacetophenone) in women who developed PE compared to gHTN. These findings support that there are systemic metabolic disruptions that are detectable in early pregnancy (8-14 weeks of gestation) among pregnant African American women who develop PE and gHTN. Furthermore, the early pregnancy metabolic disruptions associated with PE and gHTN are distinct, implying they are unique entities rather than conditions along a spectrum of the same disease process despite the common clinical feature of high blood pressure.


Early postoperative feeding in resectional gastrointestinal surgical cancer patients.
Malnutrition is present in the majority of patients presenting for surgical management of gastrointestinal malignancies, due to the effects of the tumour and preoperative anti-neoplastic treatments. The traditional practice of fasting patients until the resumption of bowel function threatens to further contribute to the malnutrition experienced by these patients. Furthermore, the rationale behind this traditional practice has been rendered obsolete through developments in anaesthetic agents and changes to postoperative analgesia practices. Conversely, there is a growing body of literature that consistently demonstrates that providing oral or tube feeding proximal to the anastomosis within 24 h postoperatively, is not only safe, but might be associated with significant benefits to the postoperative course. Early post operative feeding should therefore be adopted as a standard of care in oncology patients undergoing gastrointestinal resections.


HumanLectome, an update of UniLectin for the annotation and prediction of human lectins.
The UniLectin portal (https://unilectin.unige.ch/) was designed in 2019 with the goal of centralising curated and predicted data on carbohydrate-binding proteins known as lectins. UniLectin is also intended as a support for the study of lectomes (full lectin set) of organisms or tissues. The present update describes the inclusion of several new modules and details the latest (https://unilectin.unige.ch/humanLectome/), covering our knowledge of the human lectome and comprising 215 unevenly characterised lectins, particularly in terms of structural information. Each HumanLectome entry is protein-centric and compiles evidence of carbohydrate recognition domain(s), specificity, 3D-structure, tissue-based expression and related genomic data. Other recent improvements regarding interoperability and accessibility are outlined.


Polyvinyl alcohol and amino acids as substitutes for bovine serum albumin in culture media for mouse preimplantation embryos.
The effect of replacing bovine serum albumin (BSA) in a simple defined medium (KSOM) with polyvinyl alcohol (PVA) and/or amino acids on the percentages of mouse zygotes that develop to at least the blastocyst stage and that hatch at least partially or completely is reported. Blastocysts could form when BSA was replaced with only PVA, but at a moderately reduced rate; however, partial hatching, and hence complete hatching, were severely impaired when BSA was replaced with only PVA. The substitution of BSA with amino acids alone resulted in a high rate of blastocyst formation and moderate impairment of hatching. The addition of PVA to BSA-free KSOM supplemented with amino acids had no extra effect. BSA had significant effects when added to BSA-free KSOM supplemented with amino acids. The BSA caused a significant increase in the rate of partial hatching, and may even have had a small effect on the rate of blastocyst formation. The results also showed that glucose, at a high concentration of 5.56 mM, does not inhibit the development of mouse zygotes to hatched blastocysts when cultured in KSOM supplemented with amino acids.


Quantitative examination of video-recorded NHS Health Checks: comparison of the use of QRISK2 versus JBS3 cardiovascular risk calculators.
Quantitatively examine the content of National Health Service Health Check (NHSHC), patient-practitioner communication balance and differences when using QRISK2 versus JBS3 cardiovascular disease (CVD) risk calculators. RIsk COmmunication in NHSHC was a qualitative study with quantitative process evaluation, comparing NHSHC using QRISK2 or JBS3. We present data from the quantitative process evaluation. Twelve general practices in the West Midlands (England) conducted NHSHC using JBS3 or QRISK2 (6/group). Patients were eligible for NHSHC based on national criteria (aged 40-74, no existing cardiovascular-related diagnoses, not taking statins). Recruitment was stratified by patients' age, gender and ethnicity. Video recordings of NHSHC were coded, second-by-second, to quantify who was speaking and what was being discussed. Outcomes included consultation duration, practitioner verbal dominance (ratio of practitioner:patient speaking time (pr:pt ratio)) and proportion of time discussing CVD risk, risk factors and risk management. 173 video-recorded NHSHC were analysed (73 QRISK, 100 JBS3). The sample was 51% women, 83% white British, with approximately equal proportions across age groups. NHSHC duration varied greatly (6.8-38.0 min). Most (60%) lasted less than 20 min. On average, CVD risk was discussed for less than 2 min (9.06%±4.30% of consultation time). There were indications that, compared with NHSHC using JBS3, those with QRISK2 involved less CVD risk discussion (JBS3 M=10.24%, CI: 8.01-12.48 vs QRISK2 M=7.44%, CI: 5.29-9.58) and were more verbally dominated by practitioners (pr:pt ratio JBS3 M=3.21%, CI: 2.44-3.97 vs QRISK2=2.35%, CI: 1.89-2.81). The largest proportion of NHSHC time was spent discussing causal risk factors (M=37.54%, CI: 32.92-42.17). There was wide variation in NHSHC duration. Many were short and practitioner-dominated, with little time discussing CVD risk. JBS3 appears to extend CVD risk discussion and patient contribution. Qualitative examination of how it is used is necessary to fully understand the potential benefits of these differences. ISRCTN10443908.


A LATENT FACTOR MODEL FOR SPATIAL DATA WITH INFORMATIVE MISSINGNESS.
A large amount of data is typically collected during a periodontal exam. Analyzing these data poses several challenges. Several types of measurements are taken at many locations throughout the mouth. These spatially-referenced data are a mix of binary and continuous responses, making joint modeling difficult. Also, most patients have missing teeth. Periodontal disease is a leading cause of tooth loss, so it is likely that the number and location of missing teeth informs about the patient's periodontal health. In this paper we develop a multivariate spatial framework for these data which jointly models the binary and continuous responses as a function of a single latent spatial process representing general periodontal health. We also use the latent spatial process to model the location of missing teeth. We show using simulated and real data that exploiting spatial associations and jointly modeling the responses and locations of missing teeth mitigates the problems presented by these data.


Position of the American Dietetic Association: the impact of fluoride on health.
Fluoride is an important element for mineralization of body tissues. The use of topical and systemic fluoride for oral health has resulted in major reductions in dental caries and its associated disability. Fluoridation of public water supplies has been endorsed by over 90 professional health organizations as the most effective dental public health measure in existence. Still, about half of the US population fails to receive the maximum benefits possible from community water fluoridation and the use of fluoride products. Fluoride also plays a role in bone health. The role of high doses of fluoride for prevention of osteoporosis is undergoing active study and is considered experimental at this point. Dietetics professionals should routinely monitor and promote the use of systemic and topical fluorides, especially in children and adolescents. The American Dietetic Association strongly reaffirms its endorsement of the use of systemic and topical fluorides, including water fluoridation, at appropriate levels of intake, as an important public health measure. However, clients should be cautioned that experimental use of high intakes of fluoride should be avoided unless they are participating in clinical trials.


Nanotechnology for modern medicine: next step towards clinical translation.
The field of nanotechnology has been a significant research focus in the last thirty years. This emphasis is due to the unique optical, electrical, magnetic, chemical and biological properties of materials approximately ten thousand times smaller than the diameter of a hair strand. Researchers have developed methods to synthesize and characterize large libraries of nanomaterials and have demonstrated their preclinical utility. We have entered a new phase of nanomedicine development, where the focus is to translate these technologies to benefit patients. This review article provides an overview of nanomedicine's unique properties, the current state of the field, and discusses the challenge of clinical translation. Finally, we discuss the need to build and strengthen partnerships between engineers and clinicians to create a feedback loop between the bench and bedside. This partnership will guide fundamental studies on the nanoparticle-biological interactions, address clinical challenges and change the development and evaluation of new drug delivery systems, sensors, imaging agents and therapeutic systems.


In the shadow: The emerging role of long non-coding RNAs in the immune response of Atlantic salmon.
The genomic era has increased the research effort to uncover how the genome of an organism, and specifically the transcriptome, is modulated after interplaying with pathogenic microorganisms and ectoparasites. However, the ever-increasing accessibility of sequencing technology has also evidenced regulatory roles of long non-coding RNAs (lncRNAs) related to several biological processes including immune response. This study reports a high-confidence annotation and a comparative transcriptome analysis of lncRNAs from several tissues of Salmo salar infected with the most prevalent pathogens in the Chilean salmon aquaculture such as the infectious salmon anemia (ISA) virus, the intracellular bacterium Piscirickettsia salmonis and the ectoparasite copepod Caligus rogercresseyi. Our analyses showed that lncRNAs are widely modulated during infection. However, this modulation is pathogen-specific and highly correlated with immuno-related genes associated with innate immune response. These findings represent the first discovery for the widespread differential expression of lncRNAs in response to infections with different types of pathogens in Atlantic salmon, suggesting that lncRNAs are pivotal player during the fish immune response.


The epidemiology and effects of video game addiction: A systematic review and meta-analysis.
With the increasing popularity and accessibility of video games, the public concern about their effects - positive and negative - has also increased. In this regard, this systematic review sought to identify and thematically analyze recent studies (in the last five years) and report on video games' epidemiological characteristics and outcomes. A systematic database search was done on ScienceDirect, APA PsycINFO, Emerald, and Scopus databases for articles published from January 1, 2017, to April 1, 2022. The Meta XL software - an add-in for Microsoft Excel - was used to calculate the pooled prevalence level of video game addiction. The database search yielded a total of 693 non-duplicate articles. After applying the inclusion and exclusion criteria, 27 articles were selected to be included in the systematic review. Along with this, 12 articles were considered for the final meta-analysis. The pooled prevalence level of gaming addiction was 5.0 % (95 % CI, 2.1-8.8 %). The I2 value was 99.297 with a p-value of 0.000. The factors that accompanied addictive video gaming were psychological, social, and personal. An addictive gaming behavior was characterized by spending an above-average time on gaming, doing most of the gaming online, and gaming activities interfering with sleep patterns. Some predictors of addictive gaming were emotional dependence, social detachment, increased gaming time, preference for playing online than offline, and increased emotional and psychological stress. Engaging in addictive gaming led to adverse outcomes such as lower academic scores, depression, and anxiety, as well as decreased self-esteem, life satisfaction, and social support. From the collected findings it could be concluded that extreme playing of video games can be classified as addictive. Following the identification of risk factors, appropriate corrective or interventional measures should be developed and applied coherently to newer statistical data.


The effect of temperature on the initial development of Brycon amazonicus Spix & Agassiz, 1829 as tool for micromanipulation of embryos.
Primordial germ cell (PGC) transplant is a promising tool in aquaculture; however, successful use of this technique requires in depth knowledge of the early stages of embryo and larval development. The aim of this study was to analyse the effect of different temperatures (22, 26, and 30°C) on the early development of B. amazonicus. The newly fertilized eggs were distributed into tanks with controlled temperature and oxygenation. Samples were collected at pre-established times and analysed under light and fluorescence microscopy. Temperature influenced the speed and duration of each stage of early development, including hatching time. The highest pronuclei fusion rate was observed 8 min post-fertilization (mpf) at 22 and 26°C, and 6 mpf at 30°C. The duration of the 512-1000 blastomeres phase during in the blastocyst stage was 1 h 30 min at 22°C, and 25 min at 26 and 30°C. Hatching occurred at 24 h 30 mpf at 22°C, 16 h post-fertilization (hpf) at 26°C, and 11 h 30 mpf at 30°C. The rate of morphologically normal larvae was 88.34% at 22°C, 90.49% at 26°C, and 73% at 30°C. Malformations of the head, yolk sac, heart, and tail were observed in all temperatures. Nevertheless, B. amazonicus embryos were able to develop satisfactory in all three temperatures tested. These results enable embryo manipulation at different temperatures to optimize the micromanipulation time of embryos and larvae for biotechnological studies.


Health and production of feedlot cattle following supplementation with urea-molasses in starter pens.
To determine the effect of providing a urea-molasses supplement to cattle during feedlot introduction on average daily gain, carcase weight and bovine respiratory disease (BRD) morbidity and mortality. Commercial mixed sex, mixed breed cattle (387.4 ± 0.2 kg) were systematically allocated to receive 2.1 L/animal of urea-molasses during feedlot introduction (n = 2307) or remain untreated (n = 2336). Cattle remained in the feedlot for an average of 40 days until reaching slaughter weight. Body weight data was collected prior to feedlot induction and all cases of BRD morbidity and mortality were determined during feeding. Hot standard carcase weight and P8 fat thickness were determined at slaughter. Average daily gain (1.94 ± 0.06 vs 1.93 ± 0.06, P = 0.650), BRD incidence (6.46% vs 5.53%, P = 0.183) and BRD mortality (0.17% vs 0.21%, P = 0.752) did not differ between supplemented and unsupplemented cattle. The BRD incidence was higher (P = 0.017) when cattle without permanent incisors were supplemented with urea-molasses (7.26%) compared with unsupplemented cattle (5.26%), and was also higher in steers compared with heifers (12.7% vs 7.8%, P < 0.001) and higher in cattle purchased from saleyards compared with cattle purchased off paddocks (12.4% vs 5.7%, P < 0.001). Health and production were not significantly improved following supplementation of cattle with urea-molasses during feedlot introduction. BRD incidence was, however, significantly related to cattle sex and source. Further research is required to understand the relationship between feeding high non-protein nitrogen sources and BRD morbidity in young cattle.


A TFIIB-like protein is indispensable for spliced leader RNA gene transcription in Trypanosoma brucei.
The lack of general class II transcription factors was a hallmark of the genomic sequences of the human parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania major. However, the recent identification of TFIIA as part of a protein complex essential for RNA polymerase II-mediated transcription of SLRNA genes, which encode the trans splicing-specific spliced leader RNA, suggests that trypanosomatids assemble a highly divergent set of these factors at the SLRNA promoter. Here we report the identification of a trypanosomatid TFIIB-like (TFIIB(like)) protein which has limited overall sequence homology to eukaryotic TFIIB and archaeal TFB but harbors conserved residues within the N-terminal zinc ribbon domain, the B finger and cyclin repeat I. In accordance with the function of TFIIB, T.brucei TFIIB(like) is encoded by an essential gene, localizes to the nucleus, specifically binds to the SLRNA promoter, interacts with RNA polymerase II, and is absolutely required for SLRNA transcription.


[The infection of ixodid ticks collected from humans with the tick-borne encephalitis virus in Tomsk city and its suburbs].
The ticks Ixodes persulcatus and I. pavlovskyi collected from people visited gardens and suburban forests have been examined by the IFA methods on the presence of tick-borne encephalitis virus (TEV). It was established, that the most part of ticks collected from humans belongs to I. persulcatus, despite the fact that I. pavlovskyi dominates on the territory of the city and its suburbs. TEV infection was registered more often in fed ticks, in comparison with those without signs of preceding feeding. Infected specimens constituted 9.4% of 53 I. persulcatus individuals examined. In I. pavlovskyi 3.7% of 27 examined specimens were infected. In fed ticks (41 specimens of I. persulcatus and 20 I. pavlovskvi) the rates of infected specimens were higher and constituted 48.8 and 35%, respectively. In suburban forests, as well as in the city, I. persulcatus was found to attack humans more often than I. pavlovskyi. TEV infection was recorded in 12.7% of 220 unfed I. persulcatus specimens examined and in 41.6% of 142 fed individuals. In I. pavlovskyi, 6.6% of unfed and 25% of fed specimens was infected (33 unfed and 24 fed specimens were examined). Thus, in all territories examined, percent of infected specimens was significantly lower in I. pavlovskyi, and in fed ticks of both species, TEV was recorded more often.


Trabecular Bone Score in Men and Women with Impaired Fasting Glucose and Diabetes.
Diabetes is associated with increased skeletal fragility, despite higher bone mineral density (BMD). Alternative measures are necessary to more accurately determine fracture risk in individuals with diabetes. Therefore, we aimed to describe the relationship between trabecular bone score (TBS) and normoglycaemia, impaired fasting glucose (IFG) and diabetes and determine whether TBS-adjusted FRAX (Aus) score differed between these groups. This study included 555 men (68.7 ± 12.2 years) and 514 women (62.0 ± 12.0 years), enrolled in the observational Geelong Osteoporosis Study. IFG was considered as fasting plasma glucose (FPG) ≥ 5.5 mmol/L and diabetes as FPG ≥ 7.0 mmol/L, with the use of antihyperglycaemic medication and/or self-report. Using multivariable regression, the relationship between groups and TBS was determined. Men and women (all ages) with diabetes had lower mean TBS compared to those with normoglycaemia, in models adjusted for age, height and weight/waist circumference (all p < 0.05). Men with IFG had lower mean TBS in the age-adjusted models only (all p < 0.05). The addition of TBS to the FRAX score improved the discrimination between glycaemia groups, particularly for younger women (< 65 years). There was no difference in TBS detected between normoglycaemia and IFG; however, those with diabetes had lower TBS. Thus, the increased fracture risk in men and women with diabetes may be a result of BMD-independent bone deterioration. TBS adjustment of FRAX scores may be useful for younger women (< 65 years) with diabetes. This suggests that halting or reversing progression from IFG to diabetes could be important to prevent skeletal fragility in diabetes.


Spatial variation, mapping, and classification of moss families in semi-arid landscapes in NW Turkey.
Geostatistics and remote sensing techniques are frequently used in analyzing the spatial variability of terrestrial ecosystems. We analyzed spatial variation of moss families by geostatistics and Landsat imagery in a typical semi-arid landscape in North Central Anatolia, Turkey. We sampled 49 sites, chosen based on elevation, slope steepness, and slope aspect. Moss families were determined in a 10-m(2) representative area at each sampling site. The samples were transported to a laboratory and identified for moss families. In total, 10 families were found. Semivariogram analysis was performed to analyze the spatial structure of these families. The semivariogram analysis showed that the moss families were spatially dependent within 117 m in the study area. Thirteen thematic classes were categorized by Landsat Thematic Mapper (TM) image in the study area. The classification resulted in an overall kappa statistic of 0.8535, producer accuracy of 74.29, and user accuracy of 86.67. The family with the lowest classification accuracy was Orthotrichaceae (kappa of 0.6379, producer accuracy of 64.52, and user accuracy of 66.67). The moss families and the other classes were identified with a 0.78 kappa statistic value and an 80.74 % accuracy level by using the Landsat TM. The classification showed that Brachytheciaceae, Pottiaceae, Bryaceae, and Grimmiaceae were the most abundant moss families in this semi-arid environment.


[Affinity modification of creatine kinase and ATP-ADP translocase in heart mitochondria: determination of their stoichiometric ratio].
The interaction of mitochondrial creatine kinase and ATP-ADP translocase with 2.3-dialdehyde derivatives of ADP and ATP (oADP and oATP) has been studied. It was shown that these compounds are irreversible and specific inhibitors of creatine kinase (KioADP = 0.6mM, KioATP = 1.12 mM) and ATP-ADP translocase (KioADP = 0.065mM, KioATP = 0.14 mM). The substrates protect both enzymes from inactivation by these compounds. The maximal pseudo-first order rate constants for the 2,3-dialdehyde nucleotide derivative interaction with creatine kinase are 0.2 min-1 for oADP (pH 6.5) and 0.11 min-1 for oATP (pH 7.0). A decrease in the creatine kinase activity correlates with the incorporation of the reagent into the protein. The completely inactivated, isolated and purified enzyme contains 1 mol of oADP per mole of active sites. A procedure for simultaneous determination of the creatine kinase and translocase content in mitochondria and mitoplasts has been developed, which is based on the application of [3H]oADP in combination with specific treatment of mitochondria (or mitoplasts) with carboxyatractyloside 2,4-dinitrofluorobenzene and a mixture of creatine kinase substrates (MgADP + phosphocreatine). It has been found that for heart mitochondria from different animals the content of creatine kinase and translocase is 2.1-2.6 and 2.4-2.9 mol per mol of cytochrome c oxidase, respectively. Thus, the stoiochiometric ratio of creatine kinase and ATP-ADP translocase is close to 1.0 for all mitochondrial preparations under study (i.e. rat, dog, rabbit and chicken).


[The biologization of ethics].
Three ethics exist as a condition of possibility of any possible ethics, following a material and biological foundation. This content argument (not logical-formal) supposes a refutation of the naturalistic fallacy that the analytical philosophy attributes to Hume, in three areas of the ethical human experience: body, society and nature. These are: the ethics of the species [J. Habermas], the ethics of liberation [E. Dussel] and the ethics of the responsibility [H. Jonas]. This material argument is a philosophical foundation to considering for three types of applied ethics: medical bioethics, development ethics and environmental ethics.


Women are more disabled in basic activities of daily living than men only in very advanced ages: a study on disability, morbidity, and mortality from the Kungsholmen Project.
We explored the effect of morbidity, mortality, and occurrence of new disability on gender differences in activities of daily living (ADL) functioning in different age groups in the elderly population. All 77+-year-old members of a community-based cohort were clinically examined by physicians, assessed by psychologists, and interviewed by nurses at baseline and after a 3-year interval. Diseases were diagnosed according to ICD-9 and the DSM-III-R criteria for dementia. The Katz index of ADL was used to measure basic functional status. After adjustment for socio-demographic characteristics, the oldest women (90+ years) had higher disability prevalence and a tendency for higher long-term disability incidence. Women aged 85+ years also had higher morbidity prevalence. Mortality among disabled subjects was similar for both genders, whereas higher mortality was found in younger nondisabled men (77-84 years). We conclude that gender differences in disability, morbidity, and mortality vary with age in the elderly population. Gender differences in morbidity and basic functional dependence were evident only in the oldest old. Based on current and previous findings, we speculate that more women may be at higher risk of developing severe disability than men in the advanced ages due to longer survival with slight disability earlier in adult life.


Influence of obstructive sleep apnea on left ventricular mass and global function: sleep apnea and myocardial performance index.
Obstructive sleep apnea (OSA) is associated with cardiovascular mortality and morbidity. It may predispose patients to left ventricular hypertrophy and heart failure. The aim of this study was to determine the left ventricular mass (LVM) and myocardial performance index (MPI) reflecting left ventricular global function in uncomplicated OSA patients. Sixty-four subjects without hypertension, diabetes mellitus, and any cardiac or pulmonary disease referred for evaluation of OSA underwent overnight polysomnography and complete echocardiographic assessment. According to the apnea hypopnea index (AHI), subjects were divided into three groups: group 1, control subjects with nonapneic snorers (AHI < 5, n = 18); group 2, patients with mild to moderate OSA (AHI: 5-30, n = 25); and group 3, severe OSA (AHI > 30, n = 21). Basic echocardiographic measurements, LVM, and LVM index were measured. Left ventricular MPI was calculated as (isovolumic contraction time+isovolumic relaxation time)/aortic ejection time by Doppler echocardiography. There were no significant differences in age, sex, body mass index, heart rate, and systolic and diastolic blood pressure among the three groups. Left atrium, interventricular septum, left ventricular posterior wall, left ventricular end-diastolic and end-systolic diameters, LVM mass, and LVM index were not significantly different among the three groups. Left ventricular MPI was significantly higher in severe OSA patients (0.64 +/- 0.18) than in controls (0.49 +/- 0.18; P < 0.05). There was no significant difference between controls (0.49 +/- 0.18) and mild to moderate OSA (0.61 +/- 0.16; P = 0.08) and between mild to moderate OSA (0.61 +/- 0.16) and severe OSA (0.64 +/- 0.18; P = 0.84). The present study demonstrates that patients with severe OSA have global left ventricular dysfunction.


A narrative review of the modern surgical management of pediatric choledochal cysts.
Choledochal cysts (CC) ae rare congenital dilations of the biliary tract that harbor lifelong malignancy risk. CC are treated with surgical excision and bilioenteric reconstruction. In the modern era, the surgical approach to pediatric patients has enjoyed significant innovation with regards to minimally invasive techniques. In this review, we discuss these advances, including laparoscopic, single-incision laparoscopic, and robotic strategies, with a focus on the clinical outcomes of patients undergoing these procedures. By presenting an overview of the technical pearls emphasized by pioneers of these procedures, we examine the benefits and limitations of various minimally invasive techniques and analyze the utility and effectiveness of laparoscopy and robotics in comparison to each other and open techniques. Additionally, we highlight the importance of surgeon experience and skill in the management of this rare pediatric disease and explore the significance of the surgical learning curve in minimally invasive approaches in the excision of CC. We discuss the challenge of achieving surgical competency along this learning curve, and present proposed strategies to improve skill sets in the face of low case volumes. Finally, the relative dearth of data discussing long-term follow-up in these patients is discussed, and additional research regarding outcomes, malignancy risk and surveillance, and quality of life is necessary to better understand this disease and the implications of its surgical management.


Genetic diversity and population history of the endangered killifish Aphanius baeticus.
The secondary freshwater fish fauna of the western-Iberian Peninsula basin is primarily restricted to local coastal streams, and man-made salt evaporation ponds, etc., which are susceptible to periodical flood and drought events. Despite its uniqueness in ecological adaptation to high saltwater tolerance, very little is known about this fauna's population dynamics and evolutionary history. The killifish, Aphanius baeticus (Cyprinodontidae) is an endemic species restricted to river basins on Spain's southern Atlantic coastline, considered as "Endangered." In this study, the genetic structure, diversity and historical demography of A. baeticus were analyzed using mitochondrial (cytochrome b, N=131) and nuclear (4 out of 19 microsatellites tested, N=288) markers across its distribution range. The phylogenetic and networking reconstruction revealed subtle phylogeographic structuring. A scattered expansion at the beginning of the interglacial periods, coupled with posterior events of extinction and colonization caused by periodical cycles of flooding, could explain the absence of well-defined phylogenetic relationships among populations. Moreover, very low genetic diversity values and a weak population differentiation were detected. We proposed that dispersals allowed by periodic floods connecting river drainages may have promoted a wide genetic exchange among populations and could have contributed to the current genetic relatedness of these populations.


Probiotics for induction of remission in ulcerative colitis.
Ulcerative colitis is an inflammatory condition affecting the colon, with an annual incidence of approximately 10 to 20 per 100,000 people. The majority of people with ulcerative colitis can be put into remission, leaving a group who do not respond to first- or second-line therapies. There is a significant proportion of people who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of ulcerative colitis are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response. To assess the efficacy of probiotics compared with placebo or standard medical treatment (5-aminosalicylates, sulphasalazine or corticosteroids) for the induction of remission in people with active ulcerative colitis. We searched CENTRAL, MEDLINE, Embase, and two other databases on 31 October 2019. We contacted authors of relevant studies and manufacturers of probiotics regarding ongoing or unpublished trials that may be relevant to the review, and we searched ClinicalTrials.gov. We also searched references of trials for any additional trials. Randomised controlled trials (RCTs) investigating the effectiveness of probiotics compared to standard treatments or placebo in the induction of remission of active ulcerative colitis. We considered both adults and children, with studies reporting outcomes of clinical, endoscopic, histologic or surgical remission as defined by study authors DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE methodology. In this review, we included 14 studies (865 randomised participants) that met the inclusion criteria. Twelve of the studies looked at adult participants and two studies looked at paediatric participants with mild to moderate ulcerative colitis, the average age was between 12.5 and 47.7 years. The studies compared probiotics to placebo, probiotics to 5-ASA and a combination of probiotics plus 5-ASA compared to 5-ASA alone. Seven studies used a single probiotic strain and seven used a mixture of strains. The studies ranged from two weeks to 52 weeks. The risk of bias was high for all except two studies due to allocation concealment, blinding of participants, incomplete reports of outcome data and selective reporting. This led to GRADE ratings of the evidence ranging from moderate to very low. Probiotics versus placebo Probiotics may induce clinical remission when compared to placebo (RR 1.73, 95% CI 1.19 to 2.54; 9 studies, 594 participants; low-certainty evidence; downgraded due to imprecision and risk of bias, number needed to treat for an additional beneficial outcome (NNTB) 5). Probiotics may lead to an improvement in clinical disease scores (RR 2.29, 95% CI 1.13 to 4.63; 2 studies, 54 participants; downgraded due to risk of bias and imprecision). There may be little or no difference in minor adverse events, but the evidence is of very low certainty (RR 1.04, 95% CI 0.42 to 2.59; 7 studies, 520 participants). Reported adverse events included abdominal bloating and discomfort. Probiotics did not lead to any serious adverse events in any of the seven studies that reported on it, however five adverse events were reported in the placebo arm of one study (RR 0.09, CI 0.01 to 1.66; 1 study, 526 participants; very low-certainty evidence; downgraded due to high risk of bias and imprecision). Probiotics may make little or no difference to withdrawals due to adverse events (RR 0.85, 95% CI 0.42 to 1.72; 4 studies, 401 participants; low-certainty evidence). Probiotics versus 5-ASA There may be little or no difference in the induction of remission with probiotics when compared to 5-ASA (RR 0.92, 95% CI 0.73 to 1.16; 1 study, 116 participants; low-certainty evidence; downgraded due to risk of bias and imprecision). There may be little or no difference in minor adverse events, but the evidence is of very low certainty (RR 1.33, 95% CI 0.53 to 3.33; 1 study, 116 participants). Reported adverse events included abdominal pain, nausea, headache and mouth ulcers. There were no serious adverse events with probiotics, however perforated sigmoid diverticulum and respiratory failure in a patient with severe emphysema were reported in the 5-ASA arm (RR 0.21, 95% CI 0.01 to 4.22; 1 study, 116 participants; very low-certainty evidence). Probiotics combined with 5-ASA versus 5-ASA alone Low-certainty evidence from a single study shows that when combined with 5-ASA, probiotics may slightly improve the induction of remission (based on the Sunderland disease activity index) compared to 5-ASA alone (RR 1.22 CI 1.01 to 1.47; 1 study, 84 participants; low-certainty evidence; downgraded due to unclear risk of bias and imprecision). No information about adverse events was reported. Time to remission, histological and biochemical outcomes were sparsely reported in the studies. None of the other secondary outcomes (progression to surgery, need for additional therapy, quality of life scores, or steroid withdrawal) were reported in any of the studies. Low-certainty evidence suggests that probiotics may induce clinical remission in active ulcerative colitis when compared to placebo. There may be little or no difference in clinical remission with probiotics alone compared to 5-ASA. There is limited evidence from a single study which failed to provide a definition of remission, that probiotics may slightly improve the induction of remission when used in combination with 5-ASA. There was no evidence to assess whether probiotics are effective in people with severe and more extensive disease, or if specific preparations are superior to others. Further targeted and appropriately designed RCTs are needed to address the gaps in the evidence base. In particular, appropriate powering of studies and the use of standardised participant groups and outcome measures in line with the wider field are needed, as well as reporting to minimise risk of bias.


[Recurrence and survival after surgical treatment of lung cancer].
2500 new cases of lung cancer are diagnosed in Norway annually. Patients with limited disease can be operated, but many will die from the disease despite surgical treatment. The aim of the study was to review survival and recurrence, and factors which affect survival, in patients operated for lung cancer. The risk of death and recurrence of disease was assessed retrospectively in patients who had non-small lung cancer and were operated at St. Olavs University Hospital, Trondheim in the period 1994-2001. Patient data were retrieved from medical records and a database with records from thoracosurgical procedures. 190 patients (30 % women) were included in the study. Average observation time after surgery was 58.3 months (range 21-99). Adenocarcinoma was the most common histological cancer type and occurred in 57.9 % of women and 39.1 % of the men (p = 0.02). The 30-day mortality rate was 3.2 % and the 60-day rate was 4.7 %. Recurrence of the disease was found in 45.8 %, among them median time to recurrence was 9 months after the operation. 5-year survival was 42 %, as analysed by the Kaplan-Meier estimate, and survival was best for early stages of the disease. 5-year survival was better for women (53.3 %) than men (36.8 %), p = 0.05. Prognostic factors for survival, estimated by Hazard ratio for death with Cox multiple regression analysis, were sex, age at the time of operation, type of operation, tumour diameter and postoperative N-stage. Postoperative mortality and survival corresponded to data in the literature. Early stage lung cancer can be cured with surgical treatment. Our study confirms an increase in the incidence of adenocarcinoma among lung cancer patients during the last decades. Female sex is a positive prognostic factor for survival, as is young age, small tumor size, standard lobectomy, and absence of lymph node metastases.


Human omental adipose-derived mesenchymal stem cell-conditioned medium alters the proteomic profile of epithelial ovarian cancer cell lines in vitro.
Mesenchymal stem cells (MSCs) have been reported to participate in the formation of supportive tumor stroma. The abilities of proliferation and invasion of human epithelial ovarian cancer (EOC) cells were significantly enhanced when indirectly cocultured with human omental adipose-derived MSCs (O-ADSCs) in vitro. However, the underlying mechanisms remain poorly understood. In this study, EOC cells were cultured with conditioned medium (CM) from O-ADSCs (O-ADSC), and the effect of O-ADSC CM on the proteomic profile of EOC cells was assessed by two-dimensional gel electrophoresis (2-DE), followed by liquid chromatography and tandem mass spectrometry. The 2-DE assays revealed a global increase in protein expression in the EOC cells treated with CM. Nine proteins were identified from 11 selected protein spots with differential expression after treatment with CM from O-ADSCs. All the nine proteins have been linked to carcinoma and apoptosis, and the migration ability of tumor cells can be regulated by these proteins. Moreover, the upregulation of prohibitin and serine/arginine-rich splicing factor 1 in EOC cells treated with CM was further confirmed by quantitative real-time polymerase chain reaction. These results suggest that O-ADSCs affect the proteomic profile of EOC cells via paracrine mechanism in favor of EOC progression.


Electric impedance tomography enables portable and non-invasive approach to screen and monitor chronic kidney disease.
Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Here, we explore the potential of using home-based frequency-difference electrical impedance tomography (fdEIT) to evaluate CKD based on bio-conductivity characteristics. We performed bio-conductivity measurement in vivo paired with standard estimated glomerular filtration rate (eGFR) measurements on a N=126 CKD patients by EIT and traditional blood and urine tests, respectively. We developed an EIT processing pipeline that extracts the kidney regions from EIT images. We further developed a regression model and a CKD classification scheme. Our results showed a significant correlation between EIT-features and eGFR, and the classification scheme shows sensitivity and specificity of 76.2% and 74.6% respectively considering stages 1 and 2 CKD versus stages 3, 4 and 5 CKD. These results suggest the feasibility of EIT to be used as a portable, self-administrated and home-based approach for CKD early diagnostic screening and longitudinal monitoring.Clinical Relevance-The results presented here demonstrates a cost-effective, home-based and self-administrative screening process on chronic kidney disease patients, thereby enhancing the quality and area of possible application of telemedicine. By achieving this, the process presented here can relieve the burden of public health system.


Murine leukemia: a virus-induced autoimmune disease?
Thymocytes from mice carrying Moloney murine leukemia virus since birth are cytotoxic for normal syngeneic fibroblasts; they are much less cytotoxic for the same cells infected with this virus. The cytotoxic thymocytes appear to increase in number with age of the carrier mice and are present both during preleukemic and leukemic periods. These results suggest that lymphomas in carrier mice result from a sequence of events initiated by intrathymic destruction of normal cells by virus-infected cells, and culminating in the unrestricted proliferation of autoaggressive clones in the thymic cortex.


Mild acid and alkali treated clay minerals enhance bioremediation of polycyclic aromatic hydrocarbons in long-term contaminated soil: A 14C-tracer study.
Bioremediation of polycyclic aromatic hydrocarbon (PAH)-contaminated soils requires a higher microbial viability and an increased PAH bioavailability. The clay/modified clay-modulated bacterial degradation could deliver a more efficient removal of PAHs in soils depending on the bioavailability of the compounds. In this study, we modified clay minerals (smectite and palygorskite) with mild acid (HCl) and alkali (NaOH) treatments (0.5-3 M), which increased the surface area and pore volume of the products, and removed the impurities without collapsing the crystalline structure of clay minerals. In soil incubation studies, supplements with the clay products increased bacterial growth in the order: 0.5 M HCl ≥ unmodified ≥ 0.5 M NaOH ≥ 3 M NaOH ≥ 3 M HCl for smectite, and 0.5 M HCl ≥ 3 M NaOH ≥ 0.5 M NaOH ≥ 3 M HCl ≥ unmodified for palygorskite. A14C-tracing study showed that the mild acid/alkali-treated clay products increased the PAH biodegradation (5-8%) in the order of 0.5 M HCl ≥ unmodified > 3 M NaOH ≥ 0.5 M NaOH for smectite, and 0.5 M HCl > 0.5 M NaOH ≥ unmodified ≥ 3 M NaOH for palygorskite. The biodegradation was correlated (r = 0.81) with the bioavailable fraction of PAHs and microbial growth as affected particularly by the 0.5 M HCl and 0.5 M NaOH-treated clay minerals. These results could be pivotal in developing a clay-modulated bioremediation technology for cleaning up PAH-contaminated soils and sediments in the field.


Eccentric correction for off-axis vision in central visual field loss.
Subjects with absolute central visual field loss use eccentric fixation and magnifying devices to utilize their residual vision. This preliminary study investigated the importance of an accurate eccentric correction of off-axis refractive errors to optimize the residual visual function for these subjects. Photorefraction using the PowerRefractor instrument was used to evaluate the ametropia in eccentric fixation angles. Methods were adapted for measuring visual acuity outside the macula using filtered optotypes from high-pass resolution perimetry. Optical corrections were implemented, and the visual function of subjects with central visual field loss was measured with and without eccentric correction. Of the seven cases reported, five experienced an improvement in visual function in their preferred retinal locus with eccentric refraction. The main result was that optical correction for better image quality on the peripheral retina is important for the vision of subjects with central visual field loss, objectively as well as subjectively.


Development of new drugs for chemoprophylaxis of malaria.
When U.S. troops first encountered drug resistant malaria during the Vietnam war, the United States Army responded by establishing a malaria drug research program. In 1988, the Walter Reed Army Institute of Research developed mefloquine (WR 149240) and halofantrine (WR 171669). Actually in association with SmithKline Beecham, the WRAIR is developing tafenoquine (WR 238605), an analogue of primaquine, which is expected to be effective in both preventing and treating malaria in deployed military personnel. Final phase III studies leading to U.S. Food and Drug Administration approval are planned for 2000. Applied research is also carried out with the association atovaquone-proguanil (Malarone) or with azithromycin, but also with primaquine, the associations paludrine-dapsone or lapudrine-dapsone, analogues of floxacrine (WR 243251), and a guanylhydrazone (WR 182393). The future scientific directions must focus on basic and applied research for a better understanding of the modes of action and mechanisms of resistance to standard and developmental drugs. Using new techniques, the design and synthesis of new drugs would hopefully result in the development of drugs that circumvent the malaria parasites elusive mechanisms of drug resistance.


The FAST-ED App: A Smartphone Platform for the Field Triage of Patients With Stroke.
The Emergency Medical Services field triage to stroke centers has gained considerable complexity with the recent demonstration of clinical benefit of endovascular treatment for acute ischemic stroke. We sought to describe a new smartphone freeware application designed to assist Emergency Medical Services professionals with the field assessment and destination triage of patients with acute ischemic stroke. Review of the application's platform and its development as well as the different variables, assessments, algorithms, and assumptions involved. The FAST-ED (Field Assessment Stroke Triage for Emergency Destination) application is based on a built-in automated decision-making algorithm that relies on (1) a brief series of questions assessing patient's age, anticoagulant usage, time last known normal, motor weakness, gaze deviation, aphasia, and hemineglect; (2) a database of all regional stroke centers according to their capability to provide endovascular treatment; and (3) Global Positioning System technology with real-time traffic information to compute the patient's eligibility for intravenous tissue-type plasminogen activator or endovascular treatment as well as the distances/transportation times to the different neighboring stroke centers in order to assist Emergency Medical Services professionals with the decision about the most suitable destination for any given patient with acute ischemic stroke. The FAST-ED smartphone application has great potential to improve the triage of patients with acute ischemic stroke, as it seems capable to optimize resources, reduce hospital arrivals times, and maximize the use of both intravenous tissue-type plasminogen activator and endovascular treatment ultimately leading to better clinical outcomes. Future field studies are needed to properly evaluate the impact of this tool in stroke outcomes and resource utilization.


A population study of the frequency of high-dose acetaminophen prescribing and dispensing.
Recurrent intake of 4 g/day or more of acetaminophen has been associated with elevation of serum alanine aminotransferase (ALT) levels in 30-40% of the exposed population and may result in hepatotoxicity. To describe the frequency that patients are prescribed acetaminophen doses that exceed 4 g/day across a large population. Using California's Medicaid (Medi-Cal) fee-for-service population, pharmacy claims including over-the-counter (OTC) medications were examined for prescriptions that could result in acetaminophen doses of 4 g/day or more. The period studied, October 2004 through September 2005, was before the Part D pharmacy benefit was available to dually eligible Medicare patients when all prescriptions were covered by the Medi-Cal claims process. During the pre-Part D evaluation period, approximately 3.27 million beneficiaries were enrolled in the fee-for-service Medi-Cal program. A total of 192,716 (5.9%) were potentially exposed to at least 1 day of 4 g/day or more of acetaminophen. Of those, 769 patients were potentially exposed to at least 1 day of 16 g/day or more. A total of 2664 beneficiaries were dispensed prescriptions and OTC products that, if taken as directed, would have resulted in more than 100 days of acetaminophen doses of 4 g/day or more during the study year. Despite electronic systems designed to warn dispensing pharmacists of duplications of drug class and cumulative excessive doses, potentially toxic amounts of acetaminophen are commonly prescribed and dispensed to this population. Better systems, increased awareness, and education of patients, prescribers, and pharmacists are needed to reduce this potential toxic exposure.


Neutrophil activation and mediators of inflammation in chronic venous insufficiency.
The effect of venous hypertension on the state of activation of leucocytes has been investigated in patients with venous disease and control subjects. Leucocytes become 'trapped' in the circulation of the leg during periods of venous hypertension produced by sitting or standing. This is greater in the limbs of patients with chronic venous disease than controls. Studies of the plasma levels of neutrophil granule enzymes show that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligand CD11b shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the vascular (VCAM), intercellular (ICAM) and endothelial leucocyte (ELAM) adhesion molecules show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 min of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. I believe that this may be the mechanism that initiates the pathological processes which lead to venous ulceration. It has recently been shown that the venotonic drug Daflon 500 mg (450 mg diosmin, 50 mg hesperidin, Servier, France) influences these processes. Surface expression of CD62L is reduced in neutrophils and monocytes, and plasma levels of soluble endothelial adhesion molecules are reduced. These observations may explain the anti-inflammatory effects of Daflon 500 mg.


[Progresses in the treatment of early breast cancer. A mini-review].
The treatment of breast cancer has undergone continuous and profound changes over the last three decades; breast conservation therapy has been progressively validated as a safe alternative to radical mastectomy for patients with early stage breast cancer. Several large trials have shown that overall survival time of patients treated with conservative surgery and axillary dissection followed by radiation therapy is equivalent to that of patients treated with modified radical mastectomy, with better cosmetic outcomes and acceptable rates of local recurrence. Improvements in diagnostic work-up and the wider diffusion of screening programs have allowed the detection of smaller, often non palpable tumours, furtherly facilitating the widespread use of tumour localization and breast conserving techniques. Since the removal of negative lymph nodes is useless, eventually harmful and plays no therapeutic role in breast cancer patients, techniques for staging of the axilla have also gradually evolved toward less aggressive approaches, such as lymphatic mapping and sentinel node biopsy. The introduction of "onco-plastic techniques", that combine the concepts of oncological and plastic surgery of the breast, achieve the goal of allowing more extensive excisions while improving the aesthetic results, and eventually patient's quality of life. The present work will highlight potential benefits as well as unresolved issues of the above mentioned therapeutic options, with special emphasis on technical aspects of conservative surgery in the treatment of early breast cancers.


Evaluation of a parent-delivered early language enrichment programme: evidence from a randomised controlled trial.
It is widely believed that increasing parental involvement can improve children's educational outcomes although we lack good evidence for such claims. This study evaluated the effectiveness of a parent-delivered early language enrichment programme. We conducted a randomised controlled trial (RCT) with 208 preschool children and their parents living in socially diverse areas in the United Kingdom. Families were allocated to an oral language programme (N = 103) or an active control programme targeting motor skills (N = 105). Parents delivered the programmes to their child at home in daily 20-min sessions over 30 weeks of teaching. Children receiving the language programme made significantly larger gains in language (d = .21) and narrative skills (d = .36) than children receiving the motor skills programme at immediate posttest. Effects on language were maintained 6 months later (d = .34), and at this point, the language group also scored higher on tests of early literacy (d values=.35 and .42). There was no evidence that the movement programme improved motor skills. This study provides evidence for the effectiveness of a parent-delivered language enrichment programme. Further large-scale evaluations of the programme are needed to confirm and extend these findings.


GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion.
GPRC5B is an orphan receptor belonging to the group C family of G protein-coupled receptors (GPCRs). GPRC5B is abundantly expressed in both human and mouse pancreatic islets, and both GPRC5B mRNA and protein are up-regulated 2.5-fold in islets from organ donors with type 2 diabetes. Expression of Gprc5b is 50% lower in islets isolated from newborn (<3 weeks) than in adult (>36 weeks) mice. Lentiviral shRNA-mediated down-regulation of Gprc5b in intact islets from 12 to 16 week-old mice strongly (2.5-fold) increased basal (1 mmol/l) and moderately (40%) potentiated glucose (20 mmol/l) stimulated insulin secretion and also enhanced the potentiating effect of glutamate on insulin secretion. Downregulation of Gprc5b protected murine insulin-secreting clonal MIN6 cells against cytokine-induced apoptosis. We propose that increased expression of GPRC5B contributes to the reduced insulin secretion and b-cell viability observed in type-2 diabetes. Thus, pharmacological targeting of GPRC5B might provide a novel means therapy for the treatment and prevention of type-2 diabetes.


From beat rate variability in induced pluripotent stem cell-derived pacemaker cells to heart rate variability in human subjects.
We previously reported that induced pluripotent stem cell-derived cardiomyocytes manifest beat rate variability (BRV) resembling heart rate variability (HRV) in the human sinoatrial node. We now hypothesized the BRV-HRV continuum originates in pacemaker cells. To investigate whether cellular BRV is a source of HRV dynamics, we hypothesized 3 levels of interaction among different cardiomyocyte entities: (1) single pacemaker cells, (2) networks of electrically coupled pacemaker cells, and (3) the in situ sinoatrial node. We measured BRV/HRV properties in single pacemaker cells, induced pluripotent stem cell-derived contracting embryoid bodies (EBs), and electrocardiograms from the same individual. Pronounced BRV/HRV was present at all 3 levels. The coefficient of variance of interbeat intervals and Poincaré plot indices SD1 and SD2 for single cells were 20 times greater than those for EBs (P < .05) and the in situ heart (the latter two were similar; P > .05). We also compared BRV magnitude among single cells, small EBs (~5-10 cells), and larger EBs (>10 cells): BRV indices progressively increased with the decrease in the cell number (P < .05). Disrupting intracellular Ca(2+) handling markedly augmented BRV magnitude, revealing a unique bimodal firing pattern, suggesting that intracellular mechanisms contribute to BRV/HRV and the fractal behavior of heart rhythm. The decreased BRV magnitude in transitioning from the single cell to the EB suggests that the HRV of in situ hearts originates from the summation and integration of multiple cell-based oscillators. Hence, complex interactions among multiple pacemaker cells and intracellular Ca(2+) handling determine HRV in humans and cardiomyocyte networks.


[Biochemically labelled human lymphoblastoid cell line. I. Its karyotypic, growth and physiological characteristics].
A study was made of the properties of human lymphoid cell line RPMI-6410 derived from peripheral blood of a patient with acute myeloblastic leukaemia. The lymphoblastoid cell line was found to be resistant to 5-brom-deoxyuridine and to have a low thymidine kinase activity. The modal chromosome number for RPMI-6410 is 46-47 XY. The karyotype includes marker chromosomes: two large submetacentrics --M1 and M2, and two small acrocentrics--M3 and M4. Ways of marker chromosome formation are discussed. The properties of RPMI-6410 line make it possible to use it for somatic cell hybridization, in particular, for obtaining hybridoma synthesizing human monoclonal antibodies.


Bifunctional Epimerase/Reductase Enzymes Facilitate the Modulation of 6-Deoxy-Heptoses Found in the Capsular Polysaccharides of Campylobacter jejuni.
Campylobacter jejuni is a human pathogen and the leading cause of food poisoning in the United States and Europe. Surrounding the exterior surface of this bacterium is a capsular polysaccharide (CPS) that consists of a repeating sequence of common and unusual carbohydrate segments. At least 10 different heptose sugars have thus far been identified in the various strains of C. jejuni. The accepted biosynthetic pathway for the construction of the 6-deoxy-heptoses begins with the 4,6-dehydration of GDP-d-glycero-d-manno-heptose by a dehydratase, followed by an epimerase that racemizes C3 and/or C5 of the product GDP-6-deoxy-4-keto-d-lyxo-heptose. In the final step, a C4-reductase catalyzes the NADPH reduction of the resulting 4-keto product. However, in some strains and serotypes of C. jejuni, there are two separate C4-reductases with different product specificities in the gene cluster for CPS formation. Five pairs of these tandem C4-reductases were isolated, and the catalytic properties were ascertained. In four out of five cases, one of the two C4-reductases is able to catalyze the isomerization of C3 and C5 of GDP-6-deoxy-4-keto-d-lyxo-heptose, in addition to the catalysis of the reduction of C4, thus bypassing the requirement for a separate C3/C5-isomerase. In each case, the 3'-end of the gene for the first C4-reductase contains a poly-G tract of 8-10 guanine residues that may be used to control the expression and/or catalytic activity of either C4-reductase. The three-dimensional structure of the C4-reductase from serotype HS:15, which only does a reduction of C4, was determined to 1.45 Å resolution in the presence of NADPH and GDP.